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Biomedical subjects

K R Reddy

Publications and source records attributed to K R Reddy.

At least 109 records · Page 6Linked to original sources

Antimitochondrial antibodies in kindreds of patients with primary biliary cirrhosis: antimitochondrial antibodies are unique to clinical disease and are absent in asymptomatic family members.

The 2-oxo-acid dehydrogenase family of enzymes have been identified as the major mitochondrial autoantigens of primary biliary cirrhosis. Using immunoblotting, enzyme-linked immunosorbent assay and enzyme inhibition with both purified mitochondrial proteins and recombinant autoantigens, we have studied family members and spouses of patients with primary biliary cirrhosis for the presence of antimitochondrial antibodies. Antimitochondrial antibodies and other common autoantigens were also tested for by indirect immunofluorescence. This study included 27 index patients with primary biliary cirrhosis, 15 spouses and 48 first- and second-degree relatives. Overall, 7 relatives (11%) were positive for autoantibodies to nuclear and cytoplasmic antigens by indirect immunofluorescence against mouse liver and stomach sections. However, with immunofluorescence, the reactivity strictly paralleled that of antimitochondrial antibodies in only one of these (1:640)--a sibling with mild pruritus and a liver biopsy specimen diagnostic of primary biliary cirrhosis despite normal levels of serum alkaline phosphatase. In addition, one of the mothers, who had a history of sarcoidosis, was positive by immunoblotting for antibodies to the E2 subunit of the pyruvate dehydrogenase complex and protein X. All other relatives were negative for all of the assays. Antibodies to neither the 2-oxo-acid dehydrogenase enzymes nor the recently proposed family of naturally occurring mitochondrial antibodies were found in spouses or healthy relatives. Three other first-degree relatives suffered from liver disease: two died (one from primary biliary cirrhosis and the other from an unknown type of liver disease) and one (a sibling with primary biliary cirrhosis) was unavailable for testing. Our results are consistent with a familial predisposition to primary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Effects of Pasteurella haemolytica A1 leukotoxin on bovine neutrophils: degranulation and generation of oxygen-derived free radicals.

To further define the role of Pasteurella haemolytica A1 leukotoxin in the pathogenesis of bovine pneumonic pasteurellosis, its in vitro effects on bovine neutrophils were investigated. Leukotoxin-containing culture supernatant, from P. haemolytica, stimulated a neutrophil respiratory burst as measured by the generation of oxygen-derived free radicals O2- and H2O2. This effect was immediate because preincubation of neutrophils with the culture supernatant for 5 min or longer substantially suppressed this respiratory burst. This suppression was due to cytolysis of the neutrophils. Prolonged incubation of neutrophils with the same culture supernatant caused further cytolysis and degranulation. Heat-inactivated P. haemolytica culture supernatant that had lost its cytotoxic properties failed to stimulate respiratory burst by neutrophils. Furthermore, the respiratory burst, cytolysis and degranulation were abrogated only by leukotoxin-neutralizing monoclonal and polyclonal antibodies, but not by antibodies against the lipopolysaccharide. These studies show that the leukotoxin component in the culture supernatant was responsible for the generation of oxygen-derived free radicals and proteolytic enzymes from neutrophils which may participate in direct lung injury.

Animals↗

Ancient remedies revisited: does Allium sativum (garlic) palliate the hepatopulmonary syndrome?

Hypoxia in the setting of liver disease is often multifactorial. Obstructive or restrictive lung disease, pleural effusions, and tense ascites are common underlying disorders. Less often observed and frequently unrecognized is hypoxia related to diffuse intrapulmonary shunting--the hepatopulmonary syndrome. Its etiology is unknown but may result from disordered gut peptide metabolism. Symptoms may be ameliorated by somatostatin and reversed by successful liver transplantation. Here we report a patient with severe hepatopulmonary syndrome who failed somatostatin therapy and declined liver transplantation. On her own the patient took large daily doses of powdered garlic (Allium sativum). She has experienced partial palliation of her symptoms and some objective signs of improvement over 18 months of continuous self-medication. The possible effects of garlic's main physiologically active compound, allicin, on gut peptide metabolism and pulmonary vasculature are unknown. This innocuous compound may deserve further investigation given the limited therapeutic options for this disorder.

Arteriovenous Fistula↗

Immunophenotyping of lymphocytes in liver tissue of patients with chronic liver diseases by flow cytometry.

Immunological factors are important in the pathogenesis of a spectrum of hepatobiliary diseases. To characterize the nature of specific immunological responses in liver disease, we determined lymphocyte changes in liver tissue and in blood using flow cytometry. A total of 113 liver biopsy specimens was collected from patients with the following diseases: 19 chronic hepatitis B; 39 chronic non-A, non-B hepatitis; 27 alcoholic liver disease; 10 hepatic malignancy; 8 autoimmune hepatitis; 6 fatty liver and 4 primary biliary cirrhosis. The lymphocytes were isolated from the liver biopsy specimens by mechanical and enzymatic methods. The lymphocyte yield was 7,901 +/- 575 cells/mg of liver tissue. The viability of lymphocytes was 97.7% +/- 0.3%. Lymphocytes were stained with four pairs of two-color mixed fluorescein-conjugated monoclonal antibodies, including T4-T8 (CD4/CD8), T11-B1 (CD2-CD20), NKH1-T8 (CD56-CD8), IL-2R1-T11 (CD25-CD2), and the ratios were determined by an Epics Profile flow cytometer. Immunophenotyping of lymphocytes in whole blood samples was simultaneously analyzed. Variability in lymphocyte yield and different patterns of lymphocyte subsets were found in the liver biopsy specimens. The yields of lymphocytes from patients with chronic non-A, non-B and autoimmune hepatitis were highest, and the lowest yield was from patients with fatty liver. Patients with primary biliary cirrhosis, fatty liver and hepatic malignancy had relatively high ratios of CD4/CD8, CD56/CD8 and CD25/CD2; whereas patients with chronic hepatitis B, autoimmune hepatitis and non-A, non-B hepatitis had lower ratios of CD4/CD8, CD56/CD8 and CD25/CD2. No difference in lymphocyte ratios between the patients with cirrhotic and noncirrhotic alcoholic liver disease was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Separation↗

Interferon-induced chronic active hepatitis?

A 54-year-old man with chronic B hepatitis was treated with interferon alfa. Despite resolution of the hepatitis B viral infection, he experienced severe jaundice, ascites, and encephalopathy. Further work-up showed hyperglobulinemia, chiefly immunoglobulin G, and positive smooth muscle and anti-nuclear antibodies. Because of these "autoimmune" features, the patient was treated with prednisone. One month later, a significant clinical and biochemical improvement was observed. A possible autoimmune mechanism induced by interferon alfa is proposed as the cause for the perpetuation of the necroinflammatory activity.

Autoimmune Diseases↗

Hepatobiliary cryptosporidiosis and cytomegalovirus infection mimicking metastatic cancer to the liver.

A cholestatic syndrome caused by sclerosing cholangitis and papillary stenosis has been described in patients with the acquired immunodeficiency syndrome and hepatobiliary cryptosporidiosis and cytomegalovirus infection. The case of a 41-year-old homosexual man with the acquired immunodeficiency syndrome who presented with abdominal pain, diarrhea, fever, and cholestasis is reported. A percutaneous transhepatic cholangiogram showed that the extrahepatic and right-sided intrahepatic ducts were normal. Computerized tomography of the abdomen showed multiple hypodense lesions in the liver. Guided needle biopsies of several of these lesions showed severe confluent necrotizing pericholangitis with cytomegalovirus-infected cells. Numerous cryptosporidia were seen attached to biliary epithelium. The unique histopathologic and radiographic features of this case should be added to the spectrum of hepatobiliary manifestations of the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Hepatic dysfunction accompanying acute cocaine intoxication.

We identified 39 patients with acute cocaine intoxication and rhabdomyolysis over an 8-year period. Twenty-three of the patients (59%) demonstrated biochemical evidence for hepatic dysfunction. Sixteen of these patients had severe liver injury as defined by an alanine aminotransferase (ALT) of greater than 400 U/l (group A). Seven had an ALT between 36-399 U/l (group B) and 16 showed no evidence of liver injury (group C). In contrast to those with normal ALT, the clinical course of the group A patients was more often accompanied by profound hypotension (44 vs. 0%, p less than 0.025), disseminated intravascular coagulation (50 vs. 0%, p less than 0.005), hyperpyrexia (75 vs. 25%, p less than 0.025) and acute renal failure (81 vs. 0%, p less than 0.001). Seven of the group A patients expired (44%). Histologic examination of liver tissue obtained from post-mortem samples demonstrated extensive centrilobular and midzonal necrosis in three cases and panlobular necrosis in two others. A mild lymphocytic infiltrate with bile duct proliferation was present in each specimen. We conclude that cocaine intoxication can be accompanied by liver dysfunction which is most likely multifactorial; the presence of severe dysfunction identifies a patient with potentially significant morbidity and mortality.

Adult↗

Antibody to hepatitis C is common among patients with alcoholic liver disease with and without risk factors.

Thirty-seven patients with clinically suspected alcoholic liver disease were retrospectively studied for the prevalence of antibody to hepatitis C virus (HCV) by enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. Twenty-four had biopsy-proven cirrhosis. Nineteen had identifiable risk factors for non-A, non-B viral hepatitis, and 18 did not. Five of 19 high-risk (26%) and 6 of 18 low-risk (33%) patients had positive antibody, compared with two of 179 healthy blood donors (p less than 0.01 for either group of alcoholics compared with blood donors). Nine of 11 ELISA-positive patients were also either positive or indeterminable by immunoblot testing. Histologic scores for parameters commonly associated with chronic viral hepatitis were numerically worse among anti-HCV-positive patients, but none reached statistical significance. Clinically, seven of 11 (64%) of anti-HCV-positive patients versus 14 of 26 (54%) anti-HCV-negative patients were Child's class C. Among the 21 Child's class C patients, seven (33%) were anti-HCV-positive versus four of 16 (25%) of Child's class A/B patients. A weak correlation between IgG and ELISA optical density was observed (r = 0.52). We conclude that antibody to hepatitis C by ELISA and immunoblot is common among alcoholics with liver disease even in the absence of known or suspected risk factors for viral hepatitis. Although hepatitis C-positive patients tended to have more severe histologic disease, neither histologic parameters nor clinical findings were adequate to predict antibody seropositivity.

Adult↗

Detection of hepatitis C virus sequences in liver tissue by the polymerase chain reaction.

Although sensitive assays for serum antibodies to hepatitis C virus (HCV/anti-HCV) have been developed recently, the relation of anti-HCV to HCV infection of the liver has not been clarified. Therefore, we determined the presence of HCV RNA by the reverse transcription-polymerase chain reaction (PCR) in liver biopsy specimens of 21 patients with chronic liver disease and 5 control patients. RNA was extracted from frozen liver tissues by the guanidinium method, HCV cDNA was synthesized by reverse transcription, and core region and NS3 region sequences were amplified by PCR. The sensitivity and specificity of the reaction was significantly enhanced by double PCR with nested primers followed by Southern blotting with an HCV specific oligomer probe. NS3 region sequences were detected in the liver specimens of 12 out of 15 anti-HCV positive patients. Core region sequences were detected in 9 patients, all of whom were also positive for NS3 region sequences. HCV sequences were not detected in 11 anti-HCV negative patients. In all cases, the integrity of the extracted RNA was demonstrated by successful amplification of albumin mRNA as internal control. Our findings demonstrate the feasibility of the reverse transcription-double PCR method followed by Southern blotting for the detection of HCV sequences in liver tissues. In this system, the detection rate of NS3 region sequences is higher than that of core region sequences. There is a statistically significant correlation between high titer anti-HCV antibodies in serum and NS3 region sequences in liver tissue. However, not all anti-HCV positive patients had HCV positive hepatitis. The reverse transcription-polymerase chain reaction for HCV sequences on liver tissue extracts may reveal valuable information on the diagnosis of HCV infection and the pathogenesis of chronic hepatitis C.

Base Sequence↗

Fulminant hepatic failure due to acute hepatitis B and delta co-infection: probable bloodborne transmission associated with a spring-loaded fingerstick device.

Fulminant hepatic failure (FHF) due to acute hepatitis B and delta co-infection occurred in a 74-yr-old female, who eventually died. There was no clear-cut epidemiology other than probable bloodborne transmission from a contaminated spring-loaded fingerstick device used for glucose determination, in an outpatient facility. This unusual mode of transmission reiterates the importance of using sterile cleansing and disposal procedures anytime there is a possibility of contamination with blood.

Aged↗

Hepatitis C-associated hepatocellular carcinoma.

In the United States, a large percentage of patients with hepatocellular carcinoma are serologically negative for hepatitis B. We conducted a retrospective study to determine the prevalence of hepatitis C antibody in the sera of 59 patients with hepatocellular carcinoma who were HBsAg-negative and had no evidence of alcoholic liver disease, primary biliary cirrhosis, autoimmune hepatitis, hemochromatosis or alpha 1-antitrypsin deficiency. Twenty patients (34%) were hepatitis C antibody-positive and hepatitis B core antibody-negative. All twenty patients had underlying cirrhosis, and seven (35%) had histories of transfusions. Eleven (19%) additional patients were also hepatitis C antibody-positive but were hepatitis B core antibody-positive as well. Twenty-one (36%) patients were both hepatitis C antibody- and hepatitis B core antibody-negative and seven (12%) were hepatitis C antibody-negative but hepatitis B core antibody-positive. The prevalence of hepatitis C antibody was also determined among three other population groups serving as controls and found to be 14% in 28 HbsAg-positive patients with hepatocellular carcinoma, 44% in 76 patients with cryptogenic cirrhosis and 0.5% in 200 consecutive volunteer blood donors. We conclude that hepatitis C antibody is prevalent among patients with hepatocellular carcinoma and may therefore be a common causative agent of this disease. A significant number of patients with and without cirrhosis, negative for hepatitis C antibody and hepatitis B core antibody, remain without a discernible cause for this malignancy. Perhaps a second- or third-generation test will detect hepatitis C antibody in some of these patients.

Carcinoma, Hepatocellular↗

Hepatitis C infection in two urban hemodialysis units.

We determined the prevalence of antibodies to the hepatitis C virus (anti-HCV) in 90 patients and 37 staff members of two hemodialysis units utilizing a recently developed anti-HCV recombinant based assay. Eleven patients (12%) were anti-HCV(+). Of these, eight (73%) had antibodies to the hepatitis B core antigen (anti-HBc) indicating prior hepatitis B infection; one patient was hepatitis B surface antigen (HBsAg)(+). All staff members were anti-HCV(-), although seven (19%) of them were anti-HBc(+). Alanine aminotransferase elevations were present at the time of the study in four anti-HCV(-) patients and in only one anti-HCV(+) patient. All anti-HCV(+) (mean 59 +/- 74; range 3 to 269 units) and 85% of anti-HCV(-) patients (mean 16 +/- 27; range 0 to 204 units) had received multiple blood transfusions (P = 0.348). Among 50 patients tested for human immunodeficiency virus (HIV), 43% of anti-HCV(+) as compared to only 7% anti-HCV(-) were positive (P = 0.003). There was a history of intravenous drug abuse (IVDA) in eight (72%) of the anti-HCV(+) patients and in only seven (9%) of the anti-HCV(-) group (P = 0.00001). The results of this serologic survey suggests that anti-HCV positivity is prevalent, although much less than anti-HBc, among our dialysis patients, whereas it was not detected among staff members. The prevalence rate of anti-HCV was statistically significantly higher among anti-HIV(+) and IVDA patients but not in multi-transfused patients.

Adult↗

Complete amino acid sequence of arachin subunit of molecular weight 21,000.

A subunit of molecular weight 21,000 from arachin, the major peanut protein, was isolated in pure form and primary structure was determined. The subunit was fragmented with CNBr, trypsin, and NBS; the fragments were separated and isolated by PAGE, gel filtration, Dowex treatment, and paper electrophoresis, and Edman degradation on each fragment, including the intact subunit, was performed. The PTH-amino acids thus obtained were identified by UV spectroscopy and TLC. The complete sequence of 176 residues was established by overlapping technique.

Amino Acid Sequence↗

Total gastrectomy after shunt failure as therapy for recurrent gastric variceal bleeding due to portal and mesenteric vein thrombosis.

A 37-yr-old man with portal hypertension due to portal vein thrombosis was referred because of recurrent episodes of variceal hemorrhage. He had previously undergone two portal-systemic shunt procedures. Both of the shunts, as well as the superior mesenteric vein, ultimately thrombosed. Endoscopic variceal sclerotherapy was able to control the bleeding from his esophageal varices, but he repeatedly bled from large gastric varices. The patient underwent a total gastrectomy and has had no further gastrointestinal hemorrhage during a follow-up of 36 months.

Adult↗