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Biomedical subjects

G F Grady

Publications and source records attributed to G F Grady.

At least 55 records · Page 3Linked to original sources
PubMed1977

Immunization with Shigella dysenteriae type 1: evaluation of antitoxic immunity in prevention of experimental disease in rhesus monkeys (Macaca mulatta).

The role of serum antitoxic antibody in protection against the dysentery caused by Shigella dysenteriae type 1 (Shiga's bacillus) was studied in monkeys fed 10(10) virulent organisms after parenteral immunization with a formalin-inactivated Shiga toxoid preparation standardized in mice. Two 125-microgram doses of toxoid adsorbed on aluminum hydroxide adjuvant and given 14 days apart provided mice with a 54-fold increase in resistance to parenteral toxin. In rhesus monkeys (Macaca mulatta), the same regimen of toxoid permitted the safe parenteral administration of toxin in incremental doses ranging from 100 to 1,000 mouse 50% lethal doses and resulted in correspondingly high titers of antitoxin in serum. Nevertheless, the immunized monkeys responded to orally administered Shiga bacilli by development of diarrhea and dysentery that was as severe as (or more severe than) the response of unimmunized controls. The failure of extraordinarily high levels of circulating antibody to protect against experimental shigellosis suggests that the intestinal mucosal sites of toxinmediated response are beyond the reach of systemic antitoxin.

Animals↗
PubMed1977

Antibody to hepatitis B core antigen in chronic hepatitis and primary biliary cirrhosis: evaluation by a new autologous solid phase radioimmunoassay.

Anti-HBc, the antibody to core antigen of hepatitis B virions, was assayed by a new solid phase sandwich radioimmunoassay inhibition method in the sera of 26 patients with HBsAg-negative chronic active hepatitis (CAH) and 31 patients with primary biliary cirrhosis (PBC). The sensitivity of the method was validated by finding anti-Hb titers averaging greater than 1:1000 in a group of 8 chronically HBsAG-positive individuals, 4 of whom had chronic persistent hepatitis and 4 of whom had no histological or biochemical evidence of liver disease. However, anti-HBc was not detectable in any of the 26 patients with HBsAg-negative CAH. Sera from 2 of the 31 PBC patients contained anti-HBc but only in low titers, a distribution of anti-HBc similar to that found among a comparison group of medical personnel. Anti-HBc testing among PBC patients and control subjects identified a few persons in whom negative tests for HBsAg and anti-HBs failed to identify previous hepatitis B infections. Nevertheless, the uniformly negative tests for anti-HBc among our HBsAg-negative patients with CAH provide additional evidence that this subgroup, typically young-middle age females, seldom derive CAH from hepatitis B infection.

Adolescent↗
PubMed1975

Clinical trials of hepatitis B immune globulin. Development of policies and materials for the 1972-1975 studies sponsored by the National Heart and Lung Institute.

Plasma from persons with high titers of hepatitis B antibody (anti-HBs) was used to manufacture one lot of hepatitis B "immune" globulin sufficient for four interlocking clinical trials of prevention or modification of hepatitis B infections. The trials were carried out in renal dialysis units, in medical personnel with accidental exposures to hepatitis B, in transfused patients, and in patients with fulminant hepatitis. A single policy board developed protocols that allowed comparisons among the four studies while respecting the unique requirements of each.

Antibodies↗
PubMed1975

Hepatitis B "immune" globulin: effectiveness in prevention of dialysis-associated hepatitis.

A randomized, double-blind, multicenter study of hepatitis prevention by immune serum globulin with high anti-HBs titer ("hepatitis B immune globulin") was carried out among 318 new patients and 296 staff members of renal dialysis units. Three milliliters of high titer globulin, repeated at four months, was compared with equal doses of intermediate or normal titer globulin. Among staff members, the cumulative percentages developing hepatitis or HBs Ag, or both, within eight months were 6.9, 11.7, and 11.1 in the high, intermediate, and normal titer groups respectively. The lower incidence associated with high titer globulin was not significant (P greater than 0.05). However, among the patients the respective percentages were 7.9, 21.3, and 23.1 and the lower incidence in the high titer globulin group was significant.

Antibodies↗
PubMed1975

Hepatitis B immune globulin--prevention of hepatitis from accidental exposure among medical personnel.

The role of anti-HBs antibody in reducing the probability of hepatitis after accidental exposure to serum from patients with hepatitis or carriers of HBs Ag was studied prospectively among 712 medical workers. One fourth of the workers were anti-HBs positive and less than one per cent of them developed hepatitis, in contrast to 11 per cent among those who were anti-HBs negative. Three coded immune-serum globulin preparations of varying anti-HBs titer were randomly assigned. Among 251 persons passively immunized with globulin having a conventionally low anti-HBs titer, hepatitis developed in 17 (seven per cent) within six months. Comparative rates among those receiving intermediately high titer and high titer globulin, respectively, were five per cent (11 of 208) and two per cent (5 of 253). The significantly lower incidence among the latter (P less than 0.05) was offset by six additional cases, all in recipients of high titer globulin, detected when follow-up was extended to nine months.

Adult↗
PubMed1975

Kinetics of absorption of toxin of Vibrio cholerae.

Autoradography of rabbit intestine exposed in vivo to purified tritiated toxin of Vibrio cholerae showed that pharmacologically important amounts of toxin can be rapidly absorbed despite the relatively large size of the toxin molecule and its affinity for binding to the brush border. Cholera toxin and tritiated nontoxic and tritiated nontoxic control substances of comparable size followed a similar time course in spreading down the surface of the villus, and with respect to the villus greater than crypt gradient of labeling of cytoplasm of the mucosal epithelial cells. Absorption of toxin or biologically active toxin fragments provides a mechanism whereby the basal and lateral areas of the cell, which are rich in adenyl cyclase, could participate in the hypersecretory process.

Absorption↗
PubMed1975

Production and characterization of exotoxin(s) of Shigella dysenteriae type 1.

A semicontinuous fermenter system was developed in which broth culture filtrates of Shigella dysenteriae type 1 yielded substantial amounts of exotoxin. Biologic activity of the exotoxin was characterized by means of three assays: the rabbit ileal loop for fluid evocation (enterotoxicity), mouse lethality after parenteral injection (neurotoxicity), and HeLa cell toxicity in vitro (cytotoxicity). Although the culture filtrate was highly active, disc electrophoresis revealed that the toxin is a minor component of the mixture of proteins in the crude preparation, and that the minor representation contrasts with the relative prominence of exotoxins in cultures of other bacteria, such as Vibrio cholerae, Corynebacterium diphtheriae, and Clostridium tetani. Filtrate toxin, when purified by isoelectric focusing in polyacrylamide gel, was found to contain two toxic moieties. One was resolvable as a single band with an isoelectric joint (pI) of 7.25, a molecular weight of 72,000, and all three types of biological activity. The second moiety was isoelectric at pH 6.00, contained two subcomponents, and further contrasted with the pI 7.25 toxin by being more cytotoxic while being devoid of enteroneurotoxic activity.

Animals↗
PubMed1975

Hepatitis B antibody in conventional gamma-globulin.

Recent lots of conventional gamma-globulin prepared from the plasma of outdated blood collected from voluntary donors in Massachusetts contain substantially more antibody (anti-HBs) to the hepatitis B surface antigen (HBs Ag) than do lots manufactured from plasma collected before 1970. Variations in titer of anti-HBs may have been related in part to local variations in the incidence of hepatitis B. However, data available since 1949 suggest that one must consider whether antibody excess (anti-HBs) or antigen excess (HBs Ag) prevailed among individuals contributing to the plasma pools. The titers of anti-HBs have continued to rise since 1971, when screening of blood donors for HBs Ag became mandatory, a step which presumably resulted in the removal of much of the HBs Ag that would otherwise adsorb anti-HBs. The anti-HBs titer in gamma-globulin routinely produced in Massachusetts now equals or exceeds the titer in other lots of gamma-globulin found to be effective in recent studies of preexposure prophylaxis of hepatitis B.

Antibodies, Viral↗