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Biomedical subjects

D Mital

Publications and source records attributed to D Mital.

33 records · Page 2Linked to original sources
PubMed1996

Granulocyte colony-stimulating factor immunomodulation in the rat cardiac transplantation model.

Granulocyte colony-stimulating factor (G-CSF) administration decreases tumor necrosis factor(TNF) release, an important mechanism in allograft rejection. to study G-CSF's possible antirejection effects, 30 Lewis rats underwent heart transplantation using Brown-Norway donors and were assigned varying dosages of recombinant human G-CSF (0, 20, 100, 250 and 500 microgram/kg/day) for 14 days following the operation. Recipients receiving 250 microgram/kg/day experienced an improvement in graft survival (12.3+/-4 days vs. 7.0+/-0.6 days, P>0.05, Breslow). In a separate cohort, G-CSF-treated recipients (250 microgram/kg/day x 14) killed at 2,4,and 6 days after transplantation revealed improved serial allograft biopsy grading scores versus untreated controls (P<0.001 stratified Wilcoxon). Significant reduction in serum TNF levels was noted in the G-CSF-treated animals (P<0.025, analysis of variance). These data describe a moderate antirejection effect of G-CSF administration. Inhibition of circulating TNF in the G-CSF-treated recipients may describe a marker or possible mechanism of this antirejection effect.

Animals↗
PubMed1995

Pharmacologically induced regression of chronic transplant rejection.

Chronic rejection, characterized by a progressive obliterative arteriopathy, is a major cause of graft failure in long-surviving human transplants for which there is no effective treatment. Leflunomide, an isoxazol derivative, has been shown to be a novel immunomodulatory drug that profoundly suppresses the immune response. In this study, 58 Fisher-344 rats received cardiac transplantation from Lewis rats. All the recipients were given CsA at 2.5 mg/kg for 5 days postoperatively. Without further treatments, the arterial intima was progressively injured by mononuclear cell infiltration and Ab deposition. Smooth muscle cell and fibroblast proliferation in the intima became a predominant phenomenon by day 90. CsA was ineffective in controlling the progress of arterial intimal thickening when treatment began on day 30. Leflunomide at 5 mg/kg failed to control arterial intimal thickening by day 60 when therapy began on day 30. However, the progress of arterial intimal thickening was significantly inhibited by day 90 when the dosage of leflunomide had been increased to 10 mg/kg on day 60. Combined therapy with leflunomide and CsA at 5 mg/kg for 30 days dramatically reversed the arterial thickening by day 60. After increasing the dosages of both leflunomide and CsA to 10 mg/kg on day 60, the combination therapy steadily controlled the chronic rejection. Only the combination therapy significantly down-regulated circulating antidonor IgM and IgG titers. In rat smooth muscle cell culture, this same drug combination had a synergistic inhibitory effect on proliferation. Therefore, the combination therapy of leflunomide and CsA could reverse and control the progress of chronic rejection, while leflunomide, at higher dosage as a monotherapy, could stabilize chronic rejection in this model. The mechanism of the regression of chronic rejection by leflunomide and cyclosporine may be related to their in vitro abilities to control not only lymphocyte but smooth muscle cell proliferation, as well. The synergistic effect of these two drugs on vascular smooth muscle cell proliferation in vitro may be an important part of this novel activity. This unique feature holds intriguing possibilities for treating established chronic rejection.

Animals↗
PubMed1995

The use of granulocyte colony-stimulating factor after liver transplantation.

Granulocyte colony-stimulating factor (G-CSF) increases the number of circulating granulocytes and decreases TNF production while improving survival in sepsis models. To study the effects of G-CSF administration on sepsis and rejection, 37 primary liver allograft recipients received intravenous recombinant human G-CSF (rhG-CSF; 5-10 micrograms/kg/day) for the first 7-10 days following transplantation, targeting a blood absolute granulocyte count of between 10,000 and 20,000 cells/mm3. These recipients were monitored prospectively for sepsis and rejection, as were the previous 49 primary liver allograft recipients who did not receive G-CSF. Both groups utilized identical protocol immunosuppression and standardized diagnosis and treatment of sepsis and rejection. Univariate and logistic regression analysis of risk factors for sepsis and rejection revealed no difference between the two patient groups. G-CSF-treated patients developed an increased absolute granulocyte count over time (P < 0.0001, repeated-measures analysis of variance). G-CSF-treated patients had a decreased number of sepsis episodes per patient (0.92 +/- 1.5 vs. 2.18 +/- 2.8, P < 0.02, t test), and a lower percentage of sepsis-related deaths (8% vs. 22%, P < 0.04, chi-square test). The incidence of acute rejection was decreased in the G-CSF-treated group (22% vs. 51%, P < 0.01, chi-square test). These pilot data support further investigation into G-CSF's favorable effects on sepsis and rejection.

Analysis of Variance↗
PubMed1994

Our experience with Roux-Y intestinal drainage in simultaneous kidney and pancreas transplantation.

Enteric drainage is a sound surgical technique in SKP, and it avoids the majority of urological as well as metabolic complications. We did not see an increase in intraabdominal complications or of graft loss due to rejection. Intestinal leak is rare and easily managed provided a Roux-Y loop of jejunum is used. Even though the number of patients was small and the follow-up short, the results of the RY group were at least comparable to the BD group. In view of our results, we plan to use this technique in all our future SKP patients.

Adult↗
PubMed1994

Management of ureteral stenosis after renal transplantation.

BACKGROUND: Ureteral stenosis is the most common urologic complication of renal transplantation. Preferred management options for this complication vary among centers. Ureteral stenosis occurred in 24 (3.4 percent) of 692 consecutive renal transplants. The diagnosis was confirmed by antegrade pyelography after ultrasonography in all instances. An attempt was made to treat all patients by percutaneous stenting, usually with dilatation of the ureter, which was possible in 21 patients. In three patients, a wire could not be passed across the stricture and these patients were treated surgically. STUDY DESIGN: The patients were divided into two groups. Patients in group 1 (14 patients) presented within three months from the date of transplantation and patients in group 2 (seven patients) presented after three months. RESULTS: The site of stenosis was the ureterovesical junction in 80 percent of the patients and the uretero-pelvic junction in 20 percent. Urinary tract infection occurred in 70 percent of the patients in group 1 and 100 percent of patients in group 2. The success rate of percutaneous stenting was 71 percent (ten of 14 patients) in group 1, but only 29 percent (two of seven patients) in group 2. The failures were treated by repeated stenting (one patient in each group) or by operation. One allograft (7 percent) was lost in group 1 and two (28 percent) were lost in group 2. The average follow-up period was 38 months in group 1 and 56 months in group 2. There was no mortality in this series. CONCLUSIONS: Ureteral stenosis in the early postrenal transplant period can be safely and effectively treated by percutaneous dilatation and stenting, with few side effects and long-term success. This method is specially efficacious in patients who present within three months from the time of their transplant. In patients who have ureteric strictures developing after three months from transplantation, percutaneous stenting is of limited value and most patients require surgical correction.

Adult↗
PubMed1992

Characterization of a phagocyte cytochrome b558 91-kilodalton subunit functional domain: identification of peptide sequence and amino acids essential for activity.

The phagocyte NADPH oxidase is a multicomponent membrane-bound electron transport chain that catalyzes the reduction of O2 to superoxide. Cytochrome b558, the terminal electron donor to O2, is an integral membrane heterodimer containing 91- and 22-kDa subunits (gp91-phox and p22-phox, respectively). Synthetic peptides, whose amino acid sequences correspond to a gp91-phox carboxyl-terminal domain, inhibit superoxide production by blocking assembly of the oxidase from membrane and cytosol components. In this study, we examined the amino acid sequence requirements of a series of synthetic truncated gp91-phox peptides for inhibition of human neutrophil NADPH oxidase activation. RGVHFIF, corresponding to gp91-phox residues 559-565, was the minimum sequence capable of inhibiting superoxide generation. Contributions of individual amino acids to overall RGVHFIF inhibitory activity were determined by comparing the abilities of alanine-substituted RGVHFIF peptides to inhibit superoxide production. Substitution of alanine for arginine, valine, isoleucine, or either of the phenylalanines (but not glycine or histidine) within RGVHFIF resulted in loss of inhibitory activity. Synthetic gp91-phox carboxyl-terminal peptides are likely to be competitive inhibitors of the corresponding carboxyl-terminal domain of native gp91-phox by virtue of amino acid identity. We conclude that properties of arginine valine, isoleucine, and phenylalanine side chains within an RGVHFIF-containing domain of gp91-phox contribute significantly to cytochrome b558-mediated activation of the oxidase.

Amino Acid Sequence↗
PubMed1989

Significance of transplant perfusion index in the diagnosis of acute rejection in live related renal allograft recipients.

The study was undertaken to assess the usefulness of transplant perfusion index (TPI) in the differential diagnosis of renal allograft dysfunction with special reference to acute rejection. It was observed that the TPI has a sensitivity of 100 per cent and specificity of 98.1 per cent in the diagnosis of acute rejection. It was also observed that the serial values of TPI provided valuable clues and guide in the management of transplant dysfunction and helped in the immediate and long term follow-up of patients with renal allografts.

Adult↗
PubMedDate not supplied

Efficient gene transfer and expression in islets by an adenoviral vector that lacks all viral genes.

Although adenoviral vector-mediated gene transfer has significant potential for gene therapy, host immune responses to virally expressed proteins and small insert capacity may limit its clinical application. In order to overcome these disadvantages, a new adenoviral vector that lacks all viral genes has been developed. Using the green fluorescent (GFP) gene as a reporter gene, we investigated the efficiency of gene transfer by this all-viral-genes-deleted and minimal cis-element remaining adenoviral vector (miniAd-GFP) in islets in vitro and ex vivo, and compared it with the E1-deleted adenoviral vector (E1-GFP). One day after in vitro infection, GFP was expressed in both miniAd-GFP- and E1-GFP-infected islets. The percentage of GFP-positive single cells was not significantly different between miniAd-GFP-infected islets and E1-GFP-infected islets. When these islets were transplanted into syngeneic diabetic mice, both miniAd-GFP- and E1-GFP-infected islet grafts reversed diabetes, and normal blood glucose levels were maintained for over 20 weeks posttransplantation. Mild lymphocyte infiltration was found in all E1-GFP-infected islet grafts at all time points. However, this was not seen in most miniAd-GFP-infected islet grafts. Our results indicate that gene transfer by an adenoviral vector that lacks all viral genes is as efficient as E1-deleted adenoviral vector-mediated gene transfer in islets. Furthermore, this adenoviral vector might be less immunogeneic than the E1-deleted adenoviral vector.

Adenoviridae↗