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A Pal

Publications and source records attributed to A Pal.

At least 55 records · Page 3Linked to original sources

Specificity of murine glutathione S-transferase isozymes in the glutathione conjugation of (-)-anti- and (+)-syn-stereoisomers of benzo[g]chrysene 11,12-diol 13,14-epoxide.

Specificities of murine glutathione (GSH) S-transferase (GST) isozymes mGSTA1-1, mGSTA2-2, mGSTA3-3 and mGSTA4-4 (alpha class), mGSTP1-1 (pi class) and mGSTM1-1 (mu class) for GSH conjugation of (-)-anti- and (+)-syn-stereoisomers of benzo[g]chrysene 11, 12-diol 13,14-epoxide (B[g]CDE), the activated metabolites of the environmental pollutant benzo[g]chrysene (B[g]C), have been determined. When GST activity was determined as a function of varying (-)-anti- or (+)-syn-B[g]CDE concentration (10-320 microM) at a fixed saturating concentration of GSH (2 mM), each isozyme obeyed Michaelis-Menten kinetics. mGSTA1-1 was significantly more efficient than other murine GSTs in the GSH conjugation of not only (-)-anti-stereoisomer but also (+)-syn-B[g]CDE. For example, the catalytic efficiency (k(cat)/K(m)) of mGSTA1-1 towards (-)-anti-B[g]CDE was approximately 2.3- to 16.6-fold higher compared with other murine GSTs. Likewise, mGSTA1-1 was approximately 2.7-, 6.7-, 4.4- and 12.4-fold more efficient than mGSTA2-2, mGSTA3-3, mGSTP1-1 and mGSTM1-1, respectively, in catalyzing the GSH conjugation of (+)-syn-B[g]CDE. Interestingly, mGSTA4-4, which also belongs to class alpha, was virtually inactive towards both stereoisomers of B[g]CDE. The results of the present study indicate that murine GSTs, especially alpha class isozymes, significantly differ in their ability to detoxify B[g]CDE stereoisomers and that mGSTA1-1 plays a major role in the detoxification of both (-)-anti- and (+)-syn-B[g]CDE, which among four B[g]CDE stereoisomers are formed from the carcinogen B[g]C as major DNA binding metabolites.

Animals↗

Clonal analysis of non-toxigenic Vibrio cholerae O1 associated with an outbreak of cholera.

We examined the clonal relationships among eight clinical isolates of non-toxigenic (NT) V. cholerae O1 associated with a cluster of cases of cholera in Warangal, Andhra Pradesh in south India and compared their relatedness to toxigenic O1 strains of classical and E1Tor biotypes and with O139 Bengal strains of V. cholerae by pulsed-field gel electrophoresis (PFGE). Phylogentic analysis of the NotI restriction fragment length polymorphism showed that all the NT. V. cholerae O1 strains formed a tight cluster with more than 80 per cent similarity. Interestingly, the NT V. cholerae O1 cluster was more closely related to V. cholerae O139 than to classical and E1Tor biotypes of V. cholerae O1 indicating closer genetic relationships between NT V. cholerae 01 and O139 Bengal strains that were isolated during the same time-frame.

Bacterial Typing Techniques↗

Shiga-toxin producing Escherichia coli from healthy cattle in a semi-urban community in Calcutta, India.

From October to December 1998, single faecal samples from 67 healthy cattle in a semi-urban community near Calcutta were examined for Shiga toxin producing Esch. coli (STEC) using a multiplex PCR primary screen followed by plating on sorbitol MacConkey agar. STEC was isolated from the faeces of 7 (10.5%) animals. The eight strains isolated belonged to eight serotypes viz, O146:H1, O149:HNT, ONT:H34, ONT:H19, O88:HN, ONT:H2, O82:H8 and O28ac:H21. Bead enzyme linked immunosorbent assay showed that three strains produced Shiga toxin 1, one produced Shiga toxin 2 and four produced both.

Animals↗

Catalytic efficiencies of allelic variants of human glutathione S-transferase P1-1 toward carcinogenic anti-diol epoxides of benzo[c]phenanthrene and benzo[g]chrysene.

Four allelic variants of glutathione (GSH) S-transferase P1-1 (hGSTP1-1) that differ in their structures at amino acid(s) in position(s) 104 and/or 113 are known to exist in human populations. However, the physiological significance of hGSTP1-1 polymorphism is not fully understood. In this communication, we report that the I104,A113 allele of hGSTP1-1, which is most frequent in human populations, is also most efficient in the GSH conjugation of carcinogenic anti-diol epoxides of benzo[g]chrysene and benzo[c]phenanthrene (anti-BGCDE and anti-BCPDE, respectively). The catalytic efficiency of hGSTP1-1(I104,A113) isoform toward anti-BGCDE, 0.36 mM(-1) x s(-1), was approximately 1.7-fold higher (P < 0.05) compared with hGSTP1-1(V104,V113). Interestingly, the frequency of codon 104-valine alleles is significantly higher in certain cancers compared with codon 104-isoleucine alleles. Like anti-BGCDE, the catalytic efficiency of hGSTP1-1(I104,A113) isoform toward anti-BCPDE was higher by about 1.4- to 2.2-fold (P < 0.05) than those of other hGSTP1-1 variants. These observations are interesting because we have shown previously (Hu, X. et al., Biochem. Biophys. Res. Commun., 238: 397-402, 1997) that the V104,V113 variant, not the I104,A113 isoform, is most efficient in the GSH conjugation of bay-region anti-diol epoxide of benzo(a)pyrene (anti-BPDE), which, unlike anti-BGCDE or anti-BCPDE, is a planar molecule. In conclusion, our results suggest that hGSTP1-1 polymorphism may be an important factor in differential susceptibility of humans to cancers where polycyclic aromatic hydrocarbons are etiological factors and that I104,A113 variant may play a major role in the detoxification of nonplanar, sterically hindered fjord-region diol epoxides (e.g., anti-BGCDE).

Alleles↗

Complexity of trypanosomatid endocytosis pathways revealed by Rab4 and Rab5 isoforms in Trypanosoma brucei.

Small G proteins of the Rab family are responsible for vesicle fusion and control flux during intracellular transport. Rab5 is important in endosome maturation and Rab4 in recycling of endocytic material. Three Rab5 isoforms identified so far in mammals and three in the yeast genome suggest that conservation of multiple Rab5 isoforms is required for sophisticated regulation of endocytosis. Trypanosoma brucei homologues of Rab5 and Rab4 (TbRab5A and TbRab4) have been identified. Here we report cloning of a second Rab5 homologue, TbRab5Bp. The TbRAB5A and -5B genes are not linked in the genome, and phylogenetic reconstruction indicates that multiple Rab5 isoforms in yeast, mammals, and trypanosomes evolved independently. Northern blots demonstrate that TbRab5A, -5B, and TbRab4 messages are expressed in bloodstream form (BSF) and procyclic forms of the parasite even though endocytosis is not very active in the latter form. mRNA levels of TbRab5A and -4 are constitutive. Multiple-sized TbRab5B messages at very low abundance are detected, with greater expression in BSF. Also, the TbRab5B mRNA has a large 3'-untranslated region suggestive of potentially complex regulation, and therefore TbRab5Bp may be an important regulator of differential endocytosis levels between BSF and procyclic stage parasites. Affinity purified antibodies raised to C-terminal peptide sequences of all three TbRab proteins recognized small vesicular cytoplasmic structures, which for TbRab5Ap and -5Bp are predominantly near the flagellar pocket. TbRab5Bp colocalizes with invariant surface glycoprotein 100 (ISG100), a protein entering the endocytotic pathway in BSF parasites, whereas in procyclic cells populations of vesicles stained with both TbRab5Ap and -5Bp substantially overlap; TbRab5 proteins are therefore components of the endocytotic pathway. TbRab4p localizes to vesicular structures throughout the cytoplasm, with some overlap with TbRab5Bp, but the majority occupying a different compartment to the TbRab5s. Therefore the trypanosome endosomal system has been functionally dissected for the first time; these reagents provide a unique opportunity for manipulation of the protozoan endosomal system to further our understanding of drug uptake mechanisms and virulence.

Amino Acid Sequence↗

Differential enantioselectivity of murine glutathione S-transferase isoenzymes in the glutathione conjugation of trans-3,4-dihydroxy-1, 2-oxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene stereoisomers.

The kinetics of the glutathione (GSH) conjugation of (+)- and (-)-enantiomers of anti- as well as syn-3,4-dihydroxy-1,2-oxy-1,2,3, 4-tetrahydrobenzo[c]phenanthrene (B[c]PDE) catalyzed by murine GSH S-transferase (GST) isoenzymes has been investigated. Murine GSTs exhibited significant differences in their enantioselectivity toward B[c]PDE stereoisomers. For example, while pi class isoenzyme mGSTP1-1 was virtually inactive toward stereoisomers with 1S configuration [(-)-syn-and (+)-anti-B[c]PDE], these stereoisomers were good substrates for alpha class isoenzyme mGSTA1-2. When GST activity was measured as a function of varying B[c]PDE concentration (10-320 microM) at a fixed saturating concentration of GSH (2 mM), each isoenzyme examined obeyed Michaelis-Menten kinetics with all four B[c]PDE stereoisomers. Alpha class isoenzyme mGSTA4-4 exhibited negligible activity toward all four stereoisomers of B[c]PDE. The catalytic efficiency of mGSTA1-2 was approximately 1.5- to 15-fold higher than other murine GSTs in the GSH conjugation of (-)-anti-B[c]PDE, which among the four B[c]PDE stereoisomers is the most potent pulmonary carcinogen in the newborn mouse model and a potent skin tumor-initiator. While alpha class isoenzymes mGSTA3-3 and mGSTA1-2 were equally efficient in the GSH conjugation of (+)-anti-B[c]PDE, their catalytic efficiencies toward this stereoisomer were significantly higher than those of mGSTP1-1 and mGSTM1-1. Likewise, mGSTA1-2 was relatively more efficient than other GSTs in the GSH conjugation of both enantiomers of syn-B[c]PDE. In summary, our results indicate that (a) murine GSTs significantly differ in their enantioselectivity in the GSH conjugation of B[c]PDE stereoisomers, which may partially account for the observed differences in the carcinogenic potency of B[c]PDE stereoisomers, and (b) mGSTA1-2 and mGSTA3-3 play a major role in the detoxification of B[c]PDE.

Animals↗

Gender-related differences in susceptibility of A/J mouse to benzo[a]pyrene-induced pulmonary and forestomach tumorigenesis.

Benzo[a]pyrene (BP) is a suspected human carcinogen and is known to produce tumors in the lung and forestomach of mice. Glutathione (GSH) S-transferases (GST) play a major role in the detoxification of the ultimate carcinogen of BP, (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene ((+)-anti-BPDE). Previous studies have shown gender-related differences in the expression of GST isoenzymes in mice. The present study was designed to test the hypothesis whether gender-related differences in the expression of GST isoenzymes can affect the susceptibility of mice to BP-induced lung and forestomach tumorigenesis. The expression of pi class isoenzyme mGSTP1-1, which is highly efficient in the detoxification of (+)-anti-BPDE, was approximately 3.0- and 1.5-fold higher in the liver and forestomach of male A/J mouse, respectively, as compared with the female. The levels of other major GST isoenzymes, mGSTA3-3 (alpha class), mGSTM1-1 (mu class) and mGSTA4-4 (alpha class), were also significantly higher in the liver of the male mouse as compared with the female. While pulmonary mGSTP1-1 expression did not differ significantly between male and female A/J mice, the expression of mGSTA3-3, mGSTM1-1 and mGSTA4-4 was significantly higher (1.4-4.0-fold) in the lung of the male A/J mouse as compared with the female. At lower concentrations of BP (0.5 mg BP/mouse), the tumor incidence/multiplicity was significantly higher in the lung as well as in the forestomach of female mice as compared with male mice. For example, while 30% of the female mice developed pulmonary tumors 26 weeks after the first 0.5 mg BP administration, none of the male mice had tumors in their lungs. At higher doses of BP (1.5 mg BP/mouse), however, this differential was either abolished or relatively less pronounced. Our results suggest that up to a certain threshold of BP exposure the levels of GST isoenzymes may be an important determinant of susceptibility to BP-induced tumorigenesis in mice.

Animals↗

Cloning, expression, and biochemical characterization of a functionally novel alpha class glutathione S-transferase with exceptional activity in the glutathione conjugation of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene.

The present study describes cDNA cloning, expression, and kinetic characterization of the two subunits of a murine alpha-class glutathione (GSH) S-transferase (GST) isoenzyme (previously designated as GST 9.5), which, unlike other alpha-class mammalian GSTs, is exceptionally efficient in the GSH conjugation of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene [(+)-anti-BPDE] [X. Hu, S. K. Srivastava, H. Xia, Y. C. Awasthi, and S. V. Singh (1996) J. Biol. Chem. 271, 32684-32688]. The cDNAs for both subunits of GST 9.5 (GST 9.5-1 and GST 9.5-2) were cloned by RT-PCR. The deduced amino acid sequences of GST 9.5-1 and GST 9.5-2 clones were identical to those of mGSTA1 and mGSTA2, respectively. Both these subunits were expressed in Escherichia coli to determine the relationships between recombinant mGSTA1-1 and mGSTA2-2 and corresponding subunits of tissue-isolated GST 9.5. The pI values of recombinant mGSTA1-1 and mGSTA2-2 (9.49 and 9.45, respectively) were similar to that of the tissue-isolated isoenzyme (pI 9.5). The reverse-phase HPLC elution profiles and immunological cross-reactivities of recombinant mGSTA1-1 and mGSTA2-2 were also similar to those of the corresponding subunits of tissue-isolated GST 9.5. The catalytic efficiency of recombinant mGSTA1-1 toward (+)-anti-BPDE, 131 mM-1.s-1, was approximately 9.5-to 655-fold higher compared with tissue-isolated mGSTP1-1, mGSTA3-3, mGSTM1-1, and mGSTA4-4. Moreover, the catalytic efficiency of mGSTA1-1 toward (+)-anti-BPDE was about 3.3-fold higher compared with recombinant mGSTA2-2. The mGSTA1 and/or mGSTA2 subunits were expressed to varying degrees in female A/J mouse tissues. For example, mGSTA1, but not mGSTA2, subunit expression was observed in the skin, which is a target organ for benzo(a)pyrene (BP)-induced cancer in mice. On the other hand, the expression of either mGSTA1 or mGSTA2 subunit could not be detected in the lung, which is another target organ for BP-induced cancer in mice. Interestingly, relatively large amounts of both mGSTA1 and mGSTA2 subunits were detected in the kidney. In conclusion, the results of the present study clearly indicate that the A1-type subunit of GST 9.5 is responsible for its exceptional catalytic efficiency in the GSH conjugation of (+)-anti-BPDE, which is the ultimate carcinogen of widespread environmental pollutant BP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Specificities of human glutathione S-transferase isozymes toward anti-diol epoxides of methylchrysenes.

The specificities of human glutathione (GSH) S-transferase (GST) isozymes of class alpha (hGSTA1-1), mu (hGSTM1-1) and pi (hGSTP1-1), including the three allelic forms of hGSTP1-1 [hGSTP1-1(I104,A113), hGSTP1-1(V104,A113) and hGSTP1-1(V104,V113)], in catalyzing the GSH conjugation of anti-diol epoxide stereoisomers of 5-methylchrysene (anti-5-MeCDE) have been examined. The specific activities of human GSTs were significantly higher toward (+)-anti-5-MeCDE than toward the (-)-enantiomer of anti-5-MeCDE. All three variants of hGSTP1-1 were significantly more efficient than either hGSTA1-1 or hGSTM1-1 in GSH conjugation of (+)-anti-5-MeCDE. The catalytic efficiencies of hGSTP1-1 variants toward (+)-anti-5-MeCDE were in the order hGSTP1-1(I104,A113) > hGSTP1-1(V104,V113) > hGSTP1-1(V104,A113). The present study suggests that the I104,A113 allele, which is most frequent in human populations, may play a major role in the detoxification of (+)-anti-5-MeCDE. This may point to specificity, because previous studies from our laboratory have shown that the hGSTP1-1(V104,V113) isoform is significantly more efficient than the other two variants of hGSTP1-1 in catalyzing GSH conjugation of (+)-anti-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE], the ultimate carcinogen of benzo[a]pyrene. Even though the mechanism of the differences in the activities of hGSTP1-1 variants toward anti-5-MeCDE versus anti-BPDE remains to be elucidated, it seems that the molecular configuration of the diol epoxide is an important determinant of the activity of hGSTP1-1 isoforms toward polycyclic aromatic hydrocarbon diol epoxides.

Carcinogens↗

Self-expanding metal oesophageal endoprostheses, covered and uncovered: a review of 30 cases.

OBJECTIVE: Oesophageal self-expanding metal endoprostheses (SEMS, or stents) are recognized as a safe means of palliating dysphagia caused by malignancy. Stent designs that have covered or uncovered walls are now available. The purpose of this study was to compare the outcome of use of these two designs. DESIGN: Thirty consecutive cases were reviewed. All the patients had been referred over a period of 25 months for palliation of dysphagia caused by malignant obstruction. Either a covered or an uncovered stent was placed in each patient. Palliation of dysphagia, 30 day mortality, mean survival time, and the number of endoscopic re-interventions required, were assessed. RESULTS: Uncovered Ultraflex stents were used in 14 patients, and Schneider Wallstents were used in 16 patients. Dysphagia improved by one grade or more in 69% of patients. The 30 day mortality was 27%, with an overall mean survival time of 99 days. There was no significant difference between the two groups for these three parameters. Ten patients needed a total of 28 repeat endoscopic procedures to maintain stent patency, with overall rates for each group of 1.64 procedures per patient, for uncovered stents, compared with 0.31 for covered stents (significant at the P < 0.05 level). The number of repeat procedures increased with survival time. CONCLUSION: The use of covered self-expanding metal oesophageal endoprostheses is associated with a significant reduction in the need for endoscopic reintervention after stent placement.

Adult↗

A pharmacoeconomic analysis of rimexolone for the treatment of ophthalmic inflammatory conditions.

Topical steroids are the standard first-line therapy for treating ophthalmic inflammatory conditions. However, potent ophthalmic steroids can lead to an elevation of intraocular pressure (IOP), which can result in greater medical resource utilization and increased costs. We have developed a decision analysis model from a societal perspective to evaluate the costs and consequences of the treatment of ophthalmic inflammatory conditions with two potent topical steroids: prednisolone and rimexolone. Data for the model are based on information from clinical trials, national data-bases, published literature, and responses by ophthalmologists to a questionnaire on treatment patterns for elevated IOP. Three steroid-responsive conditions are examined separately with the model: uveitis; postoperative inflammation following cataract surgery; and other ophthalmic inflammatory conditions (blepharitis, episcleritis, postoperative refractive surgery, and corneal transplant). The model evaluates patients with acute conditions versus those with chronic conditions and those with mild to moderate elevation of IOP versus those with severe elevation of IOP. Although the unit cost of rimexolone is higher than that of prednisolone, use of rimexolone leads to cost savings because the incidence of elevated IOP is decreased. If rimexolone is used instead of prednisolone for the treatment of ophthalmic inflammatory conditions, the estimated cost saved (at 1995 AWP prices) is approximately $10 million across the entire US population. The savings across the health maintenance organization population on an annualized basis is approximately $3.9 million. Even if rimexolone were priced higher than current market charges (at 130% to 150% of the AWP of prednisolone), cost savings ranging from the $2.9 million to $720,000 would accrue with use of rimexolone compared with prednisolone. However if, rimexolone were priced at 160% of the AWP of prednisolone, its use would incur an additional cost of $300,000. The primary medical resource utilized in treating elevated IOP in ophthalmic inflammatory conditions is physician visits. Medications are responsible for only one-fifth to one-third of the total cost of treating elevated IOP. This analysis indicates that rimexolone is associated with decreased medical resource utilization and cost savings to the entire healthcare system.

Anti-Inflammatory Agents↗

Secretor status and ankylosing spondylitis.

OBJECTIVE: To assess the genetic association between secretor status and ankylosing spondylitis (AS). METHODS: A restriction digest method for determining secretor status was developed; 166 patients with AS and 216 healthy British white controls were typed for secretor status using this method. RESULTS: The frequency of nonsecretors among patients with AS (47/166, 28%) was not significantly different from controls (72/216, 33%). CONCLUSION: Secretor status does not influence susceptibility to AS.

Cohort Studies↗

Chronic arsenic toxicity in west Bengal--the worst calamity in the world.

Since 1983 large number of people are being encountered with arsenic toxicity due to drinking of arsenic contaminated water (0.05-3.2 mg/l) in 6 districts of West Bengal. Clinical and various laboratory investigations were carried out on 156 patients to ascertain the nature and degree of morbidity and mortality that occurred due to chronic arsenic toxicity. All the patients studied had typical rain drop like skin pigmentation (being inclusion criteria) while thickening of palm and sole were found in 65.5% patients. Other features included weakness (70%), gastro-intestinal symptoms (58.6%), involvement of respiratory system (57.08%) and nervous system (50.6%). Lung function tests showed restrictive lung disease in 53% (9/17) and combined obstructive and restrictive lung disease in 41% (7/17) of patients. Abnormal electromyography was found in 34.8% (10/29) and altered nerve conduction velocity in 34.8% (10/29) of cases. Enlargement of liver was found in 120 cases (76.9%) while splenomegaly in 31.4% cases. Liver function test showed elevated globulin level in 15.8% and alkaline phosphatase in 51.3%, alanine amino transferase (ALT) in 11.8% and aspartate amino transferase (AST) in 27.6% of cases. Evidence of portal hypertension was found in 33.3% patients. Liver biopsy reports of 45 patients showed non-cirrhotic portal fibrosis in 41, cirrhosis in 2 and normal histology in 2 cases. There was no correlation between the quantity of arsenic taken through water and the level of arsenic in hair, nail, liver tissues and the degree of fibrosis. There were 5 deaths of which one had skin cancer. The various non-cancer manifestations which were observed in these patients were much severe than those reported in similar cases in other parts of the world.

Adolescent↗

Acute sporadic hepatitis in the Republic of Yemen.

The causes of acute icteric viral hepatitis were determined in 78 adult Yemeni patients. Acute hepatitis B (IgM anti-HBc positive) was the most common type (26.9%). Acute hepatitis E (IgM anti-HEV positive) occurred in 14% and was not associated with travel outside Yemen. Sixty percent of all 78 patients were positive for IgG anti-HEV as were 40% of a series of 48 healthy male blood donors and pregnant females, indicating that HEV is prevalent in Yemen. Acute hepatitis A (IgM anti-HAV positive) and hepatitis C and D were responsible for 5.1%, 6.4%, and 2.6% cases, respectively. This totals to 106%, as an infection with two viruses occurred in 6.4% cases. In 51.3% of all cases, no virological markers of acute hepatitis were detected, suggesting an as yet undiscovered agent.

Adolescent↗

In vitro characterization of adult primary human immunodeficiency virus type 1: demonstration of distinctive single-cell killing phenotypes in spite of similar levels of viral replication.

Two primary human immunodeficiency virus (HIV)-1 biologic clones have been studied extensively in a system using CD4 T cell-enriched peripheral blood lymphocytes and anti-CD4 antibody to measure viral replication kinetics and single-cell cytopathicity. Biologic clones from a person with AIDS replicated to high levels and were cytopathic in the absence of syncytium formation. Unexpectedly, biologic clones from an adult long-term nonprogressor were noncytopathic in spite of similar levels of viral replication. A correlation has recently been demonstrated between reduced mitochondrial viability and cell death in HIV-1-infected cultures. Peripheral blood-derived CD4 T cells infected with the cytopathic clone showed a progressive reduction in mitochondrial viability, while those infected with the noncytopathic clone demonstrated functionally viable mitochondria. These studies demonstrate that primary HIV-1-induced cytopathicity is separable from syncytium formation and replication rate.

Acquired Immunodeficiency Syndrome↗

Involvement of a 70-kb plasmid of the epidemic Shigella dysenteriae type 1 (Dt66) strain in drug-resistance, lipopolysaccharide synthesis, and virulence.

The present work characterizes a 70 kb plasmid of the Indian epidemic isolate Shigella dysenteriae type 1 strain Dt66 in relation to virulence and drug-resistance characters. Curing of the plasmids of Dt66 strain by acriflavine (AF) yielded seven groups of AF-cured derivatives. One group of derivatives containing 5 plasmids (70-2.5 kb) as against 6 (120-2.5 kb) in the wild type showed resistance to chloramphenicol, pivmecillinam, streptomycin, and tetracycline (CmrPivrSmrTcr) but sensitivity for ampicillin and nalidixic acid (AmsNals). This derivative when used as donor in conjugation experiments with a plasmidless E. coli KL318 strain (AmsCmsPivsSmrTcsNalr) as recipient, transferred only its 70 kb plasmid into the recipient with concomitant transfer of the CmrPivr phenotype. Both the donor and the transconjugant exhibited a diffuse pattern of adherence and produced keratoconjunctivitis in guinea pigs. Transconjugants contained a 42 kDa lipopolysaccharide band which was absent in recipient. Moreover, both donor and transconjugants showed Congo red binding ability. The results suggest that the 70 kb plasmid of S. dysenteriae Dt66 strain encodes not only Cmr,Pivr character but also is associated with virulence-related characters such as Congo red binding, LPS-biosynthesis, HeLa cell adherence, and keratoconjunctivitis related to virulence.

Animals↗

Primary pulmonary hypertension in non-cirrhotic portal fibrosis.

BACKGROUND: Primary pulmonary hypertension (PPH) has been reported in association with cirrhosis and extrahepatic portal venous obstruction; reports of PPH in noncirrhotic portal fibrosis (NCPF) are few. AIM: To evaluate pulmonary arterial pressure in patients with NCPF. METHODS: Twenty two patients with NCPF underwent hemodynamic studies for pulmonary arterial pressure after excluding secondary causes of pulmonary hypertension. Hemodynamic studies were carried out through the femoral route using 7F Swan-Ganz catheter. Splenoportal venography was done by percutaneous splenic puncture. RESULTS: The mean pulmonary arterial pressure was 12.9 +/- 3.1 mmHg with pulmonary capillary wedge pressure of 8.3 +/- 2.1 mmHg in 20 of 22 cases; in the remaining two cases, the corresponding pressures were 30 mmHg and 28 mmHg and 13 mmHg and 12 mmHg, respectively. CONCLUSION: Two of 22 patients with NCPF had PPH. PPH can thus develop without hepatocellular failure or recurrent embolization from portal axis thrombosis as has been described in cirrhosis.

Adult↗