Detection of an HTLV-II-seropositive blood donor in Japan.
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Biomedical subjects
Publications and source records attributed to S Yamazaki.
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The largest nationwide active surveillance of four Measles-Mumps-Rubella (MMR) vaccines was conducted in Japan. A total of 1255 pediatricians actively participated in the study, which comprised 8.6% of all members of the Japanese Pediatric Society. The total number of registered recipients of MMR vaccines was 38 203. They were arbitrarily given one of the MMR vaccines produced by three makers (Takeda, Osaka city, Kitasato Minato-ku. Tokyo and Biken Suita city, Japan) or the standard MMR vaccine made of designated strains (Kitasato's measles-AIK-C, Biken's mumps-Urabe Am9 and Takeda's rubella-To336) produced by Takeda, Kitasato and Biken and were observed for 35 days. The rates of virologically confirmed aseptic meningitis per 10,000 recipients were 16.6, 11.6, 3.2 and 0 for the standard MMR, Takeda MMR, Kitasato MMR and Biken MMR vaccines, respectively. The incidence of convulsions between 15 and 35 days was the highest with the standard MMR vaccine and the incidence of fever associated with vomiting occurring between 15 and 35 days (symptoms relevant to aseptic meningitis) were also the highest with the standard MMR vaccine. The incidence of parotid swelling was the lowest with Takeda MMR vaccine. This surveillance revealed that incidences of aseptic meningitis after administration of the standard MMR vaccine and of Biken MMR vaccine were different. This posed questions about the manufacturing consistency of the Urabe Am9 mumps virus vaccines. On the other hand, the National Institute of Health found that the biological characteristics of the Urabe Am9 mumps virus contained in the standard MMR vaccine and in the Biken MMR vaccine were different. The Biken Company reported that the mumps vaccine in the standard MMR vaccine was a mixture of two Urabe Am9 mumps vaccine bulks; one identical to that contained in the Biken MMR vaccine and the other produced by a different manufacturing process.
BACKGROUND: Detailed fluorescein angiographic findings in the disc circumference may be useful for evaluating the possible relation of the circumference to glaucomatous nerve damage. METHODS: Fluorescein angiograms of 25 eyes of 25 subjects with primary open angle glaucoma were observed after they had undertaken Octopus perimetry. Based on the retinotopic projection, disc sectors and corresponding visual field regions were set. RESULTS: Twenty three eyes (92%) showed a zone of no fluorescence around the disc (non-fluorescent zone). Of these, the zone width of the 20 eyes that had visible ciliary vessels within the zone was wider than that of the other three eyes, and showed fluorescein diffusion from the outer boundary of the zone towards the disc. The diffusion reached the disc if the zone was narrow. In those 20 eyes, a standardised difference in the zone width of inferior temporal sector minus superior temporal sector correlated with the difference in mean loss of corresponding visual field regions (r = 0.48, p = 0.0312). CONCLUSION: The visible ciliary vessels suggest the absence of the choriocapillaris in the non-fluorescent zone, the width of which correlated with the visual field defect and may affect the amount of the fluorescein diffusion to the disc. This suggests that the diffusion might be related to optic nerve damage in glaucoma.
The vessel wall properties of the common carotid artery have been noninvasively and quantitatively assessed with an ultrasonic instrument. Stiffness parameter beta, which represents the mechanical properties of the vessel, was calculated from the relationship between blood pressure and the diameter of the artery. There are no reports that quantitatively assess wall properties in Takayasu's arteritis. The authors compared, in vivo, the vessel wall properties of the common carotid artery in 14 patients with Takayasu's arteritis versus those in 60 normal subjects (controls). They measured changes in the inner diameter of the artery between systole and diastole with an ultrasonic, phase-locked, echo-tracking system. Beta was significantly higher in Takayasu's arteritis than in normal subjects (better than a 99% confidence interval). The findings for each decade were as follows: 3rd decade (20s): 35.7 +/- 28.9 vs 5.01-6.46, P=0.0001; 4th decade (30s): 19.5 +/- 9.71 vs 6.09-7.80, P=0.02; 5th decade (40s): 26.2 +/- 11.3 vs 7.26-9.28, P = 0.0001; 6th decade (50s): 19.1 +/- 4.27 vs 8.66-11.25, P = 0.0001. Takayasu's arteritis significantly impaired the mechanical performance of the common carotid artery. Thus, beta shows promise as a useful diagnostic indicator of Takayasu's arteritis.
We investigated the physicochemical and pharmaceutical properties of a solid dispersion (SD) derived from a solution of the poorly water-soluble drug (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022), hydroxypropylmethylcellulose 2910 (TC-5E) and polyoxyethylene hydrogenated caster oil 60 (HCO-60). Colloidal particles produced when the SD was dispersed into water had a mean diameter of 160 nm and contained 67-77% YM022. Powder X-ray diffractometry showed that YM022 existed in the colloidal particles in an amorphous state. The particle diameter and YM022 content remained unchanged during storage for 7 d, confirming that the colloidal solution was stable. On oral administration to rats, good absorption was observed for both the colloidal solution prepared immediately before and the sample stored for 7 d before administration. Thus, the stability of this colloidal solution of SD was confirmed by in vitro storage tests and by in vivo absorption experiments in rats.
Polymorphs of (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022) were investigated. Two crystalline forms (alpha- and beta-forms) of YM022 were confirmed by powder X-ray diffractometry and differential scanning calorimetry. alpha- And beta-forms were obtained by recrystallization from ethanol and ethanol: water (5:1), respectively. Amorphous YM022 was obtained by spray drying of YM022 methanol solution. Since both crystalline and amorphous YM022 were sparingly soluble in water, solubilization of YM022 by solid dispersion and wet grinding methods were performed. In vitro dissolution study and in vivo absorption study in dogs were carried out using spray-dried solid dispersion, heat-treated solid dispersion and mechanical mixture. Spray-dried solid dispersion and heat-treated solid dispersion showed enhanced bioavailability, whereas mechanical mixture showed no improvement.
A repeated dose toxicity study of ( +/- )-6- fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H- [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid (NM394), the active metabolite of a new antibacterial agent, prulifloxacin, was conducted in Sprague-Dawley rats. Male and female rats were given the test material intravenously for 4 weeks at doses of 0 (control), 3, 10 and 30 mg/kg. After discontinuation of the treatment, a 4-week recovery test was also conducted. There were no treatment-related effects on survival, clinical signs, body weight and food consumption. Ophthalmoscopic and hematologic examinations failed to show any abnormalities related to the treatment. Increased water consumption was observed in the 10 and 30 mg/kg groups. In these dose groups, increased urine volume and lowered urine specific gravity, and crystalline substance and small epithelial cells in urinary sediments were seen. Cloudy urine was also seen in the 30 mg/kg group. Blood chemical examination showed decreased gamma-globulin in the 10 and 30 mg/kg groups and increased BUN and creatinine in the 30 mg/kg group. Pathological changes caused by the treatment were as follows. In kidney, tubular nephrosis with crystalline substance was observed in the 10 and 30 mg/kg groups and its organ weight was increased in the 30 mg/kg group. Cecal weight was increased in the 30 mg/kg group. The above-mentioned changes were reversible except for decreased gamma-globulin. Plasma levels and urinary concentrations of the test material were increased in all dose groups with dose-related manner, whereby no sex differences were observed. No effects caused by the repeated dosing were seen in the plasma concentrations. Toxicological findings were not observed in the 3 mg/kg group. The results show that the NOAEL of NM394 is 3 mg/kg for 4-week repeated dose toxicity in rats.
A repeated dose toxicity study of prulifloxacin, a new antibacterial agent, was conducted in Sprague-Dawley rats. Male and female rats were given the test material orally for 4 weeks at doses of 0 (control), 30, 300 and 3000 mg/kg. After discontinuation of the treatment, a 4-week recovery test was also conducted. There was one case of death in the 3000 mg/kg group. Grayish green and soft feces, unkempt fur, transient deep respiration and decreased body weight gain were observed in the 3000 mg/kg group. Decreased food consumption and increased water intake were seen in the 300 and 3000 mg/kg groups. Ophthalmoscopic examination failed to show any abnormalities related to the treatment. In urinalysis, crystalline substance in the urinary sediments, cloudy urine and decreased Na+ excretion were observed in the 300 and 3000 mg/kg groups. Increased urine volume, lowered urine specific gravity and decreased K+ and Cl- excretions were seen in the 3000 mg/kg group. Hematologic examination showed decreased Hb, Ht, MCV and MCH and increased WBC in the 3000 mg/kg group. Blood chemical examination revealed increased BUN and decreased K+ and Cl- in the 3000 mg/kg group, and decreased K+ and gamma-globulin in the 300 mg/kg group. Pathological changes caused by the treatment were as follows. Cecal weight was increased in all dose groups. Cecal distention and swelling of its absorptive cells were seen in the 300 and 3000 mg/kg groups. In kidney, tubular nephrosis with crystalline substance was observed in the 300 and 3000 mg/kg groups, and its organ weight was increased in the 3000 mg/kg group. The above-mentioned changes were reversible except for decreased gamma-globulin, increased BUN and urine volume, and lowered urine specific gravity. Ulcer and small cavities associated with proliferation of fibrous tissue in the femoral articular cartilage were observed in the 3000 mg/kg group at the end of recovery period of 4 weeks. Plasma levels and urinary concentrations of active metabolite of the test material were increased in all dose groups with dose-related manner, whereby no sex difference was observed. No effects caused by the repeated dosing were seen in the plasma concentrations. Increased cecal weight in the 30 mg/kg group was considered to be attributable to the pharmacological effect of the test material. The results show that the NOAEL of prulifloxacin is 30 mg/kg for 4-week repeated dose toxicity in rats.
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A 71-year old man presented with partial rupture progressing to complete rupture of the left ventricular anterior papillary muscle after acute anterolateral myocardial infarction. The progressive rupture was demonstrated by transthoracic and transesophageal echocardiography. Transthoracic echocardiography showed exaggerated systolic prolapse of the anterior mitral leaflet with grade III mitral regurgitation and partial disruption of the anterolateral papillary muscle, but transesophageal echocardiography during surgery disclosed the progression of the partial rupture to complete rupture. The flail anterior mitral leaflet with severe mitral regurgitation and the head of the ruptured papillary muscle into the left atrium in systole were confirmed. The patient was treated by coronary artery bypass grafting and mitral valve prosthesis using a St. Jude Medical valve with good outcome.
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The Children of Alcoholics Screening Test (CAST) is a 30-item screening instrument developed to identify children who are either living with or have lived with alcoholic parents. The Japanese edition of CAST and a questionnaire on parent's drinking were administered; 572 samples of high school students and 44 samples of advanced nursing school students were obtained. The following observations were made. 1) The CAST exhibited a high level of reliability (Cronbach's alpha coefficient of internal consistency reliability = .92, reliability coefficient theta computed on principle component analysis = .92, test-retest reliability coefficient p = .96). 2) All of the 30 questions of CAST elicited affirmative responses of varying degrees, and none of the questions were found to be incongruous. 3) Factor analysis was performed to detect the potential structure model of the CAST 30 items. It revealed that the CAST is composed of and able to check, in order of relative weight, the cognitive > emotional > behavioral experiences. 4) 17.7% of the total CAST sample scored six and over, which is the score that serves as the cutoff point to identify the children of alcoholics. 5) The average CAST score of female students was found to be significantly greater than that of male students (p = 0.008). On each of the 30 items, female students had a higher rate of answering affirmatively than male students, and on 13 items (item number 2, 3, 4, 8, 9, 10, 12, 16, 19, 20, 22, 23, 28) were found to differ significantly. 6) The CAST score of the sample was found to be significantly related to the frequency of the father's drinking, and compared to male students, female students were more sensitive to and affected more seriously by their father's drinking.
A recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) vector-based vaccine that secretes the V3 principal neutralizing epitope of human immunodeficiency virus (HIV) could induce immune response to the epitope and prevent the viral infection. By using the Japanese consensus sequence of HIV-1, we successfully constructed chimeric protein secretion vectors by selecting an appropriate insertion site of a carrier protein and established the principal neutralizing determinant (PND)-peptide secretion system in BCG. The recombinant BCG (rBCG)-inoculated guinea pigs were initially screened by delayed-type hypersensitivity (DTH) skin reactions to the PND peptide, followed by passive transfer of the DTH by the systemic route. Further, immunization of mice with the rBCG resulted in induction of cytotoxic T lymphocytes. The guinea pig immune antisera showed elevated titers to the PND peptide and neutralized HIVMN, and administration of serum IgG from the vaccinated guinea pigs was effective in completely blocking the HIV infection in thymus/liver transplanted severe combined immunodeficiency (SCID)/hu or SCID/PBL mice. In addition, the immune serum IgG was shown to neutralize primary field isolates of HIV that match the neutralizing sequence motif by a peripheral blood mononuclear cell-based virus neutralization assay. The data support the idea that the antigen-secreting rBCG system can be used as a tool for development of HIV vaccines.
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Dissociated cultures of rat hypothalamic cells showed spontaneous oscillations in intracellular Ca2+ with periods of 5-8 s (ultradian rhythm). Replacement of H2O by deuterium oxide in the culture medium lengthened the period of this oscillation, while tetrodotoxin did not inhibit the deuterium oxide sensitive Ca2+ oscillation. Since these characteristics resemble those of the mammalian circadian pacemaker, the ultradian Ca2+ rhythms may be involved in the circadian rhythm or have a similar rhythm generation mechanism. The gap junction inhibitor, halothane, stopped this oscillation. Gap junctions may be necessary in order to generate rhythmic oscillations.
Seven measles virus (MV) strains were isolated from children who developed clinical signs of fever and rash 3-9 days after measles vaccination. The nucleotide sequence of the H gene, the molecular size of the H protein, the haemadsorption activity on African green monkey red blood cells, and antigenicity as determined by virus neutralization revealed that one strain was of the vaccine type and the remaining six were the wild virus type. Isolation of the virus directly from patients suspected of a vaccine-induced side-reaction and subsequent characterization of such isolated virus may be useful in differentiation between vaccine-induced side-reactions and natural measles.
The substrate specificity and enantioselectivity of DMSO reductase from Rhodobacter sphaeroides f.s. denitrificans were studied on a series of alkyl aryl sulfoxides as substrate. The enzyme was found to catalyze deoxygenation of (S)-sulfoxides predominantly. (R)-Sulfoxides were recovered with a high enantiomeric excess.
Glycoproteins are metabolized through an asialoglycoprotein metabolic pathway in vivo. They are desialylated and taken up by the liver via an asialoglycoprotein receptor. Fibroblast-derived natural human interferon-beta is a glycoprotein having a single asparagine-linked sugar chain. Although natural human interferon-beta may also be metabolized through this pathway, there is very little information about the biologic features of human asialointerferon-beta. We evaluated the pharmacokinetics and biologic activities of human native and asialointerferon-beta s. After intravenous administration to rabbits, human asialointerferon-beta was cleared from the blood circulation faster than the human native interferon-beta. More asialoprotein was distributed to the liver than the native type, but it induced less 2'5'-oligoadenylate synthetase. The human asialointerferon-beta had less activity than the human native interferon-beta on cell growth inhibition and 2'5'-oligoadenylate synthetase induction in Hep-G2 and HuH6 human hepatoblastoma cells. Southern blotting using a hepatitis B virus-transfected HuH6 cell line, HB611, revealed that the inhibition of hepatitis B virus DNA replication by the asialoprotein was weaker than that by the native protein. The results showed that the different effects exerted by the human native and asialointerferon-beta s may be a result of recognition of the sugar chains by rabbit hepatocytes or by human hepatoblastoma cells. The results also suggested that the terminal sialic acid of the sugar chains in natural human interferon-beta significantly affects its pharmacokinetics and biologic activities.