Search PubMed⌕ Search

Biomedical subjects

H Takiff

Publications and source records attributed to H Takiff.

At least 19 recordsLinked to original sources
PubMed2001

Epidemiological evidence of the spread of a Mycobacterium tuberculosis strain of the Beijing genotype on Gran Canaria Island.

Molecular epidemiological studies suggest that particular Mycobacterium tuberculosis strains have an enhanced capacity to spread within a community. One strain, the Beijing genotype, has been associated with outbreaks in a number of communities throughout the world. IS6110 restriction fragment length polymorphism (RFLP) analysis was performed on M. tuberculosis isolates from 566 of the 721 patients (78.5%) diagnosed with tuberculosis (TB) on Gran Canaria Island from 1993 to 1996, as well as 35% of isolates from 1991-1992 (85 strains). RFLP identification of the family of strains of the Beijing genotype was confirmed by spoligotyping. Medical records of all patients were reviewed and epidemiological links were identified. Of 566 M. tuberculosis isolates from 1993 to 1996 with RFLP available, 72% belonged to clusters. The largest contained 75 cases and was caused by a strain of the Beijing genotype that was introduced to the island in 1993. It was found in 10 patients in 1993 (5.5%), 12 in 1994 (8.1%), 18 in 1995 (16.4%), and 35 in 1996 (27.1%). Epidemiological linkage was confirmed for 68% of cases. This study has demonstrated rapid dissemination of this strain of the Beijing genotype. This genotype might play an important role in the future of the worldwide tuberculosis epidemic.

Adolescent↗
PubMed2001

Intrinsic resistance of Mycobacterium smegmatis to fluoroquinolones may be influenced by new pentapeptide protein MfpA.

The fluoroquinolones (FQ) are used in the treatment of Mycobacterium tuberculosis, but the development of resistance could limit their effectiveness. FQ resistance (FQ(R)) is a multistep process involving alterations in the type II topoisomerases and perhaps in the regulation of efflux pumps, but several of the steps remain unidentified. Recombinant plasmid pGADIV was selected from a genomic library of wild-type (WT), FQ-sensitive M. smegmatis by its ability to confer low-level resistance to sparfloxacin (SPX). In WT M. smegmatis, pGADIV increased the MICs of ciprofloxacin (CIP) by fourfold and of SPX by eightfold, and in M. bovis BCG it increased the MICs of both CIP and SPX by fourfold. It had no effect on the accumulation of (14)C-labeled CIP or SPX. The open reading frame responsible for the increase in FQ(R), mfpA, encodes a putative protein belonging to the family of pentapeptides, in which almost every fifth amino acid is either leucine or phenylalanine. Very similar proteins are also present in M. tuberculosis and M. avium. The MICs of CIP and SPX were lower for an M. smegmatis mutant strain lacking an intact mfpA gene than for the WT strain, suggesting that, by some unknown mechanism, the gene product plays a role in determining the innate level of FQ(R) in M. smegmatis.

Alleles↗
PubMed2001

[The role of human genetic factors in susceptibility to tuberculosis].

Tuberculosis has been one of the most important illnesses in the history of the world, but it was never understood why only some people, and not others, develop the disease. It was assumed that human genetic factors play a role in susceptibility, but until the advent of molecular markers, it was never possible to convincingly separate inheritance from the compounding factors of environment and exposure to the bacillus. In recent years particular polymorphisms of several human genes have been shown to be correlated with susceptibility to TB: NRAMP1, Vitamin D receptor, Interferon gamma receptor, IL-12 and its receptor, several HLA haplotypes and there are probably several others that will be discovered. Nevertheless, no single gene appears to play a dominant role in the total TB burden of any population, and exposure of the individual to the bacillus and the environment and nutritional state of the individual also seem to play an important role in determining who will develop the disease.

Animals↗
PubMed2001

The molecular epidemiology of tuberculosis in Caracas, Venezuela, with IS6110 DNA fingerprinting.

In this retrospective study we asses the molecular epidemiological situation of Tuberculosis of the city of Caracas, Venezuela in the year 1994, applying IS6110 DNA Fingerprinting of clinical isolates. Fingerprinting of Mycobacterium tuberculosis strains of sixty-four patients TB patients from all the 5 districts of the city revealed fifty-one distinct IS6110 patterns. Isolates from 20 patients (30%) had fingerprints that were shared with at least one other patient. Based on this sampling we conclude that at least a third of the tuberculosis cases in Caracas in the year 1994 were the result of recent and ongoing transmission, indicating micro-epidemics in the town.

Bacterial Typing Techniques↗
PubMed2001

[Characterization of the expression and function of SigM an ECF sigma factor in mycobacteria].

The survival of M. tuberculosis within the macrophage depends on its ability to respond to oxidative stress, and the ECF subfamily of sigma factors likely play an important role. We studied SigM, a sigma factor whose gene is located near the origin of DNA replication. In both M. smegmatis and M. bovis BCG, the expression of sigM was induced at high temperature and in stationary phase. Mutants of M. smegmatis without an intact sigM were defective for survival in oxidative stress and also for the induction of thioredoxin reductase activity in oxidative stress. The thioredoxin system reduces disulfide bonds that are formed in oxidative stress. SigM thus appears to regulate thioredoxins and forms part of the bacteria's complex protective responses.

DNA Replication↗
PubMed2000

Contribution of the multidrug efflux pump LfrA to innate mycobacterial drug resistance.

Multidrug resistance (MDR) in bacteria has been associated with efflux pumps that export structurally unrelated compounds and decrease cytoplasmic drug accumulation. To investigate MDR in mycobacteria, we studied the Mycobacterium smegmatis mutant mc(2)11, which is resistant to doxorubicin, tetracycline, rhodamine, ethidium bromide and the hydrophilic fluoroquinolones. A genomic library constructed from this mutant was used to select clones conferring resistance to doxorubicin. Surprisingly, the clone selected encodes the efflux pump LfrA, which has been reported to confer resistance to hydrophilic fluoroquinolones, ethidium bromide, rhodamine, and acriflavine. To define the contribution of LfrA to the innate mycobacterial drug resistance and to the MDR phenotype in mc(2)11, the lfrA gene was disrupted in both the mc(2)11 mutant and the mc(2)155 wild-type parent. LfrA disruption of the wild-type strain decreased resistance to ethidium bromide and acriflavine, and increased accumulation of ethidium bromide. However, disruption of lfrA gene results only in a 2-fold decrease in minimal inhibitory concentrations (MICs) for ciprofloxacin, doxorubicin, rhodamine, and accumulation of [(14)C]ciprofloxacin was unchanged. LfrA disruption of the MDR strain mc(2)11 produced a similar phenotype. Thus, LfrA contributes significantly to the intrinsic MICs of M. smegmatis for ethidium bromide and acriflavine, but not for ciprofloxacin, doxorubicin or rhodamine.

Acriflavine↗
PubMed2000

Alpha-1 antitrypsin deficiency and splenic artery aneurysm rupture: an association?

OBJECTIVE: Theoretically, patients with alpha 1-antitrypsin deficiency may be vulnerable to the development of splenic artery aneurysms. alpha-1 antitrypsin deficiency can induce cirrhosis with portal hypertension, and resulting protease-antiprotease imbalances may exaggerate arterial wall weakness due to proteolysis of arterial structural proteins. A splenic artery aneurysm rupture 7 days after liver transplantation provoked a reassessment of the incidence of this phenomenon in a liver transplant population. METHODS: Case records from three institutions and the results of a survey sent to 126 liver transplantation programs in the United Network for Organ Sharing database were reviewed. The incidence of splenic artery aneurysm rupture in the peritransplantation period, etiology of liver disease associated with this phenomenon, and recommendations regarding management of splenic artery aneurysms was assessed. RESULTS: Twenty-one cases of splenic artery aneurysm rupture were identified. alpha-1 antitrypsin deficiency was the most common cause of cirrhosis in the majority of identified patients who presented with splenic artery aneurysm rupture, which was associated with a mortality rate of 57%. Respondents to the survey indicated that a preoperative evaluation was warranted if a splenic artery aneurysm was suspected; however, no consensus regarding management exists. CONCLUSIONS: The presence and risk of rupture of splenic artery aneurysms may be greater in patients with alpha-1 antitrypsin deficiency. If identified before rupture, an aggressive approach to diagnosing and treating these aneurysms should be initiated. At present, no consensus exists regarding the management of splenic artery aneurysms.

Adolescent↗
PubMed2000

Overview of some biomedical research projects in tropical medicine conducted at the Instituto Venezolano de Investigaciones Cientificas.

The Instituto Venezolano de Investigaciones Cientificas (IVIC) is a government-funded multidisciplinary academic institution dedicated to research, development and technology in many areas of knowledge. Biomedical projects and publications comprise about 40% of the total at IVIC. In this article, we present an overview of some selected research and development projects conducted at IVIC which we believe contain new and important aspects related to malaria, ancylostomiasis, dengue fever, leishmaniasis and tuberculosis. Other projects considered of interest in the general area of tropical medicine are briefly described. This article was prepared as a small contribution to honor and commemorate the centenary of the Instituto Oswaldo Cruz.

Academies and Institutes↗
PubMed1999

Fluorescence-based detection of lacZ reporter gene expression in intact and viable bacteria including Mycobacterium species.

A variety of fluorescein di-beta-D-galactopyranoside (FDG)-based substrates were evaluated for measuring beta-galactosidase expression in bacteria. One substrate, 5-acetylamino-FDG (C2FDG), performed well in all bacteria tested, including the slow growing mycobacterium, Mycobacterium bovis BCG. The sensitivity of C2FDG in intact, viable BCG was similar to that of o-nitrophenyl-beta-D-galactopyranoside in cell lysates when used to measure lacZ reporter gene activity. C2FDG was approximately 70-fold more sensitive than green fluorescent protein (GFP) in BCG when assayed in a fluorescence plate reader, and comparable to GFP when measured by flow cytometry. These assays provide an important new alternative for the rapid measurement of reporter gene expression in viable bacteria.

Bacteria↗
PubMed1999

Hepatic manifestations of familial patent ductus venosus in adults.

BACKGROUND: The ductus venosus connects the umbilical vein to the inferior vena cava during fetal life and subsequently closes rapidly after birth. It is known as patent ductus venosus when it remains patent in adulthood. PATIENTS: A 43 year old man with a history of panhypopituitarism presented with recurrent bouts of pedal oedema associated with fatigue, hypoalbuminaemia, and elevated prothrombin time. An ultrasound examination of his abdomen with Doppler revealed notable attenuation of the main portal vein with diminished intrahepatic branches; a computed tomography scan with angiography revealed a large collateral vein within the liver consistent with a patent ductus venosus. Sequential liver biopsies showed a considerable reduction in the calibre and number of the portal veins. His younger brother, who was diagnosed with alcohol related cirrhosis, suffered from intermittent bouts of encephalopathy and was found to have the same vascular lesion. A third brother was found to have a patent ductus venosus as well as two large hepatic masses consistent with focal nodular hyperplasia. CONCLUSION: The syndrome of familial patent ductus venosus has only previously been described in three infant brothers who presented with hepatic encephalopathy and fatty degeneration of the liver. This report documents three brothers with a patent ductus venosus presenting in adulthood with different manifestations of liver disease. The presence of the same vascular anomaly in three brothers is highly suggestive of a recessive genetic trait with an anatomical manifestation of patent ductus venosus.

Adult↗
PubMed1997

Liver transplantation: perspectives after 250 liver transplants at the Ochsner Clinic.

At the Ochsner Clinic we recently performed our 250th liver transplant. Reaching this milestone has led us to reflect back on the history of liver transplant, both at our own institution and nationally, noting the many achievements and improvements in liver transplantation during the relatively brief history of this therapeutic modality. Furthermore, there are a number of issues both medical and political which will likely be affecting how liver transplantation is performed in the future.

Chronic Disease↗
PubMed1994

Diagnosis of cutaneous leishmaniasis and species discrimination of parasites by PCR and hybridization.

The aim of this study was to assess the efficacy of PCR methodology in establishing the diagnosis of cutaneous leishmaniasis in patients from areas of endemicity in Venezuela. Biopsies from 233 patients with cutaneous ulcers suggestive of leishmaniasis were analyzed by PCR, employing oligonucleotides directed against conserved regions of kinetoplast DNA (kDNA), and the PCR products were then hybridized to nonradioactively labeled, species-specific, cloned kDNA fragments. The ability of PCR to detect Leishmania cells was compared with those of the conventional methodologies: skin testing with killed promastigotes (Montenegro test), examination of Giemsa-stained biopsy smears, and in vitro culture of biopsy tissue. The PCR-hybridization technique detected the presence of Leishmania cells in 98% of patients clinically diagnosed as having leishmaniasis and also positive by the Montenegro skin test. In comparison, leishmania positivity was found in only 42% of cultures and 64% of biopsy smears. By hybridizing the PCR product to new kDNA probes specific for either Leishmania mexicana or Leishmania braziliensis, we found that both species are major causes of cutaneous leishmaniasis in Venezuela, and the species identification was confirmed by restriction enzyme analysis of kDNA from biopsy cultures. This work demonstrates that PCR coupled with hybridization is useful not only for the diagnosis of cutaneous leishmaniasis but also for the taxonomic discrimination essential for both epidemiology and therapy. This technique can be used to diagnose leishmaniasis in a country in which the disease is endemic and can perhaps be adapted for use in a rural clinic.

Animals↗
PubMed1993

Systemic versus nonsystemic reperfusion of the transplanted liver.

Reperfusion of the orthotopically transplanted liver can result in severe hemodynamic instability. This instability can result in the postreperfusion syndrome (PRS), which includes decreases in mean arterial pressure (MAP), systemic vascular resistance (SVR), and heart rate, and increases in central venous pressure and pulmonary capillary wedge pressure. This syndrome appears to be mediated by the left ventricular mechanoreceptor reflex (LVMRR), which can be activated by changes in preload, afterload, or left ventricular contractility, and by the infusion of alkaloids or potassium into the right atrium. In an attempt to prevent activation of the LVMRR and PRS, we have inserted a cannula into the retrohepatic vena cava and have allowed the initial 500-600 cc of portal blood reperfusing hepatic allografts to be discarded. We compared this nonsystemic reperfusion (NSRP) of livers with systemic reperfusion (SRP), in which the initial portal blood reperfusing livers is allowed to enter the systemic circulation. In the NSRP group (n = 14) there was no decrease in MAP, heart rate, or SVR, and the serum potassium did not increase after reperfusion. In the SRP group (n = 14), six patients (42%) developed PRS and there were statistically significant decreases in MAP and SVR, and increases in pulmonary capillary wedge pressure and serum potassium, as compared with the NSRP group. In conclusion, NSRP results in less hemodynamic instability during reperfusion, and should be considered the preferred method for reperfusion of the transplanted liver.

Adult↗
PubMed1993

Human leukocyte antigen class I-independent pathways may contribute to hepatitis B virus-induced liver disease after liver transplantation.

The proliferative response of peripheral blood lymphocytes to the HBcAg was compared with serological, molecular and immunohistochemical parameters of hepatitis B virus infection and with biochemical and histological parameters of liver disease in a patient who received a completely human leukocyte antigen class I-mismatched liver allograft for fulminant hepatitis. The proliferative response increased progressively after transplantation, as hepatitis B virus infection became reestablished in the hepatic allograft. Strikingly, the HBcAg-specific T cells suddenly disappeared from the peripheral blood immediately before the acute onset of a severe necroinflammatory liver disease in which more than 80% of the hepatocytes expressed HBcAg. These observations are compatible with the hypothesis that human leukocyte antigen class I-independent hepatitis B virus-specific T cells might play a previously unsuspected role in the pathogenesis of hepatitis B virus-induced liver disease.

Adult↗
PubMed1992

Focal hemorrhagic necrosis of the liver. A rare cause of hemoperitoneum.

A 44-year-old white female developed hepatic hemorrhage due to focal hepatic necrosis. This is the only reported case of its kind we have found. No other underlying processes were identified except for the chronic use of oral conjugated estrogens. The possible role of steroids and a possible relationship to the pathogenesis of peliosis hepatis is discussed.

Adult↗
PubMed1991

The use of the supraceliac aorta for hepatic arterial revascularization in transplantation of the liver.

Thrombosis of the hepatic artery during the early post hepatic transplant period results in massive hepatocyte necrosis, bile duct damage and subsequent graft loss. The incidence of this complication is increased when hepatic arterial reconstruction is possible only by the placement of an interposition infrarenal iliac artery graft. We describe 45 hepatic transplants with difficult arterial reconstruction in which the supraceliac aorta was used for arterial reconstruction. Indications for using the supraceliac aorta as the primary site for arterial reconstruction were inadequate inflow through a narrow recipient common hepatic artery in 51 per cent, previously thrombosed common hepatic artery in 27 per cent, mechanical obstruction of the celiac axis in 13 per cent or intimal dissection in 9 per cent. Direct anastomosis of the donor hepatic artery to the supraceliac aorta was achieved in 22 patients, reducing the need for a graft by 49 per cent. Short segments of iliac artery graft (17 patients) or aortic conduit (six patients) to the supraceliac aortas were required because of insufficient length of the donor artery. The incidence of arterial thrombosis and graft loss were zero per cent in adults and 12.5 per cent in children, both significantly less when compared with the 23.0 to 70.0 per cent thrombosis rate when graft is placed in an infrarenal position. We conclude that routine use of the supraceliac aorta for difficult hepatic arterial reconstruction decreases the need for arterial grafts, the incidence of hepatic arterial thrombosis and loss of hepatic grafts.

Adult↗
PubMed1989

The benefit and underutilization of sharing kidneys for better histocompatibility.

The data of the UCLA Kidney Transplant Registry were reviewed with regard to sharing. The percentage of first-cadaver cyclosporine-treated transplants since 1984 with long cold ischemia time increased with sharing distance: 25% of unshared grafts, 40% of locally shared, and 61% of distantly shared ones had cold ischemia times over 24 hr; for cold ischemia times over 36 hr the numbers were 6%, 12%, and 24%, respectively. The immediate function rate did not parallel sharing distance the way cold ischemia time did: 85.7% without sharing, 74.4% with local sharing, and 83.5% with distant sharing. The percentage of well-matched (0 HLA-B,DR mismatches) transplants was low (3-5%) regardless of sharing status. Well-matched shared grafts with cyclosporine immunosuppression had a 9% survival advantage at one year compared with poorly matched unshared ones (85% vs. 76%). Long-term, well-matched shared grafts had a half-life of 11.9 years compared with 7.5 years for poorly matched unshared ones (reflecting graft loss from 3 to 10 years posttransplant). We conclude that sharing for histocompatibility has an overall beneficial effect.

Graft Survival↗