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Biomedical subjects

B Harris

Publications and source records attributed to B Harris.

At least 19 recordsLinked to original sources

Association between postpartum thyroid dysfunction and thyroid antibodies and depression.

OBJECTIVE: To define the relation between mood and autoimmune thyroid dysfunction during the eight months after delivery. DESIGN: Double blind comparison of the psychiatric status of women positive and negative for thyroid antibodies. Clinical examination and blood sampling for free triiodothyronine and thyroxine, thyroid stimulating hormone, and thyroid antibody concentrations at four weekly intervals. Psychiatric assessment at six, eight, 12, 20, and 28 weeks post partum. SETTING: Outpatient department of district hospital. PATIENTS: 145 antibody positive women and 229 antibody negative women delivering between August 1987 and December 1989. MAIN OUTCOME MEASURES: Thyroid status. Number of cases of mental ill health by the general health questionnaire, research diagnostic criteria, Hamilton 17 item depression scale, hospital anxiety and depression scale, and Edinburgh postnatal depression scale. RESULTS: Six weeks after delivery the general health questionnaire showed 62 (43%) antibody positive women and 65 (28%) antibody negative women had mental ill health (chi 2 = 8.18, p less than 0.005). Follow up of 110 antibody positive and 132 antibody negative women showed significantly greater depression by research diagnostic criteria in antibody positive women (47%) than antibody negative women (32%) regardless of thyroid dysfunction. Antibody positive women showed higher mean scores for depression on the Hamilton (6.01 v 3.89, p = 0.0002), Edinburgh (7.45 v 5.92, p = 0.031), and hospital depression scales (4.95 v 3.79, p = 0.003). CONCLUSION: Depressive symptoms are associated with positive thyroid antibody status in the postpartum period.

Autoantibodies

Isoflurane anesthesia is stereoselective.

The anesthetic effects of the (+) and (-) isomers of isoflurane were determined in mice. Like the clinically important racemate, both isomers produced dose-dependent increases in anesthetic sleep time. A statistically significant (P less than 0.005, ANOVA) difference in the potencies of these isomers ((+) greater than (-)) was observed. To our knowledge, this is the first demonstration of a stereospecific action of a volatile anesthetic in vivo.

Analysis of Variance

Inhibition of DNA primase and polymerase alpha by arabinofuranosylnucleoside triphosphates and related compounds.

Inhibition of DNA primase and polymerase alpha from calf thymus was examined. DNA primase requires a 3'-hydroxyl on the incoming NTP in order to polymerize it, while the 2'-hydroxyl is advantageous, but not essential. Amazingly, primase prefers to polymerize araATP rather than ATP by 4-fold (kcat/KM). However, after incorporation of an araNMP into the growing primer, further synthesis is abolished. The 2'- and 3'-hydroxyls of the incoming nucleotide appear relatively unimportant for nucleotide binding to primase. Polymerization of nucleoside triphosphates by DNA polymerase alpha onto a DNA primer was similarly analyzed. Removing the 3'-hydroxyl of the incoming triphosphate decreases the polymerization rate greater than 1000-fold (kcat/KM), while a 2'-hydroxyl in the ribo configuration abolishes polymerization. If the 2'-hydroxyl is in the ara configuration, there is almost no effect on polymerization. An araCMP or ddCMP at the 3'-terminus of a DNA primer slightly decreased DNA binding as well as binding of the next correct 2'-dNTP. Changing the primer from DNA to RNA dramatically and unpredictably altered the interactions of pol alpha with araNTPs and ddNTPs. Compared to the identical DNA primer, pol alpha discriminated 4-fold better against araCTP polymerization when the primer was RNA, but 85-fold worse against ddCTP polymerization. Additionally, pol alpha elongated RNA primers containing 3'-terminal araNMPs more efficiently than the identical DNA substrate.

Animals

Demonstration by S-100 protein staining of increased numbers of nerves in the papillary dermis of patients with prurigo nodularis.

BACKGROUND: We hypothesized that hyperplasia of papillary dermal nerves was a constant feature of prurigo nodularis. OBJECTIVE: We tested this hypothesis by examining sections from 25 cases of prurigo nodularis, 25 cases of skin lesions characterized by epidermal hyperplasia without clinical pruritus, and 22 cases of clinically pruritic dermatoses with variable degrees of epidermal response for the presence of papillary dermal nerves. METHODS: We used a standard immunohistochemical assay with an antibody to S-100 protein as a means of identification of nerves. RESULTS: In 24 of 25 cases of prurigo nodularis, papillary dermal nerves were identified by immunostaining. Cutaneous nerves were present in 1 of 22 cases of epidermal hyperplasia with pruritus and were absent in the papillary dermis in nonpruritic cases. CONCLUSION: We conclude that hypertrophy of cutaneous papillary dermal nerves is a relatively constant feature of prurigo nodularis. The presence of papillary dermal nerves suggests a neurocutaneous component in the pathogenesis of prurigo nodularis.

Humans

Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers.

A great deal of interest has been focused recently on the potential use of synthetic polypeptide growth factors to stimulate healing of chronic wounds. In this pilot double-blind randomized study conducted at a single center, we used human recombinant epidermal growth factor (h-EGF) to treat 44 patients with venous ulceration of the lower extremities. An aqueous solution (10 micrograms/mL) of h-EGF was applied topically to the ulcers twice a day until healing occurred or for a maximum of 10 weeks. Patients were evaluated weekly for measurements of ulcer size and for the formation of granulation tissue suitable for grafting. Nine patients were excluded from efficacy evaluation because of protocol violations. Therefore, 35 patients (17 h-EGF, 18 placebo) were evaluable for efficacy, and 44 patients (22 h-EGF, 22 placebo) were available for safety. The median baseline ulcer size for all patients was 18.5 cm2, and was not significantly different between h-EGF and placebo group (12.9 cm2 versus 19.2 cm2, respectively, P = .27). By study end, six (35%) of h-EGF treated patients and two (11%) in the placebo group had healed completely (P = .10). Another 6 patients (2 of 17 h-EGF, 4 of 18 placebo; P = .50) developed healthy granulation tissue that was suitable for grafting. The median ulcer size reduction was 7% for h-EGF versus 3% for placebo per week (P = .29), and 73% versus 33% at study end (P = .32). No untoward side effects were related to the application of h-EGF. We conclude that topical application of h-EGF, in the dose and manner used in this study, was safe but failed to significantly enhance re-epithelialization of venous ulcers. However, a greater reduction in ulcer size and a larger number of healed ulcers with the use of h-EGF are encouraging results.

Administration, Topical

The effects of occlusive dressings on the recruitment of mononuclear cells by endothelial binding into acute wounds.

Mononuclear cell infiltration is a characteristic feature of wounds and may play an important role in the healing process. We have previously shown that the recruitment of peripheral blood mononuclear cells into wounded skin is an active, dynamic, and regulated process mediated at least in part by specific interactions between mononuclear leukocytes and specialized dermal microvascular endothelial cells in the wounded skin. The purpose of this study was to investigate the capacity of dermal microvascular endothelial cells in wounds exposed to air or covered with occlusive dressings to promote the adhesion of monocytes and lymphocytes. The results showed that dermal microvascular endothelial cells in both air-exposed and occluded wounds were capable of supporting peripheral blood mononuclear cell and monocyte adherence. However, in comparison with air exposed wounds, the level of peripheral blood mononuclear cell binding was significantly higher in occluded biopsies obtained at 0 to 9, 12, 15, and 21 days after wounding. In addition, monocyte and peripheral blood mononuclear cells binding to occluded wounds peaked earlier than peripheral blood mononuclear cell binding to air exposed wounds. These studies provide evidence that differences in the kinetics and magnitude of mononuclear cell adherence may account at least in part for the beneficial effects of occlusive dressing on wound healing.

Animals

Salivary testosterone levels and major depressive illness in men.

Studies of testosterone levels in patients with major depressive illness have produced varying results, plasma levels usually being reported. Saliva levels reflect 'free' plasma testosterone, and a pilot study of 11 men with major depression with melancholia, who underwent a standard dexamethasone suppression test, is described. There were no significant differences in testosterone levels compared with an age-matched control group. In the patient group, pre-dexamethasone levels correlated significantly and negatively with depression ratings on the 21-item Hamilton and the Montgomery and Asberg depression scales, and also with state anxiety measured on the Spielberger scale.

Adult

Differences in basal and poststimulation glucose homeostasis in nondiabetic first degree relatives of black and white patients with type 2 diabetes mellitus.

Black Americans (blacks) have a higher prevalence and earlier onset of type 2 diabetes than white Americans (whites). To examine metabolic differences in both races, we measured the basal glucose turnover rates (D-]3-3H]glucose technique) and plasma glucose, insulin, and C-peptide levels before and after an oral glucose load in 24 glucose-tolerant black and 14 white female relatives of patients with type 2 diabetes. Eight black and 8 white female subjects with no family history of diabetes served as controls. Mean fasting and postglucose plasma glucose levels were not significantly different between the black and white relatives and the control subgroups. Mean fasting plasma insulin and C-peptide levels were slightly greater but not significantly different between the relatives. After oral glucose ingestion, mean incremental integrated plasma insulin areas were significantly (P less than 0.02) greater in the black than the white relatives (70 +/- 14 vs. 29 +/- 6 nM.min). In addition, incremental integrated C-peptide areas were greater in the black than the white relatives (303 +/- 55 vs. 115 +/- 33; P less than 0.005). Similarly, we found significantly greater integrated incremental insulin (61 +/- 11 vs. 22 +/- 3 nM.min; P less than 0.02) and C-peptide (248 +/- 58 vs. 47 +/- 16; P less than 0.005) areas in the black than the white controls, respectively. The estimated basal and postglucose hepatic insulin extraction values, expressed as molar ratios of C-peptide and insulin, were not significantly different between the relatives. While basal hepatic insulin extraction was significantly (P less than 0.05) lower in the black controls, the postprandial insulin clearance was not different between the black and white controls. Mean basal hepatic glucose production was greater (P less than 0.02) in the black than the white relatives (2.49 +/- 0.13 vs. 2.02 +/- 0.12 mg/kg.min). Similarly, the black controls had greater hepatic glucose production than the white controls (2.36 +/- 0.15 vs. 1.81 +/- 0.08 mg/kg.min; P less than 0.001). We conclude that basal and poststimulation glucose homeostatic regulation appear to be different in black and white females, regardless of family history of type 2 diabetes.

Adult

Effects of concentration of dietary phosphorus on amount and route of excretion.

Objectives were to determine the effect of dietary concentration of P in DM on routes of excretion of P and to evaluate direct and indirect measures of calculating DM digestibility and P excretion. Twelve lactating Holstein cows were fed 20 kg of DM containing .41% P daily for 4 wk and then were assigned randomly to one of three diets: low (.30%), medium (.41%), or high (.56%) in P for 9 wk. Total collections of excreta (feces and urine) and milk were made during wk 4, 7, 10, and 13. At wk 4, cows excreted 88.2% of P consumed daily: 68.6% of excreted P in feces, 1.0% in urine, and 30.3% secreted in milk. Cows assigned to the low P diet decreased intake by 26.8% and excretion of P in feces by 22.7% in wk 13 compared with wk 4, whereas cows fed the high P diet increased intake by 36.5% and excretion of P in feces by 48.6%. Digestibility of DM was 62.6% when calculated from total collection of feces but only 55.7 or 56.5% when estimated indirectly using Cr or acid detergent lignin as indigestible markers. Apparent excretion of P was less than that estimated using either of the marker techniques (49.7 vs. 59.1 and 58.1 +/- .7 g/d of P) because digestibility of DM was underestimated. A prediction equation was developed for P excretion based on P intake and milk production.

Animals

Otto Fenichel and the left opposition in psychoanalysis.

David Rapaport's collection of Otto Fenichel's Rundbriefe (1934-1945) is described as a recently rediscovered, 2,500-page primary source for studying the intellectual and organizational history of European-American psychoanalysis. Beginning as the confidential newsletter of the Reich-Fenichel "Left opposition" within the International Psychoanalytic Association, its function became primarily intellectual as Fenichel's group ceased to function as a caucus. It ended when its editor decided to devote himself to the struggle against neo-Freudianism within psychoanalysis, and to practice as a licensed physician.

Freudian Theory

Recruitment of mononuclear cells into wounded skin: mechanism and modulation.

In conclusion, we have shown that the development of specialized endothelium that supports lymphocyte and monocyte adherence may be a common biologic event associated with tissue injury or disease processes in the skin. We have shown that the adherence process is potentially regulated by cytokines that are secreted by infiltrating mononuclear cells. Studies are now in progress to identify the putative endothelial ligands, their interactions with the receptors and the factors that lead to the expression of the adhesion molecules.

Animals

Comparisons of plasma and salivary cortisol determinations for the diagnostic efficacy of the dexamethasone suppression test.

The current status of the saliva dexamethasone suppression test (DST) is discussed and results from the literature reviewed. Evidence is presented that demonstrates that the efficacy of the salivary-based test is equal to that of the plasma DST provided that specifically developed radioimmunoassays are used for determination of salivary cortisol. Such evidence relied on measurement of cortisol in 300 matched samples of plasma and saliva provided by patients admitted to a routine psychiatric ward over a 2-year period. The results according to diagnosis (DSM-III categories) were in line with those generally reported. The influence of anticholinergic medication was examined: this had no significant effects on the performance of the plasma or salivary-based DST.

Depressive Disorder

Seasonal variation and the results of the dexamethasone suppression test.

There is controversy over the presence of a circannual rhythm in cortisol values in samples provided by depressed patients after a standard dexamethasone suppression test (DST). Post-DST cortisol values from patients admitted to an acute psychiatric ward over a 2-year period have therefore been analysed by appropriate statistical tests. No evidence was found for significant seasonal variation.

Depressive Disorder

Recruitment of mononuclear cells by endothelial cell binding into wounded skin is a selective, time-dependent process with defined molecular interactions.

Wound healing involves a complex series of interactions between cells in the dermis and epidermis, and important relationships exist between keratinocytes and resident dermal cells. Monocytes and lymphocytes secrete cytokines that are capable of stimulating dermal repair and influencing keratinocyte and fibroblast migration and proliferation, although the mechanism by which mononuclear cells are recruited into the wound is unknown. We have tested the hypothesis that in wounded skin specialized endothelial cells are induced to mediate peripheral blood mononuclear cell (PBMC) emigration from the vasculature into the dermis. For this purpose, partial-thickness wounds made with a keratome on the backs of domestic pigs were excised 0 to 9, 12, 15, and 21 d after wounding. The biopsies were then tested for the capacity to adhere selectively to PBMC. The results indicated that PBMC overlaid onto sections of wounds from day 4 to 15 adhered selectively to dermal endothelium, with two distinct peaks of adherence observed on day 7 and day 12. In contrast, PBMC did not adhere to the tissue sections when overlaid onto frozen sections of normal skin or 0-, 1-, 2-, 3-, and 21-d-old wounded skin. Additional studies on the binding properties of PBMC subsets revealed that monocytes adhered maximally at day 7, whereas T cells adhered optimally at day 12 post-wounding. Furthermore, the adhesion process was energy and magnesium dependent but not calcium dependent and involved surface protein and carbohydrate moieties on PBMC surface. Pre-treatment of PBMC with monoclonal antibodies against the LFA-1 adhesive receptors inhibited the binding by greater than 80%, suggesting that LFA-1 adhesive receptors play an important role in the binding process. These studies provide evidence that the recruitment of monocytes and lymphocytes into wounds is an active, dynamic, and regulated process mediated at least in part by specific adhesive interactions between mononuclear leukocytes and dermal endothelial cells.

Animals