The membrane potential of vestibular dark cells is controlled by a large Cl- conductance.

The K+ secretory epithelium of the vestibular labyrinth (dark cells) was impaled with glass microelectrodes in order to test the hypothesis that it contains a large Cl- conductance. In the first series of experiments, the short-circuited epithelium was perfused on both sides by a solution containing 150 mmol/l Cl-. The membrane voltage (PD) was -18 +/- 1 mV (N = 101), showed a Gaussian distribution, and the estimated input resistance of the cell (R 'cell') was 17 +/- 3 M omega. The PD responded to 10(-4) mol/l ouabain with a depolarization, suggesting the presence of a (Na(+) + K+)-ATPase. The PD responses to Cl- steps yielded an apparent transference number tCl = 0.34 +/- 0.03 (N = 65) and those to K+ steps yielded a tK = 0.16 +/- 0.01 (N = 48). In the second series of experiments, cells presumed to be Cl(-)-depleted were impaled in Cl(-)-free solutions. The distribution of the PD was not Gaussian; PDs as negative as -90 mV were observed. Cells with a highly negative PD also had a high R 'cell'. With the addition of Cl- the PD collapsed to -19 +/- 1 mV and R collapsed to 16 +/- 3 M omega (N = 145) which are not significantly different from values obtained in the first series of experiments when cells were impaled in a solution containing 150 mmol/l Cl-. Alternating the bath perfusate between Cl(-)-free and Cl(-)-containing solutions led to large PD transients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravenous immunoglobulin may lessen all forms of infection in patients receiving allogeneic bone marrow transplantation for acute lymphoblastic leukemia: a pediatric oncology group study

Fifty patients with refractory acute lymphoblastic leukemia underwent allogeneic bone marrow transplantation after conditioning with high-dose cytosine arabinoside and fractionated total body irradiation. Twenty-nine received intravenous immunoglobulin (i.v.Ig) infusion, primarily to prevent cytomegalovirus infection, and 21 did not. The two groups were biologically comparable. Seven (24.5%) of the i.v.Ig-treated and 14 (66.7%) of the non-i.v.Ig-treated patients developed systemic viral, fungal or bacterial infections and/or interstitial pneumonitis (p less than 0.005), which were fatal in three and 12 cases respectively (p less than 0.001). Currently, 23 (79.3%) of the 29 i.v.Ig-treated and eight (38.1%) of the 21 non-i.v.Ig-treated patients are alive and well (p less than 0.01). We conclude that prophylactic i.v.Ig infusions may reduce the frequency of all forms of serious infection in patients with acute lymphoblastic leukemia undergoing allogeneic marrow transplantation, and thereby improve their survival expectation.     

Comparison of DSM-III-R and childhood autism rating scale diagnoses of autism

The purpose of this study was to clarify the issue of whether DSM-III-R (American Psychological Association [APA], 1987) over-or underdiagnoses autism by comparing this diagnostic system to a well-established objective measure of diagnosis, the Childhood Autism Rating Scale (CARS). A secondary goal was to determine which of the 16 criteria are the best discriminators of autism. DSM-III-R, CARS, and clinical diagnoses of 138 consecutive admissions to a statewide program for the diagnosis and treatment of autistic and related communication-handicapped individuals (Division TEACCH in North Carolina) were compared. Results indicated a generally high degree of agreement on the diagnosis of autism using the three systems. Within this tratment-oriented program, the CARS and clinical ratings diagnosed a greater number of cases as autistic than did the DSM-III-R criteria, suggesting that DSM-III-R slightly underdiagnosed autism. The criteria that most strongly related to the diagnosis of autism regardless of the system were lack of awareness of others, abnormal social play, an impaired ability to make friends, abnormal nonverbal communication, stereotypic body movements, and restricted range of interests.     

Radionuclide study of platelets and prosthetic interactions: external versus specimen quantitation

Twenty-nine New Zealand white rabbits were allocated to undergo insertion of either polytetrafluoroethylene (PTFE) (n = 22) or microporous silicone rubber (SR) (n = 7), 3-mm diameter, 10-mm long aortic grafts. Animals with PTFE grafts received aspirin (ASA) 10 mg/kg/d and dipyridamole (DPM) 10 mg/kg/d (n = 11) or placebo (n = 11). Autologous In-111-oxine-labeled platelets were reinfused on reestablishment of blood flow through the graft. Using gamma camera images, an external graft platelet accumulation index (E-GPAI) was calculated as the In-111 activity in the graft area to the reference aorta at 24, 48, and 72 hours post implantation. Mean E-GPAI +/- SEM values for the ASA/DPM (n = 4) and control groups (n = 7) were 1.13 +/- 0.16 and 1.34 +/- 0.05 (NS) at 24 hours, 1.20 +/- 0.16 and 1.33 +/- 0.07 (NS) at 48 hours, and 1.38 +/- 0.07 and 1.35 +/- 0.10 (NS) at 72 hours, respectively. A similar internal graft platelet accumulation index (I-GPAI) was constructed based on In-111 activity in excised grafts and reference aorta measured in a scintillation counter. Mean I-GPAI +/- SEM values for the PTFE ASA/DPM (n = 9) and control groups (n = 8) at 48 hours post implantation were 43.1 +/- 2.7 and 216.8 +/- 73.9 (P = 0.05), respectively. I-GPAI values for the SR grafts were 192.5 +/- 43.1. Conclusion: The E-GPAI was not sensitive enough to demonstrate the effect of antiplatelet medication on platelet accumulation on the PTFE grafts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunosuppressant material in human seminal fluid. Inhibition of blast transformation and of NK activity by seminal fluid patients of a male infertility clinic

Human seminal plasma from normal or patients with abnormal parameters of the ejaculates contains an inhibitory material that expresses potent in vitro inhibitory activity on PHA-M-induced blast transformation and NK activity. Using the test of inhibition of NK activity, the semen samples from individuals with higher concentrations of fructose had higher inhibitory activity. The results described herein suggest that inhibitory activity for blast transformation may be present in the prostatic fluid while the NK inhibition aspects are correlated with the vesicle-marker (fructose). Inhibition of the immune responses by human seminal plasma of the effector functions indicates the interesting implication that soluble factors may indirectly protect against or promote human autoimmune infertility disease.     

Missense mutations and evolutionary conserved amino acids at the human hypoxanthine phosphoribosyl-transferase locus.

Molecular characterization of in vivo mutation at the human hypoxanthine phosphoribosyltransferase (hprt) locus has revealed a broad spectrum of mutation, both with regard to germ-line mutation in Lesch-Nyhan and gout patients, and somatic mutation in 6-thioguanine resistant T-lymphocytes from healthy individuals. The pattern of missense mutation shows a non-random distribution with a preferential location to codons for amino acids which are identical in human and the two parasites Schistosoma mansoni and Plasmodium falciparum. Although these 'evolutionary conserved' amino acids account for only 32% of the amino acids in the human hprt protein, they are involved in 76% of the missense mutations at the hprt locus in human T-lymphocytes, 67% in Lesch-Nyhan patients (with severe hprt-deficiency), but only 43% in gout patients (with partial hprt deficiency). This observation supports the notion that evolutionary conserved amino acids constitute functionally important sites in the hprt enzyme, and missense mutations affecting these amino acids will often lead to complete loss of enzyme activity. Substitutions of 'non-conserved' amino acids cause less severe hprt-deficiency (as seen in the gout patients), or may even escape clinical diagnosis. These considerations are important for the understanding of structure-activity relationships in the hprt protein, possible differences between hprt mutational spectra in germ-line and somatic cells, and the mutational spectra induced by specific exogeneous mutagens.