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Biomedical subjects

J Austin

Publications and source records attributed to J Austin.

At least 73 records · Page 4Linked to original sources

The W element is a positive regulator of HLA-DRA transcription in various DR+ cell types.

The W and P elements are cis-acting transcriptional regulators of the human class II MHC gene HLA-DRA necessary for maximal promoter activity in DR+ B cells. Proteins that bind specifically to W may mediate promoter activity from a DNA segment containing W and P (W/P). In this report, we demonstrate that a -143 to -123 bp region that lacks P is sufficient to mediate the W elements function and to bind the W proteins W-B1 and W-B2 in the Raji B-lymphoblastoid cell line. In contrast to previous reports, we find that W/P is not a B cell-specific element; rather that its promoter activity parallels active transcription of the endogenous DRA gene. In addition, we show that tissue-restricted regulation by W/P is not correlated with the ubiquitous (W-B1) and lymphoid-specific (W-B2) distribution of the W binding proteins. We suggest that mechanisms in addition to binding to W may account for W/P-dependent transcriptional activation in DR+ cells.

B-Lymphocytes↗

Disease and psychosocial factors related to physical functioning in rheumatoid arthritis.

One hundred and fifty-five patients with rheumatoid arthritis (RA) were randomly selected from a tertiary care outpatient rheumatology clinic. Disease, treatment, psychosocial and demographic data were collected to test a biopsychosocial model of Physical Functioning as determined by the Arthritis Impact Measurement Scales (AIMS). Cross-sectional and longitudinal hierarchical and stepwise regression analysis were performed to identify variables associated with Physical Functioning. The results of the hierarchical regression revealed that only the disease and psychosocial sets of variables were significant. Stepwise regression revealed that Disease Severity (disease set) and Arthritis Helplessness (psychosocial set) accounted for 37% (longitudinal) to 60% (cross-sectional 12 months---greater than 12 months) of Physical Functioning variance. Our results suggest a role for the inclusion of psychosocial factors in studies of the development of physical disability in patients with RA.

Adult↗

Pulp revascularization in reimplanted immature monkey incisors--predictability and the effect of antibiotic systemic prophylaxis.

In 32 monkeys 105 immature maxillary incisors were extracted and reimplanted either immediately or after 30 or 60 min wet or dry storage. Of the monkeys, 17 (group I) did not receive and 15 (group II) received prophylactic treatment with 4 mg/kg doxycycline before extraction and 2 mg/kg for 5 d after reimplantation. The observation time varied from 6 to 8 weeks. After being histologically processed, the material was evaluated with respect to the amount of vital tissue and presence of micro-organisms in the pulpal lumen. A comparison revealed no difference in the results between the groups. The results were therefore pooled and statistically analysed with respect to the significance of apical foramen width, extra-alveolar time, wet or dry storage and presence of micro-organisms in the pulpal lumen for the occurrence of complete pulp revascularization (CPR). The overall frequency of CPR was 18%. Log-linear analyses (SAS, 1985) of the material as a whole or of separate parameters consistently revealed a relationship between presence of micro-organisms and absence of CPR (P = 0.0001). A higher frequency of CPR and a lower frequency of micro-organisms (P = 0.05) was found only for the group of immediately reimplanted teeth. The presence of micro-organisms could be explained for 61 teeth. In 27 of these, blood clots containing bacteria in the apical portion of pulpal lumen indicated contamination during the extra-alveolar time, while in 34, the micro-organisms originated from plaque covered mechanical damage in the cervical part of the root surface.

Animals↗

Effect of topical application of doxycycline on pulp revascularization and periodontal healing in reimplanted monkey incisors.

Maxillary incisors in 47 monkeys, 54 in the experimental group (I) and 117 in the control group (II), were extracted and reimplanted, either immediately or after 30 or 60 min wet or dry storage. Incisors in the experimental group I were additionally kept 5 min in a suspension of 1 mg doxycycline in 20 ml physiologic saline, freshly prepared for each of the 15 animals before reimplantation. The observation time varied from 6 to 8 weeks. The teeth were removed in tissue blocks, histologically processed and evaluated for occurrence of complete pulp revascularization (CPR), presence of the micro-organisms in the pulpal lumen and ankylosis or inflammatory root resorption. Then the results were statistically evaluated, using log-linear analyses and chi-square tests (SAS, 1985) for the comparisons between group I and group II. These analyses revealed that topical application of doxycycline increased the frequency of complete pulp revascularization (P less than 0.002) and decreased the frequency of micro-organisms in the pulpal lumen (P less than 0.001). Furthermore, the frequencies of ankylosis (P less than 0.05) and inflammatory root resorption (P less than 0.001) were also decreased compared with the control group of teeth. It was concluded that the effect of topical treatment with doxycycline was most probably exerted on the micro-organisms that contaminated root surface during the extra-alveolar time; contamination of necrotic pulp tissue from the mechanical damage in the cervical part of the root surface was not affected.

Animals↗

Gastroesophageal reflux and sclerotherapy strictures.

The development of esophageal stricture is common following endoscopic variceal sclerotherapy (EVS). Gastroesophageal reflux may be at least partly responsible. Twelve randomly selected male patients underwent chronic EVS for the management of bleeding esophageal varices. Six patients developed strictures during or after EVS, six did not. There were no significant differences between stricture and nonstricture patients during 24 hour esophageal pH monitoring. Three of the six stricture patients and four of the six nonstricture patients had an abnormal amount of reflux. Gastroesophageal reflux occurs frequently in patients undergoing EVS, and it is not likely to play a major role in EVS stricture formation.

Adult↗

Transcript analysis of glp-1 and lin-12, homologous genes required for cell interactions during development of C. elegans.

The glp-1 and lin-12 genes mediate several cell interactions during C. elegans development. We have identified the glp-1 gene in a region about 20 kb from lin-12. In collaboration with Yochem and Greenwald (1989; see accompanying paper), we show that a sequence identified by its similarity to lin-12 is in fact glp-1. We find a single 4.4 kb glp-1 transcript and a distinct 4.6 kb lin-12 transcript. Expression of the glp-1 transcript during development differs from that of lin-12. As expected from genetic analyses, glp-1 RNA is primarily in the germline while lin-12 RNA is primarily in the soma. Unexpectedly, we find that glp-1 RNA is also expressed in larval somatic tissues and that lin-12 RNA is abundant in early embryos. We suggest that glp-1 and lin-12 may play broader roles in development than previously thought.

Animals↗

Genetic control of cellular interactions in Caenorhabditis elegans development.

During development of the nematode, Caenorhabditis elegans, cell interactions play a significant role in controlling cell fate. Regulatory cells in the somatic gonad control proliferation in the germline and induce formation of the vulva in the hypodermis. In the early embryo, mesodermal cells are induced in a process similar to embryonic induction. In addition, interactions between precursor cells of equivalent developmental potential direct one cell to adopt one fate and the other to adopt a second fate. Two genes have been identified in C. elegans that appear to mediate cell interactions. The glp-1 gene is required for embryonic induction and continued germline proliferation; lin-12 is required for cells of equal developmental potential to adopt different fates. Genetic mosaics indicate that glp-1 may be part of the receiving mechanism in controlling germline proliferation.

Animals↗

Genetics of intercellular signalling in C. elegans.

Cell-cell interactions play a significant role in controlling cell fate during development of the nematode Caenorhabditis elegans. It has been found that two genes, glp-1 and lin-12, are required for many of these decisions. glp-1 is required for induction of mitotic proliferation in the germline by the somatic distal tip cell and for induction of the anterior pharynx early in embryogenesis. lin-12 is required for the interactions between cells of equivalent developmental potential, which allow them to take on different fates. Comparison of these two genes on a molecular level indicates that they are similar in sequence and organization, suggesting that the mechanisms of these two different sets of cell-cell interactions are similar.

Animals↗

Hemodynamic and pathologic evaluation of a unileaflet pericardial bioprosthetic valve.

This study investigated the in vivo hemodynamics and pathologic changes of a unileaflet pericardial bioprosthetic valve 3 to 5 months after implantation in juvenile sheep. Group 1 had 10 sheep with tricuspid valve replacement. Group 2 had nine sheep with mitral valve replacement. Group 3 served as a control with 10 sheep that had tricuspid valve replacement with a trileaflet porcine bioprosthesis. Hemodynamic performance was satisfactory in all three groups despite prominent pathologic changes, particularly in unileaflet valves. Intrinsic cuspal calcification was present in 66% of the unileaflet tricuspid, 88% unileaflet mitral, and 25% porcine tricuspid valves. Neither cuspal tearing nor perforations were found. However, cuspal stretching and redundancy of the mobile cusp was present in six tricuspid, seven mitral unileaflet valves, and no porcine valves. Gross pericardial redundancy correlated with the microscopic appearance of distorted and separated collagen bundles. These findings suggest that multiple modes of primary tissue failure may limit the durability of this unileaflet pericardial valve.

Animals↗

glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans.

In the wild-type C. elegans germ line there are both mitotic and meiotic germ cells. Mutations in glp-1 cause germ cells that would normally divide mitotically to enter meiosis. This mutant phenotype mimics the effect of killing the distal tip cell, a somatic cell that interacts with the germ line to regulate the mitotic/meiotic decision. In addition, wild-type glp-1 product is required maternally for embryogenesis. Temperature-shift experiments indicate that the temporal requirement for glp-1 activity in the germ line is the same as that for distal tip cell regulation. Mosaic analyses suggest that glp-1 is produced in the germ line. We propose that glp-1 acts as part of the receiving mechanism in the interaction between the distal tip cell and germ line.

Animals↗

Hard tissue barrier formation in pulpotomized monkey teeth capped with cyanoacrylate or calcium hydroxide for 10 and 60 minutes.

Monkey incisor teeth were pulpotomized in groups of 10. After physiological hemostasis, the pulps of group I were covered with isobutyl cyanoacrylate, and those of groups II and III with calcium hydroxide for 10 and 60 minutes, respectively, whereafter this compound was washed away and the wound surfaces covered with Teflon. In group IV, calcium hydroxide was used as a positive control, and Teflon as a negative control in group V. The animals were killed after 12 weeks and the teeth removed in tissue blocks. The material was processed and evaluated histologically with respect to location and continuity of a hard tissue barrier, type of newly formed hard tissue, state of the pulp, and presence of stainable bacteria in the coronal cavity. Seven of nine teeth in group I showed a hard tissue barrier. The corresponding figure for group II was eight out of 10 teeth. All teeth in groups III and IV had a barrier. The incidence of a continuous barrier increased from group I through group IV, as did the incidence of its location below the level of the original wound surface. The condition of the pulp was related to the presence of bacteria and the continuity of the barrier to the presence of inflammation. There was no bridging in group V. The results support the theory that a low-grade irritation is responsible for the formation of a hard tissue barrier in exposed pulps.

Animals↗

Interim cardiac replacement with a mechanical heart: staged cardiac transplantation.

Lack of donor heart availability complicates the management of terminally ill patients who are candidates for cardiac replacement. The total artificial heart has been used as a bridge to transplantation in three patients with terminal cardiomyopathy. Acute allograft rejection and the lack of another donor heart prompted us to use the mechanical heart as a bridge to re-transplantation in a 33-year-old man. The cardiac prosthesis functioned well for 11 hours, when a second transplantation was performed, but the patient died of right heart failure 48 hours after the second transplantation. Critical factors in such cases include (1) a prompt decision to proceed with cardiac replacement; (2) avoidance of long periods of cardiopulmonary bypass; (3) prosthetic device availability; and (4) surgical team preparedness, with technical expertise in transplantation, allograft explantation, and total artificial heart implantation/explantation, with re-transplantation.

Journal Article↗

Spontaneous infection or vaccination as cause of acute disseminated encephalomyelitis.

This report describes an approach to determine which of 2 possible etiologies could be responsible for a disease, in this instance acute disseminated encephalomyelitis (ADEM). Information about latency periods was obtained from eighteen reference sources in the literature. Analysis of these data indicate that it would be 9-18 times more likely for ADEM to develop 5 days after a wild virus infection (measles, for example) than 28 days after a vaccination.

Encephalomyelitis↗