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Biomedical subjects

A Chan

Publications and source records attributed to A Chan.

At least 253 records · Page 14Linked to original sources

Polymorphism of the human T cell receptor alpha chain variable genes: identification of a highly polymorphic V gene probe.

In this study, we report the RFLP of the human T cell receptor (TCR) alpha chain variable gene segments. Using DNA samples from 20 individuals and three restriction endonucleases (BamHI, EcoRI and HindIII), the degree of RFLP of a number of different V gene segments was defined. Half of the V alpha subfamilies (6/12) were characterized by a predominant hybridization pattern, with only a few individuals displaying a second pattern. However, one particular V gene family, V alpha 6, has at least five allelic forms that segregated consistently in familial studies. The V alpha polymorphisms revealed in this study, together with those exhibited by V beta gene subfamilies, should prove useful in studying possible associations between TCR gene usage and disorders of the immune system.

Alleles↗

Caesarean section in South Australia, 1986.

A profile of Caesarean section in South Australia was obtained by analysing the 19,800 births in the perinatal statistics collection in 1986. The Caesarean confinement rate was 19.0%, of which 9.0% were elective sections and 9.9% emergency sections. The rates were highest in large metropolitan hospitals. Elective rates were highest in metropolitan private hospitals, among older women, among those with a previous perinatal death or where a fetal malpresentation occurred. Emergency sections were more common in primigravidas, non-Caucasian women, those with a poor pregnancy history, few antenatal visits and a medical or obstetric complication of pregnancy. The obstetric complications most commonly encountered with Caesarean sections were fetopelvic disproportion, fetal distress, malposition or malpresentation, pregnancy hypertension and uterine inertia. Neonates born by emergency section were more likely to be premature, or low birth-weight and to manifest depression of vital signs compared with vaginal births. They also required more intensive resuscitation and neonatal care, and neonatal death occurred more frequently. Morbidity was much lower in neonates born by elective than emergency section.

Adult↗

Genomic organization of the T cell receptor.

A majority of T cells recognize antigens by means of a T cell receptor (TcR) composed of either alpha-beta (alpha beta) or gamma-delta (gamma delta) chains. These TcR genes are members of the immunoglobulin gene superfamily. This family includes the major histocompatibility complex (MHC) genes, whose products are essential for recognitions of foreign antigens by the TcR. This phenomenon is known as MHC restriction. All the TcR chains have similar protein structures consisting of extracellular variable and constant domains, intracellular cytoplasmic tails, and a hydrophobic transmembrane region with several potential N-linked glycosylation sites. On the cell surface, the TcR heterodimers are found to be associated with the CD3 complex. This CD3 complex which is composed of at lease four chains (CD3 gamma, CD3 delta, CD3 epsilon, and CD3 zeta) is thought to be responsible for the transduction of antigen-binding signal through the cell membrane to facilitate the appropriate T cell function. The germline TcR genes are composed of noncontiguous variable (V), diversity (D), joining (J), and constant (C) gene segments. During T cell ontogeny, these VDJ or VJ gene segments rearrange to form a TcR gene encoding a unique variable domain, which is then joined to the C region sequences by RNA splicing following transcription. This process of rearrangement allows the generation of large numbers of new and unique TcR genomic structures, before a primary transcript can be made. In this review article, we summarize the recent findings on the genomic organization of these TcR genes in both the human and murine systems.

Animals↗

Identification of a T cell subset using a rabbit antibody raised against a T suppressor molecule.

Rabbit antiserum to a unique component of an Ag-binding Ts-factor was generated by repeated immunization with purified 30-kDa protein isolated from Fd11 Ts factor (11). This antiserum (anti-p30) was shown to recognize cell surface determinants expressed on the Ts hybridomas Fd11 and A10 but not the fusion partner BW5147. Furthermore, this antiserum was shown to bind to approximately 4% of thymocytes and 10% of nylon wool-purified splenic T cells from all strains of mice tested. Sorting nylon wool-purified T cells from DBA/2 mice for the CD4+ and CD8+ subsets revealed both populations contained cells that bound anti-p30. In addition, when CD4-8- thymocytes were examined for anti-p30 labeling, it was found that about 30% of this enriched population also expressed p30 molecules. In a functional study, anti-p30 was able to neutralize the suppressive effects of Fd11 on a specific assay for in vitro antibody synthesis against ferredoxin.

Animals↗

Ultrasound screening for clinically occult abdominal aortic aneurysm.

In a review of the records of 74 patients who had undergone repair of an abdominal aortic aneurysm at a community hospital between 1977 and 1983 we found that the aneurysm had been undiagnosed before rupture in 35%; these patients had an operative death rate of 50%, whereas elective repair carried a death rate of 4%. The characteristic patient was an obese man over the age of 55 years with hypertension, coronary artery disease, cerebrovascular disease or peripheral vascular disease. Ultrasound examination was performed in 45 patients with these characteristics, and six aneurysms were diagnosed. Either surgery or computed tomography confirmed the diagnosis. The rate of false-negative results was estimated by review of the charts of 100 men over the age of 55 years who had undergone abdominal ultrasonography for other indications: no undetected aneurysms were discovered over 3 years of follow-up. Routine screening in this high-risk group would improve the rate of diagnosis of this potentially fatal condition before rupture and offer the patient the lower mortality rate associated with elective surgery.

Aged↗

Structure-activity relationships of steroid hormones on muscarinic receptor binding.

A total of fifty steroidal compounds were tested for their inhibition on the binding of muscarinic receptor antagonist, [3H]quinuclidinyl benzilate ([3H](-)QNB), to the hypothalamic membranes prepared from male rats. Among the compounds tested, the active structures (with IC50 values less than or equal to 100 microM in parentheses) are: progesterone (40), 5 beta-pregnane-3,20-dione (40), deoxy-corticosterone (50), 5 beta-pregnane-17 alpha,21-diol-3,20-dione (30), 11-desoxy-17-hydroxycorticosterone (22), 17 alpha-hydroxyprogesterone (20), 5 beta-pregnan-17 alpha-ol-3,20-dione (24), 5 beta-androstane-3,17-dione (100), and 5 beta-dihydrotestosterone (100). By examining all the compounds tested, the following structure-activity relationship became apparent: (a) The ring A-reduced steroidal structures with a 5 beta-conformation were more potent than those with a 5 alpha-conformation; (b) 17 alpha-hydroxylation of the steroidal ring increased the steroid's inhibitory activity; (c) The C3 carbonyl group was essential for activity; (d) Reduction of the C3 carbonyl group or aromatization of the ring A abolished the steroid's inhibitory activity; (e) Oxidation of the C11 position of ring C resulted in a decrease or loss of inhibitory activity; and (f) Different modifications of the side chain of ring D by acetylation resulted in either an increase or a decrease in the inhibitory activity. The structure-activity relationship as revealed in this study might provide an insight for the synthesis of a steroidal molecule with a high affinity for the muscarinic receptor as well as for the search of a more potent and physiologically relevant steroidal metabolite possessing the ability to interact with the muscarinic receptor.

Animals↗

The effects of ovarian hormones on beta-adrenergic and muscarinic receptors in rat heart.

The in vitro and in vivo effects of estrogen and progesterone on muscarinic and beta-adrenergic receptors of cardiac tissue were studied in ovariectomized (OVX) rats. The binding assay for muscarinic receptors was performed under a nonequilibrium condition; whereas the binding assay for beta-adrenergic receptors, under an equilibrium condition. Estrogenic compounds and progesterone were found to have no effect on the binding of the radioligand, [3H]-dihydroalprenolol, to beta-adrenergic receptors in vitro. However, progestins but not estrogenic compounds inhibited the binding of the radioligand, [3H]-quinuclidinyl benzilate, to muscarinic receptors in vitro, with progesterone as the most potent inhibitor (IC50 = 37 microM, apparent Ki = 13 microM). Progesterone was found to decrease the apparent affinity of muscarinic receptors for [3H](-)QNB in vitro. Daily treatment of OVX rats with estradiol benzoate (4 micrograms) or progesterone (2.5 mg) for 4 days had no effect on the muscarinic or beta-adrenergic receptors with respect to the binding affinity and receptor density. However, administrations of these hormones together for 4 days caused an increase in the receptor density of muscarinic receptors without a significant effect on their apparent binding affinity; also these hormones induced a decrease in the binding affinity and an increase in the receptor density of beta-adrenergic receptors. The results of this study demonstrate that progestins are capable of interacting with the cardiac muscarinic receptors in vitro, and indicate that estrogen and progesterone have a synergistic effect to increase the receptor densities of muscarinic and beta-adrenergic receptors as well as to cause a decrease in the binding affinity of beta-adrenergic receptors in vivo.

Animals↗

Obstetric profiles of immigrant women from non-English speaking countries in South Australia, 1981-1983.

Obstetric profiles of non-English speaking immigrant women in South Australia are presented to assist in planning for health services. They were derived from perinatal data routinely collected by midwives and neonatal nurses. The characteristics of 5,675 immigrant women were compared with those of a random sample of approximately 5% of Australian-born women who delivered babies in 1981-1983 in South Australia. This study demonstrates that immigrant women tended to be urban dwellers and to deliver their babies in large metropolitan hospitals. They were less often from unemployed families but more often from those of low occupational status. They were older, with fewer teenagers and single women among them. They were of higher parity, and tended to commence antenatal care later. They had lower incidences of pregnancy hypertension and induced labour, but were more likely to have anaemia, antepartum haemorrhage and a Caesarean section. There were also important differences between the 7 largest immigrant groups. For example, the very high Caesarean section rate (36%) in Filipino women is of concern. Also, the mean birth-weight of babies of Vietnamese women was 263g lower than that of babies of Australian-born women. Support services need to be logistically located and address the findings of this study in a culturally acceptable way.

Adult↗

Inhibition of hypothalamic and pituitary muscarinic receptor binding by progesterone.

The in vitro effects of estrogens, progestins, and their related analogs on muscarinic receptor binding sites were studied in the hypothalamic membranes prepared from ovariectomized rats. The binding assays were performed under a nonequilibrium condition. Progestins and their metabolites were active in inhibiting the binding of [3H](-)QNB to muscarinic receptors, whereas estrogenic compounds were devoid of this effect. Progesterone was also found to be active in inhibiting the binding of [3H](-)QNB to pituitary membranes. The IC50 values of progesterone and its metabolite, 17 alpha-hydroxyprogesterone, were 34 and 24 microM, respectively. The inhibitory effect of progesterone was rapid, reversible, and not dependent on divalent metal ions (Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, and Zn2+). Analyses of the binding data with Scatchard and Lineweaver-Burke plots revealed that progesterone significantly increased the apparent Kd of muscarinic receptor binding sites from 0.54 (SE = +/- 0.08) nM to 2.44 (SE = +/- 0.49) nM in hypothalamic membranes and from 0.21 (SE = +/- 0.03) nM to 0.34 (SE = +/- 0.03) nM in pituitary membranes without a significant effect on the receptor density in both membrane preparations. Progesterone decreased the rate of association of [3H](-)QNB with muscarinic receptors without a significant effect on its rate of dissociation from the [3H](-)QNB-receptor complex. These results indicate that progesterone, but not estrogenic compounds, was capable of interacting with hypothalamic and pituitary muscarinic receptors in vitro.

17-alpha-Hydroxyprogesterone↗

Isolation of an antigen-specific T suppressor factor that suppresses the in vivo response of DBA/2 mice to ferredoxin.

A T cell hybridoma (Fd11) has been produced from B10.D2 mice that secretes a putative antigen-specific T suppressor factor (TsF). The TsF is isolable from culture supernatants of Fd11 by affinity purification over columns containing either a monoclonal antibody (B16G) shown previously to be capable of binding murine TsF or ferredoxin (Fd), the nominal antigen to which the Fd11 TsF binds. Specificity of the Fd11 TsF for Fd was established by comparing it to another TsF isolated by us (A10 TsF) in a sandwich ELISA, and by demonstrating the specific reactivity to Fd of the hybridoma in calcium flux studies. The Fd11 affinity-purified TsF was shown to contain two major unique components with m.w. in the region of 80,000 and 35,000 when run on reducing polyacrylamide gels in the presence of sodium dodecyl sulphate. Specific immunosuppressive properties of Fd11 were demonstrated when Fd11 TsF (10 micrograms) was injected i.v. into Fd-primed syngeneic mice at the time of antigen boost. Fd11 TsF specifically and significantly diminished the secondary antibody response to Fd in DBA/2 mice.

Aminoquinolines↗

The effect of estrogen on luteinizing hormone-releasing hormone binding sites in hypothalamic membranes.

The binding sites for [125I]LHRH were characterized in membranes from the hypthalamus and the effect of estrogen on the binding characteristics was studied in ovariectomized female rats. The radioligand, [125I]LHRH, was found to bind specifically to membranes from the hypothalamus at a maximal level, with an optimal temperature of 0 degrees C and a pH between 7 and 8. The binding was enhanced by NaCl at a concentration of 0.1-0.2 M. The specifically bound [125I]LHRH was only displaced by LHRH, but not by sodium iodide (NaI), bovine serum albumin and other hormones, such as thyrotropin-releasing hormone, bradykinin, oxytocin, prolactin, luteinizing hormone and growth hormone. The divalent metal ions, copper (Cu2+) and mercury (Hg2+), inhibited the specific binding of [125I]LHRH completely, whereas magnesium (Mg2+) and calcium (Ca2+) caused a decrease in binding. As revealed from Scatchard plot analysis, the binding sites for [125I]LHRH in the hypothalamus had a dissociation constant of 0.40 +/- 0.03 microM and the maximum number of binding sites was 98.55 +/- 4.34 pmol/mg protein. Treatment of female rates (ovariectomized for 3 weeks) with 4 micrograms of estradiol benzoate caused a statistically significant decrease in the maximal number of binding sites without any significant effect on the dissociation constant. However, the direct addition of estradiol hemisuccinate to the membrane preparations had no statistically significant effect on the specific binding of [125I]LHRH. The present study provides the evidence that estrogen decreases the density of binding sites for [125I]LHRH in the hypothalamus in vivo.

Animals↗

Universals and cultural differences in the judgments of facial expressions of emotion.

We present here new evidence of cross-cultural agreement in the judgement of facial expression. Subjects in 10 cultures performed a more complex judgment task than has been used in previous cross-cultural studies. Instead of limiting the subjects to selecting only one emotion term for each expression, this task allowed them to indicate that multiple emotions were evident and the intensity of each emotion. Agreement was very high across cultures about which emotion was the most intense. The 10 cultures also agreed about the second most intense emotion signaled by an expression and about the relative intensity among expressions of the same emotion. However, cultural differences were found in judgments of the absolute level of emotional intensity.

Adult↗

The management of work-related back pain.

This paper describes the Spinal Treatment Program at Columbia Hospital in Milwaukee. The primary goal of the program is to efficiently return the employee with a work-related back injury to the work setting. The two-phase program has been developed to provide treatment of acute injury, patient education, work hardening, and an assessment of the patient's ability to perform job tasks. Preliminary evaluative data are presented for patients treated from 1982 to 1984. The patient's discharge status (returned or did not return to work) was examined as a function of sex, age, educational level, employment category, duration of pain, or worker's compensation status. Results indicated that discharge status was significantly related to sex, employment category, duration of pain, and worker's compensation status.

Adult↗

Characterization of an anti-idiotypic T cell hybridoma involved in the regulation of the immune response to the P815 mastocytoma.

We report the isolation and characterization of a T cell hybridoma (A29) which secretes a factor that exhibits anti-idiotypic and immune-modulating characteristics. The A29 cell line is thought to represent the hybrid analog of the Ts2 suppressor cell population in the cascade regulating the immune response to the P815 tumor in DBA/2 mice. The putative TsF2 molecule is reactive with the monoclonal antibody B16G, shown previously by us to bind a public specificity of T suppressor factors (TsF). A29 TsF also exhibits specific binding to a TsF1 secreted by another T cell hybridoma, A10, which shows specificity for antigen from the P815 tumor (this has been described previously). A29 itself does not exhibit binding to P815 antigens. Affinity-purified material from A29 appears to share characteristics with A10 molecules in that the predominant material has an apparent m.w. of 70,000. Studies with calcium flux of A29 cells showed that they respond significantly and specifically on exposure to A10 TsF stimulus. We showed further that affinity-purified A29 TsF molecules can specifically suppress the in vitro generation of syngeneic CTL to the P815 tumor, and that panning of DBA/2 splenocytes over A29-TsF-coated plates renders cell populations capable of generating a higher in vitro CTL response to P815 than appropriately treated controls.

Animals↗

The case for scoliosis screening in Australian adolescents.

A survey of 3660 Year 10 students, with an average age of 15 years, was carried out in a random sample of Adelaide secondary schools to determine the prevalence of structural scoliosis and the need for implementing a programme of scoliosis screening. By means of the Forward Bending Test and a specially devised scoring system 144 (3.9%) children were found to have signs that were suggestive of scoliosis; all but 12 were assessed subsequently by standardized clinical and radiological examinations. One hundred and three children were found to have structural scoliosis of 5 degrees or more; this represented a prevalence of 3.1%. The prevalence in girls (4.3%) was significantly higher than in boys (1.9%), and girls tended to have more severe curves and require treatment more frequently. Only one third (34) of the cases of structural scoliosis had been detected before this survey; most (28) of these had been detected through an earlier, subsequently discontinued, school screening programme. This study concludes that screening for scoliosis by means of a scored Forward Bending Test should be carried out in South Australian schools for all students in Year 8 and for girls in Year 10. The policy of screening boys in Year 8 should be the subject of further research. An educational programme for health professionals, parents, students and physical education teachers should support the programme.

Adolescent↗