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Biomedical subjects

S Shenoy

Publications and source records attributed to S Shenoy.

At least 55 records · Page 3Linked to original sources
PubMed1998

T gamma/delta hepatosplenic lymphoma in a heart transplant patient after an Epstein-Barr virus positive lymphoproliferative disorder: a case report.

BACKGROUND: An unusual case of a peripheral T-cell lymphoma of T gamma/delta hepatosplenic type (Tgamma/deltaHSL) that arose in a child 5 years after she received a heart transplant and 9 months after she developed Epstein-Barr virus (EBV) positive, B-cell lymphoid hyperplasia involving the tonsils is presented. The majority of the reported cases of Tgamma/deltaHSL have been described in young adult men without antecedent immunodeficiency; several well documented cases of Tgamma/deltaHSL in the posttransplant setting have been described previously, but none has been described in a child (or an adult) with a previously diagnosed EBV+ B-cell lymphoid hyperplasia. METHODS: Standard histologic, immunohistochemical, flow cytometric, and molecular genetic techniques were used in the evaluation of diagnostic material. RESULTS: The patient's Tgamma/deltaHSL involved the spleen in a predominantly cordal pattern, and infiltrated the liver in an exclusively sinusoidal distribution. Bone marrow involvement was focal and interstitial. In all locations, malignant cells were of intermediate or large size and had oval nuclei with coarse chromatin, with a scant or moderate amount of eosinophilic cytoplasm. This Tgamma/deltaHSL expressed the characteristic CD2+, CD3+, [CD4- CD8-], Tdelta1+ phenotype, and malignant cells also expressed the natural killer cell marker CD56. Cytogenetic studies demonstrated isochromosome 7q with the addition of trisomy 8 as the tumor progressed. Southern blot analysis demonstrated clonal rearrangements of the gamma, delta, and beta loci of the T-cell receptor but did not identify EBV DNA within the tumor cells. CONCLUSIONS: This case highlights the fact that a full range of lymphoid proliferations is possible in the posttransplantation period, and that a prior diagnosis of a B-cell disorder does not preclude the development of a subsequent T-cell posttransplant lymphoproliferative disorder (PTLD), which should be formally evaluated, especially if clinical circumstances appear atypical for a PTLD of the "usual" (EBV-related, B-cell) type.

Antigens, CD↗
PubMed1998

Analysis of graft-versus-host disease (GVHD) and graft rejection using MHC class I-deficient mice.

GVHD is a major complication in allogeneic bone marrow transplantation (BMT). MHC class I mismatching increases GVHD, but in MHC-matched BMT minor histocompatibility antigens (mH) presented by MHC class I result in significant GVHD. To examine the modification of GVHD in the absence of cell surface MHC class I molecules, beta2-microglobulin-deficient mice (beta2m(-/-)) were used as allogeneic BMT recipients in MHC- and mH-mismatched transplants. Beta2m(-/-) mice accepted MHC class I-expressing BM grafts and developed significant GVHD. MHC (H-2)-mismatched recipients developed acute lethal GVHD. In contrast, animals transplanted across mH barriers developed indolent chronic disease that was eventually fatal. Engrafted splenic T cells in all beta2m(-/-) recipients were predominantly CD3+alphabetaTCR+CD4+ cells (15-20% of all splenocytes). In contrast, CD8+ cells engrafted in very small numbers (1-5%) irrespective of the degree of MHC mismatching. T cells proliferated against recipient strain antigens and recognized recipient strain targets in cytolytic assays. Cytolysis was blocked by anti-MHC class II but not anti-CD8 or anti-MHC class I monoclonal antibodies (MoAbs). Cytolytic CD4+ T cells induced and maintained GVHD in mH-mismatched beta2m(-/-) mice, supporting endogenous mH presentation solely by MHC class II. Conversely, haematopoietic beta2m(-/-) cells were unable to engraft in normal MHC-matched recipients, presumably due to natural killer (NK)-mediated rejection of class I-negative cells. Donor-derived lymphokine-activated killer cells (LAK) were unable to overcome graft rejection (GR) and support engraftment.

Animals↗
PubMed1998

Giardiasis in the adult population of Dakshina Kannada district of south India.

A 10-year study of Giardia intestinalis infections in adults was conducted in the Dakshina Kannada District of Karnataka State, South India. Coproparasitological investigations were made on 10,000 stool specimens collected from selected patients. The infection rate was 37.1% with a male disease rate of 91.4%. The highest incidence rate was recorded in the age group 15-26 years. A possible reason for this preponderance of giardiasis in these males, is discussed. The optimum time for transmission appeared to be during the warmer months of the year (May to October) which coincided with the greatest amount of rainfall. The most common symptoms were abdominal discomfort, flatulence, diarrhoea, weight loss and anorexia. The predominating symptoms in our series varied with socio-economic level. There appeared to be some correlation between the clinical manifestations and the immune status of the individual.

Adolescent↗
PubMed1997

Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients.

BACKGROUND: Treatment with prophylactic oral acyclovir, intravenous ganciclovir, or immunoglobulins to prevent cytomegalovirus (CMV) infection and disease in renal transplantation is associated with variable efficacy and significant expense. We studied control of CMV in renal transplant recipients using either prophylactic oral ganciclovir or deferred therapy with intensive monitoring with polymerase chain reaction (PCR) analysis. METHODS: Forty-two recipients were followed for 6 months after transplantation. Ganciclovir (1000 mg p.o. t.i.d.; n=19) or acyclovir (200 mg p.o. b.i.d.; n=23) was begun at transplantation and continued for 12 weeks. PCR for CMV was performed on buffy-coat specimens every week for 15 weeks and at months 5 and 6. RESULTS: No patients in the ganciclovir group, compared with 14 of 23 patients (61%) in the deferred-therapy group (P<0.0001), developed CMV disease during the first 12 weeks. In the ganciclovir group, 4 of 19 patients (21%) subsequently experienced 5 episodes, whereas 14 patients in the deferred-therapy group experienced 18 episodes (P=0.013 for subjects and P=0.026 for episodes). The time to disease was also delayed in the ganciclovir group compared with the deferred-therapy group (133+/-17 days vs. 51+/-7 days; P<0.0001). Oral ganciclovir also prevented CMV viremia during prophylaxis (2/19 patients [11%] vs. 23/23 patients [100%]). Time to CMV viremia was delayed in the ganciclovir group; however, 13/19 patients (68%) ultimately showed PCR evidence for CMV viremia (P=0.005). CONCLUSIONS: An initial 12-week course of oral ganciclovir prevents CMV disease and infection in renal transplant recipients during prophylaxis, and the benefits persist after discontinuation.

Administration, Oral↗
PubMed1997

Peripheral blood microchimerism in human liver and renal transplant recipients: rejection despite donor-specific chimerism.

BACKGROUND: Development of donor-specific microchimerism (DSM) has been proposed as one of the possible mechanisms for induction and maintenance of allograft tolerance. The aim of this study was to determine: (1) the state of DSM in liver transplant (LTx) and renal transplant (RTx) recipients, (2) whether the persistent presence of an allograft is a requirement for maintenance of chimerism, and (3) whether donor-specific blood transfusions (DST) facilitate chimerism development in RTx recipients and whether this correlates with allograft function. METHODS: Qualitative and quantitative analysis of DSM in peripheral blood of LTx and RTx recipients was assessed by polymerase chain reaction and competitive polymerase chain reaction using HLA-DR probes for mismatched antigens between the donor and recipient. RESULTS: LTx recipients (11 of 12) who had or were having rejection were positive for DSM in circulation compared with 4 of 11 with normal allograft function (P<0.01). The number of donor cells did not correlate with allograft function. LTx recipients (4 of 4) who lost their first allograft and underwent retransplantation retained DSM for the first donors. RTx recipients who received DST (8 of 8) were positive for DSM compared with 6 of 12 of nontransfused recipients (P<0.045). CONCLUSIONS: The results suggest that LTx and RTx recipients undergo rejection despite DSM. The development of DSM may not be a prerequisite for normal allograft function. Once DSM is established, the presence of the allograft is not required for maintenance of chimerism. DST facilitated the development of DSM in RTx recipients. Direct correlation was not observed between the development of DSM and allograft function in either DST or nontransfused RTx recipients.

Alleles↗
PubMed1997

Functional analysis of the fission yeast Prp4 protein kinase involved in pre-mRNA splicing and isolation of a putative mammalian homologue.

The prp4 gene of Schizosaccharomyces pombe encodes a protein kinase. A physiological substrate is not yet known. A mutational analysis of prp4 revealed that the protein consists of a short N-terminal domain, containing several essential motifs, which is followed by the kinase catalytic domain comprising the C-terminus of the protein. Overexpression of N-terminal mutations disturbs mitosis and produces elongated cells, Using a PCR approach, we isolated a putative homologue of Prp4 from human and mouse cells. The mammalian kinase domain is 53% identical to the kinase domain of Prp4. The short N-terminal domains share <20% identical amino acids, but contain conserved motifs. A fusion protein consisting of the N-terminal region from S. pombe followed by the mammalian kinase domain complements a temperature-sensitive prp4 mutation of S. pombe. Prp4 and the recombinant yeast/mouse protein kinase phosphorylate the human SR splicing factor ASF/SF2 in vitro in its RS domain.

Amino Acid Sequence↗
PubMed1997

Quantitative digital analysis of diffuse and concentrated nuclear distributions of nascent transcripts, SC35 and poly(A).

Digital imaging microscopy was used to analyze the spatial distribution and levels of newly synthesized RNA in relation to steady-state poly(A) RNA and to the splicing factor SC35. Transcription was monitored over time after microinjection of BrUTP and was detected using antibodies. Poly(A) RNA was detected with probes directly conjugated to fluorochromes, allowing direct detection of the hybrids. Objective methods were used to determine genuine signal. A defined threshold level to separate signal from noise was established for each nucleus. The nucleolus was used to determine poly(A) and SC35 background and the juxtanuclear cytoplasm was used for the BrUTP background. The remaining signal was segmented into high (concentrated) and low (diffuse) levels. Surprisingly, for all probes examined, most of the signal was not in concentrated areas, but rather was diffusely spread throughout the nucleoplasm. A minority (20-30%) of the SC35 signal was in concentrated areas ("speckles") and the rest was dispersed throughout the nucleoplasm. In addition, the concentrated areas had a mean intensity only twice the average. The amount and significance of the colocalization of the diffuse, or concentrated, areas of SC35 [or poly(A)] with BrUTP incorporation were analyzed. The image from one probe was translated with respect to the other in three dimensions to compare colocalization with random alignments. Both poly(A) and SC35 were found to have low colocalization with the total BrU signal. Sites of transcription were determined using an algorithm to find maxima of BrUTP signal within clusters. From 849 to as many as 3888 sites per nucleus were detected. A rim of hybridization to poly(A) coinciding with the nuclear envelope was eliminated by actinomycin treatment, suggesting that these transcripts were exiting from the nucleus. These results emphasize the importance of utilizing the full dynamic range of the image before drawing conclusions as to the distribution of nuclear components.

Algorithms↗
PubMed1997

Evidence of a role for matrix metalloproteinases in cold preservation injury of the liver in humans and in the rat.

Previous studies have determined that proteases are important in cold preservation injury to the liver. The purpose of this study was to determine the role of matrix metalloproteinases (MMPs) in cold preservation injury. Effluents were collected from rat livers after various periods of preservation either in Eurocollins solution or in University of Wisconsin (UW) solution. Effluents were also collected from 17 human donor livers stored in UW solution. To determine whether sinusoidal endothelial cells released MMPs when placed in the cold, these cells were isolated from rat livers and cultured at 4 degrees C. Gelatin zymography, quantitative assay of gelatinolytic activity, immunoprecipitation, and Western blotting were used to identify metalloproteinases and to measure their activity. Human and rat liver effluents contained gelatin-digesting bands on zymography. Their appearance was inhibited by specific metalloproteinase inhibitors and also by lactobionate, the major ingredient of UW solution. The most prominent bands in humans and the rat appeared at approximately 72 kd and 92 kd, suggesting that they were the MMPs 72-kd gelatinase and 92-kd gelatinase. Supernatants of isolated rat sinusoidal endothelial cells stored in the cold contained similar bands. In the rat, the proteinases were present in both latent and active forms, but, in humans, predominately the latent form was seen. In humans, there were four prominent bands in the gelatin zymography. By immunoprecipitation, two of the bands were identified as the 92-kd gelatinase and a dimer or polymer of 92-kd gelatinase. Using Western blotting with a monoclonal antibody, a third band was identified as 72-kd gelatinase. In quantitative terms, gelatinolytic activity increased with time of cold storage in humans and in the rat. In the rat, gelatinolytic activity was greater when Eurocollins was the preservative than when UW solution was used. Taken together, these results indicate an important role for MMPs in the injury produced by cold preservation of the liver.

Adenosine↗
PubMed1997

Renal allograft infiltrating lymphocytes: frequency of tissue specific lymphocytes.

Acute rejection, mediated by T lymphocytes recognizing donor MHC class I and II, is a major factor influencing renal transplant survival. To define the specificity of these effector cells we examined cytolytic activity of graft infiltrating T lymphocytes (GIL) from renal biopsies of individuals undergoing acute cellular rejection. The majority of these cells recognized MHC class I on both donor kidney epithelial cells (KCL) and B-lymphoblastoid cells (LCL) suggesting these T cells recognized peptides from various tissues. However, cold target inhibition experiments demonstrated a significant proportion of GIL T cells were tissue specific. We reported previously that kidney specific CTL can be isolated from biopsies of kidney allografts undergoing acute cellular rejection. Here we extend that observation showing we were able to isolate tissue specific CTL from two additional biopsies. Greater than 10% of the clones isolated (4 of 36 and 5 of 37) from these biopsies were CTL recognizing donor KCL but not LCL targets suggesting that peptides, recognized in the context of donor MHC, were tissue specific. Repeated isolation of significant numbers of tissue specific CTL suggests these T cells play a role in allograft rejection and may be important effector cells mediating rejection in HLA matched transplants.

Adult↗
PubMed1997

Liver transplantation after jejunoileal bypass for morbid obesity.

BACKGROUND: Jejunoileal (JI) bypass was developed as a therapy for morbid obesity in the late 1960s but has since been abandoned because of a high rate of complications, including cirrhosis. The need for liver transplantation after JI bypass has been infrequent, with only four previous patients reported in the literature; however, because the time to develop symptomatic end-stage liver disease after JI bypass may be quite long (25 years or more), the incidence of patients who will require liver transplantation may only now be increasing. STUDY DESIGN: We reviewed our experience with JI bypass and liver transplantation in 380 consecutive adult patients since 1985. RESULTS: Four patients underwent liver transplantation for cirrhosis after JI bypass, all within the last 48 months. The mean duration of time from JI bypass to transplantation was 22.3 years. All patients had complications, in addition to their liver disease, which were related to the JI bypass, which included nephrolithiasis, cholelithiasis, vitamin deficiencies, renal insufficiency, and d-lactic acidosis. One patient had the JI bypass taken down before transplantation, which precipitated acute liver and renal failure, necessitating urgent transplantation. One patient, who had the JI bypass taken down at the time of transplant, has developed recurrent morbid obesity, while the other three patients have not. The one patient who has not had the JI bypass taken down has not developed evidence of recurrent liver disease and is followed with monthly liver function tests and yearly biopsies. CONCLUSIONS: The incidence of patients who require liver transplantation after JI bypass may be on the increase. Take down of the JI bypass may precipitate acute liver failure in the cirrhotic patient. JI bypass should be accomplished either at the time of transplantation or if signs of liver dysfunction occur after transplantation. Liver transplant recipients can be at risk for recurrent obesity after takedown of the JI bypass. Transplantation for those patients with decompensated cirrhosis after JI bypass has demonstrated excellent early results.

Aged↗
PubMed1997

Upper extremity central venous obstruction in hemodialysis patients: treatment with Wallstents.

PURPOSE: To determine the effectiveness of using Wallstents to treat subclavian or brachiocephalic venous obstruction after unsuccessful angioplasty, in patients undergoing hemodialysis. MATERIALS AND METHODS: Dialysis records, radiology reports, and procedural images of 20 hemodialysis patients who underwent Wallstent insertion into a subclavian (n = 11) or brachiocephalic (n = 9) vein were reviewed. Technical success and primary, assisted primary, and cumulative patency rates were calculated. RESULTS: Twenty-three Wallstents were inserted for stenosis (n = 18) or occlusion (n = 2). Technical success was 100%. Eight patients underwent 11 reinterventions to maintain patency of the Wallstent during the follow-up period. Patency rates of the Wallstent were (a) primary at 1 month, 3 months, 6 months, and 1 year: 90%, 67%, 42%, and 25%; (b) assisted primary at 3 months, 6 months, and 1 year: 88%, 62%, and 47%; and (c) cumulative at 3 months, 6 months, 1 year, and 2 years: 89%, 64%, 56%, and 22%. Considerable shortening of the stent occurred in five patients. One occurred immediately during the deployment procedure, but four were discovered weeks to months later. No other complications occurred. CONCLUSION: After suboptimal angioplasty, treatment of subclavian and brachiocephalic vein stenoses with a Wallstent can provide continued use of a hemodialysis access. Close clinical surveillance and multiple reinterventions are necessary to maintain Wallstent patency.

Angioplasty↗
PubMed1997

Control of cytomegalovirus-associated morbidity in renal transplant patients using intensive monitoring and either preemptive or deferred therapy.

The objective of this randomized, prospective study was to compare preemptive to deferred treatment of cytomegalovirus (CMV) infection in high-risk renal transplant recipients. Conducted at a university-affiliated transplant center, the study included 36 renal allograft recipients with donor or recipient CMV-seropositivity who received anti-thymocyte induction therapy. Ganciclovir was administered intravenously for 21 days upon detection of CMV viremia (preemptive, N = 15) or detection of CMV viremia associated with a CMV syndrome (deferred, N = 21). Shell vial culture, conventional culture, and polymerase chain reaction (PCR) were performed upon buffy-coat specimens weekly for 12 to 16 wk. CMV and non-CMV-associated charges were calculated. The comparative sensitivities of PCR, shell vial culture, and conventional culture were 91%, 44%, and 47%, respectively. A delay in specimen processing of > 24 h severely compromised the sensitivity of culture techniques but not that of PCR. Preemptive therapy tended to decrease symptomatic CMV episodes (0.4 versus 0.6 episodes per patient randomized; P = 0.22). One patient in each group had organ involvement, and no patient died. Allograft function and survival were similar. Ganciclovir use was increased in the preemptive group (1.2 versus 0.6 courses per patient randomized; P = 0.02). CMV-associated charges were $10,368 (preemptive) versus $5,752 (deferred); P = 0.13. PCR is superior to conventional monitoring to detect CMV viremia. Culture cannot be considered the "gold standard" for detection of CMV viremia, especially when transport of specimens over distances results in processing delays. Preemptive therapy may reduce symptomatic CMV infections in renal transplant recipients. It was associated with higher CMV-related charges but equivalent overall charges versus deferred treatment with intensive monitoring. Either strategy can achieve control of CMV infection after renal transplantation.

Adult↗
PubMed1997

A pharmacoeconomic comparison of antithymocyte globulin and muromonab CD3 induction therapy in renal transplant recipients.

Antithymocyte globulin (ATG) and muromonab CD3 (OKT3) are currently the only antilymphocyte preparations that are commercially available for induction immunosuppressive therapy for renal allograft transplantation in the US. ATG, in the usually prescribed doses, is more expensive than muromonab CD3, but muromonab CD3 is associated with more severe adverse effects that may affect clinical outcome and overall cost. We performed a retrospective study of all adult recipients of a first cadaveric renal allograft, who underwent transplantation between January 1991 and December 1994 who received either ATG (n = 92) or muromonab CD3 (n = 91) for induction therapy at our transplant centre. The average age of recipients was older (50 vs 44 yrs; p = 0.001) and extended donors were more commonly used in the ATG group (41 vs 13%; p = 0.0001) compared with the muromonab CD3 group. Nevertheless, at 1 year post-transplant, the incidence of rejection was lower (34 vs 47%) and graft survival was better (93 vs 85%; p = 0.03) in the ATG group. Patients who received ATG were discharged earlier (9.4 vs 13.3 days; p = 0.0001) and had similar serum creatinine levels on the day of discharge (2.4 +/- 1.5 vs 2.1 +/- 1.1 mg/dl; p = 0.25). Overall, the 1-year hospitalisation costs of transplantation and readmissions were similar [$US39,937 +/- 17,014 vs $US42,850 +/- 20,923 (currency year 1994); p = 0.22]. This is the first comparison of ATG and muromonab CD3 in renal transplant recipients to consider clinical as well as economic outcomes. For renal transplant patients in whom induction therapy is used at our centre, the initial expense of ATG can be justified by improved graft survival, fewer rejection episodes, and shorter hospital stays, which are associated with similar overall transplantation costs.

Adult↗
PubMed1997

Allograft infiltrating cytotoxic T lymphocytes recognize kidney-specific human minor histocompatibility antigens.

The role of minor histocompatibility antigens (mH) in allograft immunity has been proposed, but the nature of these antigens and their immunogenicity are not well understood. We have shown that tissue-specific cytolytic T lymphocytes (CTL) can be isolated form graft infiltrating lymphocyte (GIL) populations from renal transplant recipients undergoing acute cellular rejection. In most cases these CTL were allorestricted recognizing donor mismatched kidney MHC class I antigens. In contrast, one patient's GIL T cells demonstrated specific lytic activity against HLA-B35 expressed on primary kidney epithelial cell lines (KCL) but not on B-lymphoblastoid cell lines (LCL). Since HLA-B35 was a shared antigen between donor and recipient, these results suggest that CTL within the GIL population are recognizing a tissue-specific minor histocompatibility antigen presented in the context of self-HLA-B35.

Acute Disease↗
PubMed1996

Biochemical and immunological evaluation of donor-specific soluble HLA in the circulation of liver transplant recipients.

MHC antigens, normally expressed as integral membrane proteins, are also present in soluble form in the peripheral circulation. These soluble human leukocyte antigens (sHLA) are found at elevated levels in patients with a variety of infections as well as in organ transplant recipients. In liver transplant recipients, however, most of the circulating sHLA are of donor phenotype, especially during the early posttransplant period. Here we report the purification and characterization of sHLA of both recipient and donor origin from liver transplant recipients. It was observed that sHLA consisted of four major polypeptides having molecular mass of 44, 41, 35-37, and 12 kD complexed with IgM and IgG antibodies. Further analysis revealed that these immunoglobulins contained anti-HLA antibodies. Analysis of the affinity-purified materials by a number of approaches failed to detect any other fragment(s) of HLA class I heavy chain polypeptides smaller than 12 kD. No significant difference was observed in the biochemical nature of the sHLA of donor and recipient origin and they were similar to those found in normal individuals. Affinity-purified HLA-A3 inhibited the cytolytic activity of an HLA-A3-specific CD8+ T cell line, whereas, purified sHLA-A2 failed to inhibit anti-HLA-A3 CTL activity. Further, the proliferation of the T cell line was not inhibited by sHLA-A3. Thus, the inhibitory activity shown by sHLA was antigen-specific and directed against a functional subset of T lymphocytes. These results support the notion that sHLA may play an important regulatory role in the immune response to allograft in humans.

Adult↗