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Biomedical subjects

C Gonzalez

Publications and source records attributed to C Gonzalez.

At least 127 records · Page 7Linked to original sources
PubMed1997

A case control study of chorioamniotic infection and histological chorioamnionitis in stillbirth.

In order to elucidate the role and aetiology of chorioamnionitis in stillbirth a case referent study was carried out in 58 pregnant women with late foetal death (cases) and in 58 pregnant women at term with live foetus (referents) matched for age and parity in Maputo Mozambique. Samples from women, stillborns and liveborns, were collected for microbiological and histological assessment. Histological chorioamnionitis was diagnosed in 96% of the cases and in 67% of the referents (OR = 13.5; 95% CI: 2.9-123.9). Escherichia coli was the species most frequently isolated in stillborns; in 14/16 (88%) cases it was isolated from intracardiac fluid. E. coli was associated with chorioamnionitis in 28% of the stillborns as compared to 5% of the referents (OR = 6.9; 95% CI: 1.4-65.4). No group B streptococci were recovered from any placenta or newborn. Vasculitis was present in 12 (21%) cases and in 3 (5%) referents (OR = 4.8; 95%, CI: 1.2-27.7). Histological chorioamnionitis was thus associated with stillbirth. E. coli was common in stillborns. The presence of vasculitis in one fifth of the stillborns indicated that the foetus was alive at the onset of infection.

Age Factors↗
PubMed1996

Optimizing the cell efficacy of synthetic ribozymes. Site selection and chemical modifications of ribozymes targeting the proto-oncogene c-myb.

Expression of the proto-oncogene c-myb is necessary for proliferation of vascular smooth muscle cells. We have developed synthetic hammerhead ribozymes that recognize and cleave c-myb RNA, thereby inhibiting cell proliferation. Herein, we describe a method for the selection of hammerhead ribozyme cleavage sites and optimization of chemical modifications that maximize cell efficacy. In vitro assays were used to determine the relative accessibility of the ribozyme target sites for binding and cleavage. Several ribozymes thus identified showed efficacy in inhibiting smooth muscle cell proliferation relative to catalytically inactive controls. A combination of modifications including several phosphorothioate linkages at the 5'-end of the ribozyme and an extensively modified catalytic core resulted in substantially increased cell efficacy. A variety of different 2'-modifications at positions U4 and U7 that confer nuclease resistance gave comparable levels of cell efficacy. The lengths of the ribozyme binding arms were varied; optimal cell efficacy was observed with relatively short sequences (13-15 total nucleotides). These synthetic ribozymes have potential as therapeutics for hyperproliferative disorders such as restenosis and cancer. The chemical motifs that give optimal ribozyme activity in smooth muscle cell assays may be applicable to other cell types and other molecular targets.

Animals↗
PubMed1996

Chemically modified hammerhead ribozymes with improved catalytic rates.

A site-specific chemical modification strategy has been employed to elucidate structure-function relationships at the only phylogenetically nonconserved position within the core of the hammerhead ribozyme (N7). Four different base substitutions at position 7 resulted in increased catalytic rates. A pyridin-4-one base substitution increased the rate of the chemical step up to 12-fold. These results are the first examples of chemical modifications within a catalytic RNA that enhance the rate of the chemical step. Four base substitutions resulted in decreased catalytic rates. The results do not correlate with proposed hydrogen bond interactions (Pley et al., 1994; Scott et al., 1995). This study demonstrates the utility of using unnatural nucleotide analogs-rather than mutagenesis with the four standard nucleotides alone-to elucidate structure-function relationships of small RNAs.

Catalysis↗
PubMed1996

Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase by nuclear variants of mycophenolic acid.

Structure-activity relationships in the region of the phthalide ring of the inosine monophosphate dehydrogenase inhibitor mycophenolic acid have been explored. Replacement of the lactone ring with other cyclic moieties resulted in loss of potency, especially for larger groups. Replacement of the ring by acyclic substituents also indicated a strong sensitivity to steric bulk. A phenolic hydroxyl group, with an adjacent hydrogen bond acceptor, was found to be essential for high potency. The aromatic methyl group was essential for activity; the methoxyl group could be replaced by ethyl to give a compound with 2-4 times the potency of mycophenolic acid in vitro and in vivo.

Animals↗
PubMed1996

The genes YNI1 and YNR1, encoding nitrite reductase and nitrate reductase respectively in the yeast Hansenula polymorpha, are clustered and co-ordinately regulated.

The nitrite reductase-encoding gene (YNI1) from the yeast Hansenula polymorpha was isolated from a lambda EMBL3 H. polymorpha genomic DNA library, using as a probe a 481 bp DNA fragment from the gene of Aspergillus nidulans encoding nitrite reductase (niiA). An open reading frame of 3132 bp, encoding a putative protein of 1044 amino acids with high similarity with nitrite reductases from fungi, was located by DNA sequencing in the phages lambdaNB5 and lambdaJA13. Genes YNI1 and YNR1 (encoding nitrate reductase) are clustered, separated by 1700 bp. Northern blot analysis showed that expression of YNI1 and YNR1 is co-ordinately regulated; induced by nitrate and nitrite and repressed by sources of reduced nitrogen, even in the presence of nitrate. A mutant lacking nitrite reductase activity was obtained by deletion of the chromosomal copy of YNI1. The mutant does not grow in nitrate or in nitrite; it exhibits a similar level of transcription of YNR1 to the wild type, but the nitrate reductase enzymic activity is only about 50% of the wild type. In the presence of nitrate the delta ynil::URA3 mutant extrudes approx. 24 nmol of nitrite/h per mg of yeast (wet weight), about five times more than the wild type.

Amino Acid Sequence↗
PubMed1996

Mixed sclerosing bone dystrophy. Report of a case and review of the literature.

A 63-year old woman was admitted because of hip pain. Radiographs showed multiple round and oval sclerotic lesions involving humeral heads, pelvis, vertebral bodies and both femoral bones. Diaphyseal periosteal proliferation was found in metatarsal bones. A diagnosis of mixed sclerosing bone dystrophy was made. We review clinical, epidemiological and radiological findings of this entity.

Aged↗
PubMed1996

Radiosynthesis and biodistribution of the S-[18F]fluoroethyl analog of McN5652.

[11C]McN5652 has been reported to exhibit favorable properties as a PET radiotracer for studying serotonin uptake sites. However, the use of this radiotracer may be limited by the short half-life of11C. To obtain a tracer with longer physical half-life, we have synthesized the S-[18F]fluoroethyl analog of McN5652 (trans-1,2,3,5,6,10b-hexahydro-6-[4-([18F]fluoroethylthio)-phenyl] pyrrolo-[2,1-a]-isoquinoline) ([18F]FEMcN) and evaluated as a PET radiotracer for imaging serotonin uptake sites. The radiosynthesis was performed via a one-pot, two-step procedure. In the first step, 1-bromo-2-[18F]fluoroethane was prepared from 2-bromoethyl triflate and K18F/Kryptofix 2.2.2. in THF at room temperature. The second step, the S-fluoroalkylation of the normethyl McN5652, a thiol, was carried out, without isolating the 1-bromo-2-[18F]fluoroethane, by adding the normethyl McN5652 to the reaction vial, which was warmed at 45 degrees C for 1 min. The fluoroalkylation reaction proceeded quickly, giving [18F]FEMcN in an average overall radio-chemical yield of 13 +/- 7%. The specific activity was 1593 +/- 625 mCi/mumol. Ex vivo autoradiographic studies revealed that [18F]FEMcN accumulated into regions with high densities of 5-HT uptake sites such as hypothalamus, substantia nigra, and raphe nuclei. With blockade by nitroquipazine, a selective and highly potent 5-HT uptake blocker, the activity level in these regions was close to that in regions low in 5-HT uptake sites such as cerebellum, suggesting that this radiotracer binds specifically to 5-HT uptake sites. The regional distribution of [18F]FEMcN at 60 min postinjection correlated with the distribution of [11C]McN5652 reported in the literature. The specific binding of this radiotracer determined as the difference in radioactivity accumulation with and without blocking by the 5-HT uptake blocker agreed with the distribution of the number of 5-HT uptake sites measured in vitro. Thus, 5-HT uptake sites were visualized in vivo with [18F]FEMcN. However, comparison with the in vivo behavior of [11C]McN5652 indicated less favorable properties of [18F]FEMcN as a PET radiotracer for imaging 5-HT uptake sites, including lower blood-brain barrier penetration and lower target-to-nontarget ratios.

Animals↗
PubMed1996

How frequently should the amniotic fluid index be performed during the course of antepartum testing?

OBJECTIVE: Our purpose was to evaluate the need for frequent amniotic fluid volume assessments in our antepartum testing unit. STUDY DESIGN: In a retrospective analysis of data accumulated over 1 year in our antepartum testing unit amniotic fluid index values performed at 3- to 4-day intervals were compared with follow-up values. Of 11,827 amniotic fluid index values, there were 6291 with follow-up values within 4 days. The results were stratified on the basis of the subsequent amniotic fluid index value and estimated gestational age. Comparisons were made relating to amniotic fluid index testing intervals of 4 versus 7 days. RESULTS: Patients with an amniotic fluid index > 8 cm had a 2.3% chance (128/5677) of having oligohydramnios (amniotic fluid index < or = 5.0 cm) in the next 4 days. Those patients with low-normal amniotic fluid index values (5 to 8 cm) had a 16.2% chance (96/593) of having oligohydramnios in the next 4 days. There were few patients with an amniotic fluid index < or = 5 cm who had subsequent amniotic fluid index values measured. Patients with an amniotic fluid index > 8 cm had a 2.2% chance (156/6946) of having oligohydramnios within 7 days, and those with low-normal amniotic fluid index values had a 16.3% chance (105/643) of having oligohydramnios with 7 days. Stratifying the results by gestational age reveals that patients at > or = 41 weeks of gestation had a 23.3% chance of having oligohydramnios within 4 days if the current amniotic fluid index was found to be 5 to 8 cm and a 7.4% chance if the current amniotic fluid index was found to be normal. Term (estimated gestational age of 37 to 40 weeks) patients had a similar risk of oligohydramnios in 4 days if the amniotic fluid index was low-normal (17.8%) but a risk of 3.6% if the amniotic fluid index was normal. CONCLUSIONS: For patients at < 41 weeks of gestation undergoing antepartum testing, weekly assessments of amniotic fluid index is probably adequate if the initial measurement is in the normal range (> or = 8 cm) because the risk of having oligohydramnios within 7 days is low (2.2%). For patients at < 41 weeks of gestation whose initial amniotic fluid index measurement is in the low-normal range (5 to 8 cm), a scheme of twice-weekly assessment is justified on the basis of a higher risk for an amniotic fluid index < or = 5 cm within 4 days (12.3%). For all patients at > or = 41 weeks of gestation, twice-weekly amniotic fluid index assessments are recommended regardless of the initial measurement.

Amniotic Fluid↗
PubMed1996

Intrafamily transmission of hepatitis C virus: sexual and non-sexual contacts.

BACKGROUND/METHODS: As a high number of patients with antibodies to hepatitis C (anti-HCV) do not have a known history of parenteral acquisition, other non-parenteral means of hepatitis C virus transmission must be studied. We investigated 1451 household contacts of 535 anti-HCV positive, human immunodeficiency virus-negative index patients. RESULTS: Overall, the prevalence of anti-HCV in household contacts was 4.5%. Thirty (7.6%) out of the 394 heterosexual stable partners were anti-HCV positive as compared to 35 (3.3%) out of 1057 non-sexual contacts (p < 0.01). The prevalence of anti-HCV was lowest in children of the index cases (1.8%). In this group, the prevalence of anti-HCV was 3% (10/330) when the mother was the index case, as opposed to 0.6% (2/328) when the father was the index case (p < 0.05). The prevalence of anti-HCV increased with age, being highest (18.6%) in family contacts older than 60 years. CONCLUSIONS: Transmission of hepatitis C virus may occur among household contacts of anti-HCV positive patients. Sexual contact or the use of non-disposable medical material in the past might explain the higher prevalence of anti-HCV found in sexual partners and in family contacts older than 60 years of age. Anti-HCV screening should be performed in family contacts of anti-HCV positive patients, particularly in those contacts older than 20.

Adolescent↗
PubMed1996

Cholera and pertussis toxins reveal multiple regulation of cAMP levels in the rabbit carotid body.

It is known that hypoxia (PO2 approximately equal to 66-18 mm Hg), acting via unknown receptors, increases carotid body cAMP levels in Ca(2+)-free solutions, indicating that low PO2 activates adenylate cyclases independently of the action of the released neurotransmitters. The aim of the present work was to investigate the involvement of G proteins in the genesis of the basal level of cAMP and on the increase in cAMP induced by low PO2. In carotid body homogenates, cholera toxin- and pertussis toxin-induced [32P]ADP-ribosylation of two protein bands of approximately equal to 42 and 45 kDa, and approximately equal to 39 and 40 kDa respectively; in both cases, prior incubation of the carotid bodies with the toxins reduced [32P]ADP-ribosylation by > 90%. In intact carotid bodies, cholera toxin treatment increased cAMP levels more in normoxic than in hypoxic organs, indicating that hypoxia releases neurotransmitters acting on receptors negatively coupled to adenylate cyclases. Cholera toxin-treated carotid bodies incubated in Ca(2+)-free solution had identical cAMP levels in normoxia and in hypoxia. In pertussis toxin-treated normoxic carotid bodies the cAMP level was close to control, but in pertussis toxin-treated hypoxic carotid bodies cAMP rose to a level similar to those seen in normoxic cholera toxin-treated organs, indicating that low PO2 releases neurotransmitters acting on receptors positively coupled to adenylate cyclases. Pertussis toxin-treated carotid bodies incubated in Ca(2+)-free solution lost their capacity to increase cAMP in response to hypoxia, indicating that a G protein sensitive to pertussis toxin is needed for this response. This implies that the carotid bodies express a pertussis toxin-sensitive G protein positively coupled to adenylate cyclases, or that a Gs protein requiring the cooperative action of Go/Gi donated beta gamma subunits mediates the increase in cAMP level produced by hypoxia.

Adenosine Diphosphate Ribose↗
PubMed1996

Syphilis seroprevalence among pregnant women and its role as a risk factor for stillbirth in Maputo, Mozambique.

OBJECTIVE: To elucidate the role of current syphilis as a risk factor for foetal death. METHODS: Sera were obtained from 57 women with third trimester foetal death (cases) and 58 women with foetus alive (controls) matched for age and parity. All sera reactive in qualitative Rapid Plasma Reagin (RPR) analyses were tested with serial twofold dilutions to determine endpoint flocculation titres and tested with the micro-haemagglutination assay for Treponema pallidum (MHA-TP). Placental biopsies were sectioned and stained by haematoxylin-eosin and Warthin-Starry for light microscopy. SETTING: Central Hospital, in Maputo, Mozambique, from January 1990 to June 1991. RESULTS: The MHA-TP was reactive in 42% of cases and in 12% of controls (OR = 5.3; 95% CI: 1.9-15.4). The RPR card test was reactive at the dilution of 1.32 or greater in 28% of cases and in 7% of controls. All these results were confirmed by MHA-TP (OR = 5.3; 95% CI: 1.5-15.4). In 9/28 (32%) MHA-TP seroreactive women (7 cases and 2 controls) placental morphological changes indicated syphilitic infection. CONCLUSION: MHA-TP seroreactivity and high titre RPR were associated with stillbirth. Morphological changes presumptive of syphilis infection were found in 32% placentas histologically studied. Syphilis is a risk factor for foetal death in Maputo, Mozambique.

Case-Control Studies↗
PubMed1996

Ultrasonographically assessed maximum carotid artery wall thickness in Mexico City residents and Mexican Americans living in San Antonio, Texas. Association with diabetes and cardiovascular risk factors.

Measurements of carotid artery wall thickness are often used as a surrogate for atherosclerosis. However, few studies have performed these measurements in populations of Mexican origin. Since Mexicans in Mexico City consume high-carbohydrate diets and have carbohydrate-induced dyslipidemia (high triglyceride and low HDL cholesterol levels) compared with Mexican Americans living in San Antonio, Tex, we questioned whether they also had more atherosclerosis than San Antonio Mexican Americans. Mean maximum intimal-medial thickness (IMT) of the common (CCA) and internal (ICA) carotid arteries were measured in 867 subjects aged 35 to 64 years (40% men) in two Mexican-origin populations, one from San Antonio (n = 202) and the other from Mexico City (n = 665). IMT's in the two cities were compared, and their associations with cardiovascular risk factors were analyzed. Older age, male sex, high levels of total cholesterol, low levels of HDL cholesterol, and high systolic blood pressure were positively associated with both CCA IMT and ICA IMT. Cigarette smoking was significantly associated with ICA IMT. CCA and ICA IMTs in diabetic subjects were thicker than in nondiabetic subjects in both men and women (all P < = .05). CCA IMT was thicker in the San Antonio than the Mexico City subjects after adjustment for cardiovascular risk factors (0.81 versus 0.76 mm in men and 0.77 versus 0.71 mm in women; P < .001 for city difference). San Antonio men also had thicker ICA IMT than their counterparts in Mexico City (0.88 versus 0.83 mm), but the reverse was true for women (0.73 versus 0.77 mm; interaction between sex and city, P < .05). Our results indicate that men had higher carotid IMTs than women. CCA IMT was thicker in San Antonio Mexican Americans than in Mexico City residents. The differences in ICA IMTs between San Antonio and Mexico City were inconsistent. Thus, since Mexico City residents consume high-carbohydrate diets, the data do not support an atherogenic effect of such diets. The interaction between sex and city on ICA IMT deserves further study.

Cardiovascular Diseases↗
PubMed1996

Irinotecan is an active agent in untreated patients with metastatic colorectal cancer.

PURPOSE: To determine the response rate, survival, and toxicity of the new anticancer agent, irinotecan (CPT-11), in the treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Forty-one chemotherapy-naive patients with measurable metastatic colorectal cancer were treated with a 90-minute infusion of irinotecan 125 mg/m2 administered weekly for 4 weeks every 6 weeks. Pretreatment tumor biopsies to assess topoisomerase-I (Topo-I) activity were obtained from 11 patients. The pharmacokinetics for irinotecan and its active metabolite, SN-38, were determined in 18 patients. RESULTS: Thirteen of 41 patients (32%) had a partial response (PR; 95% confidence interval, 18% to 46%). The median response duration was 8.1 months (range, 4.0 to 16.0) and the median survival time was 12.1 months (range, 2.1 to 21.7) for all 41 patients. Grade 3 or 4 toxicities were diarrhea (29% of patients) and neutropenia (22% of patients). Grade 3 or 4 diarrhea was substantially more prevalent in the initial 18 patients on study, with an incidence rate of 56%; a significant reduction in the incidence of severe diarrhea to 9% was noted with strict adherence to an antidiarrheal regimen of loperamide and diphenyldramine. No correlations were seen between pharmacokinetics of irinotecan/SN-38 and the clinical parameters of response, survival, or incidence of diarrhea. CONCLUSIONS: Irinotecan has activity in the treatment of patients with metastatic colorectal cancer. Strict adherence to an antidiarrheal regimen of diphenhydramine/loperamide significantly reduced the incidence of diarrhea; the agent was thereafter well tolerated in the majority of patients.

Adult↗
PubMed1996

Mutations in new cell cycle genes that fail to complement a multiply mutant third chromosome of Drosophila.

We have simultaneously screened for new alleles and second site mutations that fail to complement five cell cycle mutations of Drosphila carried on a single third chromosome (gnu, polo, mgr, asp, stg). Females that are either transheterozygous for scott of the antartic (scant) and polo, or homozygous for scant produce embryos that show mitotic defects. A maternal effect upon embryonic mitoses is also seen in embryos derived from females transheterozygous with helter skelter (hsk) and either mgr or asp. cleopatra (cleo), fails to complement asp but is not uncovered by a deficiency for asp. The mitotic phenotype of larvae heterozygous for cleo and the multiple mutant chromosome is similar to weak alleles of asp, but there are no defects in male meiosis. Mutations that failed to complement stg fell into two complementation groups corresponding to stg and a new gene noose. Three of the new stg alleles are early zygotic lethals, whereas the fourth is a pharate adult lethal allele that affects both mitosis and meiosis. Mutations in noose fully complement a small deficiency that removes stg, but when placed in trans to certain stg alleles, result in late lethality and mitotic abnormalities in larval brains.

Alleles↗
PubMed1996

A prospective analysis of the HOMA model. The Mexico City Diabetes Study.

OBJECTIVE: Both insulin resistance (IR) and decreased insulin secretion have been shown to predict the development of NIDDM. However, methods to assess insulin sensitivity and secretion are complicated and expensive to apply in epidemiological studies. The homeostasis model assessment (HOMA) has been suggested as a method to assess IR and secretion from the fasting glucose and insulin concentrations. RESEARCH DESIGN AND METHODS: We applied the HOMA model in the 3.5-year follow-up of the Mexico City Diabetes Study. RESULTS: Out of 1,449 subjects, 97 developed diabetes. When modeled separately insulin resistance but not insulin secretion predicted NIDDM. However, when both variables were entered into the same regression model, both increased IR and decreased beta-cell function significantly predicted NIDDM. CONCLUSIONS: We conclude that the HOMA provides a useful model to assess beta-cell function in epidemiological studies and that it is important to take into account the degree of IR in assessing insulin secretion.

Adult↗