Miguel Cutufia | None - Academia.edu (original) (raw)

Papers by Miguel Cutufia

Journal of Neuroimmunology, 1997

Despite convincing evidence of cooperation between IL-2 and endogenous prolactin (PRL) during T c... more Despite convincing evidence of cooperation between IL-2 and endogenous prolactin (PRL) during T cell activation, the individual role of PRL as a T-cell lineage cytokine remains to be defined. We have examined the production and function of PRL on the Jurkat human T-leukemic cell line, which does not constitutively produce IL-2. The majority of Jurkat cells expressed PRL receptor (R) under standard culture conditions, whereas appearance of the alpha chain of the IL-2-R required PHA-PMA stimulation, as did IL-2 synthesis. Western blotting revealed a predominant band at 23.5 kDa and a weaker band at 25.5 kDa in both Jurkat cell lysates and human (h) pituitary PRL. Metabolic labeling of the cell lysates with 35S-methionine and immunoprecipitation with an antiserum against hPRL showed that both forms of PRL are actively synthesized by the Jurkat cell line. PRL released in the medium was biologically active in the rat Nb2 lymphoma mitogenic assay. Depletion of medium PRL with two polyclonal anti-hPRL antisera inhibited the growth of Jurkat cells in a dose-dependent manner, as evaluated by cell number and 3H-TdR uptake. Purified pituitary or recombinant hPRL at a wide range of concentrations had no significant effect on their growth, but reversed the blocking activity of the anti-hPRL antibody. Recombinant IL-2 had no effect on the antibody-induced growth inhibition. Taken as a whole, these results demonstrate that PRL can act as an autocrine T cell growth factor independently of IL-2 and are the first evidence of its involvement in human leukemic growth and possibly in leukemic transformation.

Biochemical and Biophysical Research Communications, 1996

Transgenic mice harboring the human hemopexin promoter sequences linked to the lacZ reporter gene... more Transgenic mice harboring the human hemopexin promoter sequences linked to the lacZ reporter gene were generated and analyzed for temporal and spatial distribution of ␤-galactosidase. Upstream sequences spanning from −1800, −700 and −500 bp to the transcription start point direct regulated ␤-galactosidase expression specifically to the liver and to the brain of transgenic mice. These results suggest that the 500 bp DNA fragment flanking the 5Јend of the human hemopexin gene contains the cis-acting elements required for tissue and developmental stage-specific expression in vivo and provide evidence for a new extrahepatic site of expression of the hemopexin gene.

The American Journal of Medicine, 1992

To investigate the relationship between Helicobacter pylori infection and nonsteroidal anti-infla... more To investigate the relationship between Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) intolerance and the effect of gold use on the seroprevalence of H. pylori. We examined the frequency of discontinuation of NSAIDs in 132 unselected patients with rheumatoid arthritis attending an outpatient subspecialty clinic, and the effect of gold compound use on the seroprevalence (by IgG enzyme-linked immunosorbent assay) of H. pylori infection in this population. Logistic and multivariate regression analysis was performed adjusting for age, gender, ethnic origin, history of ulcer, and duration of rheumatoid arthritis. Fifty-four patients had a positive serology for H. pylori (41%). Twenty-seven of the seropositive patients (50%), versus 45 of the seronegative patients (57.7%), had to discontinue NSAIDs (aspirin and/or nonaspirin) at least once since their diagnosis of rheumatoid arthritis because of gastrointestinal side effects (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.63 to 1.38). Forty-one of the seropositive patients (76%) had received gold compounds as compared with 62 of the seronegative patients (79.5%) (OR: 0.96; 95% CI: 0.61 to 1.50). We did not find any relationship between H. pylori seropositivity and NSAID intolerance in patients with rheumatoid arthritis. In addition, our results do not demonstrate a reduction in H. pylori seroprevalence in rheumatoid arthritis patients treated with gold compounds.

Only a minority of patients carrying a defined viral aetiologic agent develop cirrhosis and ultim... more Only a minority of patients carrying a defined viral
aetiologic agent develop cirrhosis and ultimately
hepatocellular carcinoma (HCC), the mechanism underlying
the worsening is still undefined. Experimental infection by
Helicobacter hepaticus in mice causes chronic hepatitis and
HCC and recently, more Helicobacter species (Helicobacter
spp.) have been detected in the liver of patients suffering
from cholestatic diseases and HCC arising from non-cirrhotic
liver. We investigated whether Helicobacter spp. sequences
could be detected in the liver of patients with cirrhosis and
HCC compared to subjects with metastasis to liver from
colon cancer.
METHODS: Twenty-three liver samples from patients
operated upon for HCC superimposed on hepatitis C virus
(HCV)-related cirrhosis and 6 from patients with resected
metastases from colorectal cancer, were tested by polymerase
chain reaction for presence of genomic 16S rRNA of
Helicobacter genus using specific primers. DNA sequencing
and cag A gene analysis were also performed.
RESULTS: Genomic sequences of Helicobacter spp. were
found in 17 of 20 (85%) liver samples from patients with
HCC and in 2 of 6 samples from patients with liver metastasis.
In three samples of the first group the result was uncertain.
H pylori was revealed in 16 out of 17 positive samples and
Helicobacter pullorum in the other.
CONCLUSION: Helicobacter spp., carcinogenic in mice,
were found at a higher frequency in the liver of patients
with HCV-related cirrhosis and HCC than those in patients
without primary liver disease.

Journal of Neuroimmunology, 1997

Despite convincing evidence of cooperation between IL-2 and endogenous prolactin (PRL) during T c... more Despite convincing evidence of cooperation between IL-2 and endogenous prolactin (PRL) during T cell activation, the individual role of PRL as a T-cell lineage cytokine remains to be defined. We have examined the production and function of PRL on the Jurkat human T-leukemic cell line, which does not constitutively produce IL-2. The majority of Jurkat cells expressed PRL receptor (R) under standard culture conditions, whereas appearance of the alpha chain of the IL-2-R required PHA-PMA stimulation, as did IL-2 synthesis. Western blotting revealed a predominant band at 23.5 kDa and a weaker band at 25.5 kDa in both Jurkat cell lysates and human (h) pituitary PRL. Metabolic labeling of the cell lysates with 35S-methionine and immunoprecipitation with an antiserum against hPRL showed that both forms of PRL are actively synthesized by the Jurkat cell line. PRL released in the medium was biologically active in the rat Nb2 lymphoma mitogenic assay. Depletion of medium PRL with two polyclonal anti-hPRL antisera inhibited the growth of Jurkat cells in a dose-dependent manner, as evaluated by cell number and 3H-TdR uptake. Purified pituitary or recombinant hPRL at a wide range of concentrations had no significant effect on their growth, but reversed the blocking activity of the anti-hPRL antibody. Recombinant IL-2 had no effect on the antibody-induced growth inhibition. Taken as a whole, these results demonstrate that PRL can act as an autocrine T cell growth factor independently of IL-2 and are the first evidence of its involvement in human leukemic growth and possibly in leukemic transformation.

Biochemical and Biophysical Research Communications, 1996

Transgenic mice harboring the human hemopexin promoter sequences linked to the lacZ reporter gene... more Transgenic mice harboring the human hemopexin promoter sequences linked to the lacZ reporter gene were generated and analyzed for temporal and spatial distribution of ␤-galactosidase. Upstream sequences spanning from −1800, −700 and −500 bp to the transcription start point direct regulated ␤-galactosidase expression specifically to the liver and to the brain of transgenic mice. These results suggest that the 500 bp DNA fragment flanking the 5Јend of the human hemopexin gene contains the cis-acting elements required for tissue and developmental stage-specific expression in vivo and provide evidence for a new extrahepatic site of expression of the hemopexin gene.

The American Journal of Medicine, 1992

To investigate the relationship between Helicobacter pylori infection and nonsteroidal anti-infla... more To investigate the relationship between Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) intolerance and the effect of gold use on the seroprevalence of H. pylori. We examined the frequency of discontinuation of NSAIDs in 132 unselected patients with rheumatoid arthritis attending an outpatient subspecialty clinic, and the effect of gold compound use on the seroprevalence (by IgG enzyme-linked immunosorbent assay) of H. pylori infection in this population. Logistic and multivariate regression analysis was performed adjusting for age, gender, ethnic origin, history of ulcer, and duration of rheumatoid arthritis. Fifty-four patients had a positive serology for H. pylori (41%). Twenty-seven of the seropositive patients (50%), versus 45 of the seronegative patients (57.7%), had to discontinue NSAIDs (aspirin and/or nonaspirin) at least once since their diagnosis of rheumatoid arthritis because of gastrointestinal side effects (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.63 to 1.38). Forty-one of the seropositive patients (76%) had received gold compounds as compared with 62 of the seronegative patients (79.5%) (OR: 0.96; 95% CI: 0.61 to 1.50). We did not find any relationship between H. pylori seropositivity and NSAID intolerance in patients with rheumatoid arthritis. In addition, our results do not demonstrate a reduction in H. pylori seroprevalence in rheumatoid arthritis patients treated with gold compounds.

Only a minority of patients carrying a defined viral aetiologic agent develop cirrhosis and ultim... more Only a minority of patients carrying a defined viral
aetiologic agent develop cirrhosis and ultimately
hepatocellular carcinoma (HCC), the mechanism underlying
the worsening is still undefined. Experimental infection by
Helicobacter hepaticus in mice causes chronic hepatitis and
HCC and recently, more Helicobacter species (Helicobacter
spp.) have been detected in the liver of patients suffering
from cholestatic diseases and HCC arising from non-cirrhotic
liver. We investigated whether Helicobacter spp. sequences
could be detected in the liver of patients with cirrhosis and
HCC compared to subjects with metastasis to liver from
colon cancer.
METHODS: Twenty-three liver samples from patients
operated upon for HCC superimposed on hepatitis C virus
(HCV)-related cirrhosis and 6 from patients with resected
metastases from colorectal cancer, were tested by polymerase
chain reaction for presence of genomic 16S rRNA of
Helicobacter genus using specific primers. DNA sequencing
and cag A gene analysis were also performed.
RESULTS: Genomic sequences of Helicobacter spp. were
found in 17 of 20 (85%) liver samples from patients with
HCC and in 2 of 6 samples from patients with liver metastasis.
In three samples of the first group the result was uncertain.
H pylori was revealed in 16 out of 17 positive samples and
Helicobacter pullorum in the other.
CONCLUSION: Helicobacter spp., carcinogenic in mice,
were found at a higher frequency in the liver of patients
with HCV-related cirrhosis and HCC than those in patients
without primary liver disease.