Influence of cyclosporine on graft regeneration and function after liver transplantation: trial in pigs.
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Biomedical subjects
Publications and source records attributed to J Herrera.
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BACKGROUND: Transmission of hepatitis C virus (HCV) is strongly associated with use of contaminated blood products and injection drugs. Other "non-parental" modes of transmission including sexual activity have been increasingly recognized. We examined risk factors for acquiring HCV in patients who were referred to two tertiary care centers and enrolled in an antiviral therapy protocol. METHODS: Interviews of 148 patients were conducted apart from their physician evaluation using a structured questionnaire covering demographics and risk factors for HCV acquisition. RESULTS: Risk factors (blood products, injection/intranasal drugs, razor blades/ toothbrushes, body/ear piercing, occupational exposure, sexual activity) were identified in 141 (95.3%) of participants; 23 (15.5%) had one (most frequently blood or drug exposure), 41 (27.7%) had two, and 84 (53.4%) had more than two risk factors. No patient reported sexual activity as a sole risk factor. Body piercing accounted for a high number of exposures in women. Men were more likely to have exposure to street drugs but less exposure to blood products than women. Blood product exposure was less common in younger than older HCV patients. CONCLUSION: One and often multiple risk factors could be identified in nearly all HCV-infected patients seen in a referral practice. None named sexual transmission as the sole risk factor. The development of a more complete profile of factors contributing to transmission of HCV infection may assist in clinical and preventive efforts. The recognition of the potential presence of multiple risk factors may have important implications in the approach to HCV surveillance, and particularly the use of hierarchical algorithms in the study of risk factors.
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We have isolated and characterized a unique glial-restricted precursor cell (GRP) from the embryonic spinal cord. Clonal analysis demonstrated that these cells are able to generate oligodendrocytes and two distinct type of astrocytes (type 1 and type 2) when exposed to appropriate signals in vitro. We now show that many aspects of these cells are retained in vivo. GRP cells are restricted to the glial lineage in vivo as they seem to be unable to generate neuronal phenotypes in an in vivo neurogenic environment. GRP cells survive and migrate in the neonatal and adult brain. Transplanted GRP cells differentiate into myelin-forming oligodendrocytes in a myelin-deficient background and also generate immature oligodendrocytes in the normal neonatal brain. In addition, GRP cells also consistently generated glial fibrillary protein-expressing cells in the neonatal and adult brain, a property not consistently expressed by other glial precursor cells like the O-2A/OPC cells. We suggest that the lineage restriction of GRP cells and their ability to generate both oligodendrocytes and astrocytes in vivo together with their embryonic character that allows for extensive in vitro expansion of the population makes the cell useful for clinical application.
Intravenous iron (Fe) and recombinant human erythropoietin (rHuEPO) are routine treatments in the management of anemia in patients with chronic renal failure. We investigated the oxidative stress acutely induced by these therapies and whether pretreatment with oral melatonin (MEL) would have a beneficial effect. Nine patients (four women) were studied within 1 month of entering a chronic hemodialysis program in the interdialytic period. Plasma malondialdehyde (MDA), red blood cell glutathione (GSH), and catalase (CAT) activity were measured in blood samples obtained before (baseline) and 1, 3, and 24 hours after the administration of Fe (100 mg of Fe saccharate intravenously over 1 hour) or rHuEPO (4,000 U intravenously). One hour before these treatments, patients were administered a single oral dose of MEL (0.3 mg/kg) or placebo. Each patient was studied on four occasions, corresponding to studies performed using either placebo or MEL in association with intravenous Fe and rHuEPO administration. Baseline data showed increased oxidative stress in patients with end-stage renal failure. Increments in oxidative stress induced by Fe were more pronounced at the end of the administration: MDA, baseline, 0.74 +/- 0.09 nmol/mL; 1 hour, 1.50 +/- 0.28 nmol/mL (P: < 0.001); GSH, baseline, 2.51 +/- 0.34 nmol/mg of hemoglobin (Hb); 1 hour, 1.66 +/- 0.01 nmol/mg Hb (P: < 0.001); and CAT activity, baseline, 27.0 +/- 5.7 kappa/mg Hb; 1 hour, 23.3 +/- 4.2 kappa/mg Hb (P: < 0.001). rHuEPO-induced increments in oxidative stress were more pronounced (P: < 0.001) at 3 hours (MDA, 1.24 +/- 0.34 nmol/mL; GSH, 1.52 +/- 0.23 nmol/mg Hb; CAT activity, 18.0 +/- 3.1 kappa/mg Hb). MEL administration prevented the changes induced by Fe and rHuEPO and had no adverse side effects. These studies show that intravenous Fe and rHuEPO in doses commonly used to treat anemia in chronic hemodialysis patients acutely generate significant oxidative stress. Oral MEL prevents such oxidative stress and may be of clinical use.
This study sought to evaluate physical activity in women at moderate risk for breast cancer, the correlates of engaging in regular physical activity, and whether physical activity relates to psychological well-being. The results revealed that 55% of women were regularly active. Logistic regression models indicated that positive affect was associated with increased and negative affect was associated with decreased overall and leisure activity. Older, married, and employed women were more likely to engage in household/occupational activity, whereas women who perceived their risk for breast cancer as high were less likely. More educated women and those with higher perceived risk were more likely to engage in leisure activity, and married women were less likely. These results suggest a need to increase activity levels in women at moderate risk for breast cancer, provide variables upon which interventions can be tailored to promote activity, and point to psychological benefits of activity in this population.
BACKGROUND: To develop a test that would disclose subclinical impairment in renal function, we studied the increment in tubular secretion of creatinine (TS(Cr)) induced by intravenous creatinine administration. METHODS: Studies were done in 14 normal individuals, 7 kidney donors (KDs), and 11 transplant recipients (Tx), all of whom had normal creatinine levels (P(Cr) <133 micromol/L). Creatinine infusion studies determined that maximal stimulation of TS(Cr) resulted from P(Cr) levels of 500 to 700 micromol/L. Therefore, in the tubular stress test, clearances, urinary excretion of creatinine (U(Cr)V) and TS(Cr) were determined before and after (15 to 105 min) a single bolus injection of 88.4 mmol/kg body wt, which resulted in the target P(Cr) levels. RESULTS: Baseline determinations of P(Cr), U(Cr)V, and TS(Cr) were not significantly different in the study groups. Stimulated U(Cr)V (nmol/kg/min) was higher in normals (426 +/- 82) than in KDs (338 +/- 72, P < 0.05) and Tx patients (311 +/- 66, P < 0.01). Similarly, TS(Cr) (nmol/kg/min) was higher (P < 0.001) in normals (180 +/- 60) than in KDs (155 +/- 54) and Tx patients (86 +/- 35). Furthermore, the transplanted kidney responded worse than the solitary normal kidney (P < 0.05), despite having similar levels of glomerular filtration rate (GFR). The tubular stress test increased TS(Cr) 11.3 +/- 6.2 times in normals, 4.3 +/- 1.2 times in KDs (P < 0.01), and 2.5 times in Tx (P < 0.001). CONCLUSIONS: Impaired tubular secretory response to a creatinine load is a more sensitive index of reduced functioning renal mass than levels of P(Cr) and GFR. The tubular stress test may be useful in following the natural history of kidney disease and the results of therapeutic interventions.
To further study genetic heterogeneity of Mexican stocks of Trypanosoma cruzi, genomic Southern analyses from 54 Mexican isolates and 5 South American reference stocks were carried out. The membranes were hybridized with a homologous cDNA clone from the ribosomal protein S4 that identifies allelic bands from a single gene type locus. These allelic bands were sequentially numbered depending on their relative size. Mexican T. cruzi stocks were quite homogeneous: 31 cases (57%) showed a homozygous genotype 3/3, and 21 isolates (38%) exhibited the heterozygote genotype 2/3. Just 2 Mexican stocks (3%) showed a different genotype 2/5, but the potential parental homozygous 2/2 was never observed. Being that T. cruzi is a diploid organism, the apparent absence of the presumptive parental homozygous genotype 2/2 argues against sexual reproduction within the population, at least as a common event. Therefore, these data support a clonal population structure of T. cruzi in Mexico.
Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do not.
Pro-inflammatory cytokines including tumour necrosis factor (TNF) mediate the pathogenesis of hepatitis C virus (HCV) infection. The distribution of TNF gene polymorphisms was examined among cirrhotic and non-cirrhotic patients infected with HCV. Thirty Caucasians with cirrhosis due to chronic HCV infection and 114 HCV-infected patients histopathologically free of cirrhosis were genotyped for genetic variants in TNF, lymphotoxin alpha and TNF-receptor type I using PCR-based techniques. Variability in the progression of HCV-related cirrhosis was assessed in a multivariate model including genetic and non-genetic factors such as gender, estimated duration of infection, alcohol consumption, and viral genotype. Viral genotype and non-genetic host features were not independently related to the occurrence or rate of development of cirrhosis in the patient population. In contrast, the TNF promoter variants TNF2 (-238A) and TNF3 (-308A) conferred a 3.2-fold and 5.1-fold risk of cirrhosis respectively (P = 0.03 for both). Reciprocal effects were observed with several TNF alleles and haplotypes defined by the -238G/A and -308G/A dimorphic sequences. Polymorphisms in the TNF alpha promoter appear to be associated with variability in the histological severity of chronic hepatitis C infection.
Hepatitis C virus (HCV) RNA status and HCV genotype have become important tools in the diagnosis and monitoring of therapy in chronic HCV infection. To establish a database with respect to HCV genotype and serum HCV RNA concentrations in chronic hepatitis C patients in the United States, we analysed 6807 chronic hepatitis C patients who had HCV RNA and HCV genotype tests conducted at a central laboratory. The HCV RNA concentration cut-off for the lower 25th percentile of this population (low titre) was 0.9 x 106 copies ml-1. The median HCV RNA concentration was 3.5 x 106 copies ml-1 and the cut-off for the upper 25th percentile (high titre) was 5 x 106 copies ml-1. Male patients had a median HCV RNA concentration of 3.9 x 106 copies ml-1, which was significantly higher than the median HCV RNA level for females (2.75 x 106 copies ml-1; P < 0.001). HCV genotype 1 was detected in 73% of patients; genotype 2 in 14%; genotype 3 in 8%; mixed genotype in 4%; and genotypes 4, 5 and 6 with a frequency of < 1%. Patients from the Northeast, Southeast and Midwest had significantly (P < 0.001) more infections with genotype 1 than patients from the Western and Southern regions. African-American patients were more likely to be infected with genotype 1 when compared with Caucasian, Hispanic or Asian Pacific Islanders (P < 0.001). Patients infected with HCV genotype 1 and mixed HCV genotypes had significantly higher serum HCV RNA concentrations when compared with HCV genotypes 2 and 3 (P < 0.001 for all comparisons).
We studied the variation in volatile organic compounds (VOCs) in the breath of 50 normal humans, using gas chromatography and mass spectroscopy. An average breath sample contained 204.2 VOCs (SD=19.8, range 157-241). The alveolar gradient of each VOC (abundance in breath minus abundance in air) varied with rate of synthesis minus rate of clearance. A total of 3481 different VOCs were observed: 1753 with positive alveolar gradients, 1728 with negative alveolar gradients. Twenty-seven VOCs were observed in all fifty subjects. This study confirmed previous reports of wide inter-individual variations. Two new findings were the comparatively small variation in total number of breath VOCs, and the presence of a 'common core' of breath VOCs in all subjects.
> Abstract This paper reports the changes over time in the microfungal communities that inhabit three rodent species' food stores at two climatically different locations. Results reveal that microfungal diversity values calculated from above-ground food stores are highest in the more commonly disturbed portions of the rodent dens. Interactions among food-inhabiting microbes and between the rodents and food-inhabiting microbes also appear to influence the microfungal communities within the rodent dens. For example, our data suggest that transport by animal vectors, and not by air currents, is more effective at dispersing microbial propagules. Furthermore, although fungal communities inhabiting food stores within dens varied in composition and diversity over time, standardized substrates (sorghum seeds) simultaneously placed within the food stores converged in microfungal composition the longer they were left within the dens. We hypothesize that animal vectors, including rodents, make neighboring fungal communities more alike by introducing similar communities of microbes, which in turn initiate a cascade of biological interactions that, over time, result in similar microfungal communities inhabiting newly stored food items.http://link.springer-ny.com/link/service/journals/00248/bibs/38n1p79.html
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