The effect of Dextransulfate 500 on the pathogenesis of herpes simplex virus infections in weanling mice

Summary Intraperitoneal (i.p.) injection of Dextran Sulfate (D.S.) 500 during a limited period of time influences the course of herpes simplex-virus-infections. D.S.500 was found to reduce the resistance of mice for some herpes simplex-virus strains (Len, L3-2s, Haase) if given between 16 hours before and 2 hours after i.p. infection. The decrease of resistance could be correlated with an increase of the virus content of liver, spleen, brain and spinal cord. Injection of herpes simplex-virus-specific immune serum counteracted the effect of D.S.500 on the course of infections. Conversely, D.S.500 increased the resistance of mice to another group of herpes simplex-viruses (strains D-316, Thea, DD), if given 3 to 8 hours before infection.These effects are ascribed to a special interaction of D.S.500 with macrophages and probably other virus-susceptible cells of the peritoneal cavity and elsewhere with a resulting counteraction to the virus infection.With 2 FiguresIn part presented at the 76th Ordinary meeting of the Society for General Microbiology at the University of Cambridge, April 5–8, 1976.In partial fulfilment of the requirements for the MD degree.     

Inefficient delivery of yeast cells as an explanation for reduced plating efficiency of Candida albicans.

The plating efficiency for fungal yeast cells is usually less than that expected from microscopic counts, and a number of explanations for this phenomenon have been proposed. The present study was undertaken to explore possible reasons for reduced plating efficiency of Candida albicans. Explanations that we evaluated and found unlikely included: ineffectiveness of different culture media and/or incubation temperatures for growing colonies, insufficient area of the plate available for expression of individual colonies, production of microcolonies, and inaccurate counting of the organisms in the inoculum. An assay for delivery of the inoculum into tissue culture plate wells indicated that reduced delivery of the organisms accounted for lower than expected plating efficiency. C. albicans yeast cells grown under low glucose conditions and expected to have reduced adhesiveness were found to have higher values for both delivery and plating efficiency in our assays. In summary, our results indicate that reduced plating efficiency for C. albicans under the conditions used for these experiments is best explained by the loss of some yeast cells during preparation of the inocula or delivery of the yeast cells onto the plates.     

Comparison of broth microdilution,E Test,and agar dilution methods for antibiotic susceptibility testing of Campylobacter jejuni and Campylobacter coli

A standardized broth microdilution method was compared to the E test and an agar dilution method for the antimicrobial susceptibility testing of Campylobacter jejuni and C. coli isolates. A group of 47 human clinical isolates, 37 isolates from retail poultry, and 29 isolates from living turkeys (total, 113 isolates) was included in the study. These encompassed 92 C. jejuni and 21 C. coli strains. The MICs of six antimicrobial agents were determined by the broth microdilution and E test methods, and the strains of human origin were additionally tested by the agar dilution method. In general, broth microdilution MICs agreed within 1 log(2) MIC increment with 90.0% of E test results and 78.7% of agar dilution test results. The agar dilution method gave much lower gentamicin MICs than the broth microdilution method, but the data were significantly (P < 0.01) correlated and there was 100% agreement in the sensitivities and specificities in the comparison of the tests. The broth microdilution method had the highest sensitivity for analysis of the susceptibilities of Campylobacter to nalidixic acid and trimethoprim-sulfamethoxazole. The MICs of ciprofloxacin and erythromycin complied numerically by all three methods. The classification of the results and the correlation of the data demonstrated a high degree of agreement. All methods were equally suitable for the testing of the sensitivity of Campylobacter to tetracycline. Thus, the broth microdilution method appears to be an easy and reliable method for determination of the MICs of antibiotics for C. jejuni and C. coli, and it may offer an interesting alternative to MIC determination by the agar dilution technique or the E test.     

Identification of mutations in the Bruton's tyrosine kinase gene,including a novel genomic rearrangements resulting in large deletion,in Korean X-linked agammaglobulinemia patients

Mutations in the Bruton's tyrosine kinase (BTK) gene are responsible for X-linked agammaglobulinemia (XLA). We identified BTK mutations in six patients with presumed XLA from unrelated Korean families. Four out of six mutations were novel: two missense mutations (P565T, C154Y), a point mutation in a splicing donor site (IVS11+1G>A), and a large deletion (a 6.1-kb deletion including BTK exons 11–18). The large deletion, identified by long-distance PCR, revealed Alu-Alu mediated recombination extended from an Alu sequence in intron 10 to another Alu sequence in intron 18, spanning a distance of 6.1 kb. The two known mutations consisted of one missense (G462D) mutation, and a point mutation in a splicing acceptor site (IVS7−9A>G). This study suggests that large genomic rearrangements involving Alu repeats are few but an important component of the spectrum of BTK mutations.     

The affinity glycated hemoglobin in a family with hereditary spherocytosis and in other non-hemoglobinopathic hemolytic anemias

The glycated hemoglobin (GHb) is lowered by hemolytic anemia. The cation-exchange HbA1 has been shown to be lowered by hereditary spherocytosis (HS). The HbA1, however, can be increased by elevations of fetal hemoglobin (HbF). The affinity GHb, a parameter related to, but not identical with, the HbA1, and unaffected by HbF, has been shown to be low in hemoglobinopathies but not, to our knowledge, in HS and other non-hemoglobinopathic hemolytic anemias. Therefore, the affinity GHb and HbF was determined in four members of an HS family and in nine other cases of non-hemoglobinopathic hemolytic anemia, including three autoimmune hemolytic anemias, four red cell fragmentation syndromes (two "Waring blender" syndromes, one thrombotic thrombocytopenic purpura in association with tumor, and one case of disseminated intravascular coagulation), and two red cell membrane defects: paroxysmal nocturnal hemoglobinuria and another case of hereditary spherocytosis. The GHb for these nine cases was 3.6 +/- 1.7 percent (normal 6.0 +/- 2.0 percent; p less than 0.001). The reticulocyte count, available in four cases, was 0.23 +/- 0.14 and correlated negatively with the GHb. The average GHb in the HS family was 3.9 +/- 0.8 percent, which was significantly less than the normal of 6.0 +/- 2.0 percent (p less than 0.001); the HbF was less than 1.0 percent. It is concluded that the GHb is diminished in hemolytic anemias not associated with hemoglobinopathies and that this lowering reflects the shortened red cell life span in these processes. To our knowledge, this is the first report of low GHb in hemolytic anemia not associated with hemoglobinopathy, by the affinity chromatographic technique, as opposed to the cation-exchange chromatographic technique.     

A tidal ventilation model for oxygenation in respiratory failure

We develop tidal-ventilation pulmonary gas-exchange equations that allow pulmonary shunt to have different values during expiration and inspiration, in accordance with lung collapse and recruitment during lung dysfunction (Am. J. Respir. Crit. Care Med. 158 (1998) 1636). Their solutions are tested against published animal data from intravascular oxygen tension and saturation sensors. These equations provide one explanation for (i) observed physiological phenomena, such as within-breath fluctuations in arterial oxygen saturation and blood-gas tension; and (ii) conventional (time averaged) blood-gas sample oxygen tensions. We suggest that tidal-ventilation models are needed to describe within-breath fluctuations in arterial oxygen saturation and blood-gas tension in acute respiratory distress syndrome (ARDS) subjects. Both the amplitude of these oxygen saturation and tension fluctuations, and the mean oxygen blood-gas values, are affected by physiological variables such as inspired oxygen concentration, lung volume, and the inspiratory:expiratory (I:E) ratio, as well as by changes in pulmonary shunt during the respiratory cycle.     

Prevalence and correlates of HIV infection among young injection drug users in San Francisco

OBJECTIVE: We assessed the prevalence of HIV infection and associated risk behaviors among street-recruited young injection drug users (IDUs) in San Francisco. METHODS: In a cross-sectional study, 304 young (age <30 years) IDUs with a history of injecting in the previous 30 days were interviewed and tested for antibodies to HIV. Analyses assessing independent associations with HIV infection were limited to males only, due to the low number of infections in women. RESULTS: The prevalence of HIV infection was 5.3% overall but was highly stratified by gender and sexual preference (15.6% among homosexual/bisexual men vs. heterosexual men) and recruitment neighborhood (18% in the Polk Street area). Of 16 HIV infections, 14 (88%) were in males. Factors independently associated with HIV infection in males included sexual preference (homosexual/bisexual vs. heterosexual: adjusted odds ratio [AOR], 7.5; 95% confidence interval [CI], 1.5-36.6), recruitment neighborhood (Polk Street neighborhood vs. other neighborhoods: AOR, 4.8; 95% CI, 1.4-16.7), and duration of residence in San Francisco (>or=1 year vs. <1 year: AOR, 11.8; 95% CI, 1.4-95.8). CONCLUSIONS: The prevalence of HIV infection was highest among male IDUs who have sex with men. The strong associations between HIV infection and sexual orientation and HIV infection and recruitment locale suggest that risk may be attributable largely to sexual risk. In addition to successful prevention efforts aimed at reducing needle-associated risk, current intervention models aimed at young IDUs should target high-risk neighborhoods and emphasize sexual risk reduction measures, in particular among men who have sex with men.     

Ischaemic episodes of less than 5 minutes produce preconditioning but not stunning in the isolated rat heart

The aim of the present study was to examine whether ischaemic episodes of less than 5 min could induce preconditioning or stunning in the isolated rat heart. Hearts were subjected to total global ischaemia of 1, 2 and 4 min followed by 10 min of reperfusion before an 18-min main ischaemic period and 30 min of reperfusion. The effects on physiology, purine metabolism and anaerobic glycolysis were compared with a control group subjected to the main ischaemia only. The brief ischaemic episodes did not produce stunning based on the recovery of left ventricular developed pressure (LVDP) and heart rate (HR) product during the first reperfusion. Preconditioning of 11–14% increased recovery of LVDP x HR during the second reperfusion was observed in the 1- and 4-min group. In the 2-min group a low repayment of flow debt during the first reperfusion was associated with a slightly reduced recovery of LVDP x HR compared to the other preconditioned groups during the second reperfusion. Only in the 4-min group was preconditioning associated with fewer breakdown products of the purine nucleotide pool (adenosine) and anaerobic glycolysis (lactate) in both tissue and effluate after the main ischaemia. Preconditioning (reflected in recovery of function) could be produced with ischaemic episodes of less than 5 min that did not produce stunning. Thus, stunning is probably not the primary cause of preconditioning.