Using X-ray diffraction results and computer graphics to design beta-lactams.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J A Kelly.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
More than most diseases, acquired immune deficiency syndrome (AIDS) appears to elicit highly negative, fearful, and prejudicial attitudes. In the study reported here, medical students read one of four patient vignettes. The vignettes were identical in content except that the patient was identified as having either AIDS or leukemia as either homosexual or heterosexual. The students then completed a set of objective measures that assessed their attitudes toward the patient portrayed in the vignette. Multivariate and univariate analyses of variance of their responses revealed that the students held negative and prejudiced attitudes toward both the AIDS and homosexual patients. This finding suggests that medical educators should recognize that many students have stigmatizing, negative attitudes toward homosexuals and patients with AIDS. These educators should promote greater sensitivity, knowledge, and understanding among medical students of those at risk for AIDS and AIDS patients.
A screening programme was undertaken to examine the possibility of cross resistance occurring between cyromazine and conventional insecticides. The responses of nine strains of Musca domestica to treatment with cyromazine, trichlorphon, methomyl and pyrethrins with piperonyl butoxide were measured. No tolerance to cyromazine was found, neither was there a direct correlation between larval responses to cyromazine and adult responses to other insecticides. Cyromazine is a potent larvicide against M. domestica and the results of these tests show that it has good potential for the control of houseflies with high levels of resistance to other insecticides.
A randomly selected sample of physicians in three large cities was asked to read one of four vignettes describing a patient. They then completed a set of objective attitude measures eliciting their reactions to the patient described in the vignette. The vignettes were identical except that the patient's illness was identified as either acquired immunodeficiency syndrome (AIDS) or leukemia and the patient's sexual preference as either heterosexual or homosexual. Harsh attitude judgements were associated with the AIDS portrayals, as well as much less willingness to interact even in routine conversation when the patient's illness was identified as AIDS. Increasing numbers of AIDS patients will be seeking medical attention from physicians in all areas of the country and it will be important for health care professions to develop programs which counter unreasonable stigma and prejudicial attitudes that may be associated with this illness.
Explore the source record for details and available documents.
Structural data are now available for comparing a penicillin target enzyme, the D-alanyl-D-alanine-peptidase from Streptomyces R61, with a penicillin-hydrolyzing enzyme, the beta-lactamase from Bacillus licheniformis 749/C. Although the two enzymes have distinct catalytic properties and lack relatedness in their overall amino acid sequences except near the active-site serine, the significant similarity found by x-ray crystallography in the spatial arrangement of the elements of secondary structure provides strong support for earlier hypotheses that beta-lactamases arose from penicillin-sensitive D-alanyl-D-alanine-peptidases involved in bacterial wall peptidoglycan metabolism.
Induced vasodilation by classical conditioning was compared to biofeedback therapy as treatment for idiopathic Raynaud's disease. Classical conditioning therapy consisted of 54 10-min immersions of both hands in water (43 degrees C) simultaneously with whole-body exposure to cold air (0 degrees C), given three times per day, 3 days per week, for 6 weeks. Biofeedback therapy consisted of eight sessions of electromyograph feedback (frontalis) while listening to relaxation tapes, followed by 10 sessions of digital thermal feedback while listening to relaxation tapes. Both groups received 10-min cold stress tests of whole-body exposure to 0 degrees C before and after treatments. Results indicated that both therapies significantly increased the digital temperature response to cold. Although no differences between classical conditioning and biofeedback were found at the end of training, a 1-year follow-up indicated that classical conditioning was more effective.
The crystallographic structure of the penicillin-sensitive D-alanyl carboxypeptidase-transpeptidase from Streptomyces R61 has been solved to 2.8-A resolution. The 38,000-dalton serine peptidase has two regions of secondary structure, an alpha/beta cluster, and a region which contains five helical segments. The beta sheet is composed of five beta strands. The tertiary structure has no homology with the classic serine proteases or with the zinc carboxypeptidases. The binding at a common site of three types of beta-lactam (a penicillin, a cephalosporin, a monocyclic beta-lactam) and a desazacyclobutanone has been observed in Fourier difference maps. The binding site sequence is Val-Gly-Ser-Val-Thr-Lys. The beta-lactam ring lies near the enzyme's catalytic serine at position 37, and the C3 substituent of a cephalosporin falls near lysine 40.
An enzyme present in mouse brain cytosol cleaves C-terminal dipeptides from substrates including ACTH-(7-10) (Phe-Arg-Trp-Gly), and des-Tyr-[Met]- and des-Tyr-[Leu]enkephalin. By means of ion-exchange chromatography and gel filtration, the peptidase was purified to a specific activity of 1570 times that of brain homogenate. At this purification, a second peptidase, which hydrolyzes Trp-Gly and other peptides [M. E. A. Reith and A. Neidle (1979) Biochem. Biophys. Res. Commun. 90, 794-800] was still present, but could be removed by preparative polyacrylamide gel electrophoresis. The des Tyr-enkephalin-cleaving enzyme has a molecular weight of about 85,000 and a pH optimum of 7.8. It is inhibited by metal-chelating and sulfhydryl reagents. The enzyme has a strong preference for substrates with an aromatic residue in the position adjacent to the C-terminal amino acid, although some peptides meeting this criterion were competitive inhibitors rather than substrates. Peptides with less than four residues were inactive and, in general, tetrapeptides were found to be more reactive than larger analogs, when peptides with common C-terminal sequences were compared. The peptidyl dipeptidase, which has not been described previously, can be readily distinguished from angiotensin-converting enzyme (EC 3.4.15.1) and from neutral endopeptidase (EC 3.4.24.11) by its subcellular localization, substrate specificity, and response to inhibitors. It was suggested that peptidyl dipeptidase-B (PDP-B, EC 3.4.15.-) would be an appropriate name for the enzyme. PDP-B is widely distributed among mouse tissues.
Inverted nasal papillomas are rare tumors in children. Four large series include only a single patient (of a total of 269) younger than 20 years. We report the occurrence of an inverted nasal papilloma in a 10-year-old boy; this tumor exhibited clinical and histopathologic features identical to those of similar neoplasms in adults. Inverted papillomas in children should be treated by wide local excision, usually using a lateral rhinotomy approach. The rationale for such aggressive surgery is based on the high rate of recurrence (25% to 75%) and a propensity for the development of carcinomas (5% to 15%) as associated lesions.
Recent behavioral formulations suggest that child abuse can often be conceptualized in terms of skill deficits of the parent. In the present case study, training was used to improve an abusive parent's anger-assertion, child management, and personal problem-solving skills; deficits in all three areas were functionally related to prior episodes of violence. Treatment across these skill areas was introduced in multiple baseline fashion. The effectiveness of treatment was demonstrated by assessments of assertion, child management, and problem-solving knowledge following each training session; parent monitoring data on the frequency of child-related and anger problems at home throughout the intervention; performance on skill generalization measures; and objectively-rated parent-child interactions during pre- and post-training home observation probes.
Several recent investigations have shown that abusive and neglectful parents exhibit deficits in skills for interacting with their children. In the current study, an inattentive and neglectful parent was taught to provide positive verbal and physical attention towards her 4-year-old child. Training was accomplished using a "bug-in-the-ear" microphone device while the parent interacted with her child in a clinic playroom. After use of the device was discontinued, the parent continued to use the newly trained skills at rates higher than during baseline. Four month follow-up and at home observations were suggestive of skill maintenance. Training of this kind may prove useful for parents who lack skills for effective interaction with their children.
Explore the source record for details and available documents.
Tampons were tested for effect on growth and production of toxic shock syndrome toxin 1 by Staphylococcus aureus. Under good growth conditions, regular absorbency tampons had little effect on bacterial growth and inhibited toxin production two- to fourfold. In contrast, higher absorbency tampons had three different effects: 1) some tampons had no effect on bacterial growth but inhibited toxin production; 2) many tampons inhibited both growth and toxin production; 3) one tampon inhibited growth but increased exotoxin per cell. These effects were independent of degree of saturation of the tampons and were observed at incubation times of six, 12, and 18 hours. In no instance was the production of toxic shock syndrome toxin 1 per milliliter increased in the presence of tampons when compared with control.
Vocational training has long been a major part of habilitation programs for mentally retarded adults. However, even after retarded persons develop work habits and skills, they may be unable to convince potential employers of their vocational competence. The present article discusses the rationale for systematically teaching mentally retarded persons job interview and other job finding skills, and reviews applied job interview training research with mentally retarded clients and other low functioning populations. Implementation of training techniques is also discussed.
Explore the source record for details and available documents.
An aminopeptidase with specificity directed toward peptides with acidic N-terminal amino acid residues has been isolated from mouse brain cytosol. Purification by ion-exchange chromatography and gel filtration resulted in an enzyme that hydrolyzed aspartyl-phenylalanine methyl ester at a rate of 13.2 mumols/min/mg protein at pH 7.5, an increase in specific activity of 1000-fold over that of brain homogenate. Its apparent molecular weight, determined by gel filtration, is approximately 450,000. Dipeptides with N-terminal aspartyl residues are cleaved preferentially to glutamic-containing analogs, and a neutral amino acid (or histidine) is necessary in the adjacent position. For peptides of the form aspartyl-X, relative activity was 100, 81, 71, 66, 19, or 0, where X was alanine, serine, leucine, phenylalanine, histidine, or proline, respectively. Tripeptides were more rapidly hydrolyzed than dipeptides; however, activity tended to decline with increasing chain length. The acidic aminopeptidase can account for almost all of the activity of brain cytosol toward the N-terminal aspartyl residue of angiotensin II, aspartyl-phenylalanine methyl ester or aspartyl-alanine, and the N-terminal glutamyl residue of adrenocorticotropin(5-10). The enzyme was unaffected by bestatin or amastatin. It was inhibited by o-phenanthroline and EDTA. The latter effect could be reversed completely by Zn2+ and partially by Mn2+ or Mg2+; Co2+ and Fe2+ had no effect; Ca2+ was inhibitory. These properties distinguish the brain acidic aminopeptidase from aminopeptidase A isolated from human serum or pig kidney and the aspartyl aminopeptidase of dog kidney.