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Biomedical subjects

P Gomez

Publications and source records attributed to P Gomez.

At least 37 records · Page 2Linked to original sources

Carboxypeptidase E (CPE) deficiency in mice with the fat mutation have reduced stomach function.

An obese mouse model (Cpefat/Cpefat) that has hyperproinsulinemia and late onset obesity has been described. Cpefat/Cpefat mice have a missense mutation in carboxypeptidase E (CPE), a processing enzyme essential for production of biologically active endocrine and neuroendocrine peptides. We have reported previously that CPE activity was absent in the antrum of the stomach and that processing of progastrin to the amidated biologically active form of gastrin is reduced. Since gastrin is a major secretagogue for gastric acid secretion, the purpose of the present experiments was to examine gastric acid secretion in Cpefat/Cpefat mice. In addition, secretion of amidated gastrin in response to inhibition of acid secretion was tested in Cpefat/Cpefat. Both gastric acid and challenged gastrin secretion are reduced in Cpefat/Cpefat mice. We conclude that stomach CPE activity is essential for gastric secretory activity and for challenged gastrin release.

Animals↗

Intra- and intercellular Ca2+ signaling in retinal pigment epithelial cells during mechanical stimulation.

The intercellular communication (IC) was investigated between cultured rat retinal pigment epithelial (RPE) cells isolated from Long-Evans (LE) or dystrophic Royal College of Surgeons (RCS) rats and grown in solutions containing normal and high glucose concentrations, or after modulation of protein kinase C (PKC). This was performed by studying the conduction of the free Ca2+-concentration ([Ca2+]i) wave elicited by mechanical stimulation and by analyzing the fluorescence recovery after photobleaching (FRAP). Mechanical stimulation of LE-RPE cells triggers Ca2+ influx, mediated by stretch-sensitive cation channels followed by intracellular Ca2+ release. A regenerative [Ca2+]i wave was found with a lower propagation rate in RCS-RPE cells. This rate could be increased by PKC down-regulation. Mechanical stimulation caused a [Ca2+]i increase in the mechanically stimulated (MS) cell followed after a delay by a [Ca2+]i rise in the adjacent cell layers. The intercellular [Ca2+]i wave propagation could be blocked by gap junction blockers such as halothane or PKC activation. An inhibition of the [Ca2+]i-wave propagation similar to that induced by halothane could be observed in cells grown in solutions containing 14 mM or higher concentrations of glucose. PKC down-regulated cells grown in glucose-rich medium did not develop this inhibitory effect on gap junction communication (GJC). FRAP experiments confirmed that the observed changes were consistent with a PKC-mediated inhibitory effect of high glucose concentrations on GJC.

Animals↗

Outbreak of Acinetobacter spp. bloodstream infections in a nursery associated with contaminated aerosols and air conditioners.

BACKGROUND: Acinetobacter spp. are multidrug-resistant bacteria that grow well in water and cause infections with unexplained, increased summer prevalence. In August, 1996, eight infants acquired Acinetobacter spp. bloodstream infection (A-BSI) while in a nursery in the Bahamas; three infants died and an investigation was initiated. METHODS: A case patient was defined as any newborn in the nursery during August 6 to 13, 1996, with A-BSI. To identify risk factors for A-BSI we conducted a retrospective cohort study and performed environmental cultures and air sampling using settle plates. The genetic relatedness of environmental isolates was assessed by pulsed field gel electrophoresis. RESULTS: Of 33 patients in the nursery 8 (24%) met the case definition. Patients with peripheral iv catheters were more likely to develop A-BSI (8 of 21 vs. O of 10, P < 0.05). Multivariate analysis among patients with iv catheters indicated that only exposure to one nurse was an independent risk factor for developing A-BSI (P < 0.005). Nursery settle plates were more likely to grow Acinetobacter spp. than were settle plates from other hospital areas (8 of 9 vs. 0 of 5, P < 0.005); cultures from nursery air conditioners also grew Acinetobacter spp. Environmental isolates were genetically diverse. After installation of a new air conditioner in May, 1995, A-BSIs occurred more frequently during months of increased absolute humidity or environmental dew point. CONCLUSIONS: Acinetobacter spp. may cause nosocomial BSI and death among infants during periods of polyclonal airborne dissemination; breaks in aseptic technique during i.v. medication administration may facilitate transmission from the environment to the patient. Environmental conditions that increase air conditioner condensate may predispose to airborne dissemination via contaminated aerosols and increase the risk of nosocomial A-BSI.

Acinetobacter↗

Tomato flower abnormalities induced by low temperatures are associated with changes of expression of MADS-Box genes

Flower and fruit development in tomato (Lycopersicon esculentum Mill. ) were severely affected when plants were grown at low temperatures, displaying homeotic and meristic transformations and alterations in the fusion pattern of the organs. Most of these homeotic transformations modified the identity of stamens and carpels, giving rise to intermediate organs. Complete homeotic transformations were rarely found and always affected organs of the reproductive whorls. Meristic transformations were also commonly observed in the reproductive whorls, which developed with an excessive number of organs. Scanning electron microscopy revealed that meristic transformations take place very early in the development of the flower and are related to a significant increase in the floral meristem size. However, homeotic transformations should occur later during the development of the organ primordia. Steady-state levels of transcripts corresponding to tomato MADS-box genes TM4, TM5, TM6, and TAG1 were greatly increased by low temperatures and could be related to these flower abnormalities. Moreover, in situ hybridization analyses showed that low temperatures also altered the stage-specific expression of TM4.

Journal Article↗

Detection of antibodies to human immunodeficiency virus type 1 in oral fluids: a large-scale evaluation of immunoassay performance.

Paired serum and oral-fluid (OF) specimens (n = 4,448) were collected from blood donors and patients attending local sexually transmitted disease clinics in Trinidad and Tobago and the Bahamas and were tested for the presence of human immunodeficiency virus type 1 (HIV-1) antibodies. Sera were tested by Abbott AB HIV-1/HIV-2 (rDNA) enzyme immunoassay (EIA), and positive specimens were confirmed by Cambridge HIV-1 and HIV-2 Western blotting (WB). OF specimens were collected with the OraSure collection device and were tested by Murex GACELISA and by two EIAs from Organon Teknika (the Oral Fluid Vironostika HIV-1 Microelisa System [OTC-L] and the Vironostika HIV-1 Microelisa System [OTC-M]). EIA-reactive OF specimens were confirmed by miniaturized WB (OFWB). GACELISA detected all 474 HIV-1 seropositive specimens (sensitivity, 100%). OTC-L detected 470 positive specimens (sensitivity, 99.2%), while OTC-M detected 468 positive specimens (sensitivity, 98.8%). Specificities ranged from 99.2 to 100% for the three assays. Concordance of OFWB with serum WB was 99.4%, and banding patterns determined by the two methods were similar. The immunoglobulin G (IgG) concentration of OF specimens ranged from 0.21 to 100 microg/ml, with a mean of 17.1 microg/ml. Significant differences in OF IgG concentrations were observed between HIV antibody-positive and HIV antibody-negative persons (31.94 versus 15.28 microg/ml, respectively [P < 0.0001]). These data further confirm the suitability of OF specimens for detection of HIV-1 antibodies. Currently available HIV-1 antibody assays provide sensitivities and specificities with OF specimens comparable to those achieved with serum specimens.

HIV Antibodies↗

Quality of life in young adults having received a BMT during childhood: a GETMON study. Grupo Español de Trasplante de Médula Osea en el Niño.

A quality-of-life questionnaire study was administered in a group of 98 disease-free survivors more than 3 years after BMT. All participants were over the age of 17 years at the time of the survey. The transplants were performed between 1981 and 1993 in eight Spanish hospitals. Eighty-three percent of patients had undergone BMT for neoplastic disease. Seventy-three per cent received an allogeneic bone marrow transplantation. A modified version of a questionnaire applied in Stanford Hospital to evaluate quality of life in adults after BMT was used. A single investigator was responsible for interviewing all subjects by telephone. We compare these results with the same questionnaire applied in a control group of 58 healthy subjects of similar age. The most significant results were: BMT patients valued their quality of life more highly than the control group. The mean score for global quality of life was 8.19+/-0.17 in BMT group as compared to 7.54+/-0.13 in control group (P=0.0013). Studies were cited as the major concern in both groups: 24% in BMT group and in 69% in control group (C.I. 95%=0.59 to 0.30). The patients in the BMT group considered they had fewer problems in comparison with the control group regarding interpersonal relationships with family members and friends, sleep, depression and leisure possibilities. However, they considered they had more problems concerning their physical appearance, studies and work possibilities than their peers. Considerations regarding weight, height, sexual functioning, anxiety, tendency to suffer illness and problems with insurance were similar in both groups.

Adolescent↗

Decreased cerebrospinal fluid levels of neutral and basic amino acids in patients with Parkinson's disease.

We measured the CSF levels of 21, and the plasma levels of 26, amino acids in 31 patients with Parkinson's disease (PD) and in 45 matched controls. We used an ion-exchange chromatography method. When compared to controls, PD patients had lower CSF levels of taurine, alanine, valine, leucine, isoleucine, ethanolamine, citrulline, ornithine, lysine, histidine, arginine, and alpha-aminobutyric acid. PD patients not treated with levodopa or with dopamine agonists had higher CSF tyrosine and phenylalanine levels than those not treated with these drugs and also than controls. PD patients had higher plasma levels of phosphoserine, threonine, methionine, tyrosine, sarcosine and alpha-aminoadipic acid, and lower plasma levels of valine, leucine, and tryptophan, than controls. The CSF/plasma ratio of many of these amino acids was significantly lower in PD patients than those of controls, suggesting that PD patients might have a dysfunction in the transport of neutral and basic amino acids across the blood-brain barrier.

Adult↗

On the mechanism of action of ethodin in inducing myometrium contractions.

1. Ethodin (Rivanol, 6,9-diamino-2-oxyethyl acridine lactate), has been described as an effective drug to induce uterine contractions similar to those in a physiologic labor in still-birth with uterine inertia. We investigate the mechanisms involved in the effect of this compound in contracting the smooth-muscle cells of the myometrium to improve our understanding of the processes involved in the onset of labor. 2. We conclude that the contractile effect of ethodin is mediated through the activation of uterine mast cells that release mediators able to contract the myometrium.

Animals↗

Effect of carboxypeptidase E deficiency on progastrin processing and gastrin messenger ribonucleic acid expression in mice with the fat mutation.

Proforms of gastrointestinal peptides are cleaved at paired basic residues into intermediate forms. Paired basic residues at the C-terminal then are excised by carboxypeptidases before the peptide is amidated. An obese mouse, called Cpe(fat)/Cpe(fat), has a missense mutation in carboxypeptidase E (CPE) with no pancreatic CPE activity and a reduced processing of pancreatic proinsulin to insulin. The purpose of this study was 1) to look for the presence of CPE in the antrum of the stomach, duodenum, and colon in the Cpe(fat)/Cpe(fat) mouse; 2) to determine whether CPE is involved in the processing of progastrin (Pro-G) to its carboxyl-terminal amidated form; and 3) to determine whether a decrease in amidated gastrin results in an up-regulation of stomach gastrin messenger RNA (mRNA) levels. In Cpe(fat)/Cpe(fat) mice, CPE activity was absent in the antrum and colon. In Cpe(fat)/Cpe(fat) mice, amidated gastrin levels were reduced significantly. Levels of the precursor for amidated gastrin (gastrin-Gly-Arg-Arg) were markedly elevated. Gastrin mRNA levels were increased approximately 2-fold over the levels in Cpe(fat)/Cpe(fat) mice. These results indicate that CPE is needed for processing progastrin to gastrin in the stomach and that amidated gastrin exerts an inhibitory feedback effect on gastrin mRNA levels.

Animals↗

Expression of the SalI restriction-modification system of Streptomyces albus G in Escherichia coli.

The salIR and salIM genes of Streptomyces albus G encode the restriction endonuclease (ENase) and DNA methyltransferase (MTase) of the SalI restriction-modification (R-M) system. In S. albus G, the genes constitute an operon that is mainly transcribed from a promoter located upstream from salIR, the first gene of the operon. In addition, a second promoter, at the 3' end of salIR, allows independent transcription of the MTase gene. Expression of salIR and salIM in Escherichia coli was investigated. The ENase gene was not expressed in the heterologous host, probably due to inactivity of the main promoter of the salI operon. In contrast to salIR, salIM was functional in E. coli. Preliminary S1 nuclease mapping experiments suggest that the alternative promoter of the MTase gene can initiate transcription in the heterologous, as well as in the homologous host.

Cloning, Molecular↗

Rapid screening for early detection of mother-to-child transmission of human immunodeficiency virus type 1.

The testing of dried blood spots (DBSs) for the presence of human immunodeficiency type 1 (HIV-1) proviral DNA by PCR was first described in 1991. The technology has proven to be particularly valuable for resolving the infection status in HIV-1-indeterminate infants born to HIV-1-seropositive mothers. To broaden the applicability of DBS PCR, we adapted it to a standardized, commercially available microwell plate amplification and detection kit, Amplicor HIV-1, produced by Roche Diagnostic Systems. The microwell assay is rapid and easy to perform and uses equipment that is readily available in routine diagnostic laboratories. The high level of performance of the assay was demonstrated in 1,168 duplicate tests performed on 584 DBSs from 178 uninfected and 100 HIV-1-infected individuals, including 56 children with perinatally acquired HIV-1. Of 12 infants who were followed prospectively from birth, 3 (25%) were infected in utero (PCR positive at birth) and 9 (75%) were infected intrapartum (PCR negative, culture negative at birth). Overall, HIV-1 DNA was identified in 3 of 11 (27.3%) DBSs collected from infected infants during the first 4 days of life, 8 of 9 (88.9%) DBSs collected between 10 and 15 days postpartum, and 166 of 167 (99.4%) DBSs collected after 15 days of age. All 320 DBSs from uninfected children were PCR DNA negative. These findings indicate that use of the Roche microwell DBS PCR assay provides a powerful new approach for large-scale perinatal screening programs and population-based studies of vertical transmission.

Acquired Immunodeficiency Syndrome↗

Perinatal transmission of HIV-2 infection in malnourished children in Guinea Bissau.

Since there have been a few reports of pediatric HIV-2 infection. We therefore investigated the perinatal transmission of HIV-2 in 147 malnourished and 164 well-nourished children attending a health center in the northern part of Guinea Bissau. Specific HIV-2 antibodies were detected in 17 mothers and in 2 malnourished children, one of them with pediatric AIDS. This study demonstrates that mother to child transmission of HIV-2 infection occurs in Guinea Bissau and suggests that there is an increased likelihood of detecting HIV-2 infection in malnourished children. The high seroprevalence of HIV-2 in a rural population without known risk factors may represent a hidden threat to mother/child health.

Acquired Immunodeficiency Syndrome↗

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 2. Mortality and morbidity from malaria in the study area.

Background data on child mortality and morbidity from malaria were obtained in a new study area in the centre of The Gambia, south of the river, chosen as the site for a malaria intervention trial. Infant and child mortality rates were 120 and 41 per 1000 respectively. Results obtained using post-mortem questionnaires suggested that malaria was an uncommon cause of death in children under the age of one year but responsible for about 40% of deaths in children aged 1-4 years. Ninety-two percent of deaths attributed to malaria occurred during or immediately after the rainy season. Parasite and spleen rates in children aged 1-5 years at the end of the malaria transmission season were 66% and 64% respectively. Malariometric indices were similar in primary health care (PHC) villages, selected as sites for an intervention with insecticide-treated bed nets and targeted chemoprophylaxis, and in smaller, non-PHC, control villages.

Cause of Death↗

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 6. The impact of the interventions on mortality and morbidity from malaria.

The effects of insecticide-impregnated bed nets on mortality and morbidity from malaria have been investigated during one malaria transmission season in a group of rural Gambian children aged 6 months to 5 years. Sleeping under impregnated nets was associated with an overall reduction in mortality of about 60% in children aged 1-4 years. Mortality was not reduced further by chemoprophylaxis with Maloprim given weekly by village health workers throughout the rainy season. Episodes of fever associated with malaria parasitaemia were reduced by 45% among children who slept under impregnated nets. The addition of chemoprophylaxis provided substantial additional benefit against clinical attacks of malaria; 158 episodes were recorded among 946 children who slept under impregnated nets but who also received chemoprophylaxis. Chemoprophylaxis reduced the prevalence of splenomegaly and parasitaemia at the end of the malaria transmission season by 63% and 83% respectively. Thus, insecticide-impregnated bed nets provided significant protection in children against overall mortality, mortality attributed to malaria, clinical attacks of malaria, and malaria infection. The addition of chemoprophylaxis provided substantial additional protection against clinical attacks of malaria and malaria infection but not against death.

Antimalarials↗

Effect of cyclosporin on plasma lipoproteins in bone marrow transplantation patients.

The effects of cyclosporin and prednisone on plasma lipid and lipoprotein levels were studied in 20 allogeneic bone-marrow transplantation patients receiving cyclosporin plus prednisone therapy, and in 14 allogeneic patients treated only with cyclosporin during 100 days. Eighteen autologous bone-marrow patients not requiring cyclosporin were used as a control group. Patients were studied 5 days prior to transplantation, and on days 30, 60, and 100 after transplantation. To determine the reversibility of the changes, lipid parameters were analyzed 30 days after completion of the treatment. Nutritional supplementation, conditioning regimens, and concomitant medications were not significantly different between groups. Furthermore, no significant differences in age, weight, lipid, or lipoprotein levels were found at baseline. Our results indicate that cyclosporin therapy induces a reversible increase of plasma cholesterol, LDL-cholesterol, triglycerides, VLDL-triglycerides, and apolipoprotein B and a decrease of HDL-cholesterol, HDL2-cholesterol, and apolipoprotein A-I. The addition of prednisone to cyclosporin therapy induces a higher increase in plasma cholesterol mainly due to an increase in HDL-cholesterol. Total cholesterol/HDL-cholesterol ratio increased significantly in patients treated only with cyclosporin. No differences were found in this ratio in patients treated with prednisone compared to those submitted to autologous bone-marrow transplantation. Lipid changes observed in this study were reversible 30 days after cessation of cyclosporin treatment.

Adult↗