The first outbreak of acute diarrhea due to a pandemic strain of Vibrio parahaemolyticus O3:K6 in Kolkata, India.
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Acute Disease↗
Biomedical subjects
A K Mukhopadhyay
Publications and source records attributed to A K Mukhopadhyay.
Spread of cholera with newer clones of Vibrio cholerae O1 El Tor, serotype inaba, in India.
During 2004 and 2005, cholera was recorded in 15 states of India, with 7 outbreaks. The newly emerged Vibrio cholerae O1 Inaba had a different antibiogram and ribotype, different pulsotypes, and different mutations in the wbeT gene. Due to the absence of serogroup O139, the Inaba serotype may have acquired the potential to affect the population at large.
Anti-Bacterial Agents↗
Susceptibility status of some culicine mosquitoes to insecticides in Rajahmundry town of Andhra Pradesh, India.
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Animals↗
Most Helicobacter pylori strains of Kolkata in India are resistant to metronidazole but susceptible to other drugs commonly used for eradication and ulcer therapy.
BACKGROUND: Helicobacter pylori infection is very common in India, as in other developing countries, but few data exist on the susceptibility of H. pylori to antimicrobial agents commonly used for eradication here. AIM: To determine the antimicrobial susceptibility of H. pylori strains from Kolkata, in eastern India. METHODS: A total of 67 H. pylori strains isolated from gastritis and peptic ulcer patients of Kolkata were examined in the study. Minimum inhibitory concentration to the antibiotics was determined by the agar dilution method. RESULTS: Most of the strains (85%) were resistant to at least 8 microg/mL of metronidazole and 7.5% strains were resistant to tetracycline, which was high when compared with other reports in India. All Kolkata strains were highly sensitive to clarithromycin, furazolidone and amoxicillin. CONCLUSIONS: Our results differed significantly from the few available reports on drug sensitivity profile of H. pylori from other parts of India, namely, Hyderabad, Mumbai and Lucknow. This finding supports the need for rigorous susceptibility testing as a guide to empirical treatment and more generally, to define the resistance patterns of H. pylori in particular geographical areas.
Adult↗
Progesterone: the forgotten hormone in men?
'Classical' genomic progesterone receptors appear relatively late in phylogenesis, i.e. it is only in birds and mammals that they are detectable. In the different species, they mediate manifold effects regarding the differentiation of target organ functions, mainly in the reproductive system. Surprisingly, we know little about the physiology, endocrinology, and pharmacology of progesterone and progestins in male gender or men respectively, despite the fact that, as to progesterone secretion and serum progesterone levels, there are no great quantitative differences between men and women (at least outside the luteal phase). In a prospective cohort study of 1026 men with and without cardiovascular disease, we were not able to demonstrate any age-dependent change in serum progesterone concentrations. Progesterone influences spermiogenesis, sperm capacitation/acrosome reaction and testosterone biosynthesis in the Leydig cells. Other progesterone effects in men include those on the central nervous system (CNS) (mainly mediated by 5alpha-reduced progesterone metabolites as so-called neurosteroids), including blocking of gonadotropin secretion, sleep improvement, and effects on tumors in the CNS (meningioma, fibroma), as well as effects on the immune system, cardiovascular system, kidney function, adipose tissue, behavior, and respiratory system. A progestin may stimulate weight gain and appetite in men as well as in women. The detection of progesterone receptor isoforms would have a highly diagnostic value in prostate pathology (benign prostatic hypertrophy and prostate cancer). The modulation of progesterone effects on typical male targets is connected with a great pharmacodynamic variability. The reason for this is that, in men, some important effects of progesterone are mediated non-genomically through different molecular biological modes of action. Therefore, the precise therapeutic manipulation of progesterone actions in the male requires completely new endocrine-pharmacological approaches.
Animals↗
Expression of osteopontin (OPN) mRNA in bovine ovarian follicles and corpora lutea.
The matricellular protein osteopontin (OPN) plays a role in various physiological processes, including angiogenesis and tissue remodelling. As these processes are essential for the maintenance of ovarian physiology, the aim of the study was to investigate the expression of OPN (mRNA) in ovarian cells and to evaluate whether it can be regulated by gonadotrophins. Using conventional RT-PCR and real-time PCR, we have detected and quantified OPN mRNA as well as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression in bovine granulosa, theca and luteal cells. In all cells examined, both genes were found in equal amounts and no striking variations in the expression could be observed between granulosa, theca and luteal cells. Furthermore, no effect on either OPN or GAPDH mRNA expression was evident after culturing ovarian cells in the presence of gonadotrophic hormones, although the cells were still highly responsive in terms of cAMP formation. Although neither variations between different cell types nor a regulation of OPN mRNA expression by gonadotrophic hormones could be detected, the high and unambiguous mRNA expression in steroidogenic cells suggests that OPN should be added to the growing list of intraovarian factors which may be involved in ovarian physiology.
Animals↗
Peste des petits ruminants has been widely present in southern India since, if not before, the late 1980s.
Because previous authorities had suggested that small ruminants were playing a part in the dissemination of rinderpest, and a rinderpest-eradication campaign was about to begin, it was necessary to make precise virus identifications from a number of small-ruminant "rinderpest" outbreaks. When this was done using a database created from passive disease reports, we found that epidemics-reportedly due to rinderpest-were in fact due to peste des petits ruminants (PPRs). Although such cases had been common in India for a number of years, earlier clinical and laboratory reports no longer should be regarded as definitive. PPR outbreaks have been frequent in recent years. Further, we suggest that PPR is not a recent invader of India.
Animals↗
The expression of the RLF/INSL3 gene is reduced in Leydig cells of the aging rat testis.
The relaxin-like factor (RLF), which is the product of the INSL3 gene, is highly expressed in the fetal and adult-type Leydig cells of all species so far examined. In adult testes it is upregulated at puberty but appears subsequently to be expressed in a constitutive manner, independently of acute changes in the hypothalamic-pituitary-gonadal (HPG) axis. Functional hypogonadism with decreased testosterone is prevalent in the aging male. In order to test whether this is a property of the HPG axis, or of the Leydig cells themselves, RLF/INSL3 was used as an independent marker to assess rat Leydig cell differentiation status. Hybridization analysis showed that in the testes of old (2 years) rats, RLF/INSL3 mRNA expression was dramatically reduced, compared to young (3 months) animals. This was also evident at the protein level using immunohistochemistry. The results suggest that increasing functional hypogonadism in older male mammals is likely caused by a dedifferentiation of the Leydig cells themselves.
Aging↗
Molecular & evolutionary genetics & drug resistance of the gastric pathogen, Helicobacter pylori.
Helicobacter pylori colonizes the gastric mucosa of more than half of all people worldwide and is the major cause of peptic ulcer disease and an early risk factor for gastric cancer, even though most infections are asymptomatic. Infection occurs preferentially in early childhood and once established tends to persist for years or decades. Much of the pathology H. pylori causes probably results from the host response to infection, which is affected by bacterial genotype, human host characteristics and environmental conditions. H. pylori is one of the most genetically diverse of bacterial species, with different genotypes predominating in different parts of the world. In particular, strains from India differ from those of Europe and East Asia in DNA sequence of several diagnostic gene segments. This outcome invites speculation about H. pylori origins and the possibility of Indian-specific genes that might be uncommon in Western strains. Much has been learned from H. pylori genome sequences, along with epidemiological, mutational, molecular and immunologic analyses. Candidate bacterial colonization and virulence genes and host responses are being identified, and the hypotheses being developed are amenable to tests in cell culture and animal models. These research efforts, many of which are collaborative and international, provide insights into mechanisms of establishment and persistence of H. pylori infection and virulence, and should lead to new, far more potent and cost effective anti-Helicobacter therapies or vaccines, and thereby major improvement in human health worldwide.
Drug Resistance, Microbial↗
Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruption.
The functions of some CLC Cl(-) channels are evident from human diseases that result from their mutations, but the role of the broadly expressed ClC-2 Cl(-) channel is less clear. Several important functions have been attributed to ClC-2, but contrary to these expectations ClC-2-deficient mice lacked overt abnormalities except for a severe degeneration of the retina and the testes, which led to selective male infertility. Seminiferous tubules did not develop lumina and germ cells failed to complete meiosis. Beginning around puberty there was a massive death of primary spermatocytes and later also of spermatogonia. Tubules were filled with abnormal Sertoli cells, which normally express ClC-2 in patches adjacent to germ cells. In the retina, photoreceptors lacked normal outer segments and degenerated between days P10 and P30. The current across the retinal pigment epithelium was severely reduced at P36. Thus, ClC-2 disruption entails the death of two cell types which depend on supporting cells that form the blood-testes and blood-retina barriers. We propose that ClC-2 is crucial for controlling the ionic environment of these cells.
Animals↗
Lysophosphatidic acid antagonizes the morphoregulatory effects of the luteinizing hormone on luteal cells: possible role of small Rho-G-proteins.
Lysophosphatidic acid (LPA) is a biologically active phospholipid recently introduced as a new marker for ovarian cancer. Because high concentrations of LPA have also been found in the follicular fluid from healthy subjects, one can presume that this biological mediator may have relevance for normal ovarian physiology as well. We have reported earlier that luteal cells possess specific binding sites for LPA. Using these cells as a model, we show now that LPA is able to modulate the morphological cell shape changes induced by LH in that it inhibits the formation of stellate processes induced by LH. This morphoregulatory effect of LPA is mimicked by cytotoxic necrotizing factor 1, a bacterial toxin known to activate small G-proteins from the Rho family. On the other hand, C3-exotransferase that acts mainly through the inhibition of Rho A mimics the effects of LH. Furthermore, we report here that the morphoregulatory effects of LPA are accompanied by the translocation of Rho proteins from the cytosol to cell membrane, an effect generally considered to be an indicator for the activation of Rho-GTPases. During the development and rescue of the corpus luteum, major morphoregulatory effects are exerted by LH that appear to be modulated by LPA via an activation of Rho proteins.
Animals↗
Characterization of VPI pathogenicity island and CTXphi prophage in environmental strains of Vibrio cholerae.
Environmental isolates of Vibrio cholerae of eight randomly amplified polymorphic DNA (RAPD) fingerprint types from Calcutta, India, that were unusual in containing toxin-coregulated pilus or cholera toxin genes but not O1 or O139 antigens of epidemic strains were studied by PCR and sequencing to gain insights into V. cholerae evolution. We found that each isolate contained a variant form of the VPI pathogenicity island. Distinguishing features included (i) four new alleles of tcpF (which encodes secreted virulence protein; its exact function is unknown), 20 to 70% divergent (at the protein level) from each other and canonical tcpF; (ii) a new allele of toxT (virulence regulatory gene), 36% divergent (at the protein level) in its 5' half and nearly identical in its 3' half to canonical toxT; (iii) a new tcpA (pilin) gene; and (iv) four variant forms of a regulatory sequence upstream of toxT. Also found were transpositions of an IS903-related element and function-unknown genes to sites in VPI. Cholera toxin (ctx) genes were found in isolates of two RAPD types, in each case embedded in CTXphi-like prophages. Fragments that are inferred to contain only putative repressor, replication, and integration genes were present in two other RAPD types. New possible prophage repressor and replication genes were also identified. Our results show marked genetic diversity in the virulence-associated gene clusters found in some nonepidemic V. cholerae strains, suggest that some of these genes contribute to fitness in nature, and emphasize the potential importance of interstrain gene exchange in the evolution of this species.
Amino Acid Sequence↗
Roles of FrxA and RdxA nitroreductases of Helicobacter pylori in susceptibility and resistance to metronidazole.
The relative importance of the frxA and rdxA nitroreductase genes of Helicobacter pylori in metronidazole (MTZ) susceptibility and resistance has been controversial. Jeong et al. (J. Bacteriol. 182:5082--5090, 2000) had interpreted that Mtz(s) H. pylori were of two types: type I, requiring only inactivation of rdxA to became resistant, and type II, requiring inactivation of both rdxA and frxA to become resistant; frxA inactivation by itself was not sufficient to confer resistance. In contrast, Kwon et al. (Antimicrob. Agents Chemother. 44:2133--2142, 2000) had interpreted that resistance resulted from inactivation either of frxA or rdxA. These two interpretations were tested here. Resistance was defined as efficient colony formation by single cells from diluted cultures rather than as growth responses of more dense inocula on MTZ-containing medium. Tests of three of Kwon's Mtz(s) strains showed that each was type II, requiring inactivation of both rdxA and frxA to become resistant. In additional tests, derivatives of frxA mutant strains recovered from MTZ-containing medium were found to contain new mutations in rdxA, and frxA inactivation slowed MTZ-induced killing of Mtz(s) strains. Northern blot analyses indicated that frxA mRNA, and perhaps also rdxA mRNA, were more abundant in type II than in type I strains. We conclude that development of MTZ resistance in H. pylori requires inactivation of rdxA alone or of both rdxA and frxA, depending on bacterial genotype, but rarely, if ever, inactivation of frxA alone, and that H. pylori strains differ in regulation of nitroreductase gene expression. We suggest that such regulatory differences may be significant functionally during human infection.
Blotting, Northern↗
Estimation of vacuolating cytotoxin secreted by different strains of Helicobacter pylori using bead enzyme-linked immunosorbent assay & its correlation with bacterial genotype.
BACKGROUND & OBJECTIVES: A highly sensitive bead enzyme-linked immunosorbent assay was applied for the quantitative determination of vacuolating cytotoxin (VacA) released in the culture supernatant of 40 well characterized Helicobacter pylori strains in order to clarify the significance of allelic combination of the vacA gene as the predictor of the level of toxin secretion and also to determine the most appropriate genotype of H. pylori associated with high VacA release. Attempts were also made for the detection of VacA in the gastric juice of patients for the rapid diagnosis of H. pylori infection. METHODS: The genotypes of 40 H. pylori strains cultured from the gastric biopsy samples were determined by specific PCRs. The cell-free culture supernatant of the strains as well as the gastric juice of the patients were used for bead-ELISA and the purified VacA from the H. pylori strain ATCC49503 was used as positive control. RESULTS: Ninety per cent of the strains with vacAs1m1 allele combination secrete on an average 146.4 ng/ml of VacA while the corresponding value was 19.1 ng/ml for s1m2 strains. None of the s2m2 as well as the ice negative H. pylori strains produced detectable VacA in the medium while strains expressed the toxin irrespective of the presence or absence of cagA gene. Fifteen of 22 gastric juice samples yielded positive bead-ELISA results. INTERPRETATION & CONCLUSION: vacAs1, vacAm1 and iceA1 could be considered as the determinants of high VacA secretion. Also, the detection of VacA by bead-ELISA in the gastric juice could be considered as an alternative approach in the diagnosis of H. pylori infection.
Adult↗
Guanylyl cyclase-B represents the predominant natriuretic peptide receptor expressed at exceptionally high levels in the pineal gland.
The generation and function(s) of the signalling molecule cyclic GMP (cGMP) in brain are still poorly understood. One mechanism to raise intracellular cGMP levels is binding of C-type natriuretic peptide (CNP) to a membrane guanylyl cyclase (GC), termed GC-B. Here, we demonstrate an exceptionally strong expression of GC-B in the pineal gland. Crosslinking experiments performed with 125I-Tyr(0)-CNP and membranes from various rat tissues identified the receptor as a 130-kDa protein, expressed at highest levels in pineal membranes. Receptor autoradiography on brain sections confirmed a striking density of CNP binding sites in pineal tissue, whereas binding sites for the related atrial natriuretic peptide (ANP) predominate in other regions of the brain. Incubations of freshly dissected whole pineal glands in either the absence or presence of natriuretic peptides followed by immunohistochemical analyses of cGMP revealed strong accumulations of cGMP in response to CNP but not to ANP in the majority of pinealocytes. Stimulation of soluble GC (sGC) activity by use of sodium nitroprusside (SNP) resulted in a very similar pattern of cGMP immunostaining, indicating a co-expression at high levels of particulate and soluble forms of GC. These findings point to a major role of cGMP signalling in pinealocytes and suggest an important regulatory function for CNP.
Animals↗
Diversity in the arrangement of the CTX prophages in classical strains of Vibrio cholerae O1.
This study reports the results of a molecular analysis of the CTX prophages in classical biotype strains of Vibrio cholerae O1 of clinical origin isolated between 1970 and 1979 in India. All strains were sensitive to group IV classical phage and polymyxin B but resistant to group 5 El Tor phage. These phenotypic traits are consistent to that exhibited by the classical biotype. PCR studies reconfirmed their biotype assignment and showed the presence of intact CTX prophages and the presence of the recently described toxin linked cryptic plasmid. Restriction fragment length polymorphism of rRNA genes and pulsed-field gel electrophoresis showed clonal diversity among the strains. The most notable observation was the finding that one strain (GP13) has three CTX prophages while another (GP147) has four CTX prophages. This is the first time heterogeneity is reported in the arrangement of the CTX prophages among classical strains of V. cholerae O1.
Bacteriophage Typing↗
A cellular automaton model of cellular signal transduction.
On the basis of cellular automata models, a software specifically tailored to model biochemical reactions involved in cellular signal transduction was implemented on a personal computer. Recent data regarding desensitization processes in mouse Leydig cells are used to simulate the underlying reactions of signal transduction. Pretreatment of real Leydig cells with different molecules results in a modification of the signal transduction cascade leading to a diminished response of the cells during subsequent stimulations. The model is capable of simulating the complex behavior of this intracellular second messenger production in a qualitative and semi-quantitative way. The results indicate that quantitative simulations on a molecular level will be possible once appropriate computer hardware is available. The simulations and results of the cellular automaton presented are easily described and comprehended, which make it a useful tool that will facilitate research in cellular signal transduction and other fields covering complex reaction networks.
Adenylyl Cyclases↗
High prevalence of Helicobacter pylori infection with dual resistance to metronidazole and clarithromycin in Hong Kong.
BACKGROUND: Metronidazole resistance is a common problem in most Asian countries, and clarithromycin has been widely used in Hong Kong. AIM: To determine the prevalence of Helicobacter pylori strains resistant to metronidazole and clarithromycin in Hong Kong and to assess the effect on eradication rates. Also to determine the genetic mutation in relation to phenotypic divergence in clarithromycin-resistant strains. METHODS: H. pylori were cultured from gastric biopsies obtained from 87 patients during upper endoscopy. Minimal inhibitory concentrations of metronidazole and clarithromycin were determined by Etest and agar dilution methods. Mutations in clarithromycin-resistant strains were identified by polymerase chain reaction and restriction analysis. Random amplified polymorphic DNA fingerprinting was performed on clarithromycin-resistant and susceptible isolates. RESULTS: The prevalences of H. pylori strains resistant to metronidazole and clarithromycin were 49.4% and 10.8%, respectively, in Hong Kong. Dual resistance to metronidazole and clarithromycin were found in 7. 2% of patients. The agreement between E-test and agar dilution methods was determined by error-rate bound analysis as 95.4% for metronidazole and 100% for clarithromycin. Dual resistant strains reduced the eradication rate to 66.7%. Among clarithromycin-resistant strains tested, all were due to A2144G point mutation in 23S rRNA gene. Random amplified polymorphic DNA fingerprinting suggested various phenotypically mixed populations. CONCLUSIONS: The prevalence of metronidazole-resistant H. pylori strains remained static whilst the prevalence of clarithromycin-resistant strains was not rare in Hong Kong. An alarming 7.2% of patients were resistant to both the antimicrobials, which had a definite impact on treatment success. All cases of resistance to clarithromycin were due to A2144G mutation in 23S rRNA of H. pylori.
Adolescent↗