Biomedical subjects

D Krah

Publications and source records attributed to D Krah.

6 recordsLinked to original sources

PubMed1996

WC3 reassortant vaccines in children.

Bovine rotavirus strain WC3 (P7[5], G6) administered at the 12th passage level was well tolerated clinically in infants and efficiently induced serum virus neutralizing antibody (VNA) with bovine rotavirus G6 specificity. The protective efficacy of WC3 vaccine against all rotavirus disease was inconsistent, varying in four separate trials from 76% to 0%; some selective protection against severe disease was seen in all trials. WC3 reassortants containing the gene for an individual human rotavirus VP7 (G) or VP4 (P) surface antigen were also well tolerated, but preferentially induced VNA to the WC3 parent. Efficacy trials of human G1 VP7 reassortant WI79-9 (P7[5], G1) consistently led to > 60% protection against all rotavirus disease. A quadrivalent WC3 reassortant vaccine was developed to contain four separate monovalent reassortants expressing human rotaviruses surface proteins G1, G2, G3, and P1A [8] respectively. In a multicenter trial including 439 infants, this vaccine induced 67.1% protection against all rotavirus disease (defined as positive for rotavirus antigen by ELISA only [p = < 0.001]) and 72.6% protection when the standard for rotavirus diagnosis was a positive test of stool for both rotavirus antigen by ELISA and rotavirus RNA by electropherotype analysis (p = < 0.001). In this trial, episodes of the most severe rotavirus disease (clinical severity score > 16.0 eight cases) occurred only in placebo recipients.

Animals↗

PubMed1996

The development of multivalent bovine rotavirus (strain WC3) reassortant vaccine for infants.

Laboratory and clinical studies have been directed toward development of a vaccine against rotavirus gastroenteritis in infants. First, bovine rotavirus strain WC3, which did not induce neutralizing antibodies to predominant human rotavirus (HRV) serotypes, was determined to be safe and immunogenic; however, it was not protective in all efficacy trials. HRVs adapted to cell culture retained some virulence for infants, but when further attenuated by cold adaptation, they were poorly immunogenic. Reassortant rotaviruses were designed to express HRV surface proteins VP7 (G) or VP4 (P) while retaining a bovine WC3 genome background. Reassortants containing either HRV surface protein and as few as four bovine rotavirus genes were safe in infants. A monovalent WC3 reassortant of serotype G1 specificity was 64%-100% protective in placebo-controlled trials. A quadrivalent WC3 reassortant vaccine with components of HRV G1, G2, G3, and P[8] specificity induced 67% protection against all rotavirus disease in a multicenter efficacy trial.

Animals↗

PubMed1991

Safety and immunogenicity of a live attenuated hepatitis A virus vaccine in seronegative volunteers.

Seronegative adults were enrolled in a dose-escalating study of a live attenuated hepatitis A virus (HAV) vaccine that was prepared from the F' variant of HAV strain CR326F. They were injected subcutaneously with 10(4.1), 10(5.2), 10(6.1), or 10(7.3) TCID 50 of HAV vaccine (n = 40) or with placebo (n = 12) and were followed for 6 months. None of the vaccine recipients developed significant systemic reactions or aminotransferase elevations. HAV was not isolated in cell culture from any postvaccination serum or stool specimen tested. Antibody to HAV was detected by modifications of HAV antibody assays (HAVAB or HAVAB-M) in 20%, 40%, 60%, and 100% of the recipients of each vaccine dose, in ascending order. Neutralizing antibody was present in all 10(7.3) TCID50 recipients tested at 3 and 6 months after vaccination. This live attenuated HAV vaccine was well tolerated and highly immunogenic at a dose of 10(7.3) TCID50.

Adult↗

PubMed1984

Improved visualization through cataracts using intravitreal illumination.

It is known that intravitreal illumination during vitrectomy improves both contrast and resolution for the surgeon by eliminating backscatter and reflections from both cornea and lens. The experiments described in this paper set out to quantitate the amount of improvement in these optical parameters using simulated intravitreal illumination when a target was viewed behind a cataractous lens. The results show an almost fourfold increase in contrast and a twofold increase in resolution when the illumination is placed behind the cataract, ie, intravitreal illumination vs external microscope illumination where the illumination is placed between the cataract and the observer.

Animals↗

PubMed1982

Temperature-dependent alteration of cellular morphology by cholera toxin in rat liver epithelial cells which are ts for maintenance of transformed properties.

Cholera toxin via its ability to increase intracellular cyclic AMP levels can induce drastic changes in cell morphology. This report describes a temperature sensitive mutant of chemically transformed rat liver epithelial cells which only display cell shape alterations in response to cholera toxin at the permissive temperature. Shift up-shift down experiments indicate that the change in the response occurs fairly rapidly, i.e., within 2 hours at the new temperature. The behavior of the temperature sensitive cells at the nonpermissive temperature mimics that of the untransformed rat liver epithelial cells (i.e., no morphological change in response to cholera toxin) while at the permissive temperature the positive cell shape change is identical to that exhibited by chemically transformed rat liver epithelial cells. The temperature sensitive response to cholera toxin is not a function of cyclic AMP production, since the amount of cyclic AMP found as a function of either time or concentration of cholera toxin is quite similar in cells treated at either temperature.

Animals↗

PubMed1981

Differential sensitivity of normal and chemically transformed epithelial cells to cholera toxin.

We have been studying the regulation of growth by cyclic adenosine 3':5'-monophosphate (cyclic AMP) and other factors in untransformed (K16) and chemically transformed (W8) rat liver epithelial cells. Initially, we found that 8-bromocyclic adenosine 3':5'-monophosphate was a more potent inhibitor of cell replication in K16 than in W8 cells. In addition, the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine (MIX) caused marked growth inhibition in K16 but not in W8 cells. Through the use of cholera toxin (CT) with or without MIX, we elevated intracellular cyclic AMP levels in a quantifiable fashion. With CT alone or combined with MIX, we observed a dose-dependent morphological change in W8 cells, which consisted of extensive "process" formation. K16 morphology was not altered at any concentration of CT +/- MIX tested. K16 cell growth was only marginally inhibited by CT alone, but markedly inhibited by CT plus MIX. W8 cell growth was moderately inhibited by CT alone or combined with MIX. Analysis of cyclic AMP levels revealed that, at all concentrations of CT +/- MIX and at all time periods tested, W8 cells produced significantly more cyclic AMP than K16 cells. It appears that morphological changes and growth inhibition are not necessarily linked and that MIX may inhibit K16 cell replication by means other than its ability to increase intracellular cyclic AMP levels.

Animals↗