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Biomedical subjects

D L Allen

Publications and source records attributed to D L Allen.

At least 19 recordsLinked to original sources

A microcomputer program for determining turnover rates during non-steady state conditions: application to monoamine turnover.

A program to calculate the turnover rate of monoaminergic neurotransmitters was written for use on microcomputers. The program is based on non-steady state models, i.e., measuring the rate of change of levels of neurotransmitters or their metabolites after pharmacological inhibition of synthetic or degradative enzymes. Methods have been developed to estimate monoamine turnover by measuring the rate of decrease of catecholamine levels after treatment with alpha-methyl-p-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, or the increase in serotonin levels after pargyline, an inhibitor of monoamine oxidase. This program is suitable for examining either linear increases or exponential decreases in monoamine levels. The program has been tested in our laboratory for the determination of serotonin, dopamine or norepinephrine turnover after hormonal or pharmacological manipulations. The program is readily adaptable for calculation of the turnover rate of other biological molecules under non-steady state conditions.

Biogenic Monoamines

Neonatal alloimmune thrombocytopenia due to anti-HPA-5b (Br(a), Zav(a), Hca): the importance of third-generation platelet antibody detection techniques, a case report.

Investigation of the maternal serum in a case of suspected alloimmune neonatal thrombocytopenia by conventional, second-generation platelet serological assays (platelet radioactive antiglobulin test [PRAT], platelet suspension immunofluorescence test [PSIFT] and solid-phase adherence assay (SPAA, 'Capture-P') demonstrated only the presence of HLA class-I antibodies of limited specificities: no platelet-specific antibodies were detectable. The use of a third generation, glycoprotein capture assay (monoclonal antibody-specific immobilization of platelet antigens, MAIPA) revealed the additional presence of anti-HPA-5b with a titre of 1 in 32. Despite this relatively high titre, and the fact that it was able to induce a prolonged thrombocytopenia, this antibody was not detectable by conventional assays. In view of these findings we conclude that the use of MAIPA is essential when investigating cases of suspected alloimmune neonatal thrombocytopenia.

Abnormalities, Multiple

Positive correlation between proopiomelanocortin and tyrosine hydroxylase mRNA levels in the mediobasohypothalamus of ovariectomized rats: response to estradiol replacement and withdrawal.

We have investigated putative dopaminergic regulation of opiomelanotropinergic activity in the arcuate/periarcuate mediobasohypothalamus (MBH) by assessing the changes in MBH tyrosine hydroxylase (TH; rate-limiting enzyme in catecholamine synthesis) and proopiomelanocortin (POMC; opiomelanotropin precursor) mRNA levels under conditions in which endogenous tuberinfundibular dopaminergic activity exhibits marked changes. Adult Sprague-Dawley rats were sacrificed at 09.00 and 15.00 h, and individual MBH POMC and TH cytoplasmic mRNA levels were simultaneously quantified by multiplex solution hybridization-RNase protection assay with protected fragments separated by polyacrylamide gel electrophoresis. In ovariectomized (OVX) rats treated for 3 days with low-dose estradiol (E2) implants (resulting in 18 +/- 4 pg E2/ml serum), the MBH levels of POMC and TH mRNAs were approximately 17 and 31% lower than those measured in OVX controls, respectively. In OVX rats implanted for 20 days with larger E2 implants (99 +/- 9 pg E2/ml serum), POMC and TH mRNA levels were approximately 29 and 41% lower than in OVX controls, respectively. Additional groups were exposed to the higher E2 dose for 20 days and then killed 10 or 20 days after removal of the E2 implant. In these rats, POMC mRNA levels rebounded to the same level seen in OVX controls, while TH mRNA levels even exceeded control values by 22-27%. TH and POMC mRNA levels did not change significantly between 09.00 and 15.00 h, except 10 days after removal of the E2 implants, when 09.00 h POMC mRNA levels were higher than the 15.00 h levels. MBH POMC and TH mRNA levels were positively correlated with each other within individual animals. This correlation is maintained when both POMC and TH mRNA levels are suppressed in response to both 3-day low-dose and 20-day high-dose E2 treatment. However, although rat MBH opiomelanotropinergic and tuberoinfundibular dopaminergic mRNA biosynthesis thus appear to be positively correlated, the coregulation or functional interactions of these two neuronal systems remain to be determined.

Amino Acid Isomerases

Growth hormone and fibronectin expression in 3T3 preadipose cells.

In the present study we focused on the relationship between GH action and the extracellular matrix in 3T3-F442A preadipose cells. Results from Northern blotting indicated that in serum-free medium, the presence of 2 nM met-human GH down-regulated levels of fibronectin messenger RNA by approximately 40, 60, and 70% as compared with control levels on days 1, 2, and 4, respectively. GH-dependent reduction of levels of collagen alpha 1(I) mRNA expression occurred later and was less pronounced than effects on levels of fibronectin mRNA, suggesting a specificity in the matrix-altering function of GH. Western blot analyses and immunoprecipitation studies revealed that between 2 and 5 days of culture, matrix-associated fibronectin protein was reduced 70 to 90% by GH treatment. Down-regulation of fibronectin protein expression by met-human GH was dose-dependent between 2 and 0.02 nM. The presence of 2 nM insulin or insulin-like growth factor-1 promoted a 30-40% increase in fibronectin levels compared to control cells. The GH-promoted down-regulation of fibronectin expression was eliminated by concomitant addition of insulin. These data demonstrated that GH effects on matrix-associated fibronectin expression were independent of, and in opposition to, effects promoted by insulin and insulin-like growth factor-1. Treatment of culture dishes with fibronectin or collagen inhibited GH-stimulated adipogenesis 50 and 80%, respectively, compared with controls, as judged by levels of glycerol-3-phosphate dehydrogenase activity. Thus, composition of the extracellular matrix was a critical factor in GH-induced adipogenesis of 3T3-F442A fibroblasts. Our results demonstrate that GH action in 3T3 preadipose cells is intimately coupled to the biology of extracellular matrix.

3T3 Cells

Thrombocytopenia in malaria.

The relationship between platelet counts and platelet bound (direct) or platelet directed (indirect) serum antibody concentrations was studied in 17 patients with Plasmodium falciparum malaria and 12 patients with P. vivax malaria. Platelet counts rose with recovery from infection from 196 +/- 84 x 10(9)/l (mean +/- SD) and 195 +/- 34 x 10(9)/l to 319 +/- 99 and 283 +/- 62 x 10(9)/l respectively (p less than 0.002), but there was no relationship between either absolute platelet count or changes in counts and either indirect or direct platelet antibody levels. These findings suggest that a non-immunologically mediated mechanism is involved in the pathogenesis of thrombocytopenia in malaria.

Adolescent

Effect of a year-long primary care clerkship on graduates' selection of family practice residencies.

This report compares the selection of family practice residencies from 1981 through 1989 by graduates trained at two campuses of the State University of New York (SUNY)-Health Science Center at Syracuse College of Medicine, at other New York State campuses, and at all U.S. medical schools. One of the SUNY-Syracuse cohorts comprised the students who had completed all their work at the Syracuse campus, while the other comprised those who had spent their third year at the campus in Binghamton, which has a year-long, half-day-a-week primary care clerkship that is not available at the Syracuse campus, which has no primary care clerkship. Comparison of the proportions of the graduates in the two SUNY-Syracuse cohorts who chose family practice residencies, and comparisons of the proportions of graduates from other New York state schools and from all U.S. schools who selected family practice residencies during the same nine-year period, indicate that the proportion of students trained during their third year at the Binghamton campus who selected family practice residencies was significantly greater (21%; p less than .001). Additional investigation is required to determine whether the year-long nature of the required clerkship affects graduates' choices more than does the primary care content of the clerkship.

Career Choice

'Partial D' women with anti-D alloimmunization in pregnancy.

We report five women with Rh 'partial D' who were found to have anti-D during pregnancy. Two patients were category IVa, their red cells typing as Go(a+); one was category VI; and two had a 'partial Du' which could not be categorized. The maternal anti-D concentration increased during four of the eight pregnancies studied, but none reached significant levels. Three of six D-positive cord blood samples had a positive direct antiglobulin test (DAGT). Although one baby became jaundiced, no treatment was required. The policy in the Oxford Region for the management of patients with a weak expression of D is outlined.

England

Dental laboratory work authorization forms: a survey.

Dental laboratory work authorization forms embrace a diversity of material content and design. This survey examined 51 dental laboratory work authorization forms and delineated each content item and format features into a frequency percentage. This information has a high potential for use in changing prospective dental laboratory and authorization form design.

Dental Records

A perspective of dental education in the twenty-first century.

With the beginning of the twenty-first century only twelve years away, it is clearly not too early for dental educators to be planning for it. If one compares the practice of dentistry and the nature of dental education in 1888 with that of 1988, and then tries to project what they will be like in the year 2088, we have a difficult task indeed. As Alvin Toffler has pointed out in his book Future Shock, we are in an ever escalating period of change. Dentistry and dental education will change much more in the next one hundred years than they have in the last one hundred years.

Curriculum

Philosophy and rationale of curriculum change.

There are several factors in curriculum design of universal importance. Faculty members at all levels must be free to contribute but it must be recognized that decisions have to be made at department, school and university levels. Programme goals must be defined so that there is adequate education of dental practitioners and not just training for dental students. Preclinical teaching should not be an end in itself but should be closely relevant to clinical practice. Basic concepts must be taught; factual overload should be avoided and outdated material eliminated. The curriculum should meet local needs and not be based on one developed for another part of the world. In re-designing a curriculum, attention should be paid to new content, new teaching methods, the introduction of early clinical experience, evaluation methods and the effects of specialization in practice. Above all, curriculum revision must be an ongoing process.

Curriculum

Temporal effects of intrahypothalamic 5,7-dihydroxytryptamine: relationship between serotonin levels and [3H]serotonin binding.

The relationship between serotonin (5-HT) levels and [3H]5-HT binding in discrete hypothalamic areas was examined in separate groups of animals at various times, following unilateral intrahypothalamic injection of 5,7-dihydroxytryptamine (5,7-DHT). Seven days post-5,7-DHT lesion, 5-HT levels were significantly decreased in both the ipsilateral and contralateral ventromedial and dorsomedial hypothalamic nuclei (VMN, DMN). In the lateral hypothalamic area (LHA), 5-HT levels were significantly decreased only ipsilaterally. Fifty days postlesion, 5-HT levels in the ipsilateral VMN remained significantly below sham, while the DMN and LHA returned to sham values. Seven days after 5,7-DHT there was a significant increase in [3H]5-HT labeling densities in the ipsilateral and contralateral ventromedial hypothalamic area as well as in the ipsilateral LHA. In contrast, in the dorsomedial hypothalamic area there was no increase in [3H]5-HT binding. Fifty days postlesion, no significant differences in [3H]5-HT binding between 5,7-DHT and sham were observed in any areas examined. This data provides further evidence for the regeneration of 5-HT fibers in the hypothalamus and demonstrates that the relationship between [3H]5-HT binding and 5-HT levels varies from one hypothalamic area to another.

5,7-Dihydroxytryptamine

Monoamine levels and turnover in brain: relationship to priming actions of estrogen.

Norepinephrine (NE), dopamine (DA) and serotonin (5HT) levels and turnover rates were studied in 8 discrete brain nuclei of ovariectomized rats 24 hours after the administration of 5 microgram of estradiol benzoate (EB) or sesame oil vehicle. This estrogen paradigm, by itself, did not induce sexual behavior or alter LH levels at the time these parameters were evaluated. However, combined with progesterone, the estrogen treatment was sufficient to generate an LH surge and induce sexual receptivity. Steady state concentrations of NE were significantly higher in the diagonal band of Broca (NDB) and the periventricular nucleus (PVE2; anterior hypothalamic level) following EB treatment. In addition, 5-hydroxyindole acetic acid (5HIAA) concentrations were elevated in the dorsal raphe of EB treated animals. Estrogen did not affect steady state concentrations of DA or 5HT in any of the brain nuclei studied. Turnover rates (K, pg/microgram protein/hr) and rate constants (k, hr-1) for NE were increased in the lateral septum (K, 140%; k, 120%), NDB (K, 160%; k, 130%) and the PVE2 (K, 140%; k, 70%) in EB treated animals. Estrogen decreased the rate constant for NE by 30% in the medial preoptic area. In contrast, DA and 5HT turnover rates were not significantly affected by estrogen. These results localize sites where estrogen induces changes in noradrenergic activity and suggest that these changes may be involved in the priming action of the steroid in inducing sexual behavior and/or gonadotropin secretion.

Animals