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Biomedical subjects

B Johnson

Publications and source records attributed to B Johnson.

At least 271 records · Page 15Linked to original sources

Enhanced mutagenicity of 2-nitropropane nitronate with respect to 2-nitropropane--possible involvement of free radical species.

The mutagenicities of the neutral and the anionic (nitronate) forms of 2-nitropropane (2-NP) were compared in S. typhimurium strains TA98, TA100 and TA102. The latter is a special strain sensitive to compounds producing oxidative damage to DNA at thymine-adenine base pair loci. Neutral 2-NP was not mutagenic in TA98, and produced significant mutagenic response in TA100 and TA102 only at levels of 55 mumoles/plate. In contrast, 2-NP nitronate was significantly mutagenic in TA98 at 14 mumoles/plate and, in strains TA100 and TA102, at approximately 4 mumoles/plate. Inclusion of S9 slightly increased the mutagenicity of 2-NP nitronate in TA102, but decreased it in TA100. The mutagenic response in TA102, but not in TA100, was inhibited by DMSO, a scavenger of hydroxyl radicals, in a dose-dependent manner. When 2-NP nitronate was incubated with thymidine and horseradish peroxidase-H2O2, the formation of 2-NP dimer (2,3-dimethyl-2,3-dinitrobutane), a condensation product of 2-NP free radicals, was observed. This was accompanied by 2-NP nitronate-dependent oxidation of thymidine to thymidine glycol, thymine glycol, 5-hydroxymethyldeoxyuridine and thymine, indicating that hydroxyl radicals and/or other reactive oxygen species capable of causing thymidine damage are also formed in this reaction. As a working hypothesis, we suggest that the genotoxicity of 2-NP nitronate may be due to the generation of DNA-damaging reactive forms of oxygen or 2-NP free radicals.

Alkanes↗

Absence of an estradiol-induced surge of luteinizing hormone in pigs receiving unvarying pulsatile gonadotropin-releasing hormone stimulation.

The goal of this study was to pharmacologically block central nervous system (CNS) input to gonadotropes in mature ovariectomized gilts to determine the direct actions of estradiol (E2) on pituitary LH release when given at a dose sufficient to elicit a gonadotropin surge. Feeding AIMAX [N-methyl-N'-(1-methyl-2-propenyl)1,2-hydrazinedicarbothioamide; 125 mg/day] for 7 days reduced serum LH concentrations from 1.25 +/- 0.13 (mean +/- SE) to less than 0.18 ng/ml, abolished LH pulses, but did not compromise LH release in response to exogenous GnRH. Serum FSH concentrations were reduced by 27%, whereas serum concentrations of PRL, GH, thyroid hormones and cortisol were not affected after 7 days of AIMAX treatment. Behavior was not altered, aside from a slightly reduced appetite. The LH surge that peaked 48-80 h after injecting E2 benzoate (E2B) into control gilts was blocked in five of eight gilts given AIMAX. Giving GnRH pulses (1 microgram every 45 min) to AIMAX-treated gilts restored mean serum LH concentrations as well as the frequency and amplitude of LH pulses to those of untreated ovariectomized gilts. E2B suppressed the LH response to these GnRH pulses by 88% at 12 h, whereas from 24-96 h after E2B treatment, the LH response to GnRH and mean serum concentrations of LH were again similar to those of controls not given estradiol. These data indicate that induction of the gonadotropin surge by E2 in the gilt requires CNS input. The action of E2 on the pituitary in the presence of unvarying GnRH pulsation may, however, be limited to an early transient inhibition of responsiveness to GnRH, with no subsequent direct stimulation during the period of the surge.

Animals↗

C-reactive protein is involved in natural killer cell-mediated lysis but does not mediate effector-target cell recognition.

Anti-CRP and complement treatment of human peripheral blood lymphocytes significantly reduces natural killer (NK) cell-mediated cytotoxicity to K562 target cells as well as to MOLT-4 target cells. Although not all activity is eliminated by treatment of effector cells with antibody and complement, the reduction of NK function indicates that C-reactive protein (CRP) is present on a significant proportion of NK cells. Higher concentrations of anti-CRP or anti-CRP F(ab')2 fragments also reduce NK function; this suggests that CRP is not only present on these effector cells but may also play a role in NK-mediated killing. We initially suspected that CRP-ligand interactions might be involved in effector-target cell recognition. Several lines of evidence suggest that this is not the case. While F(ab')2 anti-CRP will block NK function, Fab anti-CRP will not, suggesting that the NK response is not impaired when surface CRP (S-CRP) is blocked but is only inhibited when the S-CRP is cross-linked and modulated. Neither CRP-C polysaccharide complexes (CRP-CPS) nor concentrations of CPS ranging from 0.1 microgram/ml to 200 micrograms/ml have any effect on NK cell-mediated killing. Treatment of target cells with a ligand for CRP or CRP prior to co-culture with NK effectors does not augment NK function. Single cell assays clearly demonstrate that high concentrations of anti-CRP have no effect on the formation of effector-target cell conjugates. Although these concentrations of anti-CRP do not block effector-target cell conjugation in the single cell assay, they do block the killing of conjugated target cells. In total, this evidence strongly suggests that although CRP appears to be involved in NK-mediated killing, it is not involved in effector-target cell-mediated recognition.

Antibodies↗

Retina S antigen-induced uveitis. The efficacy of cyclosporine and corticosteroids in treatment.

This study compares the efficacy of cyclosporine and corticosteroids in the treatment of retina S antigen-induced uveitis (experimental autoimmune uveitis). Forty guinea pigs were immunized with retina S antigen in complete Freund's adjuvant to induce uveitis. After 16 days, animals were divided into groups that received a two-week course of daily intramuscular injections of cyclosporine, corticosteroids, both drugs, or saline. Eyes were graded by a masked retinal specialist for amount of vitreous cells by biomicroscopy, and after enucleation by a masked ocular pathologist for histologic evidence of inflammation. Clinically and histopathologically, animals treated with cyclosporine, or cyclosporine and corticosteroids, had statistically significant reduction of intraocular inflammation compared with controls. Corticosteroids alone had a less beneficial effect. The combined use of cyclosporine and corticosteroids, at the single dose tested, did not demonstrate synergism.

Adrenal Cortex Hormones↗

Effect of acute postinfusion lipemia and free fatty acids on myocardial contractility: assessment with radionuclide ventriculography.

Equilibrium gated radionuclide ventriculography was used to evaluate the effect of intravenous fat-emulsion overload and excess of free fatty acids (FFA) on left ventricular ejection fraction (LVEF) in 20 patients with and without coronary artery disease (CAD). Fifteen of these patients had normal (greater than 50%) baseline LVEF and 5 had low (less than 50%) baseline LVEF. From 100 to 150 ml of 20% artificial fat emulsion (Liposyn) was infused over 20-25 min. At the end of the infusion, triglyceridemia reached 820 +/- 220 mg% and left ventricular ejection fraction decreased from baseline 62 +/- 19% (mean +/- SD) to 58 +/- 16% (P less than 0.05, paired t-test). After completion of Liposyn infusion, 5,000 U of heparin was administered intravenously and monitoring of LVEF was continued. One and one-half hours following heparin administration, plasma FFA levels reached 3.7 + 2.0 mmol/l and LVEF rose to 69 +/- 19% (P less than 0.001, paired t-test). Our data indicate that acute intravenous fat overload can suppress and high pathophysiologic levels of FFA can increase LVEF. This effect is more uniform and statistically more reliable in patients with normal LVEF. The study failed to demonstrate any significant difference in the effect of this pharmacologic intervention between patients with and without CAD.

Aged↗

Necropsy of the feeder and stocker calf.

Frequently occurring diseases are discussed in 2- to 12-month-old pastured or feedlot cattle. Emphasis is on gross necropsy lesions that are significant in differential diagnosis. Where applicable, practical laboratory tests that are helpful in confirming a diagnosis are described. Information about proper selection and preservation of tissues for submission to a diagnostic laboratory is included.

Animals↗

The effects of single-dose atenolol, labetalol, and propranolol on cardiac and vascular function.

The pharmacodynamic effects of single oral doses of atenolol (100 mg), labetalol (300 mg), and propranolol (80 mg) were compared with those of placebo in a randomized, double-blind, Latin square design in 12 patients with hypertension. Atenolol and propranolol both significantly reduced cardiac output (-0.55 vs. -0.31 L/min) and heart rate (-8.0 vs. -6.6 bpm), whereas labetalol had no effect on either parameter (-0.08 L/min; + 1.0 bpm). Labetalol significantly reduced vascular resistance (-339 dynes X cm/sec5), but atenolol and propranolol did not (147 vs. 62 dynes X cm/sec5). Only labetalol significantly reduced the systolic (-15.3 mm Hg), diastolic (-11.5 mm Hg), and mean blood pressures (-12.8 mm Hg). Atenolol significantly reduced only diastolic blood pressure (-5.20 mm Hg), whereas propranolol failed to lower these parameters significantly. These data indicate that the hemodynamic profile of labetalol differs from that of selective and nonselective beta-blockers. Labetalol lowered blood pressure primarily by reducing vascular resistance, whereas reductions in heart rate and cardiac output were the predominant effects of atenolol and propranolol.

Aged↗

Transformation of a human poliovirus receptor gene into mouse cells.

The first step in poliovirus replication is binding of virus to a cellular receptor. Mouse L cells, which are resistant to poliovirus infection because they do not bear a poliovirus receptor, were transformed with HeLa cell (human) DNA to poliovirus sensitivity at a frequency of approximately 1 in 50,000 transformants. Monoclonal antibody directed against the HeLa cell poliovirus receptor site was used in rosette assays to identify poliovirus-sensitive L-cell transformants in a background of L-cell tk+ transformants. A cloned cell line, CM-1, was isolated that displayed a surface component recognized by the anti-poliovirus receptor antibody. CM-1 cells were susceptible to infection with all three poliovirus serotypes, and infection could be blocked by the antireceptor antibody. Poliovirus formed plaques in CM-1 and HeLa cells with equal efficiency. CM-1 and HeLa cells produced infectious poliovirus at a similar rate, although yield of virus in CM-1 cells was about 33% less than the yield in HeLa cells. These results suggest that DNA encoding the HeLa cell poliovirus receptor has been introduced into mouse cells, resulting in the expression of the receptor and susceptibility to poliovirus infection.

Animals↗

Hepatitis delta virus infection in Kenya. Its geographic and tribal distribution.

In 1982-1984, an epidemiologic survey of the prevalence of hepatitis B virus surface antigen (HBsAg) in circulating blood (HBs-antigenemia) and of hepatitis delta virus infection was performed in Kenya. The distributions of hepatitis B virus and the delta virus were shown to be very variable. In southern Kenya, only two of 202 sera from HBsAg-positive individuals with no known liver disease and none from 123 HBsAg-positive patients with hepatitis B-related liver disease were positive for delta antibody. In contrast, in northern Kenya, there was an overall prevalence of delta antibody in healthy individuals of 31%. The distribution of delta infection is discussed in relation to lifestyle, ethnic group, and geographic area.

Adult↗

Eccrine adenocarcinoma--report of a case, treatment with Mohs surgery.

Eccrine adenocarcinomas are neoplasms with a low incidence of occurrence and a prolonged and insidious course. The diversity of the histologic findings compatible with the diagnosis contributes to the difficulty of establishing a histologic prognosis from the pathology. Tumors with histologic features consistent with benign adenomas have subsequently metastasized, reflecting both the variable behavior of these tumors and problems with diagnostic and prognostic classification. Eccrine adenocarcinoma usually presents as a discrete lesion involving the scalp or upper extremities. It may also occur on the trunk and lower extremities. The gross morphology of the tumor is not specific, therefore the clinical diagnosis of eccrine adenocarcinoma is rarely made. Herein we report a case of the malignant eccrine acrospiroma type with lymph node metastasis, an approach to therapy, and guidelines for histologic criteria of malignancy.

Adenocarcinoma↗

Retinal toxicity of amphotericin B in vitrectomised versus non-vitrectomised eyes.

The retinal toxicity of intravitreally administered amphotericin B was compared in non-vitrectomised versus vitrectomised rabbit eyes. Doses of 5 and 10 micrograms in both groups resulted in transient vitritis but had no effect on electroretinograms. Histopathological examination four weeks after injection showed vitreous cells and minimal areas of retinal necrosis in both groups at 5 or 10 micrograms doses. At these doses vitrectomy did not modify the retinotoxic effects of intravitreally administered amphotericin B. At higher doses marked toxicity was found in both vitrectomised and non-vitrectomised groups.

Amphotericin B↗

Paraocular lymphoid tumors.

Forty-two patients with paraocular lymphoid tumors were treated with radiation. Histologically, 20 tumors were classified as benign lymphoid hyperplasia (BLH), ten as indeterminate histology (IH), and 12 as malignant lymphoma (ML). Of the patients with an initial diagnosis of BLH or IH, disseminated ML developed in 23%. Cytologic and histologic studies were not helpful in predicting the malignant potential in some of these tumors. The possibility that BLH represents a premalignant condition with subsequent transformation into ML is discussed. A total of 45 eyes were irradiated in these 42 patients. Initial local control rate was 93%, with ultimate control rate of 100% after retreatment with radiation or surgery. Radiation therapy is the treatment of choice for these tumors; local control rates are high, and morbidity is minimal with proper radiation treatment planning.

Aged↗

Developing strategic planning systems for health care organizations.

Health care administrators have the unique opportunity to devise strategic planning systems (SPSs) that exclude many of the shortcomings exposed in the SPSs of companies in traditional industrial settings. Here, the problems and potentials of SPSs for health care firms are framed in terms of three major dimensions of the strategic planning system: information, communication, and involvement.

Communication↗