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Biomedical subjects

J Gavaler

Publications and source records attributed to J Gavaler.

At least 19 recordsLinked to original sources
PubMed1996

Biochemical and 31P-NMR spectroscopic evaluation of immobilized perfused rat Sertoli cells.

Cell immobilization and perfusion are used for physiologic studies of Sertoli cells with phosphorus 31 nuclear magnetic resonance (NMR) spectroscopy and biochemical methods. In this study the 31P NMR spectra of Sertoli cells isolated from 18-to 21-day-old rats and immobilized in agarose threads continuously perfused with oxygenated Dulbecco's modifed Eagle medium were obtained at 81 MHz on an NMR system. Cytosolic Ca2+, intracellular Mg2+, lactate and pyruvate, and oxygen consumption were measured with standard biochemical methods. Perfused Sertoli cells maintain a stable intracellular adenosine triphosphate concentration for more than 10 hours. Sertoli cells placed in cold storage overnight and then subjected to perfusion partially regenerate cellular adenosine triphosphate levels. Sertoli cells consume an average of 4.8 +/- 0.4 nmol O2/min/10(6) cells and maintain average ambient lactate and pyruvate levels of 7.1 +/- 0.8 mg/dl and 0.65 +/- 0.05 mg/dl, respectively, with a lactate/pyruvate ratio in the range 8 to 12. The basal Ca2+(i) of Sertoli cells is 98 +/- 0.7 nmol/L (n = 58), which declines to a level less than 10 nmol/L when the Sertoli cells are perfused with a calcium-free medium. Perfusion of Sertoli cells with a sodium-free medium, with 10(-6) mol/L carbonyl cyanide P-trifluoromethoxy-thenylhydrozone, or with Ca2+ ionophore A23187 at a concentration of 10(-6) mol/L increases the Ca2+(i) to a level of 426 +/- 107 nmol/L, 274 +/- 29 nmol/L, or 282 +/- 57 nmol/L, respectively. A bioreactor for physiologic studies of Sertoli cells in real time with NMR spectroscopy has been developed. These data demonstrate that isolated, immobilized, and perfused Sertoli cells are stable for prolonged periods. In addition, these data suggest that Sertoli cells possess a functional Na+-Ca2+ antiporter and that they sequester extracellular Ca2+ in one or more intracellular compartments.

Animals↗
PubMed1995

Effect of alcohol use on allograft rejection rates after liver transplantation for alcoholic liver disease.

Alcoholic liver disease is a major cause of liver disease and has become an ever-increasing indication for liver transplantation (LTx). Follow-up studies have reported a higher rate of alcohol recidivism in patients transplanted for alcoholic hepatitis, compared with those transplanted for endstage alcohol-associated cirrhosis. It is assumed widely that recurrent alcohol use is associated with reduced compliance with immune suppression and, as a result, an increased risk of graft rejection and loss. To assess this question, 209 alcoholic patients transplanted for either alcoholic hepatitis with cirrhosis or cirrhosis alone between January 1, 1986 and December 31, 1991 were followed, with a mean follow-up of 4.4 +/- 0.6 years. There were 175 episodes of acute cellular rejection (ACR) that occurred in 137 patients, for an overall rejection rate of 83.7% or at a rate of 1.25 episodes/patient with rejection. The rate of ACR was three times as great in those who remained alcohol-abstinent (2.24 episodes/patient), compared with those who admitted to continued alcohol use (0.75 episodes/patient) (p < 0.01). A total of 33 episodes of chronic rejection occurred in 26 patients, for an overall rate of 12.4%. As was the case for ACR, the chronic rejection rate was greater among those who were continuously alcohol-abstinent, compared with those who intermittently used alcohol after successful LTx. There were no differences in the mean FK 506 or cyclosporin A levels in the groups with and without a rejection episode at the time the rejection episode was documented by liver biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Aggressivity among sons of substance-abusing fathers: association with psychiatric disorder in the father and son, paternal personality, pubertal development, and socioeconomic status.

An association between childhood aggression and risk for subsequent development of a substance abuse disorder is now well-accepted. In order to better understand the relationship between the presence of paternal substance abuse and aggression among their offspring, 10-12 year old sons of fathers with (n = 34) and without (n = 39) a history of a substance abuse disorder were contrasted on demographics, aggressivity, biological indices of reproductive maturation, and the presence of psychiatric diagnoses. In addition, personality factors, the potential for physical abuse, and psychiatric diagnoses were also ascertained among their fathers. Sons of substance-abusing fathers were found to be significantly more aggressive than sons of nonsubstance abusers. However, they also differed from comparison boys on the basis of SES and school grade attained, as well as the proportion with specific psychiatric disorders. Substance-abusing fathers differed from nonsubstance-abusing men in terms of personality factors and the presence of specific psychiatric disorders, including antisocial personality. They also showed significantly higher child abuse potential scores. A multiple regression analysis of factors contributing to aggression in the boys revealed that a paternal personality factor characterized by stress reactivity, alienation, and aggression was the most robust contributor to aggression among the boys. The boys' diagnoses of attention deficit disorder, oppositional defiant disorder, and lower household socioeconomic status were also significant predictors of aggressivity. Contrary to expectations, paternal, psychiatric diagnoses, substance abuse status, and potential for physical abuse were noncontributory. The results suggest potential mechanisms by which both aggression and risk for substance abuse may be transmitted from father to son.

Aggression↗
PubMed1994

Circulating intercellular adhesion molecule-1 (ICAM-1) in autoimmune liver disease and evidence for the production of ICAM-1 by cytokine-stimulated human hepatocytes.

A circulating form of the membrane-bound ICAM-1 (CD54), a ligand for lymphocyte function-associated antigen-1 (LFA-1), has recently been identified in normal human serum. In this study, serum levels of soluble ICAM-1 (sICAM-1) were determined by sandwich ELISA both in normal healthy individuals of both sexes and in subjects with autoimmune liver diseases. Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis and chronic active hepatitis (autoimmune) showed significant elevations in sICAM-1 compared with normal healthy subjects. The median level in PBC was approximately seven-fold above normal. Significant elevations in sICAM-1 were also detected, however, in patients with inactive alcoholic cirrhosis, suggesting that impaired liver clearance might at least in part account for the increased serum levels seen in patients with autoimmune liver disease. In patients with PBC, sICAM-1 levels were related to summary assessment of disease severity (Child-Pugh classification) and correlated significantly with serum biochemical indices of liver function, including measures both of cholestasis and liver cell injury. In contrast, serum levels of E-selectin did not differ significantly from healthy controls. Although it has been suggested that peripheral blood mononuclear cells (PBMC) may be a source of sICAM-1, investigation of ICAM-1 gene expression by reverse transcriptase polymerase chain reaction revealed similar basal levels of ICAM-1 message in PBMC of normal individuals and those with active PBC. This suggests that PBMC may not be a significant source of sICAM-1 in this disease. Similar increases in ICAM-1 mRNA expression were found in cultured, concanavalin A (Con A)-stimulated lymphocytes of both PBC patients and controls. Significantly, stimulation of cultured, normal human hepatocytes with proinflammatory cytokines and endotoxin induced cell surface expression of ICAM-1 and the secretion/shedding of sICAM-1 into the hepatocyte culture medium. This new finding suggests that hepatocytes may be an important source of sICAM-1 in autoimmune and other chronic liver diseases. The possible role of sICAM-1 in inflammatory disorders remains to be determined.

Adolescent↗
PubMed1994

Rheumatoid arthritis: a complication of interferon therapy.

A case report of rheumatoid arthritis developing during alpha-interferon therapy of chronic hepatitis C is reported. The rheumatoid arthritis was severe, being non-responsive to the use of nonsteroidal anti-inflammatory drugs, and persisted despite discontinuation of the interferon therapy. The literature relative to this case suggesting an association between rheumatoid arthritis and interferon therapy is presented. This case suggests that interferon therapy may precipitate subclinical rheumatoid arthritis in an individual without pre-existing clinical arthritis.

Adult↗
PubMed1993

Insulin requirements after liver transplantation and FK-506 immunosuppression.

Hyperglycemia and new-onset diabetes mellitus is a well-recognized complication of solid organ transplantation. With the advent of FK-506 as a new immunosuppressive drug used in orthotopic liver transplantation (OLT), much attention has been paid to its diabetogenic effects. Currently, there are no data on the long term effects of FK-506 in glucose metabolism after OLT. In the present study, we determined the need for outpatient insulin in 52 American veterans who received 58 liver transplants using primary immunosuppression with FK-506 and PRED, with a mean follow-up of 467 days (range 17-952 days). We also analyzed their plasma glucose and FK-506 levels as well as the doses of PRED and FK-506 that they received at various intervals post-OLT. There were 7/52 (13.6%) patients who required insulin for the first time after OLT. Of these, the number of patients on insulin at 3, 6, and 12 months post-OLT was 5/47 (10.6%), 6/44 (13.6%), and 1/26 (3.8%), with none requiring insulin de novo at 18, 24, and 30 months post-OLT. Three patients required insulin temporarily but subsequently became normoglycemic without additional therapy. The need for insulin was not related to the dose of FK-506 administered nor the plasma level. Patients who required outpatient insulin were receiving higher doses of PRED than those not requiring insulin. The need for insulin did not affect the long-term graft or patient survival. In conclusion, the need for insulin with FK-506 compares favorably to that of previous immunosuppressive regimens, and FK-506 may have a reversible diabetogenic effect that is not dose dependent.

Actuarial Analysis↗
PubMed1993

Effect of ethanol on Kupffer cell function.

Kupffer cells are resident macrophages in the liver and are important in both local and systemic immune responses. We evaluated the ability of Kupffer cells in vitro to respond to immune stimulation after both acute exposure to ethanol and after long-term ethanol consumption of ethanol. Triplets of female Wistar rats were fed a liquid diet containing 0, 12, or 36% ethanol isocalorically for 112 days. When killed, the Kupffer cells were isolated by collagenase perfusion and adhered to plastic 24-well plates. They were then stimulated with 10 micrograms/ml lipopolysaccharide for 4.5 hr. Synthesis of procoagulant activity (PCA) and tumor necrosis factor (TNF), expressions of macrophage response to immune stimuli, were measured by a one-step clotting assay and L929 cytotoxicity assay, respectively. Within each of the 10 triplets, PCA and TNF levels were normalized and expressed as a percentage of the zero ethanol isocaloric control rat. The high ethanol group had significantly lower baseline and stimulated PCA and TNF levels than the low ethanol group. For evaluation of the effect of acute exposure to ethanol, Kupffer cells were stimulated with lipopolysaccharide and varying concentrations (0-400 mg/dl) of ethanol. Cells were incubated for 4.5 hr and assayed for PCA and TNF activity. There was dose-dependent inhibition of PCA and TNF, with increasing concentrations of ethanol. These results indicate that whereas exposure to high levels of ethanol depresses Kupffer cell function, lower levels may be immunostimulatory.

Alcoholism↗
PubMed1993

Effect of ethanol on energy status and intracellular calcium of Sertoli cells: a study using immobilized perfused cells.

The effects of ethanol on ATP, O2 consumption, and cytosolic ionized Ca2+ (Ca2+i) were studied in Sertoli cells isolated from the testes of 18- to 21-day-old rats. The cells were immobilized in agarose gel threads and perfused with Dulbecco's Modified Eagle's Medium. Intracellular ATP was determined by 31P nuclear magnetic resonance spectroscopy and enzymatic assay, Cai2+ was measured with the photoprotein aequorin, cell viability was assessed by trypan blue exclusion, and O2 consumption was monitored with a Clark electrode. Ethanol was used with or without pretreatment with the alcohol dehydrogenase inhibitor 4-methylpyrazole (MP). Perfusing the cells for 90 min with 500 mM ethanol produced a 50% reduction in the 31P nuclear magnetic resonance beta ATP signal, and pretreatment with 15 mM MP enhanced this decline of the beta ATP peak to 75%. Enzymatic measurements of ATP revealed that exposure to 500 mM ethanol reduced the ATP levels from 52 +/- 5 to 38 +/- 3 nmol/10(6) cells with MP pretreatment and to 28 +/- 4 nmol/10(6) cells without MP pretreatment (n = 5). Basal O2 consumption was 5.2 +/- 0.5 nmol/min.10(6) cells (n = 5), and it was reduced by ethanol or ethanol plus MP to 4 +/- 0.4 and 3.1 +/- 0.2, respectively (n = 5). The basal concentration of Cai2+ in Sertoli cells was 98 +/- 0.7 nM (n = 32). During perfusion with 500 mM ethanol, Cai2+ increased to 208 +/- 98 nM (n = 5) and was not modified further by the presence of MP. Perfusing the cells for 90 min with 500 mM ethanol with or without MP caused a decrease in cell viability from 93 +/- 2 to 76 +/- 3 and 67 +/- 3, respectively (n = 8). Exposure to 5 mM acetaldehyde produced only a minimal reduction in ATP, with no observable effect at lower concentrations, suggesting that the significant reductions in ATP, O2 consumption, and cell viability evoked by ethanol were not caused by acetaldehyde. These data suggest that ethanol is toxic to Sertoli cells, and its toxicity is not a result of ethanol metabolism.

Adenosine Triphosphate↗
PubMed1992

Cytomegalovirus infection of the upper gastrointestinal tract following liver transplantation--incidence, location, and severity in cyclosporine- and FK506-treated patients.

One hundred and forty randomly selected liver transplant recipients were studied before and after primary orthotopic liver transplantation for the presence or absence of CMV enteritis. Following OLTx, 65 patients were treated with cyclosporine A and 75 were treated with FK506. The two groups were similar with regard to the incidence, location, and outcome of their upper gastrointestinal CMV infection. Prior to OLTx, only one patient had evidence of enteric CMV infection. The incidence of CMV enteritis post-OLTx was 27.7% in the CsA-treated group and 20% in the FK-treated group. During the first posttransplant month, no patient in the FK-treated group developed CMV enteritis, compared with 11.5% of the patients who were treated with CsA (P less than 0.05). Gastric CMV was found in over 80% of those positive for any organ in either group. In addition to CMV infection of the upper gastrointestinal tract, clinically evident CMV disease involved more nonenteric organs in the CsA-treated group than in the FK-treated group. In the CsA-treated group, CMV-negative patients had a statistically higher 1-year survival rate (100%) than CMV-positive patients (77.8%) (P less than 0.05). In the FK-treated group, no difference in survival was observed between CMV-positive or CMV-negative cases at 1 year. Of the patients on CsA, 20% received OKT3 for persistent rejection, as compared with 13% in the FK-treated group. The patients receiving both CsA and OKT3 had a higher rate of upper gastrointestinal CMV infection than did FK-treated patients who also received OKT3 therapy (38.5% versus 20%, respectively). Based upon these data, it can be concluded that (1) patients receiving FK have a lower incidence of enteric CMV infection; (2) following OLTx, upper gastrointestinal CMV infection presents later in FK-treated patients; (3) the stomach is the most frequently involved organ in the UGIT; (4) FK-treated liver recipients have less severe enteric CMV infection than do CsA-treated patients; (5) enteric CMV is not a major cause of mortality in liver transplant recipients; and (6) in patients receiving FK, those who require OKT3 therapy do not appear to be at a greater risk for the development of CMV enteritis than those who do not.

Adolescent↗
PubMed1992

The protective effect of FK506 pretreatment against renal ischemia/reperfusion injury in rats.

The effect of pretreatment with FK506 on renal ischemia and reperfusion (I/R) injury was investigated using a rat model. Animals were assigned to one of two groups (20 rats each). Group 1 animals (controls) received 0.5 ml saline while group 2 animals received FK506 (0.3 mg/kg), administered intravenously 24 hr prior to the induction of renal ischemia. A 60-min period of ischemia of the right kidney was induced, and upon reperfusion a left nephrectomy was performed. Blood samples for estimation of BUN, creatinine, and tumor necrosis factor were collected on days 0 (preischemia), 1, 2, 3, 5, 7, and 10 (postischemia). Rats were sacrificed after day 10 and renal tissue was examined histologically. All animals survived the ischemic episode. FK506 pretreatment significantly reduced the serum levels of BUN (P less than 0.02), creatinine (P less than 0.02), and TNF (P less than 0.05) as compared with that seen in controls. Histologically, at day 10, the kidneys showed the expected sequelae of prior renal I/R with various degrees of tubular damage. However, no objective differences were evident between the two groups. Based upon these data, it can be concluded that (1) FK506 pretreatment ameliorates the functional renal injury associated with I/R, (2) renal ischemia induces the release of TNF, and (3) FK506 pretreatment results in a significant inhibition of TNF production. These data suggest that the release of TNF may be responsible for the increasing of BUN and creatinine levels seen after renal I/R and that pretreatment of renal donors with FK506 may improve renal function in the immediate post-transplant period.

Animals↗
PubMed1992

Large hiatal hernias, anemia, and linear gastric erosion: studies of etiology and medical therapy.

Patients with large diaphragmatic hiatal hernias occasionally manifest severe iron deficiency anemia. The etiology is believed to be that of small erosions at the waist of the hernia which bleed slowly. Our study attempts to determine the incidence of this condition in clinical practice, and whether acid plays a role in the pathophysiology. Sixteen such patients were identified prospectively in a series of 5219 consecutive patients (0.31%) accrued over a 5-yr interval. Anemia was the presenting feature, rather than symptoms of gastroesophageal reflux disease. The erosions were endoscopically identified and biopsied. Anemia was treated and recurrence was prevented for a mean of 24.6 months with long-term iron replacement. Of eight patients treated with iron alone, four were willing to undergo follow-up endoscopy. Of these four, none demonstrated healing. Three of these nonhealers and eight additional patients were treated with both iron and H2 antagonists. Thus, 11 patients were treated with H2 antagonists and iron, whereas four patients were treated with iron alone. At 6 wk, reendoscopy showed healing of the erosions in seven of 11 patients on H2 antagonists, but in none of those treated with iron alone (p less than 0.05). The anemia was corrected in all patients with iron therapy. We conclude that 1) gastric acid appears to have some role in the pathogenesis of this lesion; 2) short-term therapy with H2-receptor antagonists promote healing of the erosions; and 3) long-term iron therapy alone is adequate for initial and maintenance therapy of the anemia.

Aged↗
PubMed1991

Effect of short-term ethanol feeding on rat testes as assessed by 31P NMR spectroscopy, 1H NMR imaging, and biochemical methods.

31P Nuclear magnetic resonance (NMR) spectroscopy and 1H NMR imaging were used to examine the effect of short-term ethanol feeding on the rat testis. Weanling rats were pair-fed for 10 weeks either on ethanol containing liquid diet (36% ethanol of total calories) or a diet in which dextrimaltose was isocalorically substituted for the ethanol of the alcohol-containing diet. In vivo 31P NMR of the testes was used to determine the intratesticular pH and the relative concentrations of various phosphorus-containing metabolites. The integrity of the blood-testes barrier was evaluated using 1H NMR imaging following a gadolinium diethylene tetramine pentaacetic acid derivative (Gd-DTPA) administration as a vascular contrast agent. After the completion of NMR studies, the testis and the liver were freeze-clamped to allow for the assay of their adenosine-5'-triphosphate (ATP) contents. Serum was assayed for its content of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alcohol and testosterone. Ethanol feeding resulted in the following: (a) a reduction in the body weight (p less than 0.05), (b) a reduction in the testicular phosphodiesters (PDE) PDE/ATP ratio (p less than 0.05), (c) an increased change in the testis image intensity difference between pre- and post-iv Gd-DTPA images, (c) a reduction in the testicular and hepatic content of ATP, and (d) increased serum levels of AST and ALT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1989

T-cell populations in liver and renal transplant recipients with infectious esophagitis.

Individuals undergoing hepatic and renal transplants are susceptible to infections of the gastrointestinal tract, particularly the esophagus. The most common responsible agents are Candida and herpes simplex virus (HSV) with cytomegalovirus (CMV), Aspergillus, and other agents being regarded as unusual pathogens even in this unique population. Altered T-cell populations have been associated with CMV colitis in healthy homosexuals and in individuals with the acquired immunodeficiency syndrome (AIDS). Similarly, individuals with Epstein-Barr virus infections have altered T-cell populations. Whether these infections alter T-cell populations in infected individuals or the abnormalities in T-cell subpopulations occur first and enhance the likelihood of an infection in susceptible populations is as yet unknown. In this study peripheral blood T-cell populations in individuals before (19 patients) and after (47 patients) liver transplantation and after receiving a renal allograft (21 patients) were compared. Those individual having any symptoms related to esophageal disease underwent upper gastrointestinal endoscopy combined with mucosal biopsies, brushings, and cultures and were subdivided into those with and without infectious esophagitis. CMV esophagitis was found to be associated with an arithmetically decreased T-cell helper/suppressor (H/S) ratio principally due to an increase in the suppressor cell number. Such a reduction in the TH/S ratio and in the number of circulating suppressor cells was not found in esophagitis due to either HSV or Candida and was unrelated to the serum cyclosporine level or prednisone dosage prescribed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Biologically active phytoestrogens are present in bourbon.

The nonethanol congeners of bourbon have been found to possess estrogenic activity when tested using an in vivo oophorectomized rat bioassay, as well as an in vivo estrogen receptor assay system. The phytoestrogen, biochanin A, as well as the plant sterol, beta-sitosterol, were identified in the bourbon preparation using gas chromatography/mass spectrometry. These findings, using three methodological approaches, demonstrate that bourbon contains at least one biologically active phytoestrogen and suggest that the effects of alcoholic beverage use or abuse, particularly as they relate to endocrine systems, should not be viewed as resulting solely from exposure to ethanol.

Alcoholic Beverages↗