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Biomedical subjects

J B Bishop

Publications and source records attributed to J B Bishop.

51 records · Page 3Linked to original sources
PubMed1982

Development of a new biochemical mutation test in mice based upon measurements of enzyme activities. I. Theoretical concepts and basic procedure.

A test procedure is described for detecting germ cell mutations which alter activity of enzymes in in vivo mammalian tissues. The objective is to identify those individuals, among a population of F1 animals from treated parents, that are heterozygous for a mutation at an unspecified locus which results in an altered activity of one or more of the enzymes monitored. Animals are evaluated through three analysis screens with emphasis on identification of mutant individuals. In the first screen, activity values of a battery of enzymes are compared to their respective normal ranges to identify those which are aberrant. The mean activities and coefficients of variation useful in defining the normal ranges for 19 enzymes in C57BL/6J Nctr mice are presented along with a set of theoretical normal animal misclassification probabilities for each of these enzymes. The second screen is a Michaelis-Menten kinetic analysis of aberrant enzymes, the goal of which is to correct misclassifications of normal animals made in the first screen. A third screen of aberrant enzyme activities in a subsequent generation is used to demonstrate inheritance and confirm the mutation. The advantages and the limitations, as well as possible variations of the basic procedure are discussed.

Animals↗
PubMed1982

Development of a new biochemical mutation test in mice based upon measurement of enzyme activities. II. Test results with ethyl methanesulfonate (EMS).

An experiment with ethyl methanesulfonate (EMS) was conducted to determine the feasibility of detecting chemically induced mutations in mice by quantitative analysis of metabolic characters using the test procedure of Feuers et al. (1982). A test population of 518 F1 mice from matings of untreated C57BL/6J females to C57BL/6J males treated with 0, 100, 175 or 200 mg/kg EMS was evaluated according to a set of multi-level biochemical and genetic screening criteria. The goal of the assay was identification of F1 individuals heterozygous at an unspecified locus for an induced mutant allele which altered the activity of one or more of 19 enzymes in brain and liver tissues of their F2 and F3 progeny, 8 individuals among a population of 345 F1's from the EMS-dosed groups were classified as confirmed mutants having at least 2 of their F2 progeny exhibiting the same enzyme aberrancy and transmitting this aberrancy to the F3 generation. No confirmed mutants were detected in the control population of 173 F1 individuals. These results indicate that this test method can be used to detect chemically induced mutations expressed as quantitative alterations in enzyme activity.

Animals↗
PubMed1982

A method for preparing chromosomes from peripheral blood of the mouse.

A modified Triman et al. (1975) procedure for preparing metaphase chromosomes from mouse peripheral blood is described. Modifications include: isolation of white blood cells using a ficoll-hypaque gradient; seeding cultures with a known concentration of leucocytes such that the PHA/cell concentration can be controlled for optimum stimulation through 72 h with no media change; and visual monitoring of cell growth to determine when there should be sufficient numbers of dividing cells for harvest and thus eliminate unnecessary harvest of non-productive cultures. We have found this modified procedure to be highly reproducible with the final 0.5 ml fixed cell suspension yielding 50-75 quality metaphase spreads per drop.

Animals↗
PubMed1980

The heritable translocation assay: its relationship to assessment of genetic risk for future generations.

The Heritable Translocation Assay (HTA) is an in vivo mammalian mutation test which measures specific clastogenic damage. It can be subjected to rigorous statistical scrutiny and detects a type of heritable genetic damage that is known to contribute to the human disease burden. Because of these factors the HTA is one of the major tests of the battery used in regulatory evaluation of potential environmental mutagens. Although tests for detecting inherited translocations have been developed and improved over the past 40 years, further emphasis on several statistical considerations affecting the precision and reliability of HTA animal model data applied to regulatory hazard evaluation and risk assessment seems warranted. In this paper we have presented a brief history and the basic methodology for the HTA. Statistical concepts related to the design and implementation of HTA studies, such as the incorporation of false classification error probabilities in determination of required sample size and use of the single sample binomial versus Fisher's exact test for analysis of data, hory and the basic methodology for the HTA. Statistical concepts related to the design and implementation of HTA studies, such as the incorporation of false classification error probabilities in determination of required sample size and use of the single sample binomial versus Fisher's exact test for analysis of data, hory and the basic methodology for the HTA. Statistical concepts related to the design and implementation of HTA studies, such as the incorporation of false classification error probabilities in determination of required sample size and use of the single sample binomial versus Fisher's exact test for analysis of data, have been examined in detail. We have also suggested a simplified method of extrapolating HTA animal data to man similar to that used with carcinogenesis data and propose other developmental needs and perspectives for application of this assay to regulatory assessment of environmental mutagens.

Animals↗
PubMed1980

Persistent tracheostomy stoma.

Prolonged presence of a tracheostomy tube or prolonged tracheostomy stoma can result in a failure of spontaneous closure. The stoma may remain open until surgically closed. Muscle flaps as well as skin flaps can be used to close the persistent tracheostomy stoma. These flaps seal the stoma, provide soft tissue between the trachea and the skin, and allow a satisfactory cosmetic result. The sternohyoid muscle is readily accessible for this purpose. This procedure was used in five patients with a satisfactory result in each.

Fistula↗
PubMed1980

Heritable translocation test in mice.

The status of the heritable-translocation test in mice with respect to its usefulness in practical testing was evaluated by using information available in the open literature. A total of 47 reports were evaluated; 29 were judged to contain adequate information to classify whether or not a given chemical induced heritable translocations. Heritable-translocation data were available for 32 compounds; data were not adequate for 15 compounds. Of the remaining 17 compounds, clear-cut determination of positive or negative effects was made for 14 compounds, while data for 3 compounds were only suggestive of either negative or positive effects. 10 chemicals have been shown to induce heritable translocations. These chemicals are either direct or indirect alkylating agents. The heritable-translocation test needs to be improved before it can be used in wide-scale practical testing. The most important question is whether or not historical controls can be used in tests for significance; the cost of concurrent controls is prohibitive. There is a need to standardize methods used in testing laboratories with respect to the size of error involved in classifying translocation heterozygotes and the power of the test. There is also a need to study in the effectiveness of non-alkylating clastogens in inducing heritable translocations in mice.

Animals↗
PubMed1980

Infected median sternotomy wound. Successful treatment by muscle flaps.

The purpose of this paper is to present the experience at Emory University Hospital with the infected median sternotomy wound and to offer a treatment plan for those patients recalcitrant to the usual therapy of debridement and closed catheter irrigation with antimicrobial agents. When standard treatment fails, we proceed not only with the necessary thorough debridement to convert the wound to a relatively clean one but also concomitant closure by pectoralis major muscle flaps to completely obliterate dead space. Transposition flaps of rectus abdominus muscle or omentum are used when necessary to complete the closure. In the initial phase of this study, there were 3,239 patients who underwent open heart procedures through a median sternotomy approach in the years 1975 through 1978. In the 50 patients who had wound infections (1.54%), there were nine deaths. Three were thought to be unrelated to the sternal wound infection, four patients ruptured the ventricle or aorta, two patients died of generalized sepsis. Of these 50 patients, 22 responded to simple drainage; 28 had involvement of the mediastinum (0.86%). Of the 28 patients, 25 had debridement and closed mediastinal irrigation by catheter. Fourteen of these 25 did not respond. In these failing patients, 12 were treated by further debridement and closure by muscle flaps. Nine of these 12 were rescued. In the past nine months, an additional 1,052 patients had an open heart procedure. Of these, 11 had a median sternotomy infection. There have been no deaths in this latter group of patients, most of whom were treated by the muscle flap procedure. In addition to the improvement in mortality, morbidity has been reduced substantially. This procedure provides for a rational approach that we have found to permit salvage of a high percentage of patients who failed conventional closed irrigation techniques.

Anti-Bacterial Agents↗
PubMed1980

The burned female breast.

Historically, treatment of the burned female breast has been unsatisfactory. By using the latissimus dorsi myocutaneous flap, many patients can be reconstructed in a single operation. A more aggressive approach in adolescent patients whose breasts are developing may result in more normal breasts. In such patients, nipple reconstruction is delayed until a later time.

Adult↗
PubMedDate not supplied

Developmental response of zygotes exposed to similar mutagens.

Exposure of mouse zygotes to ethylene oxide (EtO) or ethyl methanesulfonate (EMS) led to high incidences of fetal death and of certain classes of fetal malformations (Generoso et al., 1987, 1988; Rutledge and Generoso, 1989). These effects were not associated with induced chromosomal aberrations (Katoh et al., 1989) nor are they likely to be caused by gene mutations (Generoso et al., 1990). Nevertheless, the anomalies observed in these studies resemble the large class of stillbirths and sporadic defects in humans that are of unknown etiology, such as cleft palate, omphalocoel, clubfoot, hydrops and stillbirths (Czeizel, 1985; Oakley, 1986). Therefore, we continue to study the possible mechanisms relating to induction of these types of zygote-derived anomalies in mice. Effects of zygote exposure to the compounds methyl methanesulfonate (MMS), dimethyl sulfate (DMS), and diethyl sulfate (DES), which have similar DNA-binding properties as EtO and EMS, were studied. DMS and DES, but not MMS, induced effects that are similar to those induced by EtO and EMS. Thus, no site-specific alkylation product was identifiable as the critical target for these zygote-derived anomalies. We speculate that the developmental anomalies arose as a result of altered programming of gene expression during embryogenesis.

Animals↗
PubMedDate not supplied

Toxicokinetics of sulfasalazine (salicylazosulfapyridine) and its metabolites in B6C3F1 mice.

The toxicokinetics of salicylazosulfapyridine (SASP) and its metabolites were investigated in male and female B6C3F1 mice either following single intravenous (5 mg/kg) or oral (67.5, 675, 1350, and 2700 mg/kg) doses, or following three consecutive daily oral doses (675, 1350, and 2700 mg/kg). Plasma concentrations of SASP and its metabolites were quantified by HPLC. Upon intravenous administration, SASP rapidly disappeared from blood with a mean residence time of 0.45-0.78 hr. The only metabolite of SASP found in plasma after an intravenous dose was sulfapyridine (SP). In both sexes, the absolute oral bioavailability of SASP ranged between 16.6-18.2% at a dose of 67.5 mg/kg, and between 2.6-8.7% at doses of 675-2700 mg/kg. Following oral administration of SASP, both SP and AcSP were identified in plasma. The area under the plasma concentration-time curves (AUC) of SP at all four oral doses were approximately 21- to 32-fold or 5- to 25-fold greater than those of SASP in male or female mice, respectively. The acetylated form of SP and AcSP, produced AUC values higher than SASP but much less than SP. Multiple oral doses with SASP did not alter the temporal patterns of SASP absorption and elimination in comparison to a single dose. However, SP accumulated in both sexes following multiple oral doses. A gender-dependent difference in toxicokinetic profiles for SASP and SP was also observed. Female mice displayed a higher Cmax of SASP and SP than did male mice. Although the volume of distribution of SASP was similar in both sexes, the systemic clearance of SASP in males was about twice that observed in females.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗