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141.
Homozygous transcobalamin II deficiency maintained on oral hydroxocobalamin   总被引:1,自引:0,他引:1  
Zeitlin  HC; Sheppard  K; Baum  JD; Bolton  FG; Hall  CA 《Blood》1985,66(5):1022-1027
A case of transcobalamin II (TCII) deficiency in which a total absence of TCII was demonstrated both functionally and immunologically is reported. Unlike previously described patients, this child has been maintained on oral hydroxocobalamin, 2 mg daily, without any parenteral supplementation for the last five years. At the age of six years her development is normal and her health is good. Plasma cobalamin levels are in the range of 3,000 ng/L and most of this appears to be bound to a molecule, which on gel filtration, elutes with albumin. In an extended family study, a clear separation of heterozygotes from both the propositus and from normal subjects suggests that the underlying defect in this condition is confined to a single gene.  相似文献   
142.
Protein-energy malnutrition (PEM) affects millions of children in the developing world. The relationship between malaria and PEM is controversial. The goal of this study was to evaluate whether undernutrition is associated with increased or decreased malaria attributable morbidity. Three cross-sectional surveys were conducted using insecticide-treated bed nets (ITNs) among children aged 0-36 months living in an area with intense malaria transmission. Data were collected on nutritional status, recent history of clinical illness, socioeconomic status, current malaria infection status, and hemoglobin. In multivariate models, stunted children had more malaria parasitemia (odds ratio [OR] 1.98, P < 0.0001), high-density parasitemia (OR 1.84; P < 0.0001), clinical malaria (OR 1.77; P < 0.06), and severe malarial anemia (OR 2.65; P < 0.0001) than nonstunted children. The association was evident in children with mild-to-moderate (-3 < height-for-age Z-score [HAZ] < -2) and severe stunting (HAZ < -3). The cross-sectional nature of the study limits the interpretation of causality, but the data provide further observational support that the presence of undernutrition, in particular chronic undernutrition, places children at higher, not lower risk of malaria-related morbidity.  相似文献   
143.
We previously described loop-mediated isothermal amplification (LAMP) for detection of Schistosoma haematobium and S. mansoni DNA in infected snails. In the present study, we adapted the LAMP assay for application in field laboratories in schistosomiasis-endemic areas. Isolation of DNA was simplified by blotting snail tissue (extracted in NaOH/sodium dodecyl sulfate) onto treated membranes, which enabled preservation at ambient temperatures. A ready-mix of LAMP reagents, suitable for shipment at ambient temperature and storage in minimal refrigeration, was used. Local survey teams without experience in molecular biology acquired operational expertise with this test within a few hours. Fifty-four field-caught snails were tested locally by LAMP and 59 were tested at similar conditions in Jerusalem. The LAMP results were consistent with those of a polymerase chain reaction; only four samples showed false-negative results. Results indicate that LAMP assays are suitable for detection of S. haematobium and S. mansoni in low-technology parasitology laboratories in which schistosomiasis elimination activities are undertaken.  相似文献   
144.
Malaria parasites infecting host red blood cells degrade hemoglobin by detoxifying heme into hemozoin. This conversion of heme to hemozoin is performed by a potent protein called heme detoxification protein (HDP), making HDP an attractive target for antimalarial drug development. We studied the genetic variation in Plasmodium falciparum HDP and also investigated if HDP due to its involvement in the heme detoxification pathway is under any potential chloroquine (CQ) selection pressure. We sequenced the complete HDP gene encompassing three exons and two introns (AT and ATTT repeats in intron 1; AT repeats in intron 2) from five P. falciparum laboratory strains with known CQ sensitivity and 50 field isolates from Venezuela (n = 26) and Kenya (n = 24), with high levels of CQ resistance. Sequencing revealed two mutations, C41F and F91L in exon 1 and exon 2, respectively. The F41 mutation was present only in the CQ sensitive (CQS) HB3 strain. However, all the isolates harbored the 91L mutation, except for the CQS 3D7 strain. The sequencing of the intron 2 region revealed no variation in the number of AT repeats. In contrast, there was a wide variation in the AT and ATTT repeats in intron 1. Overall with respect to the intron 1 repeats, the Venezuelan isolates (Expected heterozygosity, He = 0.685) showed less genetic variation as compared to the Kenyan isolates (He = 0.986). Furthermore, we also genotyped the 72–76 codons of the pfcrt gene but did not observe any correlation of the pfcrt CQ resistant genotypes (SVMNT or CVIET) with variation in the HDP, thus indicating HDP not to be under any CQ selection pressure. In conclusion, HDP is a conserved target for future antimalarial development.  相似文献   
145.

Background and purpose:

Carbon monoxide (CO) is a potent modulator of a wide variety of physiological processes, including sensory signal transduction. Many afferent sensory pathways are dependent upon purinergic neurotransmission, but direct modulation of the P2X purinoceptors by this important, endogenously produced gas has never been investigated.

Experimental approach:

Whole-cell patch-clamp experiments were used to measure ATP-elicited currents in human embryonic kidney 293 cells heterologously expressing P2X2, P2X3, P2X2/3 and P2X4 receptors and in rat pheochromocytoma (PC12) cells known to express native P2X2 receptors. Modulation was investigated using solutions containing CO gas and the CO donor molecule, tricarbonyldichlororuthenium (II) dimer (CORM-2).

Key results:

CO was a potent and selective modulator of native P2X2 receptors, and these effects were mimicked by a CO donor (CORM-2). Neither pre-incubation with 8-bromoguanosine-3′,5′-cyclomonophosphate nor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (a potent blocker of soluble guanylyl cyclase) affected the ability of the CO donor to enhance the ATP-evoked P2X2 currents. The CO donor caused a small, but significant inhibition of currents evoked by P2X2/3 and P2X4 receptors, but was without effect on P2X3 receptors.

Conclusions and implications:

These data provided an explanation for how CO might regulate sensory neuronal traffic in physiological reflexes such as systemic oxygen sensing but also showed that CO could be used as a selective pharmacological tool to assess the involvement of homomeric P2X2 receptors in physiological systems.  相似文献   
146.
Background: The exact incidence and prevalence of Budd‐Chiari syndrome (BCS) is unknown in the general population. Published reports differ in terms of the clinical characteristics, effects of therapy and survival. Aims: To investigate the epidemiology, clinical presentation and survival in patients with BCS. Methods: Retrospective multicentre study in Sweden reviewing the medical records of all patients with BCS 1986–2003, identified from the computerised diagnosis database of 11 hospitals, including all university hospitals and liver transplantation centres. Results: Forty‐three patients with BCS were identified, of whom nine (21%) had concomitant portal vein thrombosis. The mean age‐standardised incidence and prevalence rates in 1990–2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. Myeloproliferative disorders (38%), thrombophilic factors (31%) and oral contraceptives (30%) were common aetiological factors. Two or more risk factors were present in 44%. In 23%, no risk factor was evident. The median follow‐up time was 2.7 years. Seventy‐two percent were on anticoagulant therapy during follow‐up. Transjugular intrahepatic portosystemic shunting, surgical shunting procedures and liver transplantation were performed in 4, 6 and 18 patients respectively. Nineteen patients died. The overall transplantation‐free survival at 1, 5 and 10 years was 47, 28 and 17% respectively. Conclusions: Budd‐Chiari syndrome is a rare disorder; the mean age‐standardised incidence and prevalence rates in Sweden in 1990–2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. The presence of a myeloproliferative disorder was a common aetiological factor in our cohort and about half of the patients had a multifactorial aetiology. The transplantation‐free survival was poor.  相似文献   
147.
148.
149.

Objective

The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)‐coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6‐month period, in a group of 381 HIV/HCV‐coinfected patients.

Methods

Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined.

Results

Thirty‐six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28–0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20–0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15–6.68; P=0.023) were associated with persistently normal ALT levels.

Conclusion

The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis
  相似文献   
150.
Pulsed-field gel electrophoresis (PFGE) of 61 Salmonella enterica serotype Paratyphi C isolates from six countries gave five distinct clusters. Twenty-four isolates from five countries were susceptible to 10 antimicrobials tested and gave similar restriction endonuclease digest patterns of the 38-MDa plasmid. In contrast, plasmid and PFGE profiles of 37 multidrug-resistant isolates from Zaire were different from those from other countries.  相似文献   
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