Effects of methylmercury in vitro on methionine synthase activity in various rat tissues.
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Biomedical subjects
Publications and source records attributed to J G Smith.
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The myelodysplastic syndromes are a heterogenous group of hematologic disorders of myeloid progenitor cells. Oral manifestations may be among the first signs and often reflect degrees of neutropenia or neutrophil dysfunction. A patient with persistent herpes labialis and severe oral mucosal ulceration in myelodysplastic syndrome is reported. The features of myelodysplasia are reviewed and their oral manifestations and significance to dental management outlined.
This study examines the effect of cytosine arabinoside (Ara-C) on CFU-GM progenitor cells grown in methylcellulose culture from normal and myelodysplastic subjects and patients with acute non-lymphoblastic leukaemia. Light density marrow cells were incubated during culture with Ara-C concentrations ranging from 10(-4) M to 10(-12) M. After counting, colonies were cytospun and cells within the colonies examined for alkaline phosphatase positivity and expression of HLA-DR antigen, as indices of differentiation. Monocytes/macrophages were also enumerated in colonies using the monoclonal antibody CD14. In all subjects, 10(-4) M to 10(-6) M Ara-C caused significant reduction in CFU-GM colony formation compared with control (no Ara-C). In no instance did colony numbers increase. Ara-C across the dose curve had no effect on myeloid differentiation markers in any of the groups studied. Similarly, percentages of CD14 positive cells in colonies were not altered by exposure to Ara-C. Using this clonogenic model, these data suggest that Ara-C does not induce differentiation of CFU-GM stem cells in normal subjects or patients with myelodysplasia/acute non lymphoblastic leukemia.
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Tumor necrosis factor-alpha was detected in supernatants collected from BALB/c mouse peritoneal macrophages incubated continuously with Histoplasma capsulatum. The levels of TNF alpha measured by actinomycin D bioassay peaked within hours after exposure and then greatly declined by 24 h. TNF alpha was also measured in bronchoalveolar lavage fluid from BALB/c mice challenged intranasally with H. capsulatum. Lavage fluid TNF alpha levels exhibited the same pattern as the in vitro supernatants; they peaked within hours after challenge and lower levels were detected at 24 h. Treatment of mice with anti-TNF alpha antibody accelerated mortality in response to systemic infection and significantly increased tissue colony counts in the liver and spleen. In the murine model, TNF alpha is produced in response to H. capsulatum and appears to play some role in host defense to infection.
This paper reports 11 cases of recurrence 10 years or more after primary treatment of clinically local cutaneous melanoma at the Peter MacCallum Cancer Institute. Using the product-limit method for estimating recurrence-free survival, two late recurrence rates have been calculated. The estimated late recurrence rate among all treated patients is 5 percent (95 percent confidence interval: 2 to 8 percent), and the estimated late recurrence rate for the group who survived the first 10 years without recurrence is 7 percent (95 confidence interval: 3 to 11 percent). No prognostic factors were found that could identify a patient subgroup significantly at risk of late recurrence. Recurrence-free survival curves show that most recurrences have presented by the end of 6 years, but later recurrences are seen, the latest in this series being 18.2 years following treatment. While patients probably do not require long-term follow-up in specialist clinics provided they are adequately educated in the nature of their disease, this paper shows the value of long-term statistical surveillance.
Acute hypoglycaemia provokes rapid changes in peripheral blood cell counts. To examine possible adrenergic mechanisms modulating these changes, counts of peripheral blood cells including lymphocytes, granulocytes and erythrocytes were measured in response to acute hypoglycaemia in a group of six normal subjects in control conditions (study 1), and during alpha-adrenergic blockade with phentolamine (study 2). In study 1 hypoglycaemia provoked a biphasic leucocyte response, with an early rise in lymphocyte count and a later rise in granulocyte count. The erythrocyte count increased modestly following hypoglycaemia. During alpha-adrenergic blockage, the rise in total leucocyte count was diminished, with the rise in the lymphocyte count being greatly obtunded. These findings suggest that the increments of peripheral lymphocyte and erythrocyte counts in response to acute insulin-induced hypoglycaemia are mediated via alpha-adrenoreceptors.
In a mouse model of pneumonia caused by murine Chlamydia trachomatis (mouse pneumonitis agent [MoPn]), tumor necrosis factor alpha (TNF-alpha) antigen and bioactivity were demonstrated in vivo in the lung during MoPn infection in both athymic (nude) and heterozygous (nu/+) mice. Antibody to TNF-alpha that was exogenously given neutralized the TNF-alpha in the lung, significantly accelerated mortality, and caused a borderline increase in MoPn counts in the lung by culture in nu/+ mice. Lipopolysaccharide-induced TNF-alpha activity or injections of recombinant murine TNF-alpha significantly but modestly protected nu/+ mice against MoPn-induced mortality. TNF-alpha is produced in vivo during C. trachomatis infection and plays a role in host defense.
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Peripheral blood leukocyte counts and plasma hormonal changes in response to acute insulin-induced hypoglycaemia were examined in 16 patients undergoing assessment of pituitary function. Eight subjects had a normal cortisol secretory response (Group 1), and 8 patients had definite hypopituitarism in whom the cortisol responses were deficient or absent (Group 2). An equivalent degree of hypoglycaemia was achieved in both groups. In Group 1a biphasic rise in leukocyte count occurred following hypoglycaemia, with an early rise in lymphocytes at 15 minutes after the acute hypoglycaemic reaction, and a later rise in granulocytes. A similar rise in lymphocytes was observed in Group 2, but the rise in the granulocyte count was attenuated, increasing from a basal value of 3.6 +/- 0.6 x 10(9) cells/L to a peak of 7.4 +/- 1.1 x 10(9) cells/L, compared with a peak of 11.7 +/- 1.2 x 10(9) cells/L in Group 1 (P less than 0.05). The usual increment in plasma cortisol in response to hypoglycaemia occurred in Group 1, but plasma cortisol did not rise in Group 2. A correlation was observed between the magnitude of the granulocyte rise and the increment in plasma cortisol in individual subjects (r = 0.64, P less than 0.02). This suggests that the rise in peripheral granulocytes following insulin-induced hypoglycaemia in man is mediated by cortisol released from the adrenal gland, following activation of the hypothalamic-pituitary-adrenal axis.
A 45-year-old Caucasian female with seropositive rheumatoid arthritis was found coincidentally to have a circulating lymphocytosis (6.4 x 10(9)/l) and neutropenia (0.1 x 10(9)/l). Initial presentation was with mouth ulceration and recurrent infections. A spleen scan showed no evidence of splenomegaly and serum titres against EBV, CMV and toxoplasmosis were negative. No anti-neutrophil antibodies were found. Marrow aspiration demonstrated a lymphocytosis of 60% with reduced numbers of granular precursors. Lymphocytes in both blood and bone marrow were CD3, CD8, CD16 and HLA-DR positive. Lymphocyte conditioned medium (LCM) generated from the patient's blood lymphocytes (without phytohaemagglutinin) was found to inhibit allogeneic colony-forming unit, granulocyte-macrophage (CFU-GM) stem cells in semi-solid culture compared with control LCM. This inhibitory activity was abrogated by the cytolytic removal of CD8 cells prior to LCM production and was significantly reduced by co-culture with indomethacin. Culture of the patient's marrow at autostimulatory light density marrow cell concentrations showed poor spontaneous CFU-GM colony formation until marrow CD8 lymphocytes were removed cytolytically. Prednisolone was used therapeutically (40 mg/d) and resulted in the patient's neutrophil count rising from 0.06 x 10(9)/l to 1.1 x 10(9)/l and a fall in the total lymphocyte count to 1.9 x 10(9)/l. Reevaluation of the patient's LCM post steroid therapy showed loss of the previous inhibitory effect. The patient's neutrophil count is maintained on oral azathioprine and indomethacin.
The urinary erythrocyte morphology of 120 patients with haematuria of diagnosed cause (41 glomerular, 79 non-glomerular) was examined by red cell analyser (RCA) and by phase contrast microscopy (PCM). By RCA three distinct ranges of modal erythrocyte cell volume (ECV) were observed. The modal ECVs in glomerular haematuria (35-50 fl) were significantly lower than in non-glomerular haematuria (65-148 fl) and both were clearly distinct from 'debris patterns' (12-33 fl). In duplicate specimens very similar ECVs were observed before and after centrifugation and after storage for up to 15 h. There was no correlation between the modal urinary ECV and the urinary specific gravity or the peripheral venous ECV. The source of the haematuria (glomerular or non-glomerular) was identified correctly by RCA (PCM) in 100% (60%), 68% (71%) and 22% (39%), respectively, of patients with macroscopic, 3+ microscopic and 1-2+ microscopic haematuria. In no patient was the haematuria localised incorrectly by RCA as compared with 10% incorrect localisation by PCM. RCA and PCM are complementary non-invase tests and both should be performed whenever possible in the investigation of haematuria.
Hepatitis B is now the most commonly reported hepatitis in the United States and the physician's greatest infectious occupational hazard. Although dermatologists are at increased risk for contracting and transmitting hepatitis B virus, surveys continue to indicate that a substantial number do little to decrease this risk. We have summarized the recent developments regarding the transmission, diagnosis, and clinical presentation and course of hepatitis B virus infection, and have offered specific preventive measures to assist the dermatologist in keeping hepatitis B out of his medical practice. By employing these measures, dermatologists can do their part in contributing to the future eradication of this disease.
An 18-year-old white woman admitted for an incomplete septic abortion was found to have thrombocytopenia, anemia, and increased activated partial thromboplastin time (PTT). Additionally, results of nontreponemal serologic tests for syphilis were positive, and the fluorescent antinuclear antibody was weakly positive. A mixture of the patient's plasma with normal control plasma showed that the elevation in activated PTT was the result of a circulating anticoagulant, not an inherent clotting defect. Sclerodermoid features were present and consisted of bound-down, hairless skin and scattered subcutaneous indurated plaques. A faint pattern consistent with livedo reticularis was recognized on all extremities. Biopsy specimens of sclerodermoid lesions showed increased and thickened dermal collagen consistent with morphea. We believe that this patient's condition represents an unusual connective tissue disease syndrome consisting of abortion, livedo reticularis, thrombocytopenia, circulating "anticoagulant," negative or slightly positive antinuclear antibodies, and false positive results on nontreponemal serologic tests for syphilis. Sclerodermoid lesions were also a unique feature in our patient.
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