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Biomedical subjects

J W Hooper

Publications and source records attributed to J W Hooper.

9 recordsLinked to original sources
PubMed1996

Role of the mu 1 protein in reovirus stability and capacity to cause chromium release from host cells.

The reovirus M2 gene is associated with the capacity of type 3 strain Abney (T3A) intermediate subviral particles (ISVPs) to permeabilize cell membranes as measured by chromium (51Cr) release (P. Lucia-Jandris, J. W. Hooper, and B. N. Fields, J. Virol. 67:5339-5345, 1993). In addition, reovirus mutants with lesions in the M2 gene can be selected by heating virus at 37 degrees C for 20 min in 33% ethanol (D. R. Wessner and B. N. Fields, J. Virol. 67:2442-2447, 1993). In this report we investigated the mechanism by which the reovirus M2 gene product (the mu 1 protein) influences the capacity of reovirus ISVPs to permeabilize membranes, using ethanol-selected T3A mutants. Each of three T3A ethanol-resistant mutants isolated (JH2, JH3, and JH4) exhibited a decreased capacity to cause 51Cr release relative to that of wild-type T3A. Sequence analysis of the M2 genes of wild-type T3A and the T3A mutants indicated that each mutant possesses a single amino acid substitution in a central region of the 708-amino-acid mu 1 protein: JH2 (residue 466, Tyr to Cys), JH3 (residue 459, Lys to Glu), and JH4 (residue 497 Pro to Ser). Assays performed with reovirus natural isolates, reassortants, and a set of previously characterized type 3 strain Dearing (T3D) ethanol-resistant mutants revealed a strong correlation between ethanol sensitivity and the capacity to cause 51Cr release. We found that ISVPs generated from the T3A and T3D mutants were stable when heated to 50 degrees C, whereas wild-type T3A ISVPs are inactivated under these conditions. Together, these data suggest that amino acid substitutions in a central region of the mu 1 protein affect the capacity of the ISVP to permeabilize L-cell membranes by altering the stability of the virus particle.

Amino Acid Sequence↗
PubMed1996

Monoclonal antibodies to reovirus sigma 1 and mu 1 proteins inhibit chromium release from mouse L cells.

Reovirus intermediate subviral particles (ISVPs) but not intact virions or cores have been shown to possess the capacity to permeabilize mouse L cells as determined by a 51Cr release assay. We used monoclonal antibodies (MAbs) directed against proteins exposed on the ISVP surface (sigma 1, mu 1, and lambda 2) to probe the role(s) of these proteins in membrane interaction and penetration. One sigma 1-specific MAb (MAb-G5) and two mu 1-specific MAbs (MAb-10H2 and MAb-8H6) inhibited reovirus-induced 51Cr release when added pre- or post-ISVP attachment to L cells. MAb-G5 inhibits 51Cr release by interfering with ISVP attachment (via sigma 1) to L-cell receptor sites. The mu 1-specific MAbs (MAb-10H2 and MAb-8H6) inhibit 51Cr release by interfering with an undefined post-L-cell-attachment event that involves bivalent binding of the mu 1-specific MAbs to an epitope located in a central region of the mu 1 protein.

Animals↗
PubMed1995

Application issues in bioanalytical method validation, sample analysis and data reporting.

Although some degree of consensus has been reached concerning the requirements for acceptable method validation, the procedures used to establish them vary significantly between laboratories. Also, issues arising from application of these requirements during validation and subsequent sample analysis need to be addressed. The purpose of this paper is to discuss application issues concerning prerequisites to method validation, and all validation criteria for evaluation of method reliability and overall performance. Other poorly addressed issues such as re-validation, cross-validation, partial sample volume, multicomponent analysis and reporting will also be discussed. Although many issues discussed are of a general nature, the scope of this presentation is primarily to address issues arising from the validation and routine application of chromatographic methods.

Animals↗
PubMed1993

Reovirus M2 gene is associated with chromium release from mouse L cells.

In this study, we investigated the interaction of reovirus particles with cell membranes by using a 51Cr release assay. We confirmed prior observations (J. Borsa, B. D. Morash, M. D. Sargent, T. P. Copps, P. A. Lievaart, and J. G. Szekely, J. Gen. Virol. 45:161-170, 1979) that intermediate subviral particles (ISVPs) of reovirus type 3 strain Abney (T3A) induced the release of 51Cr from preloaded L cells and showed that the intact virion and core forms did not. Reovirus type 1 strain Lang (T1L) ISVPs were found to be less efficient at 51Cr release than T3A ISVPs. Reassortants between these strains indicated that the 51Cr release phenotype segregates with the M2 gene segment. Biochemical studies indicated that the ISVPs' acquisition of the capacity to induce 51Cr release followed the cleavage of the viral M2 gene product mu 1/mu 1C to fragments delta and phi during virion conversion to ISVP but did not directly correlate with this cleavage. These studies suggest that the reovirus M2 gene product (in its cleaved form) plays a role in interacting with cell membranes.

Animals↗
PubMed1986

The effect of age on ranitidine pharmacokinetics.

Oral ranitidine was given to 68 healthy subjects between 18 and 75 years old at a dosage of 150 mg twice a day for seven doses. Fifteen subjects were 18 to 35 years old (group I), 19 subjects were 36 to 50 years old (group II), 19 subjects were 51 to 65 years old (group III), and 15 subjects were 66 to 75 years old (group IV). Venous blood samples were drawn and the AUC from 0 to 12 hours, the maximum plasma concentration, the time of the maximum plasma concentration, the minimum plasma concentration, and the elimination t1/2 were determined. When groups III and IV were compared with groups I or II, significant (P less than 0.05) increases were seen in the AUC(0-12) (42% and 50%), the maximum plasma concentration (36% and 41%), the minimum plasma concentration (91% and 85%), and the elimination t1/2 (29% and 33%). Positive linear correlations were found when the AUC(0-12) (r = 0.68; P less than 0.01), the maximum plasma concentration (r = 0.34; P less than 0.01), the minimum plasma concentration (r = 0.55; P less than 0.01), and the elimination t1/2 (r = 0.46; P less than 0.01) were regressed with age. Our results suggest that it may be appropriate to consider dosage adjustments for patients over 50 years of age who take ranitidine.

Administration, Oral↗
PubMed1985

Fecal blood loss during isoxicam and piroxicam administration for 28 days.

After an 11-day baseline period, groups of eight healthy men received isoxicam, 200 mg once a day, or piroxicam, 20 mg once a day, for 28 days. Fecal blood loss (FBL) was quantitated by the 51Cr-labeled erythrocyte method. FBLs for both isoxicam and piroxicam were only slightly higher than baseline for the first 3 drug dosing days, confirming the results of a previously published 4-day study of piroxicam, but FBL subsequently steadily increased, with maxima occurring for most subjects receiving isoxicam in 2 or 3 weeks and for most subjects receiving piroxicam in 3 or 4 weeks. This implies that dosing for 7 days or less, as is frequent in FBL studies of nonsteroidal anti-inflammatory drugs, may be insufficient to detect the peak drug-induced FBL. In week 4, FBL for both drugs was elevated approximately 0.6 ml/day over baseline. FBLs in week 4 were comparable to those reported for naproxen and less than those reported for indomethacin and acetylsalicylic acid. Statistical analyses of weekly plasma drug minimum concentrations suggest steady state was reached at week 2 for isoxicam and week 3 for piroxicam. There were large between-subject variations in steady-state plasma drug concentrations for both drugs. One subject in each drug group indulged in excessive alcohol consumption during the medication period, with a concomitant significant increase in FBL, which suggests exacerbation of the drug effect.

Adolescent↗
PubMed1985

Minimization of gastric damage with enteric-coated aspirin granules compared to buffered aspirin.

This study involved a randomized parallel groups comparison of the effects of aspirin formulated as enteric-coated granules (25 subjects) or as buffered tablets (26 subjects) with that of a lactose placebo (5 subjects), on the gastric and duodenal mucosa, as determined by endoscopic examination 2 h after a fasting single 975-mg dose. A grading scale of 0 (no damage) to 4 (severe damage) was used. The granule formulation produced a statistically significant (p less than 0.05) lower severity (mean 0.40 +/- 0.58 vs. 3.00 +/- 0.94) and incidence (36% of subjects vs. 100%) of gastric lesions than the buffered aspirin formulation. None of the lesions produced by the granule formulation or the placebo was considered clinically significant by the blinded endoscopist, whereas 17 subjects on the buffered formulation (65%) had clinically meaningful stomach damage. The incidence of duodenal lesions was minimal and comparable for the two formulations.

Adolescent↗
PubMed1980

Acquired hypertrichosis lanuginosa. Rare manifestation of urinary bladder carcinoma.

Hypertrichosis lanuginosa developed in a patient with carcinoma of the bladder. After regional lymph node metastases became evident, soft, fine, blond hair developed on his entire body, with the exception of the soles and the palms. Extensive endocrinologic evaluation demonstrated depressed testosterone levels and elevated levels of leutinizing hormone, changes not thought to be related to the hair growth. To our knowledge, this patient constitutes the second reported case of this rare syndrome in association with bladder carcinoma.

Aged↗