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Biomedical subjects

S M Kang

Publications and source records attributed to S M Kang.

At least 37 records · Page 2Linked to original sources
PubMed1999

Vascular endothelial growth factor expression in preoperative biopsy specimens correlates with disease recurrence in patients with early gastric carcinoma.

BACKGROUND: Recently many studies have demonstrated that the degree of tumor angiogenesis is related to the aggressiveness of the tumor and clinical outcome. Vascular endothelial growth factor (VEGF) is a well characterized inducer of angiogenesis. In this study, the authors investigated the prognostic significance of VEGF expression in patients with early gastric carcinoma together with p53 gene abnormality and tumor cell proliferation. METHODS: One hundred ninety-five endoscopically biopsied specimens obtained preoperatively from patients with early gastric carcinoma were studied immunohistochemically. RESULTS: According to conventional clinicopathologic factors, submucosal invasion, lymph node metastases, and tumor size were associated significantly with the incidence of disease recurrence. According to conventional biologic factors, VEGF expression was observed more frequently in patients with disease recurrence compared with those without disease recurrence whereas neither p53 abnormality nor tumor cell proliferation were correlated with prognosis. Moreover, multivariate analysis indicated that VEGF expression (as well as submucosal invasion and lymph node metastases) is an independent predictor of disease recurrence. CONCLUSIONS: The results of the current study show that VEGF expression may be a useful prognostic factor for patients with early gastric carcinoma.

Adult↗
PubMed1999

Identification of a human immunodeficiency virus type 1 that stably uses tRNALys1,2 rather than tRNALys,3 for initiation of reverse transcription.

HIV-1 virions contain approximately equal amounts of tRNALys,3 and tRNALys1,2, yet tRNALys,3 has been found to be exclusively used for initiation of reverse transcription. Since previous studies have shown that even if the primer binding site (PBS) was mutated to be complementary to tRNALys1,2, the virus did not stably use tRNALys1,2 to initiate reverse transcription, the virus must have evolved a mechanism for the exclusive use of tRNALys,3 to initiate reverse transcription. To investigate how HIV-1 discriminates tRNALys1,2 from tRNALys,3 for initiation of reverse transcription, two proviral genomes that contain nucleotide changes in U5 and a PBS to be complementary to regions of tRNALys1,2 were constructed. One genome contains 5 [HXB2(L12-AC)] nucleotides while another contains 15 [HXB2(L12-ACgg)] nucleotides in U5 complementary to the anticodon region of tRNALys1,2. Viruses derived from the transfection of the proviral genomes were infectious in SupT1 cells. Analysis of the endogenous reverse transcription reactions from viruses derived from HXB2 (L12-AC) and HXB2 (L12-ACgg) obtained from transfection revealed that both exclusively used tRNALys1,2 to initiate reverse transcription. Following extensive in vitro culture, though, sequence analysis of proviral genomes revealed that while the virus derived from HXB2(L12-AC) stably maintained a PBS complementary to tRNALys1,2, the virus derived from HXB2 (L12-ACgg) had reverted back to contain a PBS complementary to tRNALys,3. RNA modeling of the U5-PBS of the genome from HXB2(L12-AC) supports the conclusion that the fine specificity for discrimination between tRNALys,3 and tRNALys1,2 for use as a primer for HIV-1 reverse transcription resides in the structure of the U5-PBS region of the viral genome.

Animals↗
PubMed1999

Generalized peritonitis with pneumoperitoneum caused by the spontaneous perforation of pyometra without malignancy: report of a case.

Spontaneous perforation is a very rare complication of pyometra. We report herein the case of an 88-year-old woman who presented with muscular rigidity and free air on abdominal X-ray films. Perforation of the gastrointestinal tract was diagnosed preoperatively, and an emergency laparotomy was performed. A total hysterectomy with bilateral salpingo-oophorectomy was carried out under the diagnosis of generalized peritonitis caused by the spontaneous perforation of pyometra. The culture of purulent fluid from the abdominal cavity showed only Escherichia coli, with no anaerobic bacteria. Histological examination revealed pyometra with necrosis of the endometrium and no evidence of malignancy. The patient was discharged on postoperative day 68 without any major complications. Pyometra is an unusual cause of peritonitis, but it must be considered as a possible diagnosis in elderly women presenting with an acute abdomen. Following this case report, we discuss the problems associated with establishing a correct preoperative diagnosis of generalized peritonitis caused by the spontaneous perforation of pyometra.

Aged↗
PubMed1999

Invasiveness of Helicobacter pylori into human gastric mucosa.

BACKGROUND: Helicobacter pylori has generally been observed only in the gastric mucous layer or in the spaces between gastric mucus-secreting cells and not in the gastric epithelial cells or in the lamina propria. The purpose of this study is to determine whether H. pylori invades the gastric mucosa, using an immunoelectron microscopical examination of human gastric mucosa infected with H. pylori. MATERIALS AND METHODS: Five hundred gastric antral biopsy specimens were fixed in a periodate-lysin-paraformaldehyde solution, embedded in Lowicryl, sectioned, and examined with a light microscope. One hundred specimens moderately or severely infected with H. pylori were selected and were incubated with polyclonal rabbit anti-H. pylori antibody. The specimens were washed, incubated with 20 nm of colloidal gold-conjugated goat anti-rabbit IgG, stained with uranyl acetate and lead citrate, and observed with a transmission electron microscope. RESULTS: In one case, a bacterium was observed within the cytoplasm of a gastric mucus-secreting cell; in another case, a few bacteria were observed within the cytoplasm of a stromal cell in the lamina propria. The bacteria could be differentiated from degenerated intracellular organelles by gold particles attached to the bacteria. CONCLUSION: H. pylori rarely invade the lamina propria and gastric cells.

Adult↗
PubMed1999

Genetic analysis of a unique human immunodeficiency virus type 1 (HIV-1) with a primer binding site complementary to tRNAMet supports a role for U5-PBS stem-loop RNA structures in initiation of HIV-1 reverse transcription.

Human immunodeficiency virus type 1 (HIV-1) exclusively uses tRNA3Lys to initiate reverse transcription. A novel HIV-1 mutant which stably utilizes tRNAMet rather than tRNA3Lys as a primer was previously identified [HXB2(Met-AC] (S.-M. Kang, Z. Zhang, and C. D. Morrow, J. Virol. 71:207-217, 1997). Comparison of RNA secondary structures of the unique sequence (U5)-primer binding site (PBS) viral RNA genome alone or complexed with tRNAMet of HXB2(Met-AC) revealed structural motifs in common with the U5-PBS of the wild-type virus. In the current study, mutations were constructed to alter the U5-PBS structure and disrupt the U5-PBS-tRNAMet interaction of the virus derived from HXB2(Met-AC). All of the mutant viruses were infectious following transfection and coculture with SupT1 cells. Analysis of the initiation of reverse transcription revealed that some of the mutants were impaired compared to HXB2(Met-AC). The genetic stability of the PBS from each virus was determined following in vitro culture. Two mutant proviral constructs, one predicted to completely disrupt the stem-loop structure in U5 and the other predicted to destabilize contact regions of U5 with tRNAMet, reverted back to contain a PBS complementary to tRNA3Lys. All other mutants maintained a PBS complementary to tRNAMet after in vitro culture, although all contained multiple nucleotide substitutions within the U5-PBS from the starting proviral clones. Most interestingly, a viral mutant containing a 32-nucleotide deletion between nucleotides 142 and 173, encompassing regions in U5 which interact with tRNAMet, maintained a PBS complementary to tRNAMet following in vitro culture. All of the proviral clones recovered from this mutant, however, contained an additional 19-nucleotide insertion in U5. RNA modeling of the U5-PBS from this mutant demonstrated that the additional mutations present in U5 following culture restored RNA structures similar to those modeled from HXB2(Met-AC). These results provide strong genetic evidence that multiple sequence and structural elements in U5 in addition to the PBS are involved in the interaction with the tRNA used for initiation of reverse transcription.

Base Sequence↗
PubMed1998

Genetic evidence of the interaction between tRNA(Lys,3) and U5 facilitating efficient initiation of reverse transcription by human immunodeficiency virus type 1.

Previous studies using in vitro chemical and enzyme methods demonstrated that, in addition to the primer-binding site (PBS), two regions upstream of the PBS in U5 of HIV-1 RNA interact with tRNA(Lys,3) during the initiation of reverse transcription. One region corresponds to nucleotides 167-172 of U5, which are complementary to the anticodon region of tRNA(Lys,3); a second region corresponds to nucleotides 142-145 of U5, which interacts with nucleotides 43-46 of tRNA(Lys,3). To study the importance of these viral RNA-tRNA interactions in reverse transcription and viral replication, we mutated the two corresponding regions in the infectious HIV-1 proviral DNA (HXB2). Changing nucleotides 167-172 from GAAAAU to CCACAA (which is complementary to the anticodon of tRNA(His)) or changing nucleotides 142-144 from CCC to GGG did not affect protein expression or production of virus from transfected proviral DNAs. Analysis of these viruses revealed that, although all were infectious, the initial replication was delayed compared with wild-type virus. Using an endogenous reverse transcription-PCR assay, we found that the initiation of the reverse transcription in the mutant viruses was less efficient than that for the wild-type virus. Analysis of the proviral DNA sequences after 2 months of in vitro culture revealed that most progeny viruses derived from the mutant that contained the CCACAA motif had acquired nucleotide substitutions within and surrounding the CCACAA nucleotides. All the viruses recovered from the mutant that originally contained the GGG nucleotides reverted back to contain the wild-type CCC sequence. The majority of the proviral clones derived from virus containing the double mutations had gained additional mutations within the CCACAA and GGG motifs. The replication of the mutant viruses was now similar to that of the wild type. The results of these studies demonstrate that interactions between the tRNA and U5 are important for generation of an optimized initiation complex required for efficient reverse transcription.

Animals↗
PubMed1998

Prediction and limitation of hepatic tumor resection without blood transfusion in cirrhotic patients.

BACKGROUND: The need for blood transfusion in cirrhotic liver resection is difficult to determine because of inaccurate estimation of operative blood loss. Moreover, blood transfusion is detrimental to cirrhotic patients. OBJECTIVE: To investigate the predictors and limitations of hepatectomy without blood transfusion for cirrhotic patients. DESIGN: Retrospective study. SETTING: University hospital, a tertiary referral center. PATIENTS: A consecutive 163 cirrhotic patients underwent resection for liver tumor(s) under a policy of restrictive blood transfusion. INTERVENTIONS: Estimated blood losses and clinicopathological features of patients who received and those who did not receive a blood transfusion were compared. MAIN OUTCOME MEASURES: Estimated operative blood losses, preoperative assessments, and operative procedures. RESULTS: There were 48 patients in the group who received a blood transfusion, with 1275 +/- 650 mL (mean +/- SE) of blood transfused, and 115 patients in the group who did not receive a blood transfusion. From discriminant analysis, the cutoff value of estimated blood loss for blood transfusion was 1685 mL. Tumor size and site of hepatectomy were found to be independent variables influencing blood transfusion under logistic regression analysis. CONCLUSIONS: Most cirrhotic patients tolerate hepatectomy without blood transfusion when the estimated operative blood loss is less than 1600 mL. Hepatectomy can be performed in cirrhotic patients without blood transfusion if the tumor is small (<5 cm), and/or the resection area is confined to Couinaud segments II, III, and VI. In this study, the largest amount of estimated blood loss in cirrhotic liver resection without blood transfusion was 2350 mL, but the uppermost limit remains to be determined.

Adult↗
PubMed1998

Preferential completion of human immunodeficiency virus type 1 proviruses initiated with tRNA3Lys rather than tRNA1,2Lys.

All retroviral genomes contain a nucleotide sequence designated as the primer binding site (PBS) which is complementary to the tRNA used for initiation of reverse transcription. For human immunodeficiency virus type 1 (HIV-1), all naturally occurring genomes have a PBS complementary to tRNA3Lys. However, within HIV-1 virions, there are approximately equal amounts of tRNA1Lys, tRNA2Lys, and tRNA3Lys. We have used an endogenous reverse transcription-PCR technique specific for the tRNA species within isolated HIV-1 virions to demonstrate that in addition to tRNA3Lys, tRNA1Lys and tRNA2Lys could be used for initiation of HIV-1 reverse transcription. Using a single-round infection assay which employed an HIV-1 genome with a gpt gene encoding xanthine-guanine phosphoribosyl transferase in place of the env gene, we generated cell lines resistant to mycophenolic acid. Analysis of the U5-PBS from single-cell clones revealed PBS complementary to tRNA3Lys, not tRNA1Lys or tRNA2Lys. A mutant HIV-1 genome was then created which would favor the completion of reverse transcription with tRNA1,2Lys. Using this provirus in the complementation system, we again found only genomes with a PBS complementary to tRNA3Lys from proviral DNA isolated from gpt-resistant single-cell colonies. Finally, infection of cells with a mutant HIV genome with a PBS complementary to tRNA1,2Lys resulted in gpt- resistant cell colonies which contained integrated provirions with a PBS complementary to tRNA1,2Lys. The results of these studies suggest that the selection of tRNA3Lys for initiation of HIV-1 reverse transcription occurs both at the initiation and at a postinitiation step in reverse transcription prior to integration of the proviral DNA.

Base Sequence↗
PubMed1998

Index of myocardial performance using Doppler-derived parameters in the evaluation of left ventricular function in patients with essential hypertension.

We analyzed Doppler echocardiographic data in 120 subjects with normal sinus rhythm; normals (NL, n = 60, ages 54.1 +/- 15.1) and essential hypertensive patients (HT, n = 60, ages 57.3 +/- 10.2). The IMP was calculated as follows: IMP = (ICT + IRT)/ET, ICT; isovolumic contraction time, IRT; isovolumic relaxation time, ET; ejection time. There were no significant differences in ejection fraction (EF), stroke volume index (SVI), cardiac index (CI), ET and ICT between NL and HT. There were, however, significant differences in deceleration time (DT), E/A ratio, IRT and the IMP between the two groups (199.5 +/- 45.6 msec vs 222.3 +/- 54.3 msec, p < 0.01; 1.4 +/- 0.7 vs 0.9 +/- 0.2, p < 0.01; 113.6 +/- 30.2 msec vs 134.2 +/- 29.6 msec, p < 0.01; 0.6 +/- 0.1 vs 0.8 +/- 0.3, p < 0.05). In HT, there were no differences in EF, SVI, CI, E/A ratio and DT between the NYHA I (Gp I, n = 36) and II (Gp II, n = 24) groups. However, ET of Gp II was significantly shorter than that of Gp I (259.4 +/- 43.5 msec vs 297.8 +/- 33.6 msec, p < 0.01). ICT, IRT and the IMP were significantly increased in Gp II, compared to those of Gp I (64.4 +/- 23.9 msec vs 89.4 +/- 46.2 msec, p < 0.05; 120.3 +/- 21.0 msec vs 155.2 +/- 28.5 msec, p < 0.001; 0.6 +/- 0.2 vs 1.0 +/- 0.4, p < 0.001). There were no differences in heart rate and mean blood pressure between Gp I and Gp II (70.9 +/- 11.4/min vs 66.3 +/- 11.4/min, p > 0.05; 138.4 +/- 21.2 mmHg vs 131.3 +/- 19.9 mmHg, p > 0.05). These data suggest that the IMP may be a useful parameter and an early indicator of left ventricular dysfunction in essential hypertensive patients with normal systolic function.

Adult↗
PubMed1998

Genetic analysis of the U5-PBS of a novel HIV-1 reveals multiple interactions between the tRNA and RNA genome required for initiation of reverse transcription.

A novel HIV-1 genome that stably utilizes tRNA(His) rather than tRNA(Lys,3) to initiate reverse transcription was used to study features for the interaction between the tRNA and viral RNA genome. In addition to a primer binding site (PBS) complementary to tRNA(His), this virus contains a six-nucleotide sequence in U5 complementary to the anticodon-loop of tRNA(His) and three additional substitutions: U174-to-G, G181-to-A, and U200-to-C [HXB2(His-AC-GAC)]. Mutations in these three nucleotides resulted in viruses with three different genotypes: one group maintained a PBS complementary to tRNA(His) with restored G174A181C200 or G174A181U200 configurations, one group reverted to a PBS complementary to tRNA(Lys,3), and one group contained two or more PBSs complementary to different tRNAs on the same viral genome. Characterization of a previously identified virus with additional C152-to-A and C160-to-U substitutions [HXB2(His-AC-A152U160-GAC)] revealed that this virus maintained a PBS complementary to tRNA(His), whereas a mutant HXB2(His-AC-U152A160-GAC) reverted after culture to contain dual PBS complementary to tRNA(Lys,3) and tRNA(His), respectively. Our results demonstrate that regions in U5 act in concert with the PBS to promote use of the tRNA primer for initiation of reverse transcription. These results are discussed with respect to structural models for the U5-PBS interactions with tRNA.

Anticodon↗
PubMed1997

Insights into the interaction between tRNA and primer binding site from characterization of a unique HIV-1 virus which stably maintains dual PBS complementary to tRNA(Gly) and tRNA(His).

Previously our laboratory constructed an HIV-1 which stably maintained a primer binding site (PBS) complementary to tRNA(His) by mutating the region of the provirus within U5 postulated to interact with the anticodon of tRNA(His) (J. Wakefield, S-M Kang, and C. D. Morrow, 1996, J. Virol, 70, 966-975). From the analysis of the virus obtained after long-term culture, we identified an unusual proviral DNA in which the U5-PBS region contained a dual PBS complementary to tRNA(Gly) and tRNA(His), respectively, separated by a 21-nucleotide intervening sequence. To determine if this U5-PBS region containing the dual PBS would give rise to an infectious virus, the mutant U5-PBS containing the dual PBS was subcloned into an infectious HIV-1 proviral clone, pHXB2; the resultant proviral DNA was designated as pHXB2(Gly-His). Transfection of pHXB2(Gly-His) into cells gave rise to infectious virus. Analysis of the U5-PBS region revealed that the virus stably maintained the dual PBS rather than revert back to the wild-type PBS. In addition to genomes with the PBS complementary to tRNA(Gly) and tRNA(His), proviral genomes were identified after extended in vitro culture which contained dual PBS complementary to tRNA(Gly) and tRNA(Phe). To determine which PBS could be used for reverse transcription, we utilized an endogenous reverse transcription/PCR method which could discriminate (based on molecular size of the products) between the minus strand DNA initiated from the two PBSs. The results of this assay demonstrated that either the PBS complementary to tRNA(Gly) or tRNA(His) could be used for the initiation of reverse transcription. The results of our study highlight the complex interrelationship between U5-PBS and primer tRNA required for positioning the tRNA at the PBS and provides new insights into how the tRNA primer used to initiate reverse transcription is selected.

Animals↗
PubMed1997

Combined analysis of p53 and vascular endothelial growth factor expression in colorectal carcinoma for determination of tumor vascularity and liver metastasis.

Recent studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. We examined the expression of p53 and vascular endothelial growth factor (VEGF), a well-characterized angiogenic inducer, together with microvessel density to investigate the role of p53 in the regulation of angiogenesis and its clinical significance in human colorectal carcinoma. Surgically resected specimens of 163 colorectal carcinomas were studied by immunohistochemical staining for p53 protein, VEGF and factor VIII-related antigen. Positive p53 protein accumulation and VEGF expression was found in 41.7% and 49.1% of tumors, respectively. p53 and VEGF staining status was identical in 65.6% of tumors. The incidence of p53- or VEGF-positive tumors was significantly higher in patients with venous invasion and liver metastases than in those without. The microvessel count (MVC) in p53- or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53- and VEGF-positive tumors was significantly higher than that in the other subgroups. Neither synchronous nor metachronous hepatic metastases were found in patients with p53- and VEGF-negative tumors, while 52.2% of patients with both-positive tumors had liver metastases and had a poorer prognosis than those with both-negative tumors. Our findings suggest the presence of a p53-VEGF pathway regulating tumor angiogenesis in human colorectal carcinoma. Combined analysis of p53 and VEGF expression might be useful for predicting the occurrence of liver metastasis in patients with this disease.

Adult↗
PubMed1997

Combined analysis of vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression in gastric carcinoma.

Solid tumours require neovascularization for growth and metastasis. Both vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) are well-characterized inducers of angiogenesis. In this study we examined the expressions of these antigens and their relationship with microvessel density and also determined their prognostic significance. Ninety-five specimens resected from patients with gastric carcinoma were investigated using immunohistochemical methods. Microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in tumours that were both VEGF+ and PD-ECGF+ than in tumours that were both VEGF- and PD-ECGF-. According to prognosis, patients with VEGF+ tumours had a significantly worse prognosis than did those with VEGF- tumours. Although there was no significant correlation between PD-ECGF expression and prognosis, patients with PD-ECGF+ tumours tended to have a shorter survival than did those with PD-ECGF- tumours. Moreover, the frequency of hepatic recurrence was significantly higher in patients with tumours that were both VEGF-positive and PD-ECGF+ than in all other patients.

Adult↗
PubMed1997

Overexpression of cyclin D1 and p53 associated with disease recurrence in colorectal adenocarcinoma.

Multiple genetic changes occur during the evolution of normal cells into cancer cells. It has been reported that both cyclin D1 and p53 genes play major roles in oncogenesis and/or cell cycle control in various cancers. In this study, we examined the overexpression of cyclin D1 and p53 by the immunohistochemical method and investigated the correlation between expression of these antigen and prognosis in patients with colorectal adenocarcinoma. Disease-free survival was significantly lower in the patients with cyclin D1-strongly positive tumors than in those with cyclin D1-negative tumors. Similarly, disease-free survival of the patients with p53-strongly positive tumors was significantly lower than that of those with p53-negative tumors. Moreover, multivariate analysis indicated that both cyclin D1 and p53 overexpression are independent prognostic factors in patients with colorectal adenocarcinoma. In conclusion, both cyclin D1 and p53 overexpression may be useful predictors of disease recurrence in patients with colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Stability of HIV type 1 proviral genomes that contain two distinct primer-binding sites.

The initiation of human immunodeficiency virus type 1 (HIV-1) reverse transcription occurs by the extension of a tRNALys,3 positioned at an 18-nucleotide sequence in the RNA genome referred to as the primer-binding site (PBS). We have found that mutations within the PBS and a region upstream in U5, designated the A loop, influenced the selection of the tRNA primer used to initiate reverse transcription. Surprisingly, a proviral genome that contained a PBS and A loop complementary to tRNAPro resulted in the generation of viruses that contained two PBSs within the same genome: one of the PBSs in the virus was complementary to tRNALys,3 while the second PBS was complementary to tRNAIle, tRNAPro, or tRNALys,3. There were 14 nucleotides separating the two PBSs in the viral genome. In the current study, DNA encompassing U5 and the dual PBS complementary to the different tRNAs were amplified by PCR and exchanged for the corresponding region in an infectious HIV-1 clone, HXB2. Transfection of the different proviruses into cells resulted in the production of viruses that were infectious as determined by coculture with SupT1 cells. PCR was used to amplify the PBS regions from the different proviral DNAs followed by DNA sequencing of individual PCR clones. Proviruses containing the dual PBS complementary to tRNALys,3 and tRNAIle stably maintained the dual PBS complementary to both of these tRNAs following in vitro culture, although we noted consistent G-to-T and AA-to-GG substitutions in the 14-nucleotide region between the PBSs. The viruses derived from genomes that contained the dual PBS complementary to tRNALys,3 and tRNAPro also maintained both PBSs following in vitro culture; a single mutation was noted after in vitro culture in the 14-nucleotide region between the PBSs, which changed a consensus integration site (CA dinucleotide) prior to the PBS complementary to tRNAPro. In contrast, the proviral genomes containing the dual PBS complementary to tRNALys,3 were not stable and reverted back to a single PBS complementary to tRNALys,3. The results of our studies suggest that only the 5'-proximal PBS has been used to initiate reverse transcription. On the basis of our results, a mechanism is proposed for the generation of a dual PBS, which provides new insights into HIV-1 reverse transcription.

Animals↗
PubMed1997

Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction.

Fas ligand is believed to mediate immune privilege in a variety of tissues, including the eye, testis, and a subset of tumors. We tested whether expression of Fas ligand on pancreatic islets either following adenoviral or germline gene transfer could confer immune privilege after transplantation. Islets were infected with an adenoviral vector containing the murine Fas ligand cDNA (AdFasL), and were transplanted into allogenic diabetic hosts. Paradoxically, AdFasL-infected islets underwent accelerated neutrophilic rejection. The rejection was T cell and B cell independent and required Fas protein expression by host cells, but not on islets. Similarly, transgenic mice expressing Fas ligand in pancreatic beta cells developed massive neutrophilic infiltrates and diabetes at a young age. Thus, Fas ligand expression on pancreatic islets results in neutrophilic infiltration and islet destruction. These results have important implications for the development of Fas ligand-based immunotherapies.

Adenoviridae↗