Anti-cytomegalovirus immunoglobulin M titer for congenital infection in first-trimester pregnancy with primary infection: a multicenter prospective cohort study.

OBJECTIVE: We evaluated cytomegalovirus (CMV) immunoglobulin M (IgM) titer in pregnant women with primary infection as a predictive factor for congenital infection. STUDY DESIGN: Maternal CMV antibody screening during the first trimester was conducted prospectively at 16 centers in Japan between September 2013 and 2015. Women with confirmed maternal primary infection underwent testing for fetal congenital infection, and we investigated the positive predictive value of CMV IgM titer levels for congenital infection in women with a low IgG avidity. RESULTS: We identified 6 (8.6%) cases of congenital infection among 70 pregnant women with positive/borderline IgG, positive IgM and IgG avidity index ⩽35.0% and 11 (39.3%) among 28 women with IgG and/or IgM seroconversion. IgM titer level ⩾6.00 index showed the highest positive predictive value (17.1%). CONCLUSION: High titer of CMV IgM during the first trimester in pregnant women with primary infection is a risk factor for congenital infection.

[Clinical evaluation of the bladder tumor marker "Tu-MARK-BTA"].

Bladder tumor antigen (BTA) is a tumor marker isolated from the urine of individuals with TCC of the bladder. This antigen can be detected by the Tu-MARK BTA test, a simple and rapid slide latex agglutination test performed on freshly voided urine. Sensitivity and specificity of BTA were calculated, and the correlation with pathological grade, histological stage, and urinary findings were statistically evaluated (chi 2-test) in 110 patients (72 male, 38 female; age: 16-91, mean age 54.4) examined between September, 1989 and April, 1990 including 46 TCC of the bladder (primary 28, secondary 18; grade 1:10, grade 2:27, grade 3:9, pTis: 2, pTa: 2, pT1: 23, pT2: 5, pT3: 4, pT4: 2), and 64 benign diseases. Sensitivity was 45.6%, specificity was 60.9%. In bladder tumor cases a correlation was seen between BTA and stage (p less than 0.02), and between BTA and grade (P less than 0.05). The positive ratio was higher in T1-T4 (55.9%) than in Tis.Ta (p less than 0.02). A high positive ratio of BTA was seen in bladder tumor cases with hematuria (70%, p less than 0.01) and pyuria (86.7%, p less than 0.01). This method is easy and rapid and the values are highly correlated with stage. Therefore, it should be useful for not only screening but followup of bladder tumor. Furthermore, BTA in combination with urine cytology is a more useful way for diagnosing TCC of the bladder.

Enhanced natural killer cell activity in patients with pulmonary tuberculosis.

The natural killer (NK) cell activity of patients with pulmonary tuberculosis (TB) was studied using blood samples. The patients with pulmonary TB showed higher NK activity to 10 out of 12 NK-sensitive target cell lines than healthy subjects did. When NK activity was compared between active and inactive stages of the disease, the patients with active TB demonstrated higher NK activity than did patients with inactive TB. Furthermore, active patient displayed cytolysis to one out of 4 NK-resistant target cell lines. In study of NK cell cyotoxicity at single cell level, higher killing activity than binding activity to target cells was observed in patients at an active stage. Morphological and surface marker analysis of peripheral mononuclear cells showed an increase in CD16+ cells in patients with pulmonary TB. These results suggested that NK cell activity is augmented qualitatively and quantitatively in patients with pulmonary TB.

Membrane responses of B-16 melanoma cells to single exposure to ultraviolet light.

Electron spin resonance spectroscopy using the spin probe (5-, 12- and 16-deoxylstearic acid) was employed to analyze the changes in membrane fluidity in B-16 melanoma cells following UV-B exposure. The UV exposure resulted in the immediate accumulation of lipid peroxide, being accompanied by a change in membrane fluidity. The 12-DSA is the most sensitive to the changes in membrane organization caused by UV light. Na+,K+-ATPase activity was regulated by a change in membrane fluidity. Following UV exposure, the release of the prelabeled arachidonic acid from the cells was observed immediately. Ca2+-dependent calmodulin-dependent phospholipase A2-like activity was involved in the UV-stimulated arachidonic acid release from phospholipid.

[The analysis of prognostic factors on postsurgical pyuria of benign prostatic hypertrophy].

The outcome of postsurgical pyuria in benign prostatic hypertrophy was studied in 87 patients, and the factors that might affect the outcome were determined. No significant differences were found between operation method and duration until normalization of pyuria, which was 75.5 +/- 46.0 days for transurethral resection of the prostate, 72.7 +/- 30.6 days for suprapubic prostatectomy and 69.3 +/- 32.7 days for retropubic prostatectomy. Prognostic factors were statistically analyzed preoperatively, at operation, and postoperatively. The definite prognostic factors were preoperative diabetes mellitus, preoperative pyuria, preoperative bacteriuria, and postoperative hypoproteinemia. The probable prognostic factors were old-age, preoperative indwelling catheters, heavy prostate tissue, postoperative bacteriuria, postoperative anemia and postoperative complications.

Studies of monoamine oxidase and semicarbazide-sensitive amine oxidase. I. Inhibition by a selective monoamine oxidase-B inhibitor, MD 780236.

In vitro studies of the effect of MD 780236, a selective monoamine oxidase (MAO)-B inhibitor, on a semicarbazide-sensitive amine oxidase (SSAO) in rat testis and lung showed that this compound dose-dependently inhibited SSAO activity. The extents of inhibition of MAO-A, -B and SSAO in these two rat tissues by this compound after 30 min of preincubation were found to be MAO-B greater than MAO-A greater than SSAO. This selectivity was also evident in preparations without preincubation. Degree of inhibition of SSAO was not significantly influenced by pretreatment with either 10(-3) M clorgyline, I-deprenyl or 10(-4) M SKF 525A. Inhibition of SSAO was not enhanced by varying the time of preincubation of the enzyme and the compound, indicating direct action on and reversible inhibition of SSAO. The inhibition of SSAO by MD 780236 was non-competitive with or without preincubation, with a K1 value of 110 muM. Although MD 780236 is a selective and "suicide substrate" inhibitor of MAO-B, these present results indicate that this compound may also inhibit SSAO activity, but by a mechanism different from that for MAO-B. These findings confirm an earlier hypothesis that compounds that inhibit both MAO and SSAO have totally different modes of action on these two different amine oxidases.

[Clinical studies of efficacy of piperacillin against complicated urinary tract infections].

Clinical efficacy of piperacillin against 74 cases with complicated urinary tract infection was examined. Piperacillin was administered at the dose of 4 g (2 g twice daily) through intravenous drip infusion. The overall clinical value was rated in "excellent", in 9 cases, "moderate" in 34 cases and "poor" in 31 cases with a total efficacy of 58.1%. In the analysis of clinical values based on background, its efficacy was statistically significantly lower in the patients at a higher age, those with complication of diabetes mellitus, and those with indwelling catheter. In operated cases compared to non-operated cases, it was suggested to be more effective for improving the disturbances in urinary flow as a result of the removal of the underlying conditions by the operation. As to bacteriological efficacy, 64 out of 95 strains (67.4%) isolated were eradicated following its administration. Microbes which appeared after its dosing belonged to 9 classes of 18 strains, of which 5 strains (27.8%) of Serratia were identified. Side effects were 2.5% (3/119), no serious cases appeared. Changes in laboratory examination results were elevated GOT (2.5%), GPT (1.7%), and ALP (0.8%) values, all being transient hanges.

Inhibition of monoamine oxidase A-form and semicarbazide-sensitive amine oxidase by selective and reversible monoamine oxidase-A inhibitors, amiflamine and FLA 788(+).

In vitro studies demonstrated that two selective monoamine oxidase (MAO)-A inhibitors, amiflamine and FLA 788(+), have been shown to inhibit semicarbazide-sensitive amine oxidase (SSAO) in rat testis and lung homogenates in a concentration-dependent way. The inhibition was not greatly influenced by pretreatment of the preparations with either clorgyline (10(-3) mol/l), l-deprenyl (10(-3) mol/l) or SKF 525A (10(-4) mol/l). The two compounds showed a time-dependent inhibition of SSAO, and for the initial phase of the inhibition, amiflamine is a competitive inhibitor with a Kislope of 135 mumol/l, but FLA 788(+) is a noncompetitive inhibitor with a Ki value of 180 mumol/l. After preincubation for 60 min at 37 degrees C, however, inhibition by amiflamine was found to be essentially irreversible whereas that produced by FLA 788(+) was still noncompetitive and reversible. These two compounds also reversibly and competitively inhibited rat testis MAO-A with FLA 788(+) being much more selective towards this MAO (Kislope = 0.26 mumol/l for FLA 788(+) and 7 mumol/l for amiflamine, respectively). The present results indicate that both MAO-A-selective inhibitors also inhibit SSAO in vitro, but their properties as SSAO inhibitors differ from those as MAO-A inhibitors.

[Adipocyte insulin binding and glucose transport in normal pregnancy and streptozotocin-induced diabetic pregnancy in the rat: evidence for a postreceptor abnormality in insulin action].

To investigate the effect of pregnancy on the course of streptozotocin (STZ) induced diabetes, insulin binding to receptors and glucose transport activity were studied in isolated adipocytes from normal nonpregnant, normal pregnant, STZ-treated nonpregnant and STZ-treated pregnant rats. Experimental diabetes was induced by the administration of 40 mg/kg of STZ, and those exhibiting blood sugar concentrations between 150 and 250 mg/100 ml (198.8 +/- 6.4 mg/100 ml, mean +/- SEM) 7 days after treatment, were then used for the experiments as diabetic animals. Rats were mated at least 10 days after STZ administration. All studies were performed on gestational day 19. Fetuses of the diabetic mothers tended to be heavier than those of the control rats (2.49 +/- 0.31 vs. 2.38 +/- 0.22 g, mean +/- SD), but the difference was not statistically significant. Placental weights were significantly greater in the diabetics than in the controls (0.60 +/- 0.12 vs. 0.48 +/- 0.097 g, mean /+- SD, p less than 0.05). Insulin binding to receptors at an insulin concentration of 0.2 ng/ml was increased by 21% in the STZ-treated nonpregnant group as compared with the untreated non-pregnant group, by 32% in the STZ-treated pregnant group as compared with the untreated pregnant group due to increased receptor affinity without increasing the receptor number. However, no change in insulin binding was detected between the normal nonpregnant and normal pregnant, STZ-treated nonpregnant and STZ-treated pregnant groups. Glucose transport activity was decreased in adipocytes from the normal pregnant group as compared with that of the normal nonpregnant group. The effect was also observed between adipocytes from the sTZ-treated pregnant group and from the STZ-treated nonpregnant group. Adipocytes from rats belonging to either the normal pregnant group or the STZ-treated nonpregnant group showed a similar decrease in glucose transport activity, suggesting an equal effect of pregnancy and mild diabetes on glucose transport. Furthermore, adipocytes from the STZ-treated pregnant group showed the lowest transport activity of the four groups studied, suggesting an additive effect of pregnancy and diabetes on glucose transport activity. In conclusion, although insulin action in isolated adipocytes is reduced by pregnancy whether diabetes is induced or not, insulin binding to receptors is not changed by pregnancy. Thus, the effect on insulin action in adipocytes from diabetic rats as well as normal rats might lie at a site distal to the receptor. Insulin action in isolated adipocytes is reduced additively by pregnancy and diabetes.

Inhibition of carp liver mitochondrial monoamine oxidase by some commonly-used detergents.

The inhibitory effects of some detergents commonly used in biochemical research on carp liver mitochondrial monoamine oxidase were examined. Sodium dodecylsulfate, octyl-beta-D-glucopyranoside, sodium cholate and Triton X-100 at relatively low concentrations caused strong dose-dependent inhibition of the activity towards tyramine, but digitonin caused only weak inhibition. Sodium dodecylsulfate, octyl-beta-D-glucopyranoside and sodium cholate caused almost complete inhibition of activity in the concentration ranges tested. The extent of inhibition by Triton X-100 was greater after preincubation at 37 degrees C for 30 min than that without preincubation, but with or without preincubation, the inhibition was not substrate-selective and was not complete at a relatively high concentration (2%) of Triton X-100. Without preincubation, the mode of inhibition by Triton X-100 was competitive and reversible with respect to the oxidations of 5-HT, tyramine and PEA, but after preincubation (37 degrees C for 30 min), it became noncompetitive and irreversible, depending on the concentration of detergent used. These findings suggest that it had different actions on the enzyme depending on preincubation. Triton X-100 also slightly changed enzyme sensitivity towards clorgyline and deprenyl, regardless of the preincubation time or the substrate used. Some possible mechanisms of the inhibitory effect of Triton X-100 are discussed.

[Metabolic significance of cyclic nucleotides in the environment for fetal growth--effects of PGI2-like substance on fetal platelet function].

Prostacyclin (PGI2), the major active metabolite of arachidonic acid in the vascular endothelium, is characterized by antiaggregatory and vasodilator properties. In this report, the significance of PGI2 and TxA2 on fetal platelets was studied. Platelet aggregation induced by ADP, collagen and adrenalin were found to be augmented in maternal blood but suppressed in umbilical cord blood. A much larger amount of PGI2-like substance was released from the umbilical cord artery and vein than from the intraplacental vein and chorionic tissue. On the other hand, the generation of this substance was reduced in the umbilical cord artery (4.4 +/- 2.7 nmoles/mg tissue/hour) and vein (2.9 +/- 2.1 nmoles/mg/tissue/hour) in patients with severe pre-eclampsia associated with IUGR. The plasma beta-thromboglobulin level is higher in maternal and umbilical cord blood, than in control group. Plasma 6-Keto-PGF1 alpha, TxB2, cyclic AMP and cyclic GMP values were significantly (p less than 0.05) higher in umbilical cord blood than in maternal blood, but serum phosphodiesterase activity showed no difference between mother and fetus. These results indicate that various factors, such as PGI2, TxA2 and cyclic nucleotides, may co-exist in high levels in the fetus, and the balance is needed for the maintenance of physical interaction between the platelet and vascular wall in the fetal blood vessels. PGI2 in particular may play an important role in this balance and in the regulation of placental-fetal circulation.

[Glucose oxidation and insulin receptors in isolated adipocytes from rats treated with progesterone and estradiol].

To find the cause of insulin resistance in pregnancy, the effects of estradiol (0.002 mg/day) treatment in male (n = 6) and ovariectomized (n = 8) rats, progesterone (0.05 mg/day) treatment in male (n = 9) and female (n = 6) and ovariectomized (n = 8) rats and combined estradiol and progesterone treatment in male (n = 7) and ovariectomized (n = 8) rats on (1-14C) glucose oxidation and insulin receptors in isolated fat cells were examined. All groups were treated for 5 days. Control rats were treated with the solvents. The results were as follows: 1) Decreased responsiveness to insulin on (1-14C) glucose oxidation was observed in adipocytes from male rats treated with estradiol and estradiol + progesterone, female rats treated with progesterone and ovariectomized rats treated with estradiol + progesterone. 2) There was no significant difference among the insulin bindings to adipocytes from rats treated with estradiol, progesterone and estradiol + progesterone. These results suggest that estradiol itself is potent in inducing insulin resistance in male rats, but in female rats progesterone primed with estradiol is necessary to induce insulin resistance, and that they may act at some post-receptor sites. These sex hormones may play an important role in inducing the insulin resistance in pregnancy.

A modified technique of guinea pig testing to identify delayed hypersensitivity allergens.

A modified guinea pig testing technique was developed for the detection of weak allergens and allergenicity of materials unsuitable for testing by intradermal injection. This test involved the use of Freund's complete adjuvant to stimulate the immune system of the animal, and external application instead of intradermal injection of the test compound in the induction stage. The allergenicity of Sudan III, Brilliant Lake Red R and Sudan I was tested by this procedure. In the dose-effect study of Sudan I, the dose dependency of a positive reaction of the induction and challenge concentrations was recognized. The test was compared with three other guinea pig sensitization tests. The results obtained with this test correlated well with those obtained with the guinea pig maximization test.

In vitro growth of mouse hair root.

Hair roots from mouse dorsal skin continued to grow in culture medium for 10 h or more after isolation. Under observation by time-lapse cinematography, the cultured hair roots appeared to grow downward. We observed both the downward growth of the cultured hair roots as well as the transfer of melanosomes from melanocytes to cortical cells. The hair roots were also capable of incorporating the labelled amino acid and thymidine.

Transfer mechanism of melanosomes in epidermal cell culture.

The mode of melanosome transfer from melanocytes to keratinocytes in epidermal cell cultures has been examined with time-lapse cinematography and electron microscopy. A tip of a melanocyte dendrite containing melanosomes became enfolded by a recipient keratinocyte. It was then pinched off to form a cluster of melanosomes which initially seemed to be surrounded by two layers of membranes. The phagocytized dendrite was gradually decomposed and became an aggregate of melanosomes surrounded by a single membrane of the keratinocyte. The individual melanosomes were dispersed from the aggregate into the keratinocyte cytoplasm, depending on the size of melanosomes. The larger ones were single and smaller ones were complex. The mechanism of melanosome transfer in vitro is a type of cytophagocytosis. The entire process consists of two steps: the first is a cytophagic process and the second a melanosome dispersion process. The process is influenced by various exogenous factors.

Phototoxic reaction to xanthene dyes induced by visible light.

Many dyes, for instance methylene blue, rose bengal, and eosin, are known as photosensitizers, and in the presence of molecular oxygen they induce cell lethality and skin photosensitivity (1-4). Several dyes are used in cosmetic products, particularly in lipsticks. Human lip skin is therefore exposed to potential danger from dye-sensitized phototoxic reactions. Using an in vivo system of mammalian skin, such as the abdominal skin of rabbits, we established screening tests for the phototoxic potential of synthetic dyes in two ways: (a) intracutaneous injection; (b) topical application with and without damaging the barrier property of the stratum corneum. In the intracutaneous injection assay, distinct phototoxic reactions were induced by rose bengal, eosin Y.S., and dibromofluorescein. When these dyes were applied topically to intact skin, no phototoxic reactions were observed. Phototoxic reactions were, however, elicited when the dye solutions were applied to abraded or scratched skin. The intensity of phototoxic reaction was found to be influenced by the vehicle in which the dyes were suspended. Phototoxic reaction to the dyes was induced by artificial light as well as by sunlight. By using commercially available fluorescent lamps with different spectral emissions, the action spectra for the phototoxic reaction to these dyes were investigated and it was found that the maximum phototoxicities of the dyes were manifested by light within a spectral range of 400-600 nm. Further studies on action spectra, using a monochromatic irradiation system, revealed a high correlation between the action spectra of the dyes and their absorption spectra. Maximum effective wavelength for the phototoxic reaction of eosin Y.S. was 525 nm. This topical as well as intradermal assay for assesing phototoxic reaction to synthetic dyes in living skin will be a practical and useful measure for studying the phototoxicity of the dyes.