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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 973 records · Page 54Linked to original sources

A strain theory of malaria transmission.

Does the fact that the risk o f getting malaria is high in most endemic areas mean that it will be impossible to control through vaccination? Not if malaria is composed of several mildly transmissible strains, and what we are measuring as the high risk is the probability of being infected by any one of the several strains circulating independently within the same area. In this article, Sunetra Gupta and Karen Day discuss a strain theory of malaria transmission that fits both recent serological and molecular observations and more conventional epidemiological data on age distributions of infection and disease. Their analyses suggest that the transmissibility of malaria has been grossly overestimated, and that the control of malaria through vaccination may be far easier than previously assumed.

Journal Article↗

Human immunodeficiency virus-1 recombinant gp120 induces changes in protein kinase C isozymes--a preliminary report.

Human immunodeficiency virus 1 (HIV-1) and its purified proteins activate target cell functions. Because protein kinase C (PKC) plays a crucial role in signal transduction and there is a molecular heterogeneity of PKC, we compared the effect of recombinant HIV-1 gp120 and phorbol ester (PMA) on PKC isozymes in monocytic U937 cells, with isozyme-specific antibodies using flow cytometry. All PKC isozymes except PKC-gamma were present in U937 cells. Both PMA and HIV-1 gp120 increased levels of calcium-dependent and -independent PKC isozymes. The most striking change was observed in PKC-zeta isozymes levels. This study for the first time demonstrates that HIV-1 gp120 affects calcium-independent PKC isozymes in U937 cells.

Enzyme Activation↗

Transcatheter hepatocyte transplantation: preclinical studies of anatomic consequences in the portal vascular bed.

RATIONALE AND OBJECTIVES: Intrasplenic transplantation deposits hepatocytes in host hepatic sinusoids with amelioration of chronic liver failure and genetic deficiency states. Because portal resistance can be altered by intrasinusoidal transplanted cells, we examined whether hepatocyte recipients would develop deleterious portal hypertension or portosystemic collaterals. METHODS: Syngeneic hepatocytes in suspension were transplanted into recipient rats by transcatheter injection into the splenic parenchyma. Subjects included recipients of 2 x 10(7) hepatocytes representing approximately 3% of the host hepatic mass, recipients of 7.5 x 10(7) hepatocytes representing approximately 12.5% of the host hepatic mass, normal control rats, and positive control rats with portal hypertension induced by partial portal vein constriction. Portal pressures were recorded with a sensitive transducer, portosystemic collaterals were demonstrated with direct splenoportography, and survival of transplanted cells was determined with an endogenous dipeptidyl peptidase IV reporter gene. RESULTS: In normal rats, the portal pressure was 6.25 +/- 1.9 mm Hg with no portosystemic collaterals. By contrast, portal pressures were significantly increased in portal vein-constricted rats, 20.7 +/- 3.9 mm Hg (P < 0.001), with extensive portosystemic collaterals. In hepatocyte recipients, portal hypertension observed during transcatheter cell injection but proved transient. When animals were examined up to 16 weeks after hepatocyte transplantation, portal pressures were in the normal range (after 2 x 10(7) cells, 7.5 x 2.6 mm Hg; after 7.5 x 10(7) cells, 9.5 +/- 4.2 mm Hg, P = not significant). No portosystemic collaterals developed in hepatocyte recipients at various times up to 8 months after transplantation. Transplanted hepatocytes expressing the reporter gene were present in recipients with assimilation in host hepatic cords. CONCLUSION: Despite injection of a massive number of cells, transcatheter hepatocyte transplantation was devoid of any significant portal vascular alterations or toxicity in recipients. These findings are consistent with assimilation of transplanted hepatocytes into host hepatic cords and will facilitate therapeutic applications in metabolic diseases or acute liver failure.

Animals↗

Review of urinary tract abnormalities in 100 patients with spinal cord paralysis.

The importance of long term follow up of neurological status of patients with spinal cord injuries is well recognised. Although there is a general agreement about continued radiological surveillance of these patients, there is lack of uniformity of approach and guidelines as to how frequently such screening should be undertaken and for how long it should be continued. The present study, following analysis of clinical and radiological data of 100 sequential patients, indicates that morphological complications of urinary tract are common (63% in patients studied) and that a significant number (70-75%) develop complications within the first year following onset of spinal cord dysfunction. The development of these changes appears to be related to more than 8 weeks of presence of continuous indwelling catheter during patients' initial bladder management. The study further suggests that the risk of developing demonstratable abnormalities after 10 years of normal radiology is very small (approximately 1%). It is, therefore, suggested that patients with spinal cord paralysis should have surveillance of urinary tract annually for 10 years and that the follow up beyond 10 years should be determined by clinical necessity rather than a fixed protocol.

Adult↗

Hepatocytes exhibit superior transgene expression after transplantation into liver and spleen compared with peritoneal cavity or dorsal fat pad: implications for hepatic gene therapy.

For hepatic gene therapy or applications of hepatocyte transplantation in liver failure, survival and function of transplanted cells is critical. Insights into site-specific gene regulation will significantly facilitate development of appropriate strategies for transplanting hepatocytes. To assess the function of transplanted cells, we used a transgenic hepatitis B virus (HBV) hepatocyte system, which allowed analysis of cellular gene expression with HBV surface antigen (HBsAg) mRNA expression, as well as secretion of HBsAg into peripheral circulation. When congeneic HBV hepatocytes were transplanted into the liver (via spleen), serum HBsAg promptly appeared in circulation and persisted for the entire duration of the studies. In contrast, transplantation of hepatocytes into the peritoneal cavity or dorsal fat pad resulted in serum HBsAg levels that were either significantly lower or gradually rose after a lag period. HBsAg mRNA expression was several-fold greater in transplanted hepatocytes in liver or spleen versus in peritoneal cavity or dorsal fat pad. Despite persistence of transplanted hepatocytes in peritoneal cavity or dorsal fat pad, serum HBsAg was cleared by antibody to HBsAg (anti-HBs) but this was not observed after hepatocyte transplantation into spleen. As the function of transplanted hepatocytes is optimally regulated in the liver, hepatic reconstitution with cell transplantation will be most appropriate for gene therapy.

Adipocytes↗

Salmonella typhimurium induces expression of P glycoprotein (multidrug resistance 1 gene product) in a promonocytic cell line chronically infected with human immunodeficiency virus type 1.

This investigation showed that phagocytosis of virulent Salmonella typhimurium by promonocytic leukemia cell line U1, which contains human immunodeficiency virus type 1 (HIV-1) provirus but produces minimal or no virus, and not by uninfected U937 cell line resulted in expression of a functional P glycoprotein. Anti-tumor necrosis factor-alpha (TNF alpha) monoclonal antibody failed to inhibit S. typhimurium-induced P glycoprotein expression. Furthermore, recombinant TNF alpha had no effect on the induction of P glycoprotein expression in U1 cells. These data demonstrate that phagocytosis of virulent S. typhimurium results in an induction of P glycoprotein in association with HIV-1 infection; however, TNF alpha does not appear to play a significant role. Thus, secondary microbial infection in HIV-1-positive persons may play a role in multidrug resistance against antiviral and other antimicrobial agents by an induction of P glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Serum trace elements and Cu/Zn ratio in malignant lymphomas in children.

Serum copper and zinc levels, and Cu/Zn ratio were measured in 40 children with Hodgkin's (n = 18) and non-Hodgkin's (n = 22) lymphomas, and 30 controls using Atomic Absorption Spectrophotometry. The mean serum copper levels were higher in lymphoma patients than in controls (199.8 micrograms/dl v. 95.8 micrograms/dl) P < 0.001). The increase in serum copper level correlated with the stage of disease being maximum in Stage IV (219.4 micrograms/dl v. 143.2 micrograms/dl) (P < 0.01). On the other hand, there was a decrease in the serum zinc levels in lymphoma patients as compared to controls (86.1 micrograms/dl v. 117.4 micrograms/dl) (P < 0.001), but this was significant only in patients with advanced disease. The Cu/Zn ratio was therefore markedly increased in these patients (2.46 v. 0.83) (P < 0.001). Following successful treatment the abnormal serum copper and zinc levels returned towards normal. The exact mechanisms responsible for these alterations are yet to be elucidated. We conclude that serum copper and zinc levels and Cu/Zn ratio are easily measurable biochemical indices that can be used as predictors of successful treatment in pediatric patients with lymphomas.

Adolescent↗

Proximal splenorenal shunts for extrahepatic portal venous obstruction in children.

OBJECTIVE: The results of proximal splenorenal shunts done in children with extrahepatic portal venous obstruction were evaluated. SUMMARY BACKGROUND DATA: Extrahepatic portal venous obstruction, a common cause of portal hypertension in children in India, is being treated increasingly by endoscopic sclerotherapy instead of by proximal splenorenal shunt. It is believed that surgery (or the operation) carries high mortality and rebleeding rates and is followed by portosystemic encephalopathy and postsplenectomy sepsis. However, a proximal splenorenal shunt is a definitive procedure that may be more suitable for children, particularly those who have limited access to medical facilities and safe blood transfusion. METHODS: Between 1976 and 1992, the authors performed 160 splenorenal shunts in children. Twenty were emergency procedures for uncontrollable bleeding and 140 were elective procedures--102 for recurrent bleeding and 38 for hypersplenism. RESULTS: The overall operative mortality rate was 1.9%--10% (3/160-2/20) after emergency operations and 0.7% (1/140) after elective operations. Rebleeding occurred in 17 patients (11%), and pneumococcal meningitis developed in 1 patient who recovered later. Encephalopathy did not develop in any patient. Four patients died in the follow-up period--two of rebleeding, one of chronic renal failure and a subphrenic abscess, and one of unknown causes. The 15-year survival rate by life table analysis was 95%. CONCLUSIONS: A proximal splenorenal shunt, a one-time procedure with a low mortality rate and good long-term results, is an effective treatment for children in India with extrahepatic portal venous obstruction.

Adolescent↗

Nocardial necrotizing scleritis after trauma. Successful outcome using cefazolin.

Nocardial necrotizing scleritis is uncommon, but potentially sight threatening. We report the occurrence of necrotizing scleritis in a 58-year-old farm worker after he sustained trauma with vegetable matter. Microbiological studies isolated Nocardia asteroides, sensitive only to cefazolin. Clinically the patient responded well to this drug, attaining a final visual acuity of 20/40, with complete resolution of the scleritis. Early isolation and testing for antibiotic sensitivity were responsible for the successful management of this patient.

Cefazolin↗

Phakomorphic glaucoma--an unusual cause of postoperative vomiting.

A 60-year-old female patient receiving epidural buprenorphine for postoperative analgesia developed intractable nausea and vomiting not responding to antiemetics. Ophthalmic consultation for congestion of the left eye was sought and the patient was diagnosed as having phakomorphic glaucoma. Extracapsular extraction of the left lens was performed after primary anti-oedema measures. Glaucoma as a cause of intractable postoperative nausea and vomiting should be considered in susceptible patients.

Analgesia, Epidural↗

A theoretical framework for the immunoepidemiology of Plasmodium falciparum malaria.

Molecular genetic analyses of P. falciparum have led to the cloning and sequencing of a number of antigens that are potential candidates for vaccination against malaria. Seroepidemiological studies in endemic areas have attempted to assess the relative importance of these antigens in protection against malaria. In this paper, we attempt to evaluate the relative contributions of conserved and strain-specific immune responses by modelling their influence of age-specific patterns of infection and disease. The modelling exercises in this paper clearly demonstrate that the observed patterns of age-prevalence are best explained by proposing that the accumulation to a threshold of an immune response against a conserved determinant is required for protection against infection, while 'anti-disease' immunity develops more linearly with exposure. This is compatible with the conjecture that the parasite population is structured into several independently transmitted strains, that each confers some degree of 'anti-disease' immunity, but does not protect against further infection by the same strain. Within this framework, the average duration of parasitaemia increases with age, as previously encountered strains endure for longer periods at a subclinical level. Indirect evidence for the increase in duration of parasitaemia with age may be obtained from a comparison of age-prevalence curves between dry and rainy seasons. By using mathematical methods to structure epidemiological and immunological information, we provide a coherent theoretical framework for the dissection of the important components of naturally acquired immunity to malaria.

Adolescent↗

The radionuclide assessment of pre-natally diagnosed hydronephrosis.

OBJECTIVE: To determine if a pre-operative non-invasive radionuclide study can predict the results of surgery in infants with pre-natally diagnosed hydronephrosis. PATIENTS AND METHODS: Eight male infants with prenatally diagnosed hydronephrosis were treated by pyeloplasty within the first 4 months of life. All infants underwent a pre-operative diuresis renogram and a dimercapto-succinic acid (DMSA) scan, followed by a further renogram 6 months after surgery to assess renal function and drainage. RESULTS: There was a significant difference between the results of the relative renal function estimates obtained by the pre-operative renogram and the pre-operative DMSA scan (P = 0.001). In all patients the recovery in renal function following surgery was accurately predicted by the pre-operative DMSA scan. CONCLUSION: The results of this preliminary study suggest that a pre-operative DMSA scan could replace the use of invasive nephrostomy drainage to assess the potential for recovery in the poorly functioning neonatal kidney and give an indication of those kidneys most likely to benefit from reconstructive surgery.

Humans↗

Epidemiological and clinical correlates of familial and sporadic schizophrenia.

We studied 68 schizophrenic cases with a schizophrenic first-degree relative (familial group) and 62 cases without such a family history (sporadic group). We compared them on: (i) clinical variables, including premorbid adjustment, age of onset and severity of symptoms; (ii) neural abnormalities, including abnormal involuntary movements, neural "soft" and "hard signs"; (iii) neuropsychological tests, including the Wechsler Adult Intelligence Scale and the Continuous Performance Test and (iv) environmental risk factors, including winter birth and obstetrical complications. Sporadic cases were more likely to be born in winter and had more severe psychotic symptoms, but most analyses yielded no difference between the groups. Our results offer some support that sporadic schizophrenia is a more environmental subtype, but they also suggest that the familial vs sporadic distinction of schizophrenia has limited power to identify distinct subgroups.

Adaptation, Psychological↗

Positive and negative symptoms of schizophrenia: past, present, and future.

The "group of schizophrenias," normally referred to with a single nominative, is phenomenologically heterogeneous. Its symptoms represent multiple psychological domains, including perception, inferential thinking, language, attention, social interaction, emotion expression, and volition. Studies of psychopathology have simplified this complex array in several ways; one has been a subdivision into positive and negative symptoms. Reports by our group and others suggest that the symptoms of schizophrenia fall into three natural dimensions: positive symptoms subdivided into psychotic and disorganized dimensions, while a third negative dimension also emerges. Since these dimensions have impressive consistency across studies, future work must examine their relationship to clinically relevant concepts such as prognosis or etiology and examine four different aspects: longitudinal course, neural mechanisms, relationship to treatment, and interrelationships in other pathological conditions.

Brain↗

Speech fluency in aphasia. Regional cerebral blood flow correlates of recovery using single-photon emission computed tomography.

This study investigated the relationship between diminished regional cerebral blood flow (rCBF) and the recovery of fluent speech in aphasia. Single-photon emission computed tomographic brain scans using [123I]N-isopropyl-p-iodoamphetamine were obtained from 14 nonfluent aphasic patients within 30 days of cerebral infarction. Measurements of speech fluency were acquired initially and at 3 months after infarction. Nearly all of the patients exhibited significant hypoperfusion to combinations of the anterior and posterior regions of the basal ganglion, the periventricular white matter, and the inferior frontal regions. Only the inferior frontal area was significantly associated with recovery of fluent speech. This region was hypoperfused in 4 of 5 patients with poor recovery while 8 of the 9 patients with good speech fluency recovery demonstrated normal rCBF to the inferior frontal region.

Aged↗