The occurrence of fluoride stimulated membrane phosphoprotein phosphatase

Membrane preparations from rabbit peritoneal granulocytes and dog blood platelets possess an active phosphoprotein phosphatase. The enzyme is stimulated by fluoride and to a lesser extent by prostaglandin E₁ (PGE₁). It dephosphorylates ³²P labeled, catalytically active phosphoglucomutase (PGM) and labeled endogenous membranes to yield, in both cases, inorganic phosphate. It is inactive towards denatured PGM, denatured endogenous membranes and thymus histone labeled with ³²P.     

The formation of glucosides of isoflavones and of some other phenols by rabbit liver microsomal fractions

1. Rabbit liver microsomal fractions in vitro effected the transfer of glucuronic acid from UDP-glucuronic acid to biochanin A, formononetin, daidzein, genistein and equol. Only monoglucuronides were formed. 2. The same isoflavones were converted into monoglucosides when UDP-[6-(3)H]glucose was substituted for UDP-glucuronic acid in the incubation medium in vitro. The glucosides were formed in much lesser yield than were the glucuronides. 3. The glucoside of genistein was identified as genistin (genistein 7-glucoside) by Sephadex chromatography and reverse isotope dilution. 4. The specificity of the glucuronyl- and glucosyl-transfer mechanisms was compared for a series of steroids and other phenols in addition to the isoflavones. It was concluded that separate transferases were responsible for the formation of the two types of glycosides.     

Pneumocystis Carinii Pneumonia—Problems in Diagnosis and Therapy in 24 Cases

Twenty-four instances of Pneumocystis carinii pneumonia were recognized in 23 patients at the Stanford University Hospitals between 1962 and 1970. The affected persons could be broadly characterized as “compromised” hosts. All but one were receiving immunosuppressive drug therapy for such underlying disease as hematopoietic malignant disease, collagen vascular disorder, and organ transplant rejection. The one patient not receiving immunosuppressant medication had congenital dysgammaglobulinemia and suffered two discrete bouts of pneumocystis pneumonia. Most of the patients were concomitantly infected with other “opportunistic” pathogens.Open lung biopsy remained the most reliable method of antemortem diagnosis of pneumocystis infection during this eight-year period. It resulted in little morbidity. Unfortunately, direct examination of appropriately stained sputum specimens for cysts was almost uniformly nonproductive.The majority of patients received specific antipneumocystis drug treatment (pentamidine isethionate or pyrimethamine and sulfadiazine). “Cure” was achieved when institution of therapy was prompt and duration of therapy approached the empirically recommended two-week course.The fact that pneumocystis pneumonia can be controlled if recognized early is compelling reason to pursue diagnosis of pneumocystosis in an appropriate clinical setting, namely, in patients with impaired host defenses who have pulmonary infection unresponsive to conventional therapy. There is hope that a noninvasive (serological) technique will be developed shortly to simplify identification of this not uncommon cause of diffuse interstitial pneumonitis.     

Long term increase of mucosal mast cells in the rat induced by administration of Compound 48/80

Summary Administration of Compound 48/80 to rats for 5 days resulted in an increase of the specific type of mucosal mast cell, while connective tissue mast cells elsewhere were almost completely degranulated. The number of mucosal mast cells increased slowly for another 5 days and then returned to the control level, in an exponential manner. The half life of the newly formed mast cells was calculated to be about 40 days. This value may be taken as an estimate of the half life of mucosal mast cells. These cells, therefore, constitute a fraction of mast cells with rapid turnover. Available evidence indicates that the classical connective tissue mast cell has a very long life span, without significant turnover in terms of cell death and cell renewal. We suggest that the increase of mucosal mast cells is an indirect effect of Compound 48/80, related to its effect on other mast cells and mediated by material(s) released from these cells during the secretory process.Supported by grants from the Swedish Medical Research Council, Project no 2235     

Blockade of glutamatergic transmission as treatment for dyskinesias and motor fluctuations in Parkinson's disease

Summary In animal models of Parkinson's disease (PD), glutamate antagonists diminish levodopa (LD)-associated motor fluctuations and dyskinesias. We sought to investigate if these preclinical observations can be extended to the human disease, by evaluating the effects of three non-competitive NMDA antagonists (dextrorphan, dextromethorphan and amantadine) on the motor response to LD in patients with advanced PD. In four separate trials, adjuvant therapy with these drugs reduced LD-induced dyskinesias and motor fluctuations. These findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate LD associated motor response complications.     

The mutation rates of di-, tri- and tetranucleotide repeats in Drosophila melanogaster

In a recent study, we reported that the combined average mutation rate of 10 di-, 6 tri-, and 8 tetranucleotide repeats in Drosophila melanogaster was 6.3 x 10(-6) mutations per locus per generation, a rate substantially below that of microsatellite repeat units in mammals studied to date (range = 10(-2)-10(-5) per locus per generation). To obtain a more precise estimate of mutation rate for dinucleotide repeat motifs alone, we assayed 39 new dinucleotide repeat microsatellite loci in the mutation accumulation lines from our earlier study. Our estimate of mutation rate for a total of 49 dinucleotide repeats is 9.3 x 10(-6) per locus per generation, only slightly higher than the estimate from our earlier study. We also estimated the relative difference in microsatellite mutation rate among di-, tri-, and tetranucleotide repeats in the genome of D. melanogaster using a method based on population variation, and we found that tri- and tetranucleotide repeats mutate at rates 6.4 and 8.4 times slower than that of dinucleotide repeats, respectively. The slower mutation rates of tri- and tetranucleotide repeats appear to be associated with a relatively short repeat unit length of these repeat motifs in the genome of D. melanogaster. A positive correlation between repeat unit length and allelic variation suggests that mutation rate increases as the repeat unit lengths of microsatellites increase.      

Recent advances in genetic research on schizophrenia

Evidence for genetic factors in schizophrenia is reviewed with regard to family, twin and adoption studies, and recent advances in molecular genetic technology are applied to explore possible gene loci susceptible to schizophrenia. Application of neuropsychological and neuroimaging methodologies are also reviewed with an aim to develop criteria for defining phenotypes for genetic studies.Plenary Session, Twelfth Joint Annual Conference of Biomedical Sciences, April 20, 1997, Taipei, Taiwan.     

An experimental model of ascending pyelonephritis due toCandida albicans in rats

We developed a new experimental model of ascendingCandida pyelonephritis in female rats with leukopenia and vesicoureteral reflux. Rats were treated transperitoneally with cyclophosphamide (200 mg/kg) to induce leukopenia 3 days before and transurethrally with diluted acetic acid solution to induce vesicoureteral reflux 1 day before inoculation ofCandida albicans strain, ATCC 10259 (containing 10⁷ cells). Microscopy revealed acute pyelonephritis in whichCandida cells invaded from the fornix and/or papilla into the medulla within 3 days after inoculation. Between 7 and 28 days after inoculation, chronic pyelonephritis reached the cortex. The incidence of pyelonephritis increased gradually and was approximately 80% after 7 days.Candida colony counts of bladder urine specimens obtained by direct puncture were significantly greater in rats with pyelonephritis extending into the parenchyma than in those with pyelonephritis located along the pelvis (p<0.01). These results suggest that this rat model shows the characteristic feature of ascending pyelonephritis due toC. albicans and that the severity ofCandida pyelonephritis can be estimated fromCandida counts of bladder urine.     

Demonstration by lectin cytochemistry of rod and cone photoreceptors in the lamprey retina

Summary Lectin cytochemical analysis was undertaken to examine the distribution of glycoconjugates associated with the short and long photoreceptor cells in the lamprey retina. Concanavalin A bound preferentially to the outer segment region of the short cells. Wheat germ agglutinin bound weakly to both long and short cells. The outer segment regions of the long cells were stained intensely with peanut agglutinin. Pretreatment with neuraminidase to remove sialic acid resulted in decreased binding of wheat germ agglutinin throughout the retina and increased binding of peanut agglutinin to the outer segment region of the short cells and the region of myoid process of the long cells. These results suggest that there is a difference in the distribution of glycoconjugate residues between the long and short cells. A rod-like character of the short cell and a cone-like character of the long are tentatively discussed. Lectin-binding patterns in other retinal regions is also examined.