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Biomedical subjects

J R Wands

Publications and source records attributed to J R Wands.

At least 217 records · Page 12Linked to original sources
PubMed1980

Essential mixed cryoglobulinemia without evidence for hepatitis B virus infection.

Prompted by reports associating essential mixed cryoglobulinemia with hepatitis B, we tested for hepatitis B markers in serum and cryoprecipitates and searched for virus particles by electron microscopy in cryoprecipitates from 12 patients with essential mixed cryoglobulinemia and 22 control subjects with mixed cryoglobulinemia secondary to recognized disease processes. None of the patients with essential cryoglobulinemia had detectable serum hepatitis B surface antigen (HBsAg) or antibody (anti-HBs), whereas five of the 22 patients with secondary cryoglobulinemia were positive for either HBsAg or anti-HBs. In cryoprecipitates from 10 patients with essential cryoglobulinemia, we could not detect HBsAg by radioimmunoassay or virus particles by electron microscopy, but one cryoprecipitate was anti-HBs-positive; however, four of 12 cryoprecipitates from patients with secondary cryoglobulinemia were positive for HBsAg or anti-HBs. Evidence of liver disease was present in similarly small proportions of both groups. Thus, in almost all our patients, essential mixed cryoglobulinemia was unrelated to hepatitis B infection.

Adult↗
PubMed1979

Inhibition of hepatic regeneration in rats by acute and chronic ethanol intoxication.

We studied the effects of acute and chronic ethanol feeding on hepatic regeneration in rats after partial hepatectomy and toxic liver injury produced by D-galactosamine. Ethanol, when administered as a single dose (6 g/kg), inhibited 3H-thymidine incorporation into hepatic DNA; this effect depended in part on the time of ethanol feeding after partial hepatectomy. Multiple ethanol feedings produced an even greater inhibition, which persisted for at least 48 hr after partial hepatectomy. Rats chronically fed ethanol for 30 days also failed to achieve a hepatic proliferative response to either partial hepatectomy or D-galactosamine-induced hepatitis, comparable with isocaloric pair-fed controls. These investigations suggest that there may be a certain metabolic state in the hepatocyte cell cycle that is most susceptible to the action(s) of ethanol; inhibition of liver regeneration by acute or chronic ethanol consumption may result in delayed recovery from prior or coincident liver injury.

Alcoholic Intoxication↗
PubMed1978

Circulating immune complexes and complement activation in primary biliary cirrhosis.

We evaluated 20 patients with primary biliary cirrhosis and seven controls with extrahepatic biliary obstruction for presence of circulating immune complexes, having found serologic evidence of alternate complement-pathway activation in eight of the 20. Immune complexes were isolated by cryoprecipitation from serum and measured directly by the sensitive Raji-cell radioimmunoassay. Cryoproteins, found in high concentrations in 90 per cent of the patients with cirrhosis but undetectable in the controls, were composed of IgM (60 per cent), IgG-IgM (25 per cent) and IgA-IgM (5 per cent) and were capable of activating the complement system in vitro. Immune complexes detected by the Raji assay were found in 95 per cent of the patients with cirrhosis and circulated in exceedingly high concentrations (474 microgram per milliliter; range, 16.2 to 2192) but were absent in the controls. Furthermore, the alternate complement pathway was activated in eight cirrhotic patients. These complement-fixing immune complexes differ from immune complexes isolated from other types of liver diseases and may be important in the pathogenesis of primary biliary cirrhosis.

Adult↗
PubMed1978

Alteration in suppressor cell activity in chronic active hepatitis.

We have studied peripheral blood mononuclear cells obtained from 24 patients with acute or chronic active hepatitis to determine if there was an abnormality in concanavalin A-induced suppressor cell activity compared to control subjects. Suppressor cells were generated by preincubation of the mononuclear cells with a mitogenic concentration of concanavalin A (6 mug/ml) for 48 hr followed by treatment with mitomycin C and alpha-methyl mannoside. Suppressor cell activity was assessed in second cultures by inhibition of concanavalin A-stimulated blast transformation of fresh allogeneic lymphocytes. Concanavalin A-stimulated suppressor activity was not elicited in mononuclear cells from the majority of patients with chronic active hepatitis in contrast to patients with acute hepatitis or acute inflammatory diseases and controls (P < 0.001). This finding was demonstrable in chronic active hepatitis patients in remission and relapse, both on and off prednisone therapy, and varied considerably during the course of the disease. The extent of liver injury was not related to the measured suppressor cell activity. These studies suggest that in chronic active hepatitis, a disease in which the host immune response may be involved, there appears to be a defect in concanavalin A-stimulated suppressor cells.

Acute Disease↗
PubMed1978

Urticaria associated with acute viral hepatitis type B: studies of pathogenesis.

To determine whether skin deposition of circulating immune complexes contributes to prodromal urticaria of acute hepatitis B, we studied two patients with hepatitis B who presented with urticaria and fever. During the urticarial prodrome but not thereafter, we found activation of both classic and alternative complement pathways. Hepatitis B surface antigen (HBsAg)-antibody complexes were identified (by electron microscopy) in cryoprecipitates from both patients and IgG (by immunodiffusion) in cryoprecipitates of one patient during urticaria. Light and electron microscopy of involved urticarial skin revealed necrotizing venulitis in both patients. Immunofluorescence microscopy showed fibrin within involved cutaneous vessel walls in one patient and C3, IgM, and HBsAg, which were not detected in simultaneously obtained uninvolved skin, in both patients. Our findings suggest that deposition of circulating immune complexes containing HBsAg is important in the pathogenesis of urticaria associated with acute hepatitis B virus infection.

Adult↗
PubMed1978

Decreased suppressor cell activity in inflammatory bowel disease.

Studies were performed on eleven patients with inflammatory bowel disease to determine if there was an alteration in concanavalin A (Con A) induced suppressor cell activity. Similar investigations were also performed on twenty-one control subjects and five patients with other inflammatory conditions. Supressor cells were generated by pre-incubation of peripheral blood mononuclear cells with a mitogenic concentration of Con A, followed by treatment with mitomycin C and alpha-methyl mannoside. Under these conditions, cells obtained from normal individuals are then capable of suppressing the Con A-stimulated blast transformation responses of fresh allogeneic lymphocytes in new cultures. We found that in twenty out of twenty-one control subjects, and all five patients with other inflammatory disorders, Con A-stimulated suppressor cell activity was demonstrable. Four patients with inflammatory bowel disease, whose disease was mildly active or was in clinical remission, had elicitable suppressor cell activity which fell within the normal range. In contrast, suppressor cell activity was markedly diminished or absent in seven patients with severe and active inflammatory bowel disease. These studies suggest that an alternation in Con A-stimulated suppressor cells exists in patients with active inflammatory bowel disease, which may contribute, in part, to the persistent inflammation in the gastrointestinal tract.

Adolescent↗
PubMed1978

Plasma alpha-amino-n-butyric acid to leucine ratio: nonspecificity as a marker for alcoholism.

Recent studies suggest that the ratio of plasma alpha-amino-n-butyric acid to leucine is increased specifically by chronic heavy alcohol consumption. To test this hypothesis, we determined this ratio in normal controls and (1) currently drinking chronic heavy alcoholics; (2) currently abstaining chronic alcoholics; (3) patients with nonalcoholic liver disease; (4) chronically alcohol-fed rats and mice; (5) mice infected with murine hepatitis virus; and (6) mice exposed to carbon tetrachloride. Mean ratios in control persons, drinking alcoholics, abstaining alcoholics, and nonalcoholic liver disease patients were not statistically different. Of 5 drinking alcoholics followed serially from the beginning of abstinence, 1 had an elevated ratio on admission and a persistently elevated ratio even 2 weeks later; another had a ratio more elevated after 2 weeks of abstinence, than on admission; and 3 had ratios in the normal elevated after 2 weeks of abstinence than on admission; and 3 had ratios in the normal range. Compared to control rats, chronically alcohol-fed rats had a significantly elevated mean ratio after 1 month and an even higher ratio after 2 months (P less than 0.001). In control, alcohol-fed and carbon tetrachloride-treated mice, alpha-amino-n-butyric acid was undetectable, but in two sets of mice with severe murine hepatitis virus infection, elevated ratios were found. We conclude that because the ratio of alpha-amino-n-butyric acid to leucine is not necessarily elevated in chronic heavy alcoholics but can be elevated in acute experimental liver cell injury, it does not appear to be a specific marker for the detection of alcoholism.

Alcoholism↗
PubMed1977

Familial hemochromatosis. Physiologic studies in the precirrhotic stage of the disease.

We studied 12 members of a family with precirrhotic hemochromatosis to define the physiologic abnormalities in the asymptomatic phase of the disease. Six of 12 had increased iron stores; the mode of inheritance was consistent with an autosomal dominant trait. Serum ferritin levels were no more predictive of tissue iron levels than measurements of serum iron, transferrin saturation or chelatable iron excretion. In three affected family members intestinal iron content was normal. Liver proline hydroxylase activity and urinary hydroxyproline excretion did not correlate with tissue iron content, suggesting that, in addition to the possible role of tissue iron, hepatic fibrosis may involve other factors. "Borderline diabetes mellitus" was present in three affected family members, but extensive studies revealed that pituitary dysfunction is uncommon in early hemochromatosis. Increased levels of liver iron proved to be the most reliable marker for the disease.

Adolescent↗
PubMed1977

Familial hemochromatosis: characteristics of the precirrhotic stage in a large kindred.

Ffty asymptomatic members of a kindred with familial hemochromatosis were studied in an effort to clarify some of the physiologic abnormalities present in the pre-cirrhotic or latent stage of the disease. Using excess hepatic iron as a marker for inheritance of hemochromatosis, results of liver biopsies on 31 family members suggest an auto-somal dominant mode of inheritance with incomplete expressivity. In addition to a relationship between alcohol intake and excess liver iron, there was a strong association between the level of alcohol intake and the presence of hepatic fibrosis in those subjects with excess iron stores. Both serum iron and transferrin saturation were significantly higher in family members with iron overload than in those who were not affected. Only transferrin saturation was significantly correlated with the severity of hepatic iron deposition. Studies of glucose tolerance (OGTT, IVITT, glucose clamp studies) demonstrated a defect in carbohydrate metabolism associated with deficient insulin secretion and insulin resistance, both of which were related to the degree of hepatic iron depostion. In this kindred we have found no evidence for a contribution of inheritance to the carbohydrate intolerance of hemochromatosis. Iron overload was not related to activity of hepatic collagen proline hydroxylase or urinary excretion of peptide-bound hydroxyproline. Serum ferritin, previously thought to be a reliable marker of reticuloendothelial iron stores, was normal in 19 of 20 family members with iron overload.

Adolescent↗
PubMed1976

Normal serum ferritin concentrations in precirrhotic hemochromatosis.

We investigated 33 of 58 members of two families with latent or precirrhotic hemochromatosis to determine its pattern of inheritance and to evaluate the serum ferritin levels as an index of iron stores. In both families, the pattern of inheritance was as an autosomal dominant trait with incomplete expressivity. Mean serum ferritin values in the affected family members were 88.5 ng per milliliter (range, 28.0 to 201.9) for males and 65.2 ng per milliter (range 23.7 to 97.0) for females, which were no different from controls (P is less than 0.5). Furthermore, the serum ferritin values did not correlate with or reflect mobilizable iron stores, and there were no relations between the serum iron, iron-binding capacity and transferrin saturation (P is less than 0.2). Thus, serum ferritin concentrations in precirrhotic familial hemochromatosis appear to underestimate iron stores. Serum ferritin levels do not help to identify such patients with increased iron stores for therapeutic phlebotomy.

Adult↗
PubMed1976

Arthritis associated with intestinal-bypass procedure for morbid obesity. Complement activation and characterization of circulating cryoproteins.

Five patients were studied after intestinal-bypass operations for morbid obesity to determine if the arthritis observed in three of these patients was associated with circulating cryoproteins. Only serum from the three patients with acute arthritis contained cryoprotein complexes. The complexes comprised IgG, IgM, IgA, complement components C3, C4, C5 and IgG antibody against Escherichia coli and Bacillus fragilis. The C3-activator fragment of the properdin complex was identified in fresh serum samples obtained from two of the three patients with circulating cryoprotein complexes and arthritis. These observations suggest that systemically absorbed intestinal bacterial antigens may lead to (or contribute to) the formation of circulating cryoprotein complexes. Circulating cryoprotein complexes activated both the classical and alternate complement pathways and may be important in the pathogenesis of the arthritis associated with the intestinal-bypass procedure for morbid obesity.

Adult↗
PubMed1976

Circulating immune complexes and complement sequence activation in infectious mononucleosis.

The role of immune complex formation was investigated in a patient with infectious mononucleosis complicated by an urticarial rash. Circulating cryoprotein immune complexes were identified during the urticarial phase of the illness, and disappeared during recovery. These complexes were composed of immunoglobulins G (IgG), M (IgM) and A (IgA), complement components C3, C4 and C5, Epstein-Barr (EB) virus capsid antibody and particles resembling EB virus. The IgG subtypes identified in the immune complexes were the complement fixing IgG-1, IgG-2 and IgG-3. The C3 activator of the properdin complex was detected in serum obtained during that acute phase but not after recovery. Thus, the transient appearance of circulating complement-fixing immune complexes was associated in this patient with activation of both classic and alternate complement pathways. The findings suggest that these complexes may be involved in the rash associated with infectious mononucleosis.

Adult↗