Biomedical subjects
Publications and source records attributed to C A Martin.
In 5 latency-age boys, methylphenidate plasma concentrations following multiple doses of methylphenidate were consistently higher than those obtained after a single dose. Pharmacological and clinical implications are discussed.
Although clinical manifestations of cocaine use are similar to the signs and symptoms of hyperthyroidism and research suggests that cocaine may affect the thyroid, no occurrences of cocaine-associated thyroid toxicity have been reported. The authors report a case of Graves' disease in a cocaine-dependent patient and propose that the patient's cocaine use may have precipitated thyroid toxicity.
Death rates from coronary heart disease (CHD) have been declining in Australia and New Zealand for 20 years. Data from the three MONICA Project Centres in Newcastle (Australia), Perth (Australia), and Auckland (New Zealand) show similar trends for fatal CHD but differing trends for non-fatal myocardial infarction (MI). In Auckland, there has been a consistent decline in out-of-hospital death rates but no decline in non-fatal MI rates. In Perth, the greater contribution to the overall decline has been from out-of-hospital deaths, but in-hospital death rates and non-fatal MI rates have also declined. There is also some evidence of an increase in survival following MI in Perth. In Newcastle, both death rates and non-fatal MI rates have declined. The limited data available suggest that at least one-half of the decline in mortality can be attributed to improvements in population risk-factor levels. Improvements in medical management of both risk factors and established disease are also making contributions to the decline.
The TCA3 gene was originally isolated from a cDNA library derived from a TH1 (inflammatory) T cell clone. Expression of TCA3 RNA was limited to cells in the activated state. Based on its expression profile and the existence of a hydrophobic leader sequence with a predicted cleavage site, we proposed that TCA3 encodes a new lymphokine. In the present study, we examine the subset distribution, kinetics, and regulation of TCA3 RNA expression. We show that TCA3 is expressed in response to selected T cell-activating stimuli. TCA3 is transcribed to peak steady state levels by 4 h after stimulation in TH1, TH2 (helper), and CTL clones. Two intracellular signals, supplied in vitro by phorbol ester and one of several agents capable of increasing intracellular free calcium concentrations, are required for the initiation of TCA3 transcription. In addition, TCA3 transcription is blocked by anti-L3T4 mAb, suggesting that prior signaling through L3T4 can inhibit expression of TCA3 and other lymphokines. In contrast to IL-2, IL-4, and IFN-gamma TCA3 is uniformly expressed at high levels among all individual T cell clones examined, including four TH1, three TH2, and three CTL clones. Furthermore, activation-specific TCA3 expression can be dissociated from T cell proliferation.
Macrophage hybridoma clones prepared by fusion of splenic adherent cells with P388D1 tumor cells have previously been shown to be heterogeneous with respect to function at the clonal level. In this study the macrophage clones were phenotypically characterized by indirect RIA using a battery of rat MAbs to murine myeloid and lymphoid cell surface markers. All macrophage clones expressed the common leukocyte antigen T200 and the Mac-1 alpha and beta chains. Markers which were differentially expressed among the clones included class II antigens and the antigens detected by MAbs MIV 55, MIV 38, and 14G8. The antigens detected by the latter three MAbs were referred to as MBR-1, -2 and -3, respectively. Functional heterogeneity did not correlate with phenotypic heterogeneity among the macrophage clones. Treatment of macrophage clones with IFN-gamma resulted in a significant increase in the expression of class II antigens and induced the expression of MBR antigens on some clones which were constitutively negative for these markers. The clonal distribution and induction patterns of class II antigen as compared to MBR antigen indicated that regulation of expression of these markers was independent. In addition, the clonal distribution and induction pattern of MBR antigens, along with competitive binding studies using radiolabeled MIV 38 and 14G8 MAbs, suggested that the three MBR antigens were similar or closely associated molecules.
Variations in the ratio of "definite" to "possible" myocardial infarction for non-fatal cases were examined in studies that used World Health Organization criteria. There were large variations in this ratio, variations which appeared to be due to differences in the ascertainment of non-fatal cases of "possible" myocardial infarction, which, in turn, contributed to reported differences in the incidence of myocardial infarction. A significant proportion of cases of "possible" myocardial infarction probably do not have ischemic heart disease at all, since, in our data, cases of "possible" myocardial infarction (non-fatal) with a hospital discharge diagnosis of chest pain (undiagnosed) had a risk of death that was no worse than that in the general population. Thus the most reproducible, and possibly most accurate estimates of the incidence of myocardial infarction may come from including only fatal cases of "possible" myocardial infarction with both fatal and non-fatal cases of "definite" myocardial infarction.
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The observations presented here confirm previous reports that polyclonal ALG prepared at the University of Minnesota or ATGAM of The Upjohn Co., administered as described, rarely induced sensitization of patients to the horse gamma globulin. In addition, the phenomena of transient antibody production prior to the onset of unresponsiveness and the induction of unresponsiveness in individuals with preexisting antibodies were observed.
The first human trial utilizing the argon fluoride excimer laser at 193 nm to produce a superficial keratectomy in ten human eyes has been described with the histopathological evaluation of four eyes and the longer gross appearance of six eyes at intervals extending to 10 months post-excimer laser treatment. The process of laser superficial keratectomy has proved to be one of the promising areas of surgical intervention for reconstructive or refractive keratoplasty in the future. Intensive investigations need to be undertaken on the corneal wound healing process following laser ablation as well as the nature, and long-term stability of the corneal excisions or induced refractive corrections. It is essential that the optimal laser parameters be established for the various refractive corrections and other corneal surgical techniques, and that pathophysiologic and histopathologic changes that have been induced by the excimer laser-corneal tissue interaction in animals and humans be critically and extensively analyzed.
The validity of identifying incident cases of non-fatal acute myocardial infarction (AMI) between 1971 and 1982 in Western Australia from routine hospital records was assessed in ages 25-64 years, according to the WHO criteria defined in 1970 and 1983. This was done by reviewing original data sources and by using the Perth Coronary Register of 1971 as an external reference. Events with a coded discharge diagnosis of acute or subacute ischemic heart disease were found to be highly sensitive (97%) for cases of "definite" AMI (WHO 1983 criteria). The specificity of such events was lower (positive predictive value of about 70%) and validation of these events would be necessary for studies requiring high specificity. The sensitivity and specificity of these events for "definite" AMI seemed quite stable over time with similar values being observed in 1971 and 1978. Although the situation for "possible" AMI (non-fatal) is less clear, certainly many more records would need to be reviewed to validate this diagnosis.
The accuracy of routinely collected mortality data for ischemic heart disease (IHD) as indicators of death from acute myocardial infarction (AMI) was assessed in ages 25-64 years, according to the WHO criteria defined in 1983. Cases were identified from computer records (linked for individuals) of all death certificates and hospital discharges in Western Australia between 1971 and 1982. Where the official cause was IHD about 90% of deaths fulfilled the WHO criteria for definite or possible AMI. Up to 10% of fatal cases of definite or possible AMI were coded to other causes in the official death statistics, however it appeared that variations in this figure with changes in coding practices could cause appreciable bias in the estimation of secular trends in IHD mortality. This problem could largely be overcome by reviewing fatal events where the death certificate was coded to one of a limited number of other ICD rubrics.
The role of a child in his/her physical abuse was reviewed with particular attention to hyperactive children. A retrospective analysis of the records of children referred to a university-based hyperactive children's clinic revealed that children both with and without Attention Deficit Disorder (ADD) were more often physically abused than children in the general population. The period prevalence of physical abuse in children with ADD did not differ significantly from that in children without ADD. This suggests that hyperactivity may either contribute to, or result from, physical abuse.
Multiple serum samples originating from 110 renal allograft recipients were examined against saline extract of normal human kidney by means of double diffusion gel precipitation. Eleven recipients were found to be positive; 99 of 106 sera from these patients were positive. Pretransplantation sera were available from 7 of these recipients and 6 patients were found "positive." The precipitation reaction was composed of one line. Identity reactions were formed between the lines produced by sera from all patients except 1. Sera of patients from end-stage renal disease produced similar reaction; however, only 3 of 234 sera from patients with nonrenal diseases precipitated the kidney extract. None of 154 normal sera were positive. Several positive sera also were positive in complement fixation tests with human kidney extract. Evidence was presented that the antibodies under study combined with a nonorgan-specific but species-restricted tissue antigen. The hypothesis was advanced that these antibodies are autoantibodies formed in response to a sequestered antigen released as a result of tissue damage. Apparently, the antigen is released frequently in immunogenic form from injury to kidney but infrequently from injury to other organs.
The distribution of EcoR1 and HindIII restriction fragment length polymorphisms in the region of the gene coding for the alpha subunit of human chorionic gonadotrophin have been examined in 71 normal controls, six families, and 65 cases of hydatidiform mole, all of European origin. In control samples the genotypes generated by the presence or absence of the restriction sites, fitted a Hardy Weinberg distribution while in family studies the two polymorphisms showed Mendelian inheritance. The distribution of the genotypes in hydatidiform moles differed from that in control samples. However, the frequency of the alternative alleles R+, R- and H+, H- was not significantly different in the two populations and differences in the distribution of genotypes could be explained in terms of the unique origin of hydatidiform moles. The frequency of the rare homozygous genotype R-R-,H+H+, which has previously been suggested to be associated with the development of choriocarcinoma, was similar in those complete moles which resolved spontaneously (35 per cent) and those which progressed to trophoblastic tumours (27 per cent). No association was found between the genotype of the hydatidiform mole and the subsequent clinical outcome of the patient. Thus the pattern of restriction fragment length polymorphisms associated with the human chorionic gonadotrophin alpha subunit gene would not appear to be an appropriate marker of clinical outcome in patients with hydatidiform moles.
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It has been suggested that macrophage-like accessory cells are involved in suppressor T cell (Ts) induction. To further analyze this issue, we obtained several cloned macrophage hybridoma cell lines by somatic cell fusion of the macrophage tumor P388D1 of DBA/2 (H-2d) origin with splenic adherent cells of CKB mice (H-2k). Several cloned lines displayed the serological and functional characteristics of macrophages. We evaluated the ability of these hybridomas to induce third order or effector Ts (Ts3) to suppress the contact sensitivity response against the hapten 4-hydroxy-3-nitrophenyl acetyl (NP). In contrast to the parental P388D1 and two other macrophage hybridomas, one macrophage hybridoma clone, termed 63, when conjugated with NP, induced Ts3, which suppressed contact sensitivity responses against NP but not DNFB, showing that the Ts3 were antigen specific. Macrophage hybridoma 63 could specifically induce Ts3 activity in either H-2k, H-2d, or H-2k/H-2d heterozygous hosts. Thus, macrophage hybridoma 63 functionally expressed major histocompatibility complex-related restricting determinants, and the fusion with cells from a H-2k macrophage donor caused a functional complementation of H-2d-related, Ts-inducing elements. The genetic restriction governing induction of Ts3 was controlled by genes that mapped to I-J region. Furthermore, NP-conjugated macrophage hybridoma 63 could serve as a target for elicitation of suppressor responses after administration of I-Jk, but not I-Jb, restricted suppressor factor. The data suggest that macrophage hybridomas represent a means to dissect heterogeneity within the macrophage population. The data also imply that the I-J determinants expressed on macrophages represent a ligand for the antigen receptor of Ts.
Two C(5)-azido substituted aromatic retinoids were evaluated as photoaffinity probes for studying the mechanism of retinoid action. The secondary azide 1 and the tertiary azide 2 were equipotent with the parent C(5)-geminal-dimethyl substituted aromatic retinoid 3 in stimulating F9-cell differentiation. Both azides bound covalently to cellular retinoic acid-binding protein upon photolysis, but the secondary azide was twice as efficient, likely because of lesser steric hindrance. The covalent binding of azide 1 was specific, since it was inhibited by retinoic acid. Thus substitution of a photolabile group onto aromatic retinoids does not abolish biological activity and affinity for cellular retinoic acid-binding protein.