Marilyn D | Harvard University (original) (raw)

Papers by Marilyn D

The purpose of the study was to investigate the changes in the endothelial cell count and cell’s ... more The purpose of the study was to investigate the changes in the endothelial cell count and cell’s polymegathism and
pleomorphism after selective laser trabeculoplasty (SLT) in open-angle glaucoma (OAG). SLT has been performed on
18 patients (22 eyes). Each patient underwent confocal microscopy 1 h prior to the laser surgery and then 1 h, 1 day,
1 week, and 1 month after SLT. The obtained micrographs were then analyzed in order to study the infl uence of SLT
on the corneal endothelium. The difference in the mean corneal endothelial cell density, polymegathism, and pleomorphism
at different time intervals was found to be statistically signifi cant. The mean endothelial cell count was reduced in
1 week after SLT from 2442 6 326 per mm2
to 2352 6 460 per mm2
; polymegathism was increased from 46.1 6 11.7%
to 50.9 6 13.4%; and pleomorphism was decreased from 46.2 6 11.2% to 40.9 6 7.2%. Cellular damage was also
observed on the micrographs that were made in the follow-up after SLT. The highest quantity of damaged cells was
observed 1 h after SLT. After 1 month, endothelial integrity was completely restored. If damaging does occur after SLT, it
is not severe enough to induce serious changes in the endothelial monolayer. Nevertheless, extra care should be taken
when choosing an approach to treating patients with low endothelial cell density.

Hypermethylation of the gene regulatory regions is documented for many cancer diseases. Such an a... more Hypermethylation of the gene regulatory regions is documented for many cancer diseases. Such an aberrant DNA
methylation in cancer cells is catalyzed by DNA methyltransferases Dnmt3a and Dnmt3b, which predominantly recognize
and methylate RCGY sequences with formation of R(5mC)GY sites. Recently, based on a new methyl-directed
DNA endonuclease GlaI, we developed a GLAD-PCR assay, which allows determining R(5mC)GY site in a defi ned position
of the genomic DNA. In this work we applied GLAD-PCR assay for identifi cation of the methylated RCGY sites in the
regulatory regions of some downregulated genes associated with colorectal cancer (CRC). This list includes ADHFE1,
ALX4, CNRIP1, EID3, ELMO1, ESR1, FBN1, HLTF, LAMA1, NEUROG1, NGFR, RARB, RXRG, RYR2, SDC2, SEPT9,
SFRP2, SOCS3, SOX17, THBD, TMEFF2, UCHL1, and VIM genes. GLAD-PCR analysis of selected RCGY sites within
the regulatory regions of some of these genes demonstrates a good prognostic potential with relatively high sensitivity
and specifi city of CRC detection in tumor DNA.

The efficient development of stable monoclonal antibody-producing mammalian cells is a tedious an... more The efficient development of stable monoclonal antibody-producing mammalian cells is a tedious and time-consuming
process due to the structural complexity of these molecules. The ratio of the light-chain to heavy-chain expression is
critical for the assembly and successful production of functional antibodies. Different vector-design strategies have been
employed for the optimal expression of monoclonal antibodies in mammalian cells. In the current study, a bicistronic
expression based on the encephalomyocarditis virus internal ribosomal entry site (ECMV IRES) element was used for
the development of Chinese hamster ovary (CHO)–stable cell pools expressing an anti-CD52 antibody. The successful
expression of the monoclonal antibody in CHO cells was achieved with the maximum titer of 20 µg/l. Our results
here show that IRES-mediated bicistronic expression is an efficient method for the stable expression of monoclonal
antibodies in CHO cells.

Bone strength is determined by bone mineral density (BMD) and bone quality. Bone fractures are se... more Bone strength is determined by bone mineral density (BMD) and bone quality. Bone fractures are serious adverse events in men receiving androgen deprivation therapy (ADT) for prostate cancer. Although it is established that ADT reduces BMD, it is unclear how ADT alters bone quality. Vitamin K is a bone quality marker which aids to carboxylates osteocalcin to form bone matrix. Serum undercarboxylated osteocalcin (ucOC) is accumulated in vitamin K deficiency, which is used as a surrogate for vitamin K status. As little is known as to the impact of ADT on serum ucOC, we investigated the changes of serum ucOC in PC patients during ADT. Fifty consecutive hormone naïve PC patients were enrolled. Serum ucOC, serum osteocalcin (OC), serum Nteloptide of type 1 collagen (NTx) and hip bone mineral density (BMD) were measured at baseline, 6 month and 12 months since the start of ADT. Serum ucOC levels at 6 and 12 months (3.86 ± 2.28 and 4.32 ± 1.76 ng/ml) were significantly higher than those at baseline (2.46 ± 1.46 ng/ml). Serum OC levels at 12 months (7.82 ± 2.65 ng/ml) were significantly higher than those at baseline (5.26 ± 1.86 ng/ml). Furthermore, the ratio of ucOC/OC at 1 year (0.54 ± 0.15) were significantly higher than at baseline (0.42 ± 0.18). Both serum NTx levels and hip BMDs at 6 and 12 months were also significantly higher than those at baseline. Our results first demonstrated that ADT induced vitamin K loss in men with prostate cancer. Further investigations are required to determine whether vitamin K supplement is useful to prevent bone fractures in men on ADT.

Although the prognosis of acute promyelocytic leukemia (APL) are favorable because of disease-spe... more Although the prognosis of acute promyelocytic leukemia (APL) are favorable because of disease-specific drugs, such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), early death due to fatal intracranial hemorrhage has been observed in many cases. The aim of this study is to examine the relationship between the treatment and intracranial hemorrhage complication in APL patients.46 patients diagnosed of APL during a period from 2000 to 2014 in our hospital were examined. The distribution of fatal intracranial hemorrhage (FICH) risk score in the 46 APL patients showed 23.9%, 58.6% and 17.3% for low, intermediate, and high categories, respectively. Among the 46 patients, 5 patients developed intracranial hemorrhage before remission, including 4 patients who developed such hemorrhage after chemotherapy and ATRA administration, and 1 patient who developed intracranial hemorrhage before treatment. All of the 5 patients were included in the high risk group of FICH score, including 1 patient who died and 3 patients who had serious paralysis. These hemorrhage tended to expand for several days because of progression of disseminated intravascular coagulation (DIC) accompanied by tumor lysis syndrome after chemotherapy. Based on this experience, we firstly provided single administration of ATRA for 5 days to a patient with intracranial hemorrhage and then added chemotherapy after improvement of DIC. As a result, we could lead remission with no expansion of intracranial hemorrhage. In most of induction therapy protocols for APL, patients with high white blood cell counts are recommended to receive combination of chemotherapy and ATRA with a focus on ATRA syndrome, but the risk of fatal intracranial hemorrhage is not reflected in the treatment regimen. Such a complication may be prevented using initial single administration of ATRA followed by concomitant chemotherapy after treatment for DIC in patients with a high-risk FICH score.

Introduction: Some patients with complicated appendicitis and no periappendiceal abscess on preop... more Introduction: Some patients with complicated appendicitis and no periappendiceal abscess on preoperative computed tomography may need the extended cecectomy, including ileocecectomy and right hemicolectomy. In this study, we determined if there are predictive factors for extended cecectomy in these patients, to assist the preoperative decision-making.

Background: Diabetes mellitus (DM) is suggested to be associated with colorectal cancer (CRC); ho... more Background: Diabetes mellitus (DM) is suggested to be associated with colorectal cancer (CRC); however, the direct relationship between DM and CRC has not been proven.

Protective action of antioxidants (mexidol, carnosine, N-acetyl cysteine) and the metal chelator ... more Protective action of antioxidants (mexidol, carnosine, N-acetyl cysteine) and the metal chelator Ca, Na2
-EDTA was
studied in the culture of human neuroblastoma SH-SY5Y cells after the addition of salts of heavy metals—lead, cadmium,
cobalt, and molybdenum—to the culture medium. Cells were incubated with heavy metals and protectors for
24 h, and cell viability and cell death were evaluated. All the metals lowered cell viability in a concentration-related
manner. Different protective agents were studied based on this model. The most pronounced capability of increasing
the cell viability in conditions of heavy-metal toxicity was demonstrated by N-acetyl cysteine (the protective effect was
demonstrated at the concentrations 0.5-1.0 mM and higher). Protective potential of carnosine was somewhat lower and
that of mexidol was minimal.

Bacterial pathogens are responsible for the most severe forms of pneumonia, bronchitis and other ... more Bacterial pathogens are responsible for the most severe forms of
pneumonia, bronchitis and other respiratory tract infections (RTI),
which have high morbidity and mortality rates especially among the
elderly and children under 5 years.

Expression of mRNA for IL-22 Binding Protein in the Broncheoalveolar Fluid after Inhaled Allergen Challenge in Subjects with Asthma

Background: T helper (Th)17/22 cells may play a role in allergic asthma. Recent findings showed i... more Background: T helper (Th)17/22 cells may play a role in allergic asthma. Recent findings showed increased mRNA expression for IL-22 in peripheral blood mononuclear cells (PBMC) from patients with asthma. Thereby, the role of the natural antagonist of IL-22, IL-22 binding protein (IL-22 BP), a soluble receptor for IL-22, remains to be elucidated. In this study, we investigate the expression of mRNA for IL-22 BP in individuals with asthma.

Local Thermal Impact on Microcirculation Assessed by Imaging Photoplethysmography, 2016

Laser Doppler Flowmetry and Laser Speckle Contrast Imaging are applied usually for assessment of ... more Laser Doppler Flowmetry and Laser Speckle Contrast Imaging are applied usually for assessment of parameters of the cutaneous blood flow during thermoregulation. Alternatively, this work explores the feasibility of blood pulsation imaging under incoherent green illumination for measuring the response of human body on local thermal impact. The proposed technique allows assessment of the cutaneous blood flow changes during thermoregulation simultaneously in different areas of the body. The preliminary experiments show that the blood pulsation amplitude (BPA) is sufficiently reliable index, which could characterize the relative change of the cutaneous blood flow similarly to the parameter measured with the Laser Doppler Flowmetry technique. It is shown that BPA grows up proportionally to the skin temperature increase in the preliminary cooled finger, whilst it is in the steady state in another finger having the constant temperature. The rate of BPA increase is individual characteristic of a subject, which could serve as a parameter of the subject's vasomotor reactivity on the temperature changes. High quality of visualized distribution of blood pulsations, good repeatability of the BPA, and revealed dependencies of its response on the skin-temperature change offer the prospect for development new system of studying microcirculation.

Background: Infections caused by multidrug resistant (MDR) bacteria remain a public health threat... more Background: Infections caused by multidrug resistant (MDR) bacteria remain a public health threat for patients and health care workers. There are scarcity of data on bacterial profiles and their drug susceptibility patterns from body fluids in Ethiopia. Hence, this study aimed at assessing bacterial profiles and their antimicrobial susceptibility patterns (AST) from body fluids at Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia.

Clinical Significance of Circulating Tumor Cells in Pancreatic Cancer, 2016

Pancreatic cancer (PC) is a highly aggressive malignancy with limited therapeutic options. Early ... more Pancreatic cancer (PC) is a highly aggressive malignancy with limited therapeutic options. Early and accurate
detection is critically important for successful cancer treatment. Currently, the most widely used and best validated
marker for pancreatic cancer is carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA).
However, inadequate sensitivity and specificity limit the use of CA 19-9 and CEA in the early screening and
diagnosis of pancreatic cancer. During past ten years, circulating tumor cells (CTCs) as a new liquid biomarker have
received enormous attention in cancer diagnosis and management. Although CTCs are extremely rare and
challenging to be isolated, their clinical significance has extensively been investigated in numerous clinical trials. In
this review, we summarize the CTC application in translational pancreatic cancer research and its outlook in the
future, specifically evaluating its clinical potential in pancreatic cancer diagnosis, prognosis, and treatments.
Development of sensitive, specific, and reliable methods is expected towards a major impact on our ability in cancer
management.

Talks by Marilyn D

Dear Colleagues, Greetings from Biology and Medicine.. It is our distinct pleasure to invite yo... more Dear Colleagues,

Greetings from Biology and Medicine..

It is our distinct pleasure to invite you and members of your research group to submit an article for the upcoming issue of Biology and Medicine. Biology and Medicine Journal provides an international forum for research in Biomedical field, publishing cutting-edge and innovative scientific topics that cover a broad spectrum of themes in Biology and Medicine.

If you are interested in contributing a manuscript to this issue, please submit your article via: http://www.editorialmanager.com/medicalsciences/

If you experience any problems with the submission system, please submit your work to:
biolmed@clinicalmedicaljournals.com

Thank you in advance for your interest and your cooperation.

Sincerely,
Marilyn D
Managing Editor
Biology and Medicine