George Kudolo - Profile on Academia.edu (original) (raw)

Papers by George Kudolo

Research paper thumbnail of Lyso-PAF:acetyl-CoA acetyltransferase and CDP-choline cholinephosphotransferase activities in the rabbit endometrium

platelet-activating factor * Corresponding author.

Research paper thumbnail of The Effect of 3-Month Ingestion of Ginkgo biloba Extract (EGb 761) on Pancreatic β-Cell Function in Response to Glucose Loading in Individuals with Non-Insulin-Dependent Diabetes Mellitus

Ginkgo biloba, the maidenhair tree, is one of several remedies that has been used in traditional ... more Ginkgo biloba, the maidenhair tree, is one of several remedies that has been used in traditional Chinese medicine for thousands of years. 1 Only more recently has it found worldwide recognition. For example, it has been used in Europe clinically for the treatment of several diseases, including peripheral and cerebral insufficiency associated with aging. 2,3 In the United States, Ginkgo biloba extract (EGb 761) is a very popular over-the-counter dietary supplement, which is ingested primarily to enhance mental focus. The growing interest in this herb stems from the increasing reports suggesting that Ginkgo biloba may ameliorate age

Research paper thumbnail of Jones, Kudolo & Harper

Research paper thumbnail of The Effect of 3-Month Ingestion of Ginkgo biloba Extract on Pancreatic β-Cell Function in Response to Glucose Loading in Normal Glucose Tolerant Individuals

Research paper thumbnail of EC PHARMACOLOGY AND TOXICOLOGY Review Article Arachidonic Acid and Platelet-Activating Factor as Central Players in the Metabolic Syndrome. Lessons from the Use of the Ginkgo Biloba Extract

Diabetes mellitus is a chronic disease with worldwide prevalence and the toll of the disease is s... more Diabetes mellitus is a chronic disease with worldwide prevalence and the toll of the disease is substantially increased because it is commonly associated with several chronic disorders, collectively termed the metabolic syndrome. There is continuing efforts to identify the biochemical compound/s linking all of the disorders. I have hypothesized that arachidonic acid and platelet-activating factor, lipids found in the plasma membrane, are central players and have used Ginkgo biloba extract to test this hypothesis. The standardized Ginkgo biloba leaf extract contains approximately 24% flavonoid glycosides, to which the free radical scavenging properties have been ascribed, and 6% terpene lactones which is thought to be responsible for platelet aggregation inhibit and increase blood flow. This review summarizes the characteristics of the metabolic syndrome and results of more than two decades of clinical studies involving the ingestion of 120 mg of Ginkgo biloba extract daily, as a single dose for 3 months in open label or randomized double-blind placebo control trials. It was found that Ginkgo biloba extract: (1) decreased in vivo platelet reactivity, as seen by decreased plasma thromboxane B 2 and urinary excretion of the thromboxane B 2 metabolites, and in vitro reduction of arachidonic acid stimulated platelet thromboxane A 2 production. The later was accompanied by reduced synthesis of malondialdehyde, a reactive oxygen species, in both non-diabetic and diabetic subjects. Importantly it was discovered that Ginkgo inhibited platelet aggregation mediated predominantly by collagen, and to a lesser degree, by platelet-activating factor, (2) stimulated pancreatic -cell insulin production in both non-diabetic and type 2 diabetic subjects, especially in diabetic subjects with pancreatic exhaustion and (3) did not increase whole body insulin resistance. Taken together, it seems that cell membrane perturbation resulting in the release and metabolism of arachidonic acid and platelet-activating factor might be the underlying cause in the development of several metabolic defects commonly associated with diabetes and the use Ginkgo biloba extract allowed us to verify several aspects of the metabolic syndrome.

Research paper thumbnail of Ginkgo biloba extract and the PCOS patient: Perspectives from the San Antonio clinical trials

Journal of Clinical and Molecular Endocrinology, 2018

free androgen index and testosterone dihydrotestosterone ratio were studied, and have been found to significantly correlate with clinical parameters. There is controversy regarding thresholds for diagnosis in adolescents and peri-menopausal women and the most appropriate therapeutic approaches for these patients. Metformin is found to have significant role in the management as insulin resistance is the key etiopathogenic factor in PCOS, which was also evidenced in our randomized control trial. PCOS lies at the crossroad of metabolic and reproductive disorder and a multi-systemic approach with involvement of the concerned  specialties is required for successful outcome.

Research paper thumbnail of Loss of Pancreatic β-cell Secretory Function During Disease Progression in Type 2 Diabetes Mellitus - A Small Cross-Sectional Study

Pancreas – Open Journal, 2019

Cite this article Kudolo GB. Loss of pancreatic β-cell secretory function during disease progress... more Cite this article Kudolo GB. Loss of pancreatic β-cell secretory function during disease progression in type 2 diabetes mellitus: A small cross-sectional study.

Research paper thumbnail of Further characterization of the second oestrogen-binding species of the rat granulosa cell

Journal of Endocrinology, 1984

Rat granulosa cell cytosol contains a second oestrogen-binding species (SOB) distinguished from t... more Rat granulosa cell cytosol contains a second oestrogen-binding species (SOB) distinguished from the classical oestrogen receptor by its lower dissociation constant (approx. 45 nmol/l) and the ability to bind oestrogens, antioestrogens, androgens and progesterone but not diethylstilboestrol. The SOB and the oestrogen receptor can be further distinguished by their differential adsorption to spheroidal hydroxylapatite and Concanavalin A–Sepharose. Addition of chaotropic salts or molybdate to granulosa cell cytosol did not alter the concentration of SOB or oestrogen receptor measured, indicating that there are no 'masked' binding sites in the two species caused by aggregation phenomena. The association rate of oestradiol with SOB at 4°C (1·72 ± 0·27(s.e.m.) × 108 mol/h) and 25°C (4·50 ± 0·36 × 108 mol/h) was faster than with the oestrogen receptor (7·20 ± 0·15 × 107 mol/h and 1·23 ± 0·15 × 108 mol/h respectively). The biphasic dissociation kinetics of [3H]oestradiol from the oes...

Research paper thumbnail of Oestrogen receptor in the granulosa cell during postnatal development of the rat ovary

Oestrogen receptor in the granulosa cell during postnatal development of the rat ovary

Journal of Endocrinology, 1987

Numbers of granulosa cells obtained from follicles of immature rats increased from 1·6 × 105 cell... more Numbers of granulosa cells obtained from follicles of immature rats increased from 1·6 × 105 cells/ovary on day 8 to 7·1 × 106 cells/ovary on day 40 of age, the day of vaginal opening and first pro-oestrus. Very high levels of cytosol oestrogen receptor were found on day 8 (175 000 sites/cell) but by day 19 20 000 sites/cell were found. Nuclear receptor concentrations were highest on day 12(5400 ± 1470 (s.d.) sites/cell) and again on day 21 (5400 ± 2300 sites/cell). After day 21 both cytosol and nuclear oestrogen receptor concentrations fell and remained low until nuclear concentrations rose at day 40. Two consecutive daily injections of FSH/LH (5 i.u.) increased cell number over control in animals killed on day 22, gave no significant alteration in animals killed on day 26 or 28 but decreased numbers in animals aged 32 and 35 days. Only on day 22 was the increase in cell number associated with an increase in nuclear oestrogen receptor concentrations. Indeed on days 32 and 35 increa...

Research paper thumbnail of A novel oestrogen-binding species in rat granulosa cells

A novel oestrogen-binding species in rat granulosa cells

Journal of Endocrinology, 1984

The dissociation constants (Kd) and steroid specificities of oestrogen-binding species in rat gra... more The dissociation constants (Kd) and steroid specificities of oestrogen-binding species in rat granulosa cell cytosol and nuclei have been studied. Preliminary work, where diethylstilboestrol was employed as competitor in binding assays, identified the oestrogen receptor in whole ovarian tissue nuclei (Kd 0·35 ±0.09 nmol/l) and cytosol (Kd 0·39 ± 0·03 nmol/l). Isolation of granulosa cells revealed that the majority of this receptor (75–96%) was present in these cells. Specificity studies on the binding of [3H]oestradiol in granulosa cell cytosol indicated the presence of an additional class of oestrogen-binding sites which were, however, not present in nuclei. Saturation analysis over an extended range of [3H]oestradiol concentrations and using unlabelled oestradiol as competitor revealed a binding species of Kd 45·8± 6·9 nmol/l (capacity 16·7 pmol/mg cytosol protein) for oestradiol in addition to the cytosol oestrogen receptor of Kd 0·58 ± nmol/l (capacity 2·8 pmol/mg cytosol protei...

Research paper thumbnail of Characterization of Platelet-activating Factor Acetylhydrolase in Human Bronchoalveolar Lavage

Characterization of Platelet-activating Factor Acetylhydrolase in Human Bronchoalveolar Lavage

American Journal of Respiratory and Critical Care Medicine, 1997

Platelet-activating factor (PAF) is a mediator produced in human airways during acute and chronic... more Platelet-activating factor (PAF) is a mediator produced in human airways during acute and chronic inflammatory lung diseases. The levels of PAF are regulated by acetylhydrolase (AH), the enzyme that converts PAF to lyso-PAF. To determine whether AH was present in human bronchoalveolar lavage (BAL) fluid, BAL was obtained from normal donors (n = 18) and from adult patients with mild bronchial asthma (n = 15) or with lung fibrosis (n = 15). AH activity was consistently found in the cell-free BAL fluid. BAL-AH is an enzyme different from secretory phospholipase A2 and from plasma AH and erythrocyte AH. Furthermore, BAL-AH is inhibited as much as 95% by exposure to an oxygen radical-generating system (xanthine/xanthine oxidase). BAL-AH is significantly correlated with the number of BAL macrophages (rs = 0.63; p < 0.02). In addition, BAL macrophages release AH both spontaneously and after stimulation with tumor necrosis factor-alpha (TNF-alpha) (100 ng/ml). BAL-AH activity in patients with bronchial asthma (1.32 +/- 0.18 pmol of PAF converted to lyso-PAF/min) is significantly lower than that in normal donors (2.25 +/- 0.26 pmol/min; p < 0.001). In contrast, BAL-AH activity in patients with lung fibrosis (6.13 +/- 0.81 pmol/min) is higher than that found in normal donors (p < 0.01). The variations in BAL-AH activity in patients with bronchial asthma or lung fibrosis are due to a reduction and to an increase, respectively, in the number of active molecules rather than to changes in enzyme affinity. These data demonstrate that human BAL fluid contains an extracellular AH activity that inactivates PAF released in the airways. BAL-AH is secreted by alveolar macrophages and is highly sensitive to oxygen radical-induced damage. The secretion and inactivation of BAL-AH may influence the levels of this enzyme in BAL fluid during acute and chronic inflammatory lung diseases and, ultimately, regulate the proinflammatory activities of PAF in these disorders.

Research paper thumbnail of Cardiovascular risk factors in Mexican American adults: a transcultural analysis of NHANES III, 1988-1994

American Journal of Public Health, 1999

Hispanic Americans constitute 11% of the US population and total 29 million peo- ple.' Hispanics ... more Hispanic Americans constitute 11% of the US population and total 29 million peo- ple.' Hispanics are one of the fastest-growing ethnic minority groups in the United States, and they are expected to constitute 24% of the US population by 2050.1 Hispanic groups

Research paper thumbnail of Reproduction in the vervet monkey (Cercopithecus aethiops): III. The menstrual cycle

Reproduction in the vervet monkey (Cercopithecus aethiops): III. The menstrual cycle

American Journal of Primatology, 1989

ABSTRACT The menstrual cycles of 17 multiparous vervet monkeys were studied. Based on estradiol, ... more ABSTRACT The menstrual cycles of 17 multiparous vervet monkeys were studied. Based on estradiol, progesterone, and LH profiles, ovulation is predicted to occur on day 13 of the 32.4-day menstrual cycle. Estradiol peaked on the day preceding the LH peak in 75% of cycles. Average luteal phase length (progesterone greater than 4 nmol/l) was 18 days, with progesterone rising above 4 nmol/l on the day of the LH peak. Vaginal cytology and perianal skin coloration exhibited too much within- and among-animal variability to be reliable indicators of menstrual cycle stages. Uterine biopsies of the proliferative phase were characterized by mild pseudostratification of the columnar epithelium and absence of glandular secretion; in contrast, those of the luteal phase had marked pseudostratification of the tall columnar epithelium with glandular secretions in the lumen. A few follicular-phase samples contained structures such as tortuous uterine glands with secretions. Such structures are more characteristic of the luteal phase. It is suggested that their presence can be explained by incomplete sloughing of the endometrium at menstruation, as this is known to be light or convert in this species.

Research paper thumbnail of Estimation of platelet-activating factor receptors in the endometrium of the pregnant rabbit: regulation of ligand availability and catabolism by bovine serum albumin

Biology of Reproduction, 1990

High affinity receptors have been demonstrated for the potent phospholipid autacoid, platelet-act... more High affinity receptors have been demonstrated for the potent phospholipid autacoid, platelet-activating factor (PAP C18:O; l-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) in a variety of tissues, Including the endometrium. Because of the relative instability of PAF and our previous demonstration that lyso-PAF (l-O-alkyl.2-lyso-sn.glycero-3.phosphorylcholine), the major metabolite of PAF, displaced (3HJPAF from endometrial PM receptor sites, we have examined the ability of bovine serum albumin (BSA) to prevent degradation of PAP and have characterized PAP and lyso-PAF binding sites in purified rabbit endometrial membranes isolated on Day 6 of pregnancy. In buffer containing the phospholipase A2 inhibitors, quinacrine (10 saM) and dibromoacetophenone (2 &M), and 025% BSA, 874 ± 32% of added [3HJPAF C18:0 remained Intact after incubation at 25#{176}C for 150 mm. The metabolic products, lyso-PAF and 1 -o-alkyl-2-acyl-sn-glycero-3-phosphorylcholine (alkylacyl.GPC), only amounted to 52 ± 3.2 and 3.3 ± 1.1, respectively. At the same concentration, rabbit serum albumin (RSA) also significantly protected I5HIPAJ' Cl8:0 from metabolism, but bovine gamma globulin (BGG) was ineffective. The presence of 0.25% BSA, however, did not protect [3HJlyso-PAF Cl8 :0 from extensive catabolism: the major product formed was [3H]alkylacyl-GPC. Insignificant amounts of I3HIPAF were formed. Under the same conditions (25#{176}C,150 mm) in the presence of 0.25% BSA, saturation analysis revealed the presence of two types of PAP C18:0 receptors in the endometrial membranes. Type 1 sites had a K. of 0.42 ± 0.03 nM (mean ± SD; n = 3) and binding capacity of 0.11 ± 0.01 pmol/mg protein. Type 2 receptor sites had a K.4 of 5.96 ± 0.35 nM and a binding capacity of 1.59 ± 0.22 pmol/mg protein. Thus, In the presence of BSA, the binding capacities of the two classes of receptors were markedly reduced compared to values generated previously in its absence. The K.., of the Type 1 sites was not significantly changed by the presence of BSA. A sIngle class of saturable high-affinity binding sites was demonstrable for lyso-PAF Cl8:0: KdS ranged from 0.76 ± 0.58 to 11.1 ± 0.62 nM, depending on which method of analysis was used (Eadie-Hofstee, Scatchard-Rosenthal, or the Lundon nonlinear method). The binding capacities were equally varied, ranging from 0.15 ± 0.08 to 15.17 ± 4.95 pmol/mg protein. These results confirm the ability of BSA to bind PAP Cl8:0, but not lyso-PAF C18:0, with such high affinity that BSA-PAF complexes, but not lyso-PAF-BSA complexes, are resistant to enzymatic degradation. Because of this high affinity interaction, free I3HIPAF C18 :0 was reduced and exchange was restricted to PM receptor sites, which had even greater affinities for PAP, thus reducing the population of labeled membrane sites compared to values generated in the absence of BSA.

Research paper thumbnail of Control of Peripheral Free Estradiol Pool During the Menstrual-Cycle of the Olive Baboon (papio-Anubis)

Control of Peripheral Free Estradiol Pool During the Menstrual-Cycle of the Olive Baboon (papio-Anubis)

Ircs Medical Science, 1986

Research paper thumbnail of Estradiol and Progesterone-Receptor Dynamics in the East-African Primates

Estradiol and Progesterone-Receptor Dynamics in the East-African Primates

International Journal of Primatology, 1984

Research paper thumbnail of Oestrogen binding species in the rat granulosa cell

Oestrogen binding species in the rat granulosa cell

Research paper thumbnail of Platelet-activating factor (PAF) binding sites in the rabbit oviduct

Platelet-activating factor (PAF) binding sites in the rabbit oviduct

Research paper thumbnail of Loss of Pancreatic β-cell Secretory Function During Disease Progression in Type 2 Diabetes Mellitus -A Small Cross-Sectional Study

Openventio Publishers, 2019

Introduction: Overt type 2 diabetes mellitus (T2DM) is a chronic progressive disease which is pro... more Introduction: Overt type 2 diabetes mellitus (T2DM) is a chronic progressive disease which is produced by the collusion of three metabolic defects-increased hepatic glucose production, impaired pancreatic β-cell insulin secretion and decreased insulin action. The measurement of plasma glucose 2 hours post-ingestion of 75 g of glucose during the oral glucose tolerance test (OGTT) may be used to classify individuals as normal glucose tolerant (NGT), impaired glucose tolerant, T2DM and T2DM with pancreatic β-cell failure. Objectives: This study was undertaken primarily to show the importance of assessing the pancreatic β-cell function especially during the care of the diabetic patient. Methods: A standard 75 g glucose tolerance test (OGTT) was administered to four groups of 8 subjects (4 male, 4 female). Blood was drawn every 15 minutes for 2 hours for the measurement of glucose, insulin and C-peptide and the measurement of the area under the curve (AUC(0→2)) over the 2-hour period. Re...

Research paper thumbnail of Short-term oral ingestion of extract (EGb 761) reduces malondialdehyde levels in washed platelets of type 2 diabetic subjects

Short-term oral ingestion of extract (EGb 761) reduces malondialdehyde levels in washed platelets of type 2 diabetic subjects

Diabetes Res Clin Pract, 2005

Research paper thumbnail of Lyso-PAF:acetyl-CoA acetyltransferase and CDP-choline cholinephosphotransferase activities in the rabbit endometrium

platelet-activating factor * Corresponding author.

Research paper thumbnail of The Effect of 3-Month Ingestion of Ginkgo biloba Extract (EGb 761) on Pancreatic β-Cell Function in Response to Glucose Loading in Individuals with Non-Insulin-Dependent Diabetes Mellitus

Ginkgo biloba, the maidenhair tree, is one of several remedies that has been used in traditional ... more Ginkgo biloba, the maidenhair tree, is one of several remedies that has been used in traditional Chinese medicine for thousands of years. 1 Only more recently has it found worldwide recognition. For example, it has been used in Europe clinically for the treatment of several diseases, including peripheral and cerebral insufficiency associated with aging. 2,3 In the United States, Ginkgo biloba extract (EGb 761) is a very popular over-the-counter dietary supplement, which is ingested primarily to enhance mental focus. The growing interest in this herb stems from the increasing reports suggesting that Ginkgo biloba may ameliorate age

Research paper thumbnail of Jones, Kudolo & Harper

Research paper thumbnail of The Effect of 3-Month Ingestion of Ginkgo biloba Extract on Pancreatic β-Cell Function in Response to Glucose Loading in Normal Glucose Tolerant Individuals

Research paper thumbnail of EC PHARMACOLOGY AND TOXICOLOGY Review Article Arachidonic Acid and Platelet-Activating Factor as Central Players in the Metabolic Syndrome. Lessons from the Use of the Ginkgo Biloba Extract

Diabetes mellitus is a chronic disease with worldwide prevalence and the toll of the disease is s... more Diabetes mellitus is a chronic disease with worldwide prevalence and the toll of the disease is substantially increased because it is commonly associated with several chronic disorders, collectively termed the metabolic syndrome. There is continuing efforts to identify the biochemical compound/s linking all of the disorders. I have hypothesized that arachidonic acid and platelet-activating factor, lipids found in the plasma membrane, are central players and have used Ginkgo biloba extract to test this hypothesis. The standardized Ginkgo biloba leaf extract contains approximately 24% flavonoid glycosides, to which the free radical scavenging properties have been ascribed, and 6% terpene lactones which is thought to be responsible for platelet aggregation inhibit and increase blood flow. This review summarizes the characteristics of the metabolic syndrome and results of more than two decades of clinical studies involving the ingestion of 120 mg of Ginkgo biloba extract daily, as a single dose for 3 months in open label or randomized double-blind placebo control trials. It was found that Ginkgo biloba extract: (1) decreased in vivo platelet reactivity, as seen by decreased plasma thromboxane B 2 and urinary excretion of the thromboxane B 2 metabolites, and in vitro reduction of arachidonic acid stimulated platelet thromboxane A 2 production. The later was accompanied by reduced synthesis of malondialdehyde, a reactive oxygen species, in both non-diabetic and diabetic subjects. Importantly it was discovered that Ginkgo inhibited platelet aggregation mediated predominantly by collagen, and to a lesser degree, by platelet-activating factor, (2) stimulated pancreatic -cell insulin production in both non-diabetic and type 2 diabetic subjects, especially in diabetic subjects with pancreatic exhaustion and (3) did not increase whole body insulin resistance. Taken together, it seems that cell membrane perturbation resulting in the release and metabolism of arachidonic acid and platelet-activating factor might be the underlying cause in the development of several metabolic defects commonly associated with diabetes and the use Ginkgo biloba extract allowed us to verify several aspects of the metabolic syndrome.

Research paper thumbnail of Ginkgo biloba extract and the PCOS patient: Perspectives from the San Antonio clinical trials

Journal of Clinical and Molecular Endocrinology, 2018

free androgen index and testosterone dihydrotestosterone ratio were studied, and have been found to significantly correlate with clinical parameters. There is controversy regarding thresholds for diagnosis in adolescents and peri-menopausal women and the most appropriate therapeutic approaches for these patients. Metformin is found to have significant role in the management as insulin resistance is the key etiopathogenic factor in PCOS, which was also evidenced in our randomized control trial. PCOS lies at the crossroad of metabolic and reproductive disorder and a multi-systemic approach with involvement of the concerned  specialties is required for successful outcome.

Research paper thumbnail of Loss of Pancreatic β-cell Secretory Function During Disease Progression in Type 2 Diabetes Mellitus - A Small Cross-Sectional Study

Pancreas – Open Journal, 2019

Cite this article Kudolo GB. Loss of pancreatic β-cell secretory function during disease progress... more Cite this article Kudolo GB. Loss of pancreatic β-cell secretory function during disease progression in type 2 diabetes mellitus: A small cross-sectional study.

Research paper thumbnail of Further characterization of the second oestrogen-binding species of the rat granulosa cell

Journal of Endocrinology, 1984

Rat granulosa cell cytosol contains a second oestrogen-binding species (SOB) distinguished from t... more Rat granulosa cell cytosol contains a second oestrogen-binding species (SOB) distinguished from the classical oestrogen receptor by its lower dissociation constant (approx. 45 nmol/l) and the ability to bind oestrogens, antioestrogens, androgens and progesterone but not diethylstilboestrol. The SOB and the oestrogen receptor can be further distinguished by their differential adsorption to spheroidal hydroxylapatite and Concanavalin A–Sepharose. Addition of chaotropic salts or molybdate to granulosa cell cytosol did not alter the concentration of SOB or oestrogen receptor measured, indicating that there are no 'masked' binding sites in the two species caused by aggregation phenomena. The association rate of oestradiol with SOB at 4°C (1·72 ± 0·27(s.e.m.) × 108 mol/h) and 25°C (4·50 ± 0·36 × 108 mol/h) was faster than with the oestrogen receptor (7·20 ± 0·15 × 107 mol/h and 1·23 ± 0·15 × 108 mol/h respectively). The biphasic dissociation kinetics of [3H]oestradiol from the oes...

Research paper thumbnail of Oestrogen receptor in the granulosa cell during postnatal development of the rat ovary

Oestrogen receptor in the granulosa cell during postnatal development of the rat ovary

Journal of Endocrinology, 1987

Numbers of granulosa cells obtained from follicles of immature rats increased from 1·6 × 105 cell... more Numbers of granulosa cells obtained from follicles of immature rats increased from 1·6 × 105 cells/ovary on day 8 to 7·1 × 106 cells/ovary on day 40 of age, the day of vaginal opening and first pro-oestrus. Very high levels of cytosol oestrogen receptor were found on day 8 (175 000 sites/cell) but by day 19 20 000 sites/cell were found. Nuclear receptor concentrations were highest on day 12(5400 ± 1470 (s.d.) sites/cell) and again on day 21 (5400 ± 2300 sites/cell). After day 21 both cytosol and nuclear oestrogen receptor concentrations fell and remained low until nuclear concentrations rose at day 40. Two consecutive daily injections of FSH/LH (5 i.u.) increased cell number over control in animals killed on day 22, gave no significant alteration in animals killed on day 26 or 28 but decreased numbers in animals aged 32 and 35 days. Only on day 22 was the increase in cell number associated with an increase in nuclear oestrogen receptor concentrations. Indeed on days 32 and 35 increa...

Research paper thumbnail of A novel oestrogen-binding species in rat granulosa cells

A novel oestrogen-binding species in rat granulosa cells

Journal of Endocrinology, 1984

The dissociation constants (Kd) and steroid specificities of oestrogen-binding species in rat gra... more The dissociation constants (Kd) and steroid specificities of oestrogen-binding species in rat granulosa cell cytosol and nuclei have been studied. Preliminary work, where diethylstilboestrol was employed as competitor in binding assays, identified the oestrogen receptor in whole ovarian tissue nuclei (Kd 0·35 ±0.09 nmol/l) and cytosol (Kd 0·39 ± 0·03 nmol/l). Isolation of granulosa cells revealed that the majority of this receptor (75–96%) was present in these cells. Specificity studies on the binding of [3H]oestradiol in granulosa cell cytosol indicated the presence of an additional class of oestrogen-binding sites which were, however, not present in nuclei. Saturation analysis over an extended range of [3H]oestradiol concentrations and using unlabelled oestradiol as competitor revealed a binding species of Kd 45·8± 6·9 nmol/l (capacity 16·7 pmol/mg cytosol protein) for oestradiol in addition to the cytosol oestrogen receptor of Kd 0·58 ± nmol/l (capacity 2·8 pmol/mg cytosol protei...

Research paper thumbnail of Characterization of Platelet-activating Factor Acetylhydrolase in Human Bronchoalveolar Lavage

Characterization of Platelet-activating Factor Acetylhydrolase in Human Bronchoalveolar Lavage

American Journal of Respiratory and Critical Care Medicine, 1997

Platelet-activating factor (PAF) is a mediator produced in human airways during acute and chronic... more Platelet-activating factor (PAF) is a mediator produced in human airways during acute and chronic inflammatory lung diseases. The levels of PAF are regulated by acetylhydrolase (AH), the enzyme that converts PAF to lyso-PAF. To determine whether AH was present in human bronchoalveolar lavage (BAL) fluid, BAL was obtained from normal donors (n = 18) and from adult patients with mild bronchial asthma (n = 15) or with lung fibrosis (n = 15). AH activity was consistently found in the cell-free BAL fluid. BAL-AH is an enzyme different from secretory phospholipase A2 and from plasma AH and erythrocyte AH. Furthermore, BAL-AH is inhibited as much as 95% by exposure to an oxygen radical-generating system (xanthine/xanthine oxidase). BAL-AH is significantly correlated with the number of BAL macrophages (rs = 0.63; p < 0.02). In addition, BAL macrophages release AH both spontaneously and after stimulation with tumor necrosis factor-alpha (TNF-alpha) (100 ng/ml). BAL-AH activity in patients with bronchial asthma (1.32 +/- 0.18 pmol of PAF converted to lyso-PAF/min) is significantly lower than that in normal donors (2.25 +/- 0.26 pmol/min; p < 0.001). In contrast, BAL-AH activity in patients with lung fibrosis (6.13 +/- 0.81 pmol/min) is higher than that found in normal donors (p < 0.01). The variations in BAL-AH activity in patients with bronchial asthma or lung fibrosis are due to a reduction and to an increase, respectively, in the number of active molecules rather than to changes in enzyme affinity. These data demonstrate that human BAL fluid contains an extracellular AH activity that inactivates PAF released in the airways. BAL-AH is secreted by alveolar macrophages and is highly sensitive to oxygen radical-induced damage. The secretion and inactivation of BAL-AH may influence the levels of this enzyme in BAL fluid during acute and chronic inflammatory lung diseases and, ultimately, regulate the proinflammatory activities of PAF in these disorders.

Research paper thumbnail of Cardiovascular risk factors in Mexican American adults: a transcultural analysis of NHANES III, 1988-1994

American Journal of Public Health, 1999

Hispanic Americans constitute 11% of the US population and total 29 million peo- ple.' Hispanics ... more Hispanic Americans constitute 11% of the US population and total 29 million peo- ple.' Hispanics are one of the fastest-growing ethnic minority groups in the United States, and they are expected to constitute 24% of the US population by 2050.1 Hispanic groups

Research paper thumbnail of Reproduction in the vervet monkey (Cercopithecus aethiops): III. The menstrual cycle

Reproduction in the vervet monkey (Cercopithecus aethiops): III. The menstrual cycle

American Journal of Primatology, 1989

ABSTRACT The menstrual cycles of 17 multiparous vervet monkeys were studied. Based on estradiol, ... more ABSTRACT The menstrual cycles of 17 multiparous vervet monkeys were studied. Based on estradiol, progesterone, and LH profiles, ovulation is predicted to occur on day 13 of the 32.4-day menstrual cycle. Estradiol peaked on the day preceding the LH peak in 75% of cycles. Average luteal phase length (progesterone greater than 4 nmol/l) was 18 days, with progesterone rising above 4 nmol/l on the day of the LH peak. Vaginal cytology and perianal skin coloration exhibited too much within- and among-animal variability to be reliable indicators of menstrual cycle stages. Uterine biopsies of the proliferative phase were characterized by mild pseudostratification of the columnar epithelium and absence of glandular secretion; in contrast, those of the luteal phase had marked pseudostratification of the tall columnar epithelium with glandular secretions in the lumen. A few follicular-phase samples contained structures such as tortuous uterine glands with secretions. Such structures are more characteristic of the luteal phase. It is suggested that their presence can be explained by incomplete sloughing of the endometrium at menstruation, as this is known to be light or convert in this species.

Research paper thumbnail of Estimation of platelet-activating factor receptors in the endometrium of the pregnant rabbit: regulation of ligand availability and catabolism by bovine serum albumin

Biology of Reproduction, 1990

High affinity receptors have been demonstrated for the potent phospholipid autacoid, platelet-act... more High affinity receptors have been demonstrated for the potent phospholipid autacoid, platelet-activating factor (PAP C18:O; l-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) in a variety of tissues, Including the endometrium. Because of the relative instability of PAF and our previous demonstration that lyso-PAF (l-O-alkyl.2-lyso-sn.glycero-3.phosphorylcholine), the major metabolite of PAF, displaced (3HJPAF from endometrial PM receptor sites, we have examined the ability of bovine serum albumin (BSA) to prevent degradation of PAP and have characterized PAP and lyso-PAF binding sites in purified rabbit endometrial membranes isolated on Day 6 of pregnancy. In buffer containing the phospholipase A2 inhibitors, quinacrine (10 saM) and dibromoacetophenone (2 &M), and 025% BSA, 874 ± 32% of added [3HJPAF C18:0 remained Intact after incubation at 25#{176}C for 150 mm. The metabolic products, lyso-PAF and 1 -o-alkyl-2-acyl-sn-glycero-3-phosphorylcholine (alkylacyl.GPC), only amounted to 52 ± 3.2 and 3.3 ± 1.1, respectively. At the same concentration, rabbit serum albumin (RSA) also significantly protected I5HIPAJ' Cl8:0 from metabolism, but bovine gamma globulin (BGG) was ineffective. The presence of 0.25% BSA, however, did not protect [3HJlyso-PAF Cl8 :0 from extensive catabolism: the major product formed was [3H]alkylacyl-GPC. Insignificant amounts of I3HIPAF were formed. Under the same conditions (25#{176}C,150 mm) in the presence of 0.25% BSA, saturation analysis revealed the presence of two types of PAP C18:0 receptors in the endometrial membranes. Type 1 sites had a K. of 0.42 ± 0.03 nM (mean ± SD; n = 3) and binding capacity of 0.11 ± 0.01 pmol/mg protein. Type 2 receptor sites had a K.4 of 5.96 ± 0.35 nM and a binding capacity of 1.59 ± 0.22 pmol/mg protein. Thus, In the presence of BSA, the binding capacities of the two classes of receptors were markedly reduced compared to values generated previously in its absence. The K.., of the Type 1 sites was not significantly changed by the presence of BSA. A sIngle class of saturable high-affinity binding sites was demonstrable for lyso-PAF Cl8:0: KdS ranged from 0.76 ± 0.58 to 11.1 ± 0.62 nM, depending on which method of analysis was used (Eadie-Hofstee, Scatchard-Rosenthal, or the Lundon nonlinear method). The binding capacities were equally varied, ranging from 0.15 ± 0.08 to 15.17 ± 4.95 pmol/mg protein. These results confirm the ability of BSA to bind PAP Cl8:0, but not lyso-PAF C18:0, with such high affinity that BSA-PAF complexes, but not lyso-PAF-BSA complexes, are resistant to enzymatic degradation. Because of this high affinity interaction, free I3HIPAF C18 :0 was reduced and exchange was restricted to PM receptor sites, which had even greater affinities for PAP, thus reducing the population of labeled membrane sites compared to values generated in the absence of BSA.

Research paper thumbnail of Control of Peripheral Free Estradiol Pool During the Menstrual-Cycle of the Olive Baboon (papio-Anubis)

Control of Peripheral Free Estradiol Pool During the Menstrual-Cycle of the Olive Baboon (papio-Anubis)

Ircs Medical Science, 1986

Research paper thumbnail of Estradiol and Progesterone-Receptor Dynamics in the East-African Primates

Estradiol and Progesterone-Receptor Dynamics in the East-African Primates

International Journal of Primatology, 1984

Research paper thumbnail of Oestrogen binding species in the rat granulosa cell

Oestrogen binding species in the rat granulosa cell

Research paper thumbnail of Platelet-activating factor (PAF) binding sites in the rabbit oviduct

Platelet-activating factor (PAF) binding sites in the rabbit oviduct

Research paper thumbnail of Loss of Pancreatic β-cell Secretory Function During Disease Progression in Type 2 Diabetes Mellitus -A Small Cross-Sectional Study

Openventio Publishers, 2019

Introduction: Overt type 2 diabetes mellitus (T2DM) is a chronic progressive disease which is pro... more Introduction: Overt type 2 diabetes mellitus (T2DM) is a chronic progressive disease which is produced by the collusion of three metabolic defects-increased hepatic glucose production, impaired pancreatic β-cell insulin secretion and decreased insulin action. The measurement of plasma glucose 2 hours post-ingestion of 75 g of glucose during the oral glucose tolerance test (OGTT) may be used to classify individuals as normal glucose tolerant (NGT), impaired glucose tolerant, T2DM and T2DM with pancreatic β-cell failure. Objectives: This study was undertaken primarily to show the importance of assessing the pancreatic β-cell function especially during the care of the diabetic patient. Methods: A standard 75 g glucose tolerance test (OGTT) was administered to four groups of 8 subjects (4 male, 4 female). Blood was drawn every 15 minutes for 2 hours for the measurement of glucose, insulin and C-peptide and the measurement of the area under the curve (AUC(0→2)) over the 2-hour period. Re...

Research paper thumbnail of Short-term oral ingestion of extract (EGb 761) reduces malondialdehyde levels in washed platelets of type 2 diabetic subjects

Short-term oral ingestion of extract (EGb 761) reduces malondialdehyde levels in washed platelets of type 2 diabetic subjects

Diabetes Res Clin Pract, 2005