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Biomedical subjects

J Enriquez

Publications and source records attributed to J Enriquez.

15 recordsLinked to original sources

Green biotechnology and European competitiveness.

Europe has led many aspects of gene research and yet it has been unable to translate these discoveries into a globally dominant industrial sector. There are valid societal, political and financial reasons for its reluctance to deploy agricultural biotechnology but this reluctance might have unintended consequences. It will be hard to de-commoditize agriculture and improve farmer's lives. Research in medical biotechnology and the global environment might suffer. Europe could damage its overall economy and its global competitive standing.

Agriculture↗

Islet cell and thyroid antibody prevalence in patients with hepatitis C virus infection: effect of treatment with interferon.

An increased prevalence of hepatitis C virus (HCV) infection in patients with diabetes and a higher prevalence of diabetes in HCV-infected patients have been reported. However, the relationship between these two conditions remains controversial. In addition, although the effect of interferon treatment on thyroid autoimmunity has been extensively reported, its influence on beta-cell autoantibodies has not been investigated. The aims of the study were (1) to evaluate whether autoimmune beta-cell damage could be involved in the development of diabetes mellitus in HCV-infected patients and (2) to determine whether interferon treatment influences the appearance of beta-cell and thyroid autoantibodies. The prevalence of islet cell autoantibodies (glutamic acid decarboxylase antibodies [GADAs], tyrosine phosphatase antibodies [IA-2s], islet cell antibodies [ICAs]) was assessed in 303 non-selected HCV-infected patients (277 non-diabetic and 26 type 2 diabetic patients) and in 273 sex- and age-matched control subjects. ICAs and thyroid autoantibodies were also determined before and 6 and 12 months after treatment with interferon for 24 weeks in a subgroup of 46 HCV-infected patients. GADAs were detected in 4 of 277 (1.4%) HCV-infected non-diabetic patients, 1 of 273 (0.3%) control subjects, and 0 of 26 (0%) HCV-infected patients with diabetes. Anti-IA2s and ICAs were negative in all subjects. Both GADAs and anti-IA2s were negative in all HCV-infected patients treated with interferon. After therapy, only thyroid antibodies became positive in 5 of 46 (10.9%) treated patients, disappearing in all but 1 of these at the 12-month follow-up. Our results suggest that beta-cell autoimmunity is not associated with HCV infection, thus making it unlikely that the increased diabetes mellitus prevalence among HCV-infected patients could be mediated by autoimmune mechanisms. In addition, interferon treatment induces a transient increase in thyroid autoantibodies but does not influence the appearance of beta-cell autoantibodies.

Adult↗

[Pretreatment with prednisolone enhances the effect of human lymphoblastoid interferon in chronic hepatitis B].

Patients (n = 213) with chronic hepatitis B were randomised to prednisolone (two weeks of 0.6 mg/kg/day, one week of 0.45 mg/kg/day and one week of 0.25 mg/kg/day) or placebo followed by two weeks rest, and were then given human lymphoblastoid interferon 10 MU daily for five days followed by 10 MU thrice weekly for 11 weeks. There were statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). HBeAg disappearance and HBeAg to anti-HBe seroconversion rates were 28 vs. 44% and 23 vs. 38% (placebo vs. prednisolone). Fifteen patients (7.5%) lost HBsAg. Three out of 22 cirrhotic patients (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome. Prednisolone pre-treatment, enhances the effect of lymphoblastoid interferon in chronic hepatitis B. Interferon treatment (with and without prednisolone) should be used with caution in patients with cirrhosis and avoided in patients with evidence of hepatic decompensation.

Adult↗

Pharmacologic hemoglobin reversal: the importance of lipid intermediaries and the proposed involvement of the cAMP and phosphatidylinositol second messenger systems.

Humoral and microenvironmental influences have played a major role in recent research into reversing the Hb F to Hb A switch. Early research in this area focused on hormonal influences and showed both thyroid hormone and prolactin could induce small but statistically significant reversals in hemoglobin phenotype. Recent research has focused on the effect of certain lipids in this process. The current study shows a synergy between thyroid hormone and prolactin in inducing a significant switch in adult rat hemoglobin patterns toward the neonatal pattern. Further, it is hypothesized that this synergy is due to the hormones' effect on lipid intermediaries whose effect in turn are proposed to be mediated by the cAMP and phosphatidylinositol second messenger systems.

Animals↗

Prednisolone withdrawal therapy enhances the effect of human lymphoblastoid interferon in chronic hepatitis B. INTERPRED Trial Group.

BACKGROUND/AIMS: The aim of this multicentre, randomised, controlled, clinical trial was to evaluate the effect of prednisolone followed by lymphoblastoid interferon treatment in chronic hepatitis B. METHODS: Two hundred and thirteen patients with chronic hepatitis B were randomised to either prednisolone (2 weeks of 0.6 mg/kg/day, 1 week of 0.45 mg/kg/day and 1 week of 0.25 mg/kg/day) or matching placebo followed by a 2-week rest phase and then human lymphoblastoid interferon 10 MU daily for 5 days followed by 10 MU thrice weekly for 11 weeks. Of 200 evaluable patients, 33 (16.5%) were females, and 50 (25%) were male homosexuals. Thirty three patients (16.5%) had chronic persistent hepatitis, 145 (72.5%) had chronic active hepatitis and 22 (11%) had active cirrhosis. RESULTS: Survival analysis disclosed statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log-rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). Observed HBeAg disappearance and HBeAg to anti-HBe seroconversion rates (placebo vs. prednisolone patients) were 28% vs. 44% and 23% vs. 38%. Six months after stopping interferon, HBV DNA was negative in 51% of prednisolone patients vs. 28% of placebo patients (Chi-square test statistic 6.13; p = 0.013). Prednisolone pre-treatment tended to be more effective in patients with higher transaminase levels and in patients with low levels of HBV DNA. Fifteen patients (7.5%) (13 within 1 year of follow-up) eventually lost HBsAg; 14 of these subsequently developed anti-HBs. Interferon treatment was modified in 102 patients (51%). Three out of 22 patients with cirrhosis (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome while on interferon treatment. CONCLUSIONS: Prednisolone pre-treatment significantly enhanced the treatment effect of lymphoblastoid interferon in terms of HBeAg clearance and seroconversion to anti-HBe. Treatment should be used with caution in patients with cirrhosis and avoided in patients showing signs, or with a history, of decompensated cirrhosis.

Adult↗

Steroid 5 alpha-reductase activity in the harderian glands of male and female Syrian hamster (Mesocricetus auratus).

The activity of the enzyme steroid 5 alpha-reductase in Harderian glands of adult syrian hamsters was assessed by measuring the conversion of testosterone (T) to 5 alpha-dihydrotestosterone (DHT). The optimal conditions for this reaction were determined in vitro using whole gland homogenates and [3H]testosterone as substrate. Enzyme activity was maximal at pH 5.5. The Michaelis-Menten constant of the Harderian enzyme for T was 4.6 +/- 1.2 x 10(-6) M in females and 4.2 +/- 0.39 x 10(-6) M in males, estimated by Eadie-Hofstee plots. On the basis of relative maximum velocity values, there was 9 or 10 times more 5 alpha-reductase in females (2.8 +/- 0.67 nmol/mg protein/hr) than in males (0.289 +/- 0.029 nmol/mg protein/hr). Consistently, glands of intact male hamsters had lower 5 alpha-reductase activities than those of females. Castration of males significantly increased the enzymatic activity, which within 4 weeks reached female-like values. The levels of 5 alpha-reductase mRNA also increased with castration. There was a direct correlation between activity and mRNA levels of the enzyme in castrated male glands. Further, the administration of T or DHT to ovariectomized hamsters led to intact male values in the enzymatic activity of the gland. The sex differences in 5 alpha-reductase activity may be of relevance to the differential regulation exerted by androgen upon the physiology of male and female glands. The results are consistent with the view that 5 alpha-dihydrotestosterone is the active androgen in the Harderian gland.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

A rodent model for hemoglobin switching utilizing high performance liquid chromatography.

It has long been recognized that a treatment for beta hemoglobin chain anomalies could result if a way to reverse the Hb F to Hb A switch in humans were found. Studies of hemoglobin switching have been hampered by the fact that small animals normally used in the laboratory do not have a true Hb F. However, several small animal models which take advantage of a switch in minor beta chain proportions in certain strains of inbred mice and rats have been proposed and used. The use of these models has suffered from what, until now, could be considered technically demanding, time-consuming methodologies. In this study we report an effective, rapid and technically streamlined model of hemoglobin switching utilizing Fisher 344 rats and high performance liquid chromatography with a weakly cationic column.

Age Factors↗

Absence of monoclonal antibody detectable Kaposi sarcoma-specific antigens on lesion-derived cultured cells.

To define the histogenesis and cell origin of Kaposi sarcoma (KS), we cultured KS cells without retrovirally conditioned media from three HIV seropositive AIDS patients and then attempted to raise mouse hybrid monoclonal antibodies (Mabs) specific to these AIDS-KS cells. After both in vivo and in vitro immunization trials, all putative Mabs reacted positively to KS cells but also non-specifically with other human (CH5 and OM) and non-human (RSE-1) control endothelial cell lines. To overcome this crossreactivity, we further "absorbed" previously cloned hybrids and pre-hybrid splenocytes by incubating them with the control endothelial cell lines to eliminate splenocytes and/or hybridomas reactive to normal endothelium. Whereas absorption successfully eliminated immunoreactivity to control endothelium, it also excluded reactivity to KS cells. These findings (lack of specific antigenicity and immunoresponsiveness of KS similar to non-KS control endothelium) suggest that AIDS-KS cells are neither antigenically transformed nor neoplastic, but instead represent dedifferentiated or transdifferentiated endothelium which retains immunogenicity of its original endothelial cell prototype.

Acquired Immunodeficiency Syndrome↗

Cryptosporidiosis facilitated by murine retroviral infection with LP-BM5.

LP-BM5 murine leukemia virus infection caused alterations in splenic T cell subsets in adult C57BL/6 female mice. Prolonged infection resulted in increased immunosuppression and a concomitant decreased resistance to Cryptosporidium parvum infection. Significant Cryptosporidium colonization of the intestinal villi was seen 10 days after oral challenge in mice infected with murine retrovirus for 3 months but not in non-virally infected controls. Parasite numbers per villus of retrovirally infected mice were 20-fold higher than in controls, which showed only occasional parasites. Feces from most virally infected mice but none from controls contained oocysts. Cryptosporidium infection in mice after 4 and 5 months of retroviral infection was accompanied by severe immunosuppression and parasite levels 50-5000 times higher than in controls. A high level of infection persisted 21 days after Cryptosporidium challenge in virally infected mice, while controls cleared their transient and marginal infection. These results further characterize LP-BM5 infection as a murine model of retrovirally induced acquired immune deficiency.

Animals↗

Epidemic yellow fever in eastern Nigeria, 1986.

An epidemic of yellow fever occurred in the eastern part of Nigeria during the second half of 1986. Oju, in Benue State, was the most heavily affected region, but yellow fever also occurred in surrounding areas, particularly Ogoja, in Cross River State. In Oju, the mean attack and mortality rates were 4.9% and 2.8%, respectively. Sex and age specific rates were highest in males and in the 20-29 yr age group. The overall case fatality rate was approximately 50%. Diagnosis was confirmed by IgM capture enzyme-linked immunosorbent assay (ELISA) and complement fixation (CF) tests. Entomological investigations implicated Aedes africanus as the epidemic vector. Oju alone probably had about 9800 cases of yellow fever with jaundice, and some 5600 deaths. Outbreaks of this nature could be prevented by inclusion of yellow fever in the Expanded Programme on Immunisation, in areas subject to recurrent epidemics.

Adolescent↗

Low C3 in cirrhotic ascites predisposes to spontaneous bacterial peritonitis.

The risk of developing spontaneous bacterial peritonitis (SBP) in relation to the concentration of C3 in ascitic fluid (AF) has been studied prospectively in 33 patients with cirrhosis of the liver, seven of whom had one or more episodes of SBP during hospitalization. C3 concentrations in the AF of patients who developed infection (9.0 +/- 2.67 mg/dl) were significantly lower than in those who did not (18.26 +/- 8.11 mg/dl) (P less than 0.01). C4 concentrations were similar in both groups. A direct correlation was found between AF C3 and total protein concentrations (P less than 0.001). We conclude that a low C3 concentration in AF may predispose to SBP.

Aged↗

Effect of sulindac on prostaglandin excretion and renal function in cirrhotic patients with ascites.

The effect of sulindac, a nonsteroidal anti-inflammatory drug, on renal prostaglandin synthesis and renal function variables was investigated in six cirrhotic patients with tense ascites and marked sodium retention. We studied serum thromboxane (TXB2) production, urinary prostaglandin excretion (6-keto-prostaglandin F1 alpha and TXB2) and renal function before and after administration of a therapeutic dose of sulindac (400 mg). After treatment, no significant changes were observed in urinary prostaglandin excretion, serum creatinine concentration, urine volume, or urinary sodium and creatinine clearance, whereas the serum TXB2 concentration was reduced in 89%. In five patients systemic prostaglandins were inhibited, but renal excretion remained unchallenged. However, one patient showed marked reduction of urinary prostaglandins associated with a depression of renal function. The study suggests that sulindac could be a safe substitute for other nonsteroidal anti-inflammatory drugs in cirrhotic patients with ascites. Further pharmacological trials seem to be warranted.

Ascites↗

Attenuation of methyl tert-butyl ether in water using sunlight and a photocatalyst.

The use of methyl tert-butyl ether (MTBE) as a gasoline additive has resulted in increasing pollution of groundwater. Most of the conventional treatment technologies are inefficient or costly when the initial concentration of MTBE is low (< 200 microg/L). To find an ecology friendly and inexpensive method for MTBE remediation, we used solar radiation with titanium dioxide (TiO2) as a photocatalyst. For synthetic samples, almost complete degradation (99+%) of MTBE was observed at the end of 5-hour test run with 0.05 g/L of slurry TiO2. Intermediate products detected were tertiary butyl formate, tertiary butyl alcohol, and trace amounts of acetone. Studies conducted using contaminated groundwater samples with TiO2 and sunlight showed that aromatic organic species benzene, toluene, ethylbenzene, and xylenes (BTEX) were degraded up to a factor of 10 times faster than MTBE. However, dissolved metals (Fe2+) and chloride ions in contaminated waters decreased the photo-activity of TiO2 for the degradation of MTBE. Reducing the pH of the groundwater samples increased the MTBE degradation rate threefold. Photocatalysis accelerates the solar degradation of MTBE and reduces its half-life by more than 3 orders of magnitude. The study indicated that solar degradation is a low-cost and effective alternative to attenuate MTBE in drinking water supplies.

Carcinogens↗