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Biomedical subjects

R Khanna

Publications and source records attributed to R Khanna.

At least 19 recordsLinked to original sources
PubMed1992

Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development.

There is considerable interest in designing an effective vaccine to the ubiquitous Epstein-Barr virus (EBV). An important role for EBV-specific cytotoxic T lymphocytes (CTLs) in eliminating virus-infected cells is well established. Limited studies using a small number of immune donors have defined target epitopes within the latent antigens of EBV. The present study provides an extensive analysis of the distribution of class I-restricted CTL epitopes within EBV-encoded proteins. Using recombinant vaccinia encoding individual EBV latent antigens (Epstein-Barr nuclear antigen [EBNA] 1, 2, 3A, 3B, 3C, LP, and LMP 1), we have successfully localized target epitopes recognized by CTL clones from a panel of 14 EBV-immune donors. Of the 20 CTL epitopes localized, five were defined at the peptide level. Although CTL clones specific for nine epitopes recognized both type 1 and type 2 transformants, a significant number of epitopes (7/16 epitopes for which EBV type specificity was determined) were detected only on type 1 EBV transformants. Vaccinia recombinants encoding EBNA 3A and EBNA 3C were recognized more frequently than any other vaccinia recombinants used in this study, while no CTL epitopes were localized in EBNA 1. Surprisingly, epitope specificity for a large number of EBV-specific CTL clones could not be localized, although vaccinia recombinants used in this study encoded most of the latent antigens of EBV. These results suggest that any EBV vaccine based on CTL epitopes designed to provide widespread protection will need to include not only latent antigen sequences but also other regions of the genome. The apparent inability of human CTLs to recognize EBNA 1 as a target antigen, often the only latent antigen expressed in Burkitt's lymphoma and nasopharyngeal carcinoma, suggests that EBV-specific CTL control of these tumors will not be feasible unless the down-regulation of latent antigens can be reversed.

Amino Acid Sequence↗
PubMed1992

Roux-limb motility after total gastrectomy and Roux-en-Y anastomosis in patients with Zollinger-Ellison syndrome.

The Roux-en-Y syndrome was defined as chronic nausea, intermittent vomiting, and chronic abdominal pain worsened by eating in patients who have undergone a gastrojejunostomy Roux-en-Y reconstruction for peptic ulcer. When these patients fasted, the Roux limb showed striking abnormalities in motor function; when postprandial, they failed to convert to normal fed-state motor activity. In contrast, patients with Zollinger-Ellison syndrome do well after similar surgery; they can eat most foods and maintain their body weight. We studied the motility of the Roux limb and jejunum in six patients with Zollinger-Ellison after an esophagojejunostomy Roux-en-Y anastomosis. Roux-limb motor activity in these patients, as characterized by the migrating motor complex, was more frequent, well organized, and in synchrony with the remaining jejunum; most subjects also converted to the fed state after a liquid meal. We suggest that the enteric nervous system is intact and functions normally in patients who have had a Roux-en-Y reconstruction for ulcer disease secondary to Zollinger-Ellison, but not in patients with idiopathic peptic ulcer disease.

Adult↗
PubMed1992

Course of bipolar disorder in eastern India.

The life course of affective episodes was determined for 95 consecutively admitted patients from eastern India fulfilling RDC criteria for definite mania during the current episode, using SADS-L interviews. There was a significantly greater frequency of manic compared to depressive relapses. Presentation as recurrent mania was very common. The total numbers of affective and manic episodes were significantly higher among those with recurrent mania and in cases where the first illness episode was manic.

Adult↗
PubMed1992

Systemic-oral immunization with 56 kDa molecule of Giardia lamblia affords protection in experimental mice.

Prior systemic-oral immunization of inbred mice with Giardia lamblia surface-associated antigen of molecular mass 56 kDa not only significantly blocked colonization but also resulted in elimination of G. lamblia trophozoites by 9-11 days following challenge. The colonization and multiplication of the trophozoites in unprotected animals were accompanied by a pronounced influx of suppressor T cells in intraepithelial or lamina propria of the small intestine and a significant decline in IgA-bearing plasma cells in the lamina propria. An induction of helper/inducer T cells in the intraepithelial and lamina propria and significant enhancement of IgA and IgG-bearing cells in the lamina propria of the small gut resulted in a decline, and eventual elimination, of the trophozoites from the gut. The completion of the immunization of animals with 56 kDa G. lamblia antigen resulted in: significant enhancement of helper/inducer T lymphocytes with no effect on suppressor T cells in the intraepithelial and lamina propria of the small gut; significant enhancement of IgA- and IgG-bearing plasma cells in lamina propria; and significant elevation of antibodies to 56 kDa G. lamblia antigen in the systemic circulation. The stimulation of such effector mechanisms in 56 kDa-immunized animals appears to result in failure of the trophozoites to get established, prevention of multiplication and earlier elimination from the gut. The data suggest that the 56 kDa molecule of G. lamblia immunoregulates the giardial infection.

Administration, Oral↗
PubMed1992

Leuprolide acetate affects intestinal motility in female rats before and after ovariectomy.

Leuprolide acetate, a gonadotropin-releasing hormone (GnRH) analogue, is currently being proposed to control debilitating symptoms in women with functional bowel disease. Whether leuprolide alters gastrointestinal motility as part of its actions is unknown. This study was designed to assess, using myoelectric techniques in an animal model, the effects of leuprolide on potential mechanisms of neuromuscular function of small intestine. Female rats with (n = 6) or without (n = 8) bilateral ovariectomy were used to study jejunal motility before and after leuprolide therapy. Throughout the study, daily leuprolide dosages of 0.02, 0.2, or 0.4 micrograms/kg were injected into intact rats and 0.02, 0.2, 0.4, 1.0, or 2.5 micrograms/kg into ovariectomized rats. Recordings were made while the rats were fasted and postprandial and before and after leuprolide administration. Under control conditions, migrating myoelectric complexes (MMCs) were found in intact female rats, whether fasted or postprandial. After ovariectomy, postprandial controls and those treated with low-dose leuprolide (0.02, 0.2, and 0.4 micrograms) had typical fed-state patterns and no MMCs, but at 1.0 and 2.5 micrograms the fed state was inhibited and cycling MMCs occurred at a frequency similar to that of fasted controls. Reproductive hormones thus have a significant effect on gastrointestinal motility.

Animals↗
PubMed1992

Role of lymphatics in peritoneal dialysis.

There is a renewed interest in understanding the precise role of lymphatics in the ultrafiltration kinetics during peritoneal dialysis. In the normal state, lymphatics draining the peritoneal cavity are the principal means of removal of intraperitoneal isosmotic fluid and macromolecules. During a hypertonic peritoneal dialysis exchange, after peak intraperitoneal volume is achieved, fluid removal proceeds at an almost linear rate, causing intraperitoneal fluid volume to reduce. The isosmotic fluid removal from the peritoneal cavity could occur through the microcirculatory capillaries or through the lymphatic capillaries draining the peritoneal cavity. Animal and human studies suggest that this fluid loss occurs primarily through lymphatics. The two indirect methods of lymph flow measurements, plasma appearance and peritoneal disappearance of tracer colloid, show conflicting results. Although direct measurement of lymph flow rates through cannulation of mediastinal lymph vessels in animals suggests a significant flow through the lymph channels in response to intraperitoneal fluid instillation, lymph flow modification at the lymph node level may prevent use of this technique to assess the precise role played by lymphatics in fluid kinetics during peritoneal dialysis. By analogy with ascites and by extrapolation from previous studies of drain volumes after infusion of isotonic and hypertonic solutions, the average daily lymph absorption rate during CAPD may be predicted to be at least 1 liter per day.

Absorption↗
PubMed1992

Prospective study of neuroleptic-induced dystonia in mania and schizophrenia.

OBJECTIVE: The authors' goal was to conduct a prospective study comparing the rate of occurrence of neuroleptic-induced dystonia in a group of consecutively admitted manic and schizophrenic patients receiving typical inpatient treatment from several clinicians. METHOD: All patients met the following criteria: 1) male sex, 2) age between 17 and 45 years, 3) definite diagnosis of mania or schizophrenia according to Research Diagnostic Criteria, 4) no exposure to neuroleptics during the past month, 5) absence of past or family history of a neurodegenerative disorder with extrapyramidal symptoms. All treatment decisions were left to the treating clinicians. Fifty patients with mania and 33 with schizophrenia were included in the study. Most of these patients received high-potency neuroleptics, but the specific neuroleptic used varied in the two groups. RESULTS: Twelve (24%) of the patients with mania and five (15%) of the patients with schizophrenia developed acute dystonia. Manic patients received significantly higher peak doses of neuroleptics during the risk period for dystonia. Stepwise multiple regression analysis revealed that the peak neuroleptic dose and age were most strongly related to the occurrence of dystonia. CONCLUSIONS: This prospective study failed to support the retrospective finding of another study that acute dystonia occurred more often in manic patients than in patients with nonparanoid schizophrenia. The authors conclude that there is a need for carefully controlled prospective studies with larger groups of patients.

Adolescent↗
PubMed1992

Factors related to psychiatric hospitalisation for first contact patients.

In a consecutive series of 178 first contact patients hospitalisation was significantly related to greater distance travelled, low income, acute onset, short duration, past history of illness and history of substance abuse compared to those receiving outpatient disposition. Hospitalised manics and paranoid schizophrenics had higher BPRS scores while hospitalised non-paranoid schizophrenics had lower scores. There was a significant positive correlation between hospitalisation and BPRS items: grandiosity, excitement, elated mood, motor-hyperactivity and distractibility and negative correlation with somatic concern, anxiety, depressive mood and social incompetence. Stepwise multiple regression analysis found the combination of loss of functioning, social incompetence and grandiosity to best predict disposition decision.

Adolescent↗
PubMed1992

Swan neck presternal ("bath tub") catheter for peritoneal dialysis.

We hypothesize that the swan neck catheter for peritoneal dialysis with exit in the presternal area will have better exit site healing and a decreased incidence of exit site infection than currently used peritoneal dialysis catheters with the exit located on the abdomen. The chest is a very stable structure, with minimal wall motion, especially of the upper chest and over the sternum. Hence, a catheter exit located on the chest will be subjected to only minimal movement. Decreased piston like movement of the catheter at the exit site reduces inward transfer of outer microbial flora. Moreover, a tight garment is usually not worn on the chest and there is less pressure on the exit. Based on this rationale a new catheter (swan neck presternal) has been designed. The presternal peritoneal dialysis catheter is composed of two flexible (silicon rubber) tubes joined through a titanium connector at the time of implantation. The device has been dubbed as a "bath tube" catheter because, with the exit on the chest, a patient may take a tub bath without the risk of exit contamination due to submersion. Two such catheters were implanted in two patients. One patient had multiple problems (including chronic exit site infection) with a previously implanted swan neck Missouri 2 catheter, the other patient was originally rejected as a peritoneal dialysis candidate due to extreme obesity. Both catheters healed well in 6 weeks and the exits have not become infected during the first 8 months. These preliminary experiences with 2 catheters support the rationale of their design.

Catheters, Indwelling↗
PubMed1992

Immune surveillance against Epstein-Barr virus.

Following primary infection, EBV retains a life-long latent association with B lymphocytes and a permissive association with stratified epithelium in the oropharynx. This review presents a model for the host-virus relationships in healthy virus carriers, a relationship which, if perturbed, may result in EBV-associated disease. Cytotoxic T cells that recognise virally-determined epitopes on infected cells are the major effector arm and control the persistant infection. A strategy for developing a vaccine to EBV is discussed.

Amino Acid Sequence↗
PubMed1992

Rapid visual assay of cytotoxic T-cell specificity utilizing synthetic peptide induced T-cell-T-cell killing.

Synthetic peptides are widely used to define the specificity of CD8+ cytotoxic T-lymphocyte (CTL) clones. When many peptides need to be tested by the standard chromium release assay large numbers of a CTL clone are required. Specific synthetic peptide epitopes induce CTL clones to kill each other. This phenomenon can be directly visualized using an inverted microscope and forms the basis for a convenient assay, which can be performed with as few as 100 CTL per peptide and does not require radiolabelled targets.

Cells, Cultured↗
PubMed1992

CAPD and pancreatitis: no connection.

Autopsy studies have shown that approximately 56% of patients on long-term continuous ambulatory peritoneal dialysis (CAPD) develop various pancreatic abnormalities, such as acute and chronic pancreatitis, fibrosis, and acinar dilatation. This prevalence of anatomical abnormalities is similar to that observed in patients on hemodialysis and higher than that in those with normal renal function. However, clinical acute pancreatitis is an uncommon complication of CAPD (0.9%), and this prevalence is similar to that (1.7%) of patients on hemodialysis. We can attribute acute pancreatitis in CAPD patients to no single factor. Perhaps preexisting anatomical abnormalities of the pancreas make the CAPD patient susceptible to acute pancreatitis when exposed to a variety of physiological and nonphysiological influences. The diagnosis of acute pancreatitis in CAPD patients is difficult, because symptoms and signs are similar to those of dialysis-associated peritonitis. Serum amylase values three times greater than the upper limit of normal and effluent amylase greater than 100 U/L suggest the diagnosis of acute pancreatitis. Serum lipase, isoamylase, and pancreatic secretory trypsin inhibitor are not helpful. In confirming the diagnosis, a computed tomography (CT) scan is more helpful than ultrasound, although it is positive in only 50-60% of cases. One should harbor a high index of suspicion concerning acute pancreatitis if a CAPD patient presenting with suspected peritonitis has either a negative effluent culture or does not respond to antibiotic therapy.

Acute Disease↗
PubMed1992

Six-year experience with swan neck catheters.

From the beginning of our continuous ambulatory peritoneal dialysis (CAPD) program in January 1977 until June 1985, we used Tenckhoff and Toronto Western Hospital catheters. Throughout these years catheter survival probabilities of about 30% at three years persisted unchanged and were similar to survival probabilities reported by the National CAPD Registry special survey for these catheters. The first improvement in catheter results regarding leaks was noted after the adoption of lateral catheter insertion. Malfunction was less using swan neck prototypes from August 1985 to April 1986. The latter catheters were made of 80 degrees arc angle tubing between 8.5 cm spaced cuffs and were inserted in a reversed U-shape tunnel with the incision at the top of the tunnel. The use of these catheters was abandoned because of high cuff extrusion and exit infection rates. The next generation of swan neck catheters, the swan neck Missouri 2 and 3 catheters with straight intraperitoneal segments, improved the results dramatically. These catheters were made of 180 degrees arc angle tubing between 5 or 3 cm spaced cuffs. The estimated survival probability of 61% at three years more than doubled compared to previously used catheters. Recently we modified the intraperitoneal segment of the catheters, replacing the straight segment with a coiled one. These modified catheters, the swan neck Missouri coiled catheters, have been used exclusively since February 1990. In addition to an acceptable survival probability of 88% at one year, there are two major advantages of these catheters, the same as for other coiled catheters: elimination of infusion pain due to a jet effect and pain related to straight catheter tip pressure on the peritoneum experienced by some patients.

Bacterial Infections↗
PubMed1992

Synthesis and pharmacological evaluation of some phenothiazines as antidepressants.

10-Hydrazino acetyl phenothiazine (II) has been converted to N-10-acetyl amino phenothiazine-N-phenyl thiourea (III) which have been converted to 3-aryl-1-(10-phenothiazine acetyl amino)-2,3-dihydro-2-thioxo-4,6-(1H,5H) pyrimidinones (IV) on condensation with aryl amines and aryl aldehydes yielded 3-aryl-1-(10-Phenothiazine acetyl amino)-5-(substituted phenyl amino methyl)-2,3-dihydro-2-thioxo-4,6-(1H, 5H) pyrimidinediones (Va-k) and 3-aryl-1-(10-phenothiazine acetyl amino)-5-(substituted phenylidine)-2,3-dihydro-2-thioxo-4,6-(1H, 5H) pyrimidinediones (vl-o). The compounds were screened for their antidepressant activity against a tricyclic antidepressant (imipramine). Compounds Va, Vf, Vm and Vi exhibited activity better than imipramine with no toxicity (ALD50 greater than 1000 mg/kg) but Vi showed some side effects.

Amphetamine↗
PubMed1992

Tubeless, drainless, short-stay cholecystectomy.

Of 340 patients undergoing elective cholecystectomy for gallstone disease, 41 (12%) required an abdominal drain and 22 (65%) required a nasogastric tube postoperatively to control vomiting. Eighty six percent patients were discharged on the third post-operative day; 53% were satisfied with the early discharge. In our opinion, routine use of nasogastric tube and abdominal drain is not necessary and patients can be safely discharged on the third postoperative day after an uncomplicated cholecystectomy.

Adolescent↗
PubMed1992

Biochemical studies on mouse liver following Plasmodium berghei infection.

The lipid composition of mouse liver following infection with P. berghei was investigated. The liver lipid contents of infected animals were greatly increased mainly due to the accumulation of triacylglycerides. There was enhanced lipid concentration (85.29%). Significantly (23.7%) depleted liver cholesterol was also found in the mice. Similarly, phospholipid contents of liver were also decreased by 19.90 per cent. The liver from P. berghei infected mouse produced more lipid peroxide, as compared to control animals (314%). Significant depletion was also observed in carbohydrate, glycogen and glucose (79.1, 86.26 and 78.6% respectively) contents of liver at high parasitaemia. The lower contents of nucleic acid in the infected hosts observed in the study may be partly due to the absorption of nucleic acids by the parasites from the host cells.

Animals↗