Robust Selection of the Most Discriminative Variables in the Dichotomous Problem with Application to Some Respiratory Disease Data

A robust method for selection of variables with the greatest discriminatory power is presented in the paper. The method deals with the two groups of data problem. An application of the method to some respiratory disease data and comparisons with classical procedures are given, also.     

Pertussis toxin inhibits CAMP-induced desensitization of adenylate cyclase in Dictyostelium discoideum

cAMP binds to surface receptors of Dictyostelium discoideum cells, transducing the signal to adenylate cyclase, guanylate cyclase and to chemotaxis. The activation of adenylate cyclase is maximal after 1 min and then declines to basal levels due to desensitization, which is composed of two components: a rapidly reversible adaptation process, and a slowly reversible down-regulation of cAMP receptors. Adaptation is correlated with receptor phosphorylation.The chemotactic response and the cAMP-induced cGMP response were not significantly altered in D. discoideum cells pretreated with pertussis toxin. The initial increase of cAMP levels was identical in control and toxin treated cells, suggesting that activation of adenylate cyclase was also not affected. However, cAMP synthesis continued in toxin treated cells, due to a strongly diminished desensitization. Pertussis toxin inhibited the adaptation of adenylate cyclase stimulation, but not the down-regulation or phosphorylation of the cAMP receptors. Adenylate cyclase in D. discoideum membranes can be stimulated or inhibited by GTP, depending on the conditions used. Pertussis toxin did not affect the stimulation of adenylate cyclase but nullified the inhibition. In membranes from desensitized control cells, stimulation of adenylate cyclase by GTP was lost, whereas inhibition was retained. Stimulation of adenylate cyclase in membranes from desensitized pertussis toxin treated cells was diminished but not absent. These results indicate that receptor phosphorylation is not sufficient for adaptation of adenylate cyclase, and that a pertussis toxin substrate, possibly Gi, is also involved in this process.Abbreviations used ATPS Adenosine 5-0-(3-Thiotriphosphate) - GTPS Guanosine 5-0-(3-thiotri-phosphate) - (Sp)-cAMPS Adenosine 3,5-monophosphorothioate-Sp-isomer - dcAMP 2-deoxyadenosine 3,5-monophosphate - Hepes N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid - DTT Dithiothreitol - buffer A 10 mM KH₂PO₄/Na2HPO₄, pH 6.5 - buffer B 40 mM Hepes/NaOH, 0.5 mM EDTA, 250 mM sucrose, pH 7.7     

Six year follow up of infants with bacteriuria on screening.

OBJECTIVE--To determine the value of screening for bacteriuria in infants with special emphasis on the natural course of untreated asymptomatic bacteriuria, renal growth, and renal damage. DESIGN--Prospective six year follow up of infants with bacteriuria on screening in an unselected infant population. SETTING--Paediatric outpatient clinic. PATIENTS--50 Infants (14 girls, 36 boys) with bacteriuria on screening verified by suprapubic aspiration from an unselected population of 3581 infants in a defined area of Gothenburg. INTERVENTIONS--Children with asymptomatic bacteriuria and normal findings on initial urography were untreated, although other infections were treated. MAIN OUTCOME MEASURES--Culture of urine and determination of C reactive protein concentration every six weeks for the first six months after diagnosis, every three months from six months to two years, and every six months between two and three years; thereafter yearly urine culture. Evaluation of renal concentrating capacity with a desmopressin test; radiological examination, including first and follow up urography and micturition cystourethrography without antibiotic cover; and measurement of renal parenchymal thickness and renal surface area. RESULTS--Of the original 50 infants, 37 (12 girls, 25 boys) were followed up for at least six years. Two infants developed pyelonephritis within two weeks after bacteriuria was diagnosed; the others remained free of symptoms. 45 Infants were untreated; the bacteriuria cleared spontaneously in 36 and in response to antibiotics given for infections in the respiratory tract in eight. Recurrences of bacteriuria were observed in 10 of the 50 children, of whom one had pyelonephritis. No child had more than one recurrence. At follow up urography in 36 of the 50 children (9 girls, 27 boys) after a median of 32 months no child had developed renal damage. First samples tested for renal concentrating capacity showed significantly higher values than those from a reference population (mean SD score 0.50, 95% confidence interval 0.21 to 0.79; p less than 0.001), but the last samples showed no significant difference (mean SD score 0.08, -0.24 to 0.40; p greater than 0.05). CONCLUSIONS--Mass screening for bacteriuria in infancy results primarily in detection of innocent bacteriuric episodes and is not recommended.     

Phenylarsine oxide induces the cyclosporin A-sensitive membrane permeability transition in rat liver mitochondria

This paper reports an investigation on the effects of the hydrophobic, bifunctional SH group reagent phenylarsine oxide (PhAsO) on mitochondrial membrane permeability. We show that PhAsO is a potent inducer of the mitochondrial permeability transition in a process which is sensitive to both the oxygen radical scavanger BHT and to cyclosporin A. The PhAsO-induced permeability transition is stimulated by Ca²⁺ but takes place also in the presence of EGTA in a process that maintains its sensitivity to BHT and cyclosporin A. Our findings suggest that, at variance from other known inducers of the permeability transition, PhAsO reacts directly with functional SH groups that are inaccessible to hydrophilic reagents in the absence of Ca²⁺.     

Decalcification by perfusion. A new method for rapid softening of temporal bones.

We describe a new technique, decalcification by perfusion, for the softening of bony tissue. The blood circulatory system was perfused in 16 rats via a cannula through the left heart ventricle with a fixative followed by New Decalc (an acidic demineralizer) for 30-240 minutes. Perfusion decalcification for 120 minutes softened all heads and middle ear specimens could be easily sampled and prepared for studies by both light and electron microscope. For comparison, a conventional immersion technique required 72 hours of decalcification to accomplish softening. The perfusion technique considerably reduced the time needed to decalcify the tissue and preserved the morphology better than did the immersion procedure.     

Increased lead uptake and inhibition of ALAD-activity in isolated rat hepatocytes incubated with lead-diethyldithiocarbamate complex

Dithiocarbamates can form lipid soluble complexes with lead and are known to markedly increase tissue uptake of lead and potentiate toxic effects of lead in rats. Cellular effects of the interactions between lead and diethyldithiocarbamate were studied in primary cultures of rat hepatocytes. The cells were incubated with lead acetate (PbAc) or lead-diethyldithiocarbamate complex (Pb(DTC)2), labelled with 203Pb. The lipid soluble Pb(DTC)2 was rapidly taken up in the cells and after 30 min incubation the cellular levels of lead were approximately 40 times higher in cells incubated with Pb(DTC)2 than in cells incubated with a similar concentration of PbAc. The maximal cellular uptake of lead was reached after 4 h incubation with Pb(DTC)2, while incubation with PbAc caused a slow continuously increasing uptake of lead during the 20 h incubation. The enzyme delta-aminolevulinic acid dehydratase (ALAD) was inhibited to a much higher extent by Pb(DTC)2 compared to PbAc after incubations with similar concentrations of lead. Maximal inhibition of ALAD activity was reached at a cellular concentration of 0.5-1 nmol Pb/mg protein, irrespective of which form of lead was used in the incubation. Pb(DTC)2 was shown to inhibit ALAD activity also in vitro when incubated with purified ALAD enzyme. The rapid and high intracellular uptake and cellular response of Pb(DTC)2, shown in the present study, may explain the drastic effects of dithiocarbamates on lead distribution and toxicity previously shown in vivo.     

Non-histone chromatin protein fractions associated with ‘active’ chromatin in embryonic chicken liver

Non-histone chromatin proteins synthesized during chicken embryonic liver development were labeled with [3H]tryptophan and [3H]methionine and characterized by electrophoresis. During embryonic development protein/DNA ratio in chromatin was low (1.30-1.62) but synthesis of non-histone protein was high. Especially one characteristic fraction K (MW 18 000), tightly bound with DNA was preferentially associated with DNAase II sensitive, active transcribed sequences. In 7-day old and adult chicken synthesis of all non-histone proteins was low, fraction K was absent or synthesized only in small amounts in association with non-active sequences, however protein/DNA ratio in chromatin was high (2.30-2.33).     

Bronchodilatory properties of 2-decarboxy-2-hydroxymethyl prostaglandin E1

We evaluated in a double-blind study the bronchodilatory properties of 2-decarboxy-2-hydroxymethyl prostaglandin E₁ (PGE₁-carbinol), described recently as a nonirritant bronchodilator in animals. Fifteen asthmatic patients received by inhalation single doses of 1, 10, and 30 μg PGE₁-carbinol, 55 μg PGE₂, and placebo (10% ethanol in normal saline, which was also used as diluent for the PGs). Such pulmonary function tests as forced expiratory volume in 1 second, forced vital capacity, and maximal expiratory flow were monitored during 2 hours following inhalation of each compound. 10 and 30 μg PGE₁-carbinol produced significant but short-acting bronchodilation, similar to that caused by 55 μg PGE₂. One-third of the patients reported mild cough and throat irritation during and shortly after inhalation of 30 μg PGE₁-carbinol or 55 μg PGE₂. Placebo and 1 μg PGE₁-carbinol produced minimal side effects, but neither agent caused bronchodilation. In an adjunctive, unblinded trial, the same patients received 400 μg fenoterol. Fenoterol caused greater bronchodilation 15 and 30 minutes after inhalation than did the PGs in the double-blind study.     

Antitumor properties of vindesine-monoclonal antibody conjugates

Summary The anticancer alkaloid vindesine (VDS) was conjugated to four mouse monoclonal antibodies recognizing human tumor-associated antigens. The antibodies were 96.5 (antimelanoma, IgG2a); 791T/36 (antiosteogenic sarcoma, IgG2b); 11.285.14, and 14.95.55 (anticarcinoembryonic antigen, IgG1 and IgG2a respectively). Conjugates VDS-96.5 and VDS-791T/36 were tested in vitro and shown to be specifically cytotoxic for target cells expressing the appropriate antigen. The in vivo effects of the antibodies and conjugates were tested against human tumor xenografts in athymic or immunodeprived mice using multiple treatments. Conjugate VDS-96.5 retarded the initial growth of a melanoma xenograft, whereas free antibody was without effect. Similarly, VDS-791T/36 but not free antibody retarded the growth of osteogenic sarcoma 791T. The most marked antitumor effects observed were those obtained with VDS conjugates of the anti-CEA antibodies against a colorectal tumor xenograft. Antibody 14.95.55 suppressed tumor growth both alone and as a VDS conjugate, whereas 11.285.14 produced only a slight effect alone but an almost complete and lasting suppression of tumor growth as a VDS conjugate. Free VDS had little effect at nontoxic levels. Acute studies showed that VDS-11.285.14 conjugate was considerably less toxic than free VDS in Balb/c mice.     

Mechanism of sex determination inRumex hastatulus Baldw.

Summary The results presented indicate that the sex determination mechanism in the Texas race ofR. hastatulus 2n = 10 (XX + 8A); 2n = 10 (XX + 8A)] is intermediate between theX/Y andX/A systems. In this race, sex is determined to some extent by theX/A balance, but theY chromosome also affects sex expression, maleness or intersexuality being correlated with different ratios ofX andY chromosomes.The results obtained for the Texas race are fully compatible with data presented by Smith (1963) for the North Carolina race [ 2n = 8 (XX + 6A); 2n = 9 (XX ₁ Y ₂ + 6A)]. It may be concluded that evolution of the karyotype in this species is not accompanied by changes in the mechanism of sex determination.