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S Sharma

Publications and source records attributed to S Sharma.

At least 289 records · Page 16Linked to original sources
PubMed2001

Oral toxicity of Photorhabdus luminescens W14 toxin complexes in Escherichia coli.

Previous attempts to express the toxin complex genes of Photorhabdus luminescens W14 in Escherichia coli have failed to reconstitute their oral toxicity to the model insect Manduca sexta. Here we show that the combination of three genes, tcdA, tcdB, and tccC, is essential for oral toxicity to M. sexta when expression in E. coli is used. Further, when transcription from native toxin complex gene promoters is used, maximal toxicity in E. coli cultures is associated with the addition of mitomycin C to the growth medium. In contrast, the expression of tcdAB (or the homologous tcaABC operon) with no recombinant tccC homolog in a different P. luminescens strain, K122, is sufficient to confer oral toxicity on this strain, which is otherwise not orally toxic. We therefore infer that P. luminescens K122 carries a functional tccC-like homolog within its own genome, a hypothesis supported by Southern analysis. Recombinant toxins from both P. luminescens K122 and E. coli were purified as high-molecular-weight particulate preparations. Transmission electron micrograph (TEM) images of these particulate preparations showed that the expression of tcdAB (either with or without tccC) in E. coli produces visible approximately 25-nm-long complexes with a head and tail-like substructure. These data are consistent with a model whereby TcdAB constitutes the majority of the complex visible under TEM and TccC either is a toxin itself or is an activator of the complex. The implications for the potential mode of action of the toxin complex genes are discussed.

Administration, Oral↗
PubMed2001

Fas-mediated apoptosis of neutrophils in sera of patients with infection.

In the presence of infection, neutropenia is considered to be a marker of poor prognosis; conversely, neutrophilia may not be a determinant of a better prognosis. Since apoptotic neutrophils are compromised functionally, we evaluated the effect of infection on neutrophil apoptosis. The rate of apoptosis was greater for neutrophils isolated from patients with infection than for healthy controls. Escherichia coli did not directly modulate the rate of neutrophil apoptosis. However, sera from infected patients promoted (P < 0.001) neutrophil apoptosis. Interestingly, the sera of patients with different types of infection (gram negative, gram positive, or culture negative) exerted a more or less identical response on neutrophil apoptosis. Sera of infected patients showed a fivefold greater content of FasL compared to controls. Moreover, anti-FasL antibody partly attenuated the infected-serum-induced neutrophil apoptosis. In in vitro studies, E. coli enhanced monocyte FasL expression. Moreover, conditioned media prepared from activated macrophages from control mice showed enhanced apoptosis of human as well as mouse neutrophils. On the contrary, conditioned media prepared from activated macrophages isolated from FasL-deficient mice induced only a mild degree of neutrophil apoptosis. These results suggest that neutrophils in patients with infection undergo apoptosis at an accelerated rate. Infection not only promoted monocyte expression of FasL but also increased FasL content of the serum. Because the functional status of apoptotic cells is compromised, a significant number of neutrophils may not be participating in the body's defense. Since neutrophils play the most important role in innate immunity, their compromised status in the presence of infection may transfer the host defense burden from an innate response to acquired immunity. The present study provides some insight into the lack of correlation between neutrophilia and the outcome of infection.

Adult↗
PubMed2001

Utility values associated with blindness in an adult population.

AIM: To ascertain utility values associated with varying degrees of legal blindness. METHODS: A cross sectional study on three group of patients. There were: (1) 15 patients with complete absence of vision (no light perception) in at least one eye who were asked to assume a scenario of no light perception in the second eye as well, (2) 17 patients with light perception to counting fingers in the better seeing eye, and (3) 33 patients with 20/200-20/400 vision in the better seeing eye. Utility values were measured using the time trade-off and standard gamble methods in each of the three groups. RESULTS: The mean time trade-off utility value for the no light perception group with the theoretical scenario of bilateral absence of light perception was 0.26 (95% CI, 0.19-0.33). The mean utility value for the light perception to counting fingers group was 0.47 (95% CI, 0.33-0.61), and the mean utility value for the 20/200-20/400 group was 0.65 (95% CI, 0.58-0.72). Thus, patients with no light perception in one eye, who were presented with the same scenario in the second eye as well, were willing to trade almost 3 out of every 4 years of remaining life in return for perfect vision in each eye. Those with light perception to counting fingers would trade approximately 1 of 2 remaining years and those with 20/200-20/400 would trade approximately 1 of 3 remaining years. CONCLUSIONS: There is a wide range of utility values associated with legal blindness. The utility value decreases dramatically with perceived total loss of vision (absence of light perception in each eye), compared with counting fingers to light perception vision, indicating that the preservation of even small amounts of vision in patients with legal blindness is critically important to their wellbeing and functioning in life.

Adult↗
PubMed2001

Endothelial microtubule disruption blocks flow-dependent dilation of arterioles.

The cytoskeleton is believed to have an important role in the structural and functional integrity of endothelial cells. The role of the endothelial cytoskeleton, specifically microtubules, in the mediation of flow-induced dilation of arterioles has not yet been studied. Thus the aim of our study was to investigate the role of microtubules in the endothelial mechanotransduction of flow-induced dilation of isolated gracilis arterioles of the rat. The active diameter of arterioles at a constant perfusion pressure (80 mmHg) was approximately 63 microm, whereas their passive diameter (Ca(2+)-free solution) was approximately 119 microm. At a constant pressure, increases in flow of the perfusate solution (from 0 to 10 and from 10 to 20 microl/min) elicited increases in diameter up to approximately 95 microm (approximately a 53% increase). Intraluminal administration of nocodazole at concentrations of 5 x 10(-9) and 5 x 10(-8) M had no discernible effects on the structure of endothelial microtubules or on flow-induced dilation, whereas it disassembled microtubules and eliminated flow-induced dilation at a concentration of 5 x 10(-7) M. At this higher concentration, however, the basal diameter and dilations to acetylcholine (10(-8) M), sodium nitroprusside (10(-7) M), arachidonic acid (5 x 10(-6) M), and prostaglandin E2 (10(-8) M) were unaffected. Colchicine (5 x 10(-7) M) also disassembled microtubules and eliminated flow-induced dilation. We concluded that, in isolated arterioles, the integrity of the endothelial cytoskeleton is essential for the transduction of the shear stress signal that results in the release of endothelial factors evoking dilation.

Animals↗
PubMed2001

Incidence of Helicobacter pylori in patients with interstitial cystitis.

OBJECTIVE: Chronic gastritis has compelling similarities to interstitial cystitis (IC). It is characterised by chronic pain in a tubular organ. Histologically, epithelial damage, inflammatory response in the lamina propria and epithelial ulcerations are seen. An infective cause was rarely considered until the emergence of Helicobacter pylori over the past 15 years. We have had experience of patients with bladder pain and irritability reporting improvement with antihistamines. It has also been reported that IC symptoms improved dramatically after treatment for H. pylori infection. Previous studies have determined the incidence of H. pylori antibodies in women with IC but we examined bladder material histologically and performed the Campylobacter-like organism (CLO) test on the biopsy specimens. MATERIALS AND METHODS: A prospective controlled study was performed. Patients with urinary symptoms fulfilling the National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC underwent GA cystoscopy at which the macroscopic appearance of the bladder was noted and biopsies were taken. The biopsy material underwent histological examination and CLO test. Control patients who were undergoing cystoscopy for reasons other than investigation of IC also had biopsy taken and the CLO test was performed on these specimens. RESULTS: Five of 15 patients with symptoms and signs of IC had a positive CLO test. Three of 15 patients of the control group had a positive CLO test. With the 2-sided chi(2) test there was no statistical difference between the 2 groups. CONCLUSION: Our small prospective control study does not support the hypothesis that H. pylori is an important component in the pathogenesis of interstitial cystitis.

Cystitis, Interstitial↗
PubMed2001

Implant complications and failures: the complete overdenture.

The implant-retained overdenture has been advocated as an effective method of restoring the edentulous patient with an appliance that offers significant benefits over conventional prosthetics. However, the success and survival of such appliances have been shown to vary considerably, depending on which jaw is treated: implants supporting overdentures in the maxilla have a significantly higher failure rate. The restoration also requires considerable maintenance, which is both time consuming and costly. The purpose of this paper is to look at common restorative complications and maintenance problems following the placement of dental implants to support an overdenture. A number of implant systems have been reviewed and the results of the authors' clinical experiences with referred and their own cases are reported.

Bite Force↗
PubMed2001

A diagnostic dilemma of fever and back pain postpartum.

A 26-year-old woman presented with fever, chills, and back pain 6 weeks postpartum. An infused CT scan of the abdomen and pelvis with IV contrast confirmed septic pelvic vein thrombophlebitis as the diagnosis. To the best of our knowledge, this is the first case report describing such a massive thrombophlebitis extending from the superior vena cava to the femoral vein inferiorly responsive to conventional anticoagulation therapy. This exceptional case reminds us to entertain septic pelvic thrombophlebitis in the differential of any patient who presents with fever and back pain of unknown etiology.

Adult↗
PubMed2001

Serum activin A and follistatin in disorders of spermatogenesis in men.

OBJECTIVE: Inhibin, activin and follistatin are glycoprotein hormones produced by the gonads. Recent studies have shown that inhibin B is the predominant form of inhibin in the circulation in men. The objective of this study was to investigate circulating levels of activin A and follistatin in disorders of spermatogenesis in men and their relationship with FSH and inhibin B. DESIGN AND METHOD: Serum from five different groups of men was prospectively collected and stored at -20 degrees C. The groups were men with: (i) proven fertility (controls) (n=20), (ii) primary testicular failure (n=15), (iii) obstructive azoospermia (n=10), (iv) oligospermia (n=10) and (v) miscellaneous sperm dysfunction (n=40). WHO criteria (1992) were used for semen characterisation. Serum concentrations of 'total' activin A, follistatin, FSH and inhibin B were measured using specific two-site enzyme immunoassays. RESULTS: Activin A levels were significantly lower than in the controls in the obstructive azoospermia group and higher in the miscellaneous sperm dysfunction group. Serum follistatin levels did not significantly vary in any group compared with the controls. Circulating levels of FSH were higher than in the controls in the primary testicular failure and obstructive azoospermic group. Levels of inhibin B were lower than in the controls in all disorders of spermatogenesis studied. CONCLUSION: This study demonstrates that activin A and follistatin are in the circulation in males and activin A levels are significantly lower in obstructive azoospermia and higher in miscellaneous sperm dysfunction than in controls. The mechanism involved in altering the levels of activin A in these conditions is not clear. However, high follistatin:activin A molar ratios (>2.5) in all groups suggests that all activin A in the circulation is bound to follistatin in males.

Activins↗
PubMed2001

Fetal intracardiac echogenic foci: visualization depends on the orientation of the 4-chamber view.

OBJECTIVE: To compare the frequency of visualization of echogenic intracardiac foci in different cardiac views. METHODS: Women having ultrasonographic examinations between October 1997 and July 1998 were prospectively evaluated if a fetal echogenic intracardiac focus was seen in either ventricle. RESULTS: Echogenic intracardiac foci were seen in 89 fetuses in whom both the apical and lateral 4-chamber heart views were obtained. Eight-six fetuses (97%) had a single focus (83 in the left ventricle and 3 in the right ventricle), and 3 (3%) had 2 foci. Echogenic intracardiac foci were seen in the apical 4-chamber view in 89 (100%) and in the lateral 4-chamber view in only 26 (29%; P = .001). CONCLUSIONS: Echogenic intracardiac foci are not easily seen in the lateral 4-chamber view. Studies that suggest an increased risk of aneuploidy when echogenic foci are seen should specify the orientation of the 4-chamber view used.

Adult↗
PubMed2001

Allometric analysis of the association between cardiac dimensions and body size variables in 464 junior athletes.

Empirically derived relationships between body size variables and cardiac dimensions have not been published previously for a large sample of male and female athletes. This process would inform scaling practice and facilitate intra- and inter-group comparisons of cardiac data. Therefore we investigated the relationships of body mass (BM), height and body surface area (BS) with a range of cardiac dimensions derived by echocardiography in 464 male and female elite junior athletes (age range 14-18 years; sporting allocation included rowers, cyclists, footballers, tennis players, swimmers and a miscellaneous group). Initial linearity checks suggested that most of the relationships between the body size variables and cardiac dimensions were non-linear, thus precluding the simple ratio standard approach to scaling. Multiple log-log least-squares linear regression confirmed commonality of slopes (between males and females, across the age range and between sporting groups) for all relationships involving BM and BS. Subsequent analyses of the slope exponent (b) for left ventricular dimensions supported previous data and were dimensionally consistent (LVM-BM, b=0.91+/-0.11; LVM-BS, b=1.44+/-0.19; where LVM is left ventricular mass), except for left ventricular internal dimension in diastole (LVIDd) (LVIDd-BM, b=0.25+/-0.04). Data for the left atria internal dimension (LA) were also dimensionally consistent (LA-BM, b=0.29+/-0.09); however, this was not the case for the right ventricular internal dimension in diastole (RVIDd) (RVIDd-BM, b=0.76+/-0.14). It is possible that these results were due to a study-specific limitation in the data range (LVIDd) and the geometric peculiarities of RVIDd compared with LVIDd. The gender/age/sporting groupxbody size interaction factor for virtually all relationships between height and cardiac dimensions was significant (P<0.05), and thus whole-group b exponents could not be generated. Generally these data support previous small-sample research with athletes, and suggest that allometric scaling, as opposed to simple ratio scaling, should be adopted in studies of cardiac dimensions in athletes. This should allow, with minimal mathematical difficulty, the production of body-size-independent cardiac indices to be evaluated in laboratory or clinical work. Further research is required to develop normative 'allometrically derived' cardiac indices, and care should be taken to determine relationships in specific population groups as well as to confirm commonality of slopes in multiple group comparisons. Caution is expressed regarding the use of height as a scaling variable in future research.

Adolescent↗
PubMed2001

Patient selection for oral chemotherapy.

Oral chemotherapy has evolved with several new agents such as capecitabine and UFT in active clinical trials or already approved for use in the western world. Several distinct issues, apart from the usual criteria for selecting patients for intravenous chemotherapy, dictate patient selection for these drugs. This article discusses these issues, which include patient preference, selection, and compliance.

Administration, Oral↗
PubMed2001

Pelvic lipomatosis presenting as uraemic encephalopathy.

Pelvic lipomatosis is a benign disorder of unknown aetiology, characterised by deposition of mature fat in the pelvis. It has a variable natural history, manifesting either with symptoms attributable to the lower urinary tract or varying degrees of renal failure. Owing to the mild, non-specific initial symptoms and slow progression, presentation is delayed and patients are often lost to follow-up, only to present with advanced renal failure later on. We report a case of a young patient with pelvic lipomatosis who, after an initial diagnosis, was lost to follow-up for several years and then presented with uraemic encephalopathy. The case highlights the importance of regular follow-up and an early intervention before irreversible changes occur.

Adult↗
PubMed2001

Antibody responses of Wuchereria bancrofti patients to recombinant Brugia pahangi superoxide dismutase.

Lymphatic filarial parasite Brugia malayi contains significant amount of Cu/Zn superoxide dismutase (SOD) activity in the extract of different life stages and in the excretory-secretory product of adults. In the present study recombinant SOD from B. pahangi has been used to see the antibody response in Wuchereria bancrofti infected patients. The recombinant SOD from B. pahangi reacted specifically with W. bancrofti infected sera in ELISA and immunoblotting. The reactivity of IgM subclass was more as compared to IgG subclass both in the asymptomatic microfilaraemic and symptomatic amicrofilaraemic when tested by ELISA. Serum from other helminthic infection was very low and found to be insignificant. The antibody response to rec SOD was directly proportional to the number of microfilariae in infected patients. The circulating filarial SOD was detected in filarial patients using polyclonal antibodies raised against recombinant Cu/Zn SOD in rabbits. The apparent molecular masses as determined by immunoblotting were 29 and 22 kDa. The specificity of recombinant SOD could be explored for its use in immunodiagnosis of lymphatic filariasis.

Animals↗
PubMed2001

Influence of hypoglycaemia, with or without caffeine ingestion, on visual sensation and performance.

Full-field visual evoked potentials and visual information processing were measured in 16 normal, healthy subjects during a hyperinsulinaemic clamp. A randomized cross-over design was used across three conditions: hypoglycaemia and caffeine; hypoglycaemia and placebo; and euglycaemia and caffeine. The latency of the P100 component of the pattern-reversal visual evoked potential increased significantly from rest to hypoglycaemia, but no effect of caffeine was found. Subjects were subsequently divided into two median groups based on the increase in P100 latency in the placebo condition (Group 1, +0.5 ms; Group 2, +5.6 ms). In the absence of caffeine, an inverse correlation between the increase in P100 latency from rest and a deterioration in visual movement detection was found for Group 2, but not for Group 1. Caffeine ingestion resulted in a further increase in P100 latency, from rest to hypoglycaemia, for subjects in Group 2. Hypoglycaemia in the absence of caffeine produces changes in visual sensation from rest to hypoglycaemia. In those subjects most sensitive to the effects of hypoglycaemia (Group 2), the increase in P100 latency was associated with poorer performance in tests of visual information processing. Caffeine ingestion produced further increases in P100 latency in these subjects.

Adult↗