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Biomedical subjects

R Yoshida

Publications and source records attributed to R Yoshida.

At least 163 records · Page 9Linked to original sources
PubMed1989

Age- and sex-specific cumulative rate and risk of ATLL for HTLV-I carriers.

We have surveyed the incidence of adult T-cell leukemia/lymphoma (ATLL) in an endemic area of 290,464 inhabitants for 7 years. We now revise our previous results on the basis of additional findings and estimate the age- and sex-specific cumulative rate for HTLV-I carriers, the adoption of which is recommended by current cancer epidemiology as a new age-standardized incidence rate. An unequivocal age-dependent increase in seroprevalence was observed for both sexes with a characteristic predominance in females. The age-dependent seroconversion in females may be partly explained by additional infection from infected husbands to their wives but the reason for men remains obscure. The mean annual number of incident cases of ATLL was 11.4, giving 3.9 ATLL patients annually per 10(5) inhabitants, 6.1 per 10(5) inhabitants aged over 30, and 85.0 per 10(5) seropositives aged over 30. Crude annual incidence rate of ATLL among 10(5) male seropositives aged over 30 was 145.3 and that for females was 55.2 and 95% confidence intervals of ATLL incidence rates were 34.8 to 255.7 for males and 6.4 to 104.1 for females, respectively. Although the sex ratio of 80 ATLL patients was 1.35, males are more prone to the disease (46 male patients among 4,522 male seropositives aged over 30 vs 34 female patients among 8,801 female seropositives aged over 30; p less than 0.001) for unknown reason(s). Morbidity in male seropositives aged over 30 is 2.6 times as high as that of females. Decennial incidence rates in males in their fifties and sixties were significantly higher than those in females. The remarkable male preponderance in oncogenicity of HTLV-I may be due to the fact that men are more prone to the disease and the number of female carriers in the denominator used to calculate the incidence rate is larger than that of males. The whole life span (0-79) cumulative risk for males was 6.9% and significantly higher than that of females (2.95%).

Age Factors↗
PubMed1989

Antigenicity tests on propiverine hydrochloride in guinea pigs and mice.

Antigenicity of propiverine hydrochloride (P-4), a newly developed drug for pollakisuria, was investigated in guinea pigs and mice. 1. Two strains of mice (BALB/c and C3H/He) showed no production of antibodies against P-4 inoculated with aluminum hydroxide gel (alum) as an adjuvant, judged by the heterologous passive cutaneous anaphylaxis (PCA) test using rats. On the other hand, antibodies against P-4-ovalbumin (OVA) conjugate inoculated with alum was definitely detected. 2. In the studies with guinea pigs, both the inoculation of P-4 alone and of P-4 with Freund's complete adjuvant (FCA) as an adjuvant did not produce positive reactions in any of homologous passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA) and passive hemagglutination (PHA) tests. On the other hand, the inoculation of P-4-OVA conjugate with FCA produced positive reaction in all of PCA, ASA and PHA tests. 3. In the active cutaneous anaphylaxis (ACA) test in guinea pigs inoculated with P-4-OVA conjugate with FCA, positive reaction was produced by eliciting injection of P-4-human serum albumin (HSA). 4. In the Schultz-Dale reaction test, any animals in any groups showed no positive reaction to both eliciting antigens, P-4 and P-4-HSA. 5. These findings showed that P-4 had no antigenicity in guinea pigs and mice.

Anaphylaxis↗
PubMed1989

[Reproduction study of propiverine hydrochloride (1)--fertility study in rats by oral administration].

A fertility study was performed in Sprague-Dawley rats by oral administration of propiverine hydrochloride (P-4) at dose levels of 0 (control), 2, 10 and 50 mg/kg/day. Male rats were treated for 9 weeks before mating and following 4 weeks including mating period. Female rats were administered the test substance from 2 weeks before mating to day 7 of pregnancy. The females were sacrificed on day 21 of pregnancy for examination of their fetuses. Toxic signs consisted of mydriasis, salivation and rale were observed in both male and female animals at the dose of 50 mg/kg group and in male animals at the dose of 10 mg/kg group. Body weight gain was supressed and food intake was decreased in the 50 mg/kg group throughout the administration period. Water intake of the 50 mg/kg group was decreased temporarily at the early stage of administration period, although increased thereafter. Autopsy revealed the enlargement of the liver with yellow-brownish coloration in one male rat at the 50 mg/kg group. Fertility and reproductive ability in both sexes were not affected by administration of P-4. There was no lethal effect and no growth-inhibiting or teratogenic effects on the embryos and the fetuses. The results suggest that the non-effective dose level of P-4 was 2 and 10 mg/kg/day for general toxicity in male and female parent animals respectively, 50 mg/kg/day for reproductive ability in parent animals and in embryos and fetuses.

Abnormalities, Drug-Induced↗
PubMed1989

[Reproduction study of propiverine hydrochloride (2)--teratological study in rats by oral administration].

A teratogenicity study was performed in Sprague-Dawley rats by oral administration of propiverine hydrochloride (P-4) at dose levels of 0 (control), 2, 10 and 50 mg/kg/day to dams from day 7 to day 17 of pregnancy. Twenty two or twenty three female rats in each group were sacrificed on day 21 of pregnancy for examination of their fetuses, and thirteen female rats were allowed to deliver for the postnatal examination of their offspring. In dams, the dose of 50 mg/kg caused toxic signs consisting of mydriasis, salivation and rale, body weight loss in the early stage of administration, and reduced food intake and increased water intake. The dose of 10 mg/kg caused rale, very slight suppression of body weight gain and slight reduction of food intake. Body weight of the fetuses was decreased very slightly in the 50 mg/kg group. However, embryonal or fetal mortality and incidences of external, visceral or skeletal anomalies were not increased. In offspring, P-4 had no adverse effect on the postnatal development such as viability, growth, differentiation, emotionality, learning ability or reproductive performance. The results suggest that the non-effective dose level of P-4 is 2 mg/kg/day in maternal animals, 10 mg/kg/day in fetuses and 50 mg/kg/day in offspring.

Abnormalities, Drug-Induced↗
PubMed1989

[Reproduction study of propiverine hydrochloride (3)--teratological study in rabbits by oral administration].

A teratogenicity study was performed in New Zealand white rabbits by oral administration of propiverine hydrochloride (P-4) at dose levels of 0 (control), 2.4, 12 and 60 mg/kg/day to dams from day 6 to day 18 of pregnancy. Thirteen or fifteen pregnant rabbits in each group were sacrificed on day 29 of pregnancy for examination of their fetuses. In dams, the dose of 60 mg/kg caused mydriasis, body weight loss or decreased body weight gain and reduced food and water intakes. Autopsy and weighing of organ weight revealed no evidence due to drug administration in any group. There were no significant differences in embryo-fetal mortality, fetal body weight, or incidences of external, visceral or skeletal anomalies and skeletal variation between treated and control animals. The compound had no lethal effects on the embryos and no growth-inhibiting or teratogenic effects on the fetuses. The results suggest that the non-effective dose level of P-4 is 12 mg/kg/day in maternal animals and 60 mg/kg/day in fetuses.

Abnormalities, Drug-Induced↗
PubMed1989

[Reproduction study of propiverine hydrochloride (4)--perinatal and postnatal study in rats by oral administration].

A perinatal and postnatal study was performed in Sprague-Dawley rats by oral administration of propiverine hydrochloride (P-4) at dose levels of 0 (control), 2, 10 and 50 mg/kg/day to dams from day 17 of pregnancy to day 21 after delivery. Twenty two or twenty four dams in each group were allowed to deliver for the postnatal examination of their offspring. In dams, the dose of 50mg/kg caused toxic signs consisting of mydriasis, salivation and rale. One dam of this group showed piloerection, low body temperature, blanching of extremity and auricle, and emaciation associated with marked prolongation of delivery. Body weight gain of the dams was retarded in the 50 mg/kg group throughout the administration period. Food and water intakes were reduced in the 50mg/kg group. In gross pathology of the dam that showed prolonged delivery, the spleen and thymus were moderately or severely atrophied and the adrenal was moderately enlarged. The viability index of the offspring on day 4 was reduced in the 50mg/kg group. Body weight of pups slightly decreased in the 50mg/kg group during sucking and rearing periods. Absolute weights of some organs of the three-week aged offspring were reduced due to attributable depression of body weight gain. However, P-4 had no adverse effect on the postnatal development such as emotionality, motor activity, learning ability or reproductive performance. The results suggest that the non-effective dose level of P-4 is 10mg/kg/day in maternal animals and offspring.

Administration, Oral↗
PubMed1989

[The relationship between the physical features and medications in Reye-like syndrome in elderly patients].

With the increase in the aged population, it is expected that the number of debilitated aged people will increase and that the number of patients receiving many medications will increase. However, there have been few reports of clinical pharmacological studies on blood pharmacokinetics, metabolism, adverse effects, etc, of drugs used in debilitated aged people who have lowered physical and mental functions complicated by many diseases. Thus, for the large part, pharmacokinetics in these patients remains unelucidated. We experienced eight cases of marked hypoglycemia of unknown cause in patients who had not taken any hypoglycemic drugs or insulin and examined the relationships between the event and the physical features and medications of the patients. The eight patients included both males and females aged 66 to 88 years (mean: 78.5 years). The eight patients were all aged and showed cerebral infarction, reduced volition, etc. The onset of hypoglycemia was preceded by decreased appetite and an abrupt manifestation of severely disturbed consciousness a few days previously. Laboratory tests revealed marked hypoglycemia in 8 cases, leucocytosis in 7 cases (not examined in one case), metabolic acidosis in 3 cases, elevated GOT in 5 cases, elevated GPT in 2 cases, increased BUN in 1 case, and positive CRP in 4 cases. The patients had been taking an agent to activate brain metabolism/improve mental symptoms (Hopantene calcium: 7 cases; Idebenone: 1 case). The Idebenone-treated patient had received Hopantene calcium for eleven months prior to receiving Idebenone. Furthermore, the findings resembled those of Reye's syndrome often noted in children.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

[Multiple [3H]8-hydroxy-2-(di-n-propylamino)-tetralin binding sites in rat brain: modulation by GTP and cations].

[3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) is thought to label a single population of serotonin (5-HT)1A receptor, but some reports implicate multiple binding sites exist. In addition, while 5-HT1A receptor activates or inhibits adenylate cyclase, 5-HT1A receptor high and low affinity states are not reported. In this experiment, we found that [3H]8-OH-DPAT had multiple binding sites, which contained 5-HT1A receptor high and low affinity states, in rat brain membranes. [3H]8-OH-DPAT saturation binding experiment revealed high and low affinity binding sites existed. High affinity binding site was dense in hippocampus and sparse in striatum. 5-HT agonist and antagonist biphasically displaced [3H]8-OH-DPAT binding in frontocortical, hippocampal, and striatal membranes. These drugs potently displaced high affinity [3H]8-OH-DPAT binding, but clomipramine (5-HT reuptake inhibitor) potently displaced low affinity binding. High affinity [3H]8-OH-DPAT binding site was decreased by guanosine triphosphate and Na+, but increased by divalent cations, implicating coupling with G protein(s). Low affinity [3H]8-OH-DPAT binding site was decreased by cations, especially by monovalent cations and Ca2+. After the destruction of 5-HT neuron by parachloroamphetamine, only the low affinity binding site decreased. These results indicate that [3H]8-OH-DPAT not only labels the 5-HT1A receptor high and low affinity states but has presynaptic binding site relating to 5-HT reuptake site.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

[CT study in senile dementia of Alzheimer type].

In order to evaluated the utility of cranial CT in diagnosis of senile dementia of Alzheimer type (SDAT) various CT findings were studied. CT scans of 62 cases with SDAT (83 +/- 6 years old) were compared with those of 357 aged cases (means 78 +/- 8 years old) with out psychiatric and/or neurological illness (normal control NC). The methods of evaluating CT findings were linear measurements of the ventricle (Huckman number, Evans' ratio, lateral body ratio), observation of sulci (Sylvian fissure, cingulate sulcus and central sulcus), brain atrophy ranking of microscopic observation (I; absent, II; mild, III; mild to moderate, IV; moderate, V; maximum) and presence of periventricular lucency. When SDAT were compared with NC the cases were divided into two groups by the age (the eighth decade, 80 years old and over) in order to avoid the influence of physiological brain atrophy. The results were as follows: 1) In SDAT there was a positive correlation between the volume of the lateral ventricle in autopsy brain and each index which demonstrates the size of the lateral ventricle on CT (r = 0.65, p less than 0.001). 2) In SDAT the incidence of cases with more than III degree in brain atrophy ranking was significantly higher than in NC (p less than 0.001). It was 82.6% in SDAT, 15.7% in NC in the eighth decade and 92.3% in SDAT, 32.1% in NC in 80 years and over. 3) The mean values of indexes of lateral ventricle enlargement (Huckman number, Evans' ratio, lateral body ratio) in SDAT increased more than those in NC significantly (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

[Report of a case of lung cancer with metastasis to the myocardium which showed electrocardiographic findings similar to acute myocardial infarction and intramyocardial mass on echocardiography].

A 61-year-old man was admitted to our hospital with complaints of cough and left back and chest pain. He had suffered from left tuberculous pleurisy at the age of 20 years. Chest X-ray film and CT revealed atelectasis of the left lung, a left hilar mass and an irregular left atrial wall. Depressed P-Ta segment in the inferior limb and anterior chest leads and an abnormal P wave were found on ECG. Transbronchial lung biopsy showed squamous cell carcinoma. After radiation therapy, the patient complained of chest oppression. ECG revealed a normalized P-Ta segment deviation, markedly elevated ST segment in the inferior limb and lateral chest leads and a depressed ST segment in the anterior chest leads. These findings persisted until his death. An obscure appearance of the pericardium and an echogenic intramyocardial mass in the posteroinferior and lateral wall were evident by echocardiography. The patient died due to heart failure. Postmortem needle biopsy showed scattered intramyocardial tumor cell nests with keratinization. CPK, GOT and LDH were within normal limits throughout the course, but CPK-MB was slightly increased. Cardiac metastasis with an ECG appearance similar to that of acute myocardial infarction has been rarely reported. Our present case showed peculiar feature including 1) ECG findings similar to atrial and ventricular myocardial infarction, and 2) an echogenic intramyocardial mass and an ill-defined pericardium on echocardiography. These findings suggested direct invasion of squamous cell carcinoma of the lung to the ventricular myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell↗
PubMed1988

Tryptophan degradation in transplanted tumor cells undergoing rejection.

The depletion of an essential amino acid, tryptophan, caused by indoleamine 2,3-dioxygenase induction in vitro, has been shown to be due to a mechanism that is used in self-defense against inhaled microorganisms and tumor growth. In this communication, we report the results of measuring dioxygenase activity in the peritoneal exudate cells and tumor cytotoxicity at the transplantation loci after in vivo transplantation of tumor cells into the peritoneal cavity of syngeneic or allogeneic strains of mice. The enzyme was induced only when the tumor cells were being rejected from allogeneic animals and no change was observed when the cells continued to grow in syngeneic animals. Furthermore, when the syngeneic tumor cells in a diffusion chamber were i.p. transplanted simultaneously with i.p. injection of allogeneic tumor cells, the enzyme was induced not only in allografted tumor cells but also in the syngeneic tumor cells. Under these conditions, the tumor cells in the diffusion chamber ceased to grow and 50% of the cells were rejected. To determine the type of cells containing the induced enzyme, the peritoneal exudate cells (tumor cells and host cells--mostly small lymphocytes) were separated into six fractions by sedimentation under gravity and by differential centrifugation. Approximately 80% of total enzyme activity was localized in a tumor-rich fraction (98.9% purity), whereas only 0.2% of the activity was found in a lymphocyte-rich fraction (99.5% purity). The localization of indoleamine 2,3-dioxygenase in the tumor cells was confirmed by complement-dependent lysis with specific antibodies against tumor and host cells.

Animals↗
PubMed1988

Agonist and antagonist effects of interferon alpha and beta on activation of human macrophages. Two classes of interferon gamma receptors and blockade of the high-affinity sites by interferon alpha or beta.

H2O2-releasing capacity and limited antitoxoplasma activity could be induced in human macrophages (derived from monocytes cultured greater than or equal to 5 d) but not in monocytes themselves (cells cultured less than or equal to 4 d) by a further 3-d incubation with pure natural or rIFN-alpha or -beta. More than 3 pM (10 U/ml) of these IFNs was required, with greatest effects at approximately 300 pM (10(3) U/ml). At 300 pM, H2O2-releasing capacity was enhanced 4.4 +/- 1.6-fold over medium control (mean +/- SD for natural INF-alpha, rIFN-alpha A, rIFN-alpha D, and rIFN-beta) compared to an 8.4 +/- 4.8-fold increase with rIFN-gamma (100 pM, 100 U/ml) in the same experiments. Unexpectedly, low concentrations of IFN-alpha or -beta (3 fM-300 pM) blocked induction of H2O2-releasing capacity by rIFN-gamma (10 pM), with a 50% inhibitory dose of approximately 80 fM. However, IFN-alpha or -beta (3 fM-300 pM) could not inhibit the effect of higher concentrations of rIFN-gamma (1 nM). In contrast to results with monocytes or young macrophages, Scatchard plots of binding of 125I-rIFN-gamma to mature macrophages (day 8 of culture) indicated two classes of binding sites: approximately 2,000 high-affinity sites (Kd approximately 0.43 nM) and approximately 23,000 low-affinity sites (Kd approximately 6.4 nM) per cell. Binding of 125I-rIFN-gamma to the high- but not the low-affinity sites was blocked by simultaneously added IFN-alpha or -beta, with a 50% inhibitory dose of approximately 2 U/0.25 ml (approximately 2 pM), or reversed by subsequently added IFN-alpha or -beta. Thus, differentiation of human mononuclear phagocytes in vitro is accompanied by the emergence of (a) an agonist response to submicromolar concentrations of IFN-alpha or -beta, (b) antagonism of the effect of picomolar IFN-gamma by femtomolar IFN-alpha or -beta, (c) two classes of IFN-gamma-Rs, and (d) nonstimulatory binding of IFN-alpha or -beta to the high- but not the low-affinity IFN-gamma-Rs, with higher affinity than rIFN-gamma itself. We speculate that traces of IFN-alpha or -beta derived from stromal cells, parenchymal cells, or resident macrophages may dampen the activation of mature tissue macrophages by the small amounts of IFN-gamma that diffuse from inflammatory sites into normal tissues. Such a mechanism could constrain the potentially destructive phenomenon of macrophage activation to areas where monocytes have recently immigrated and/or the concentration of IFNs is high.

Adult↗
PubMed1988

[Peri- and postnatal study of cefodizime sodium in mice--intravenous administration from late gestation through period of lactation].

Peri- and postnatal study of cefodizime sodium (THR-221), a new developed cephem-type antibiotics, was carried out with ICR mice. THR-221 at dose levels of 0, 300, 1000 and 3000 mg/kg/day were administered intravenously to pregnant and delivered dams from day 15 of gestation through day 21 of lactation. No changes in body weights of dams in all treated groups but slight decrease in food consumptions of 3000 mg/kg/day group were observed. Treated sites, tails of a few dams in this group, were affected with inflammatory lesions because of repeated dosing. Neonates from dams treated with 3000 mg/kg/day were slightly decreased in body weight at birth. At term sacrifice of F 1 of 10 weeks age, absolute and relative spleen weights were decreased in male 3000 mg/kg/day group and in female 1000 and 3000 mg/kg/day group. No effects on other physical, behavioral or reproductive ability examinations of F 1 offspring were showed. It is suggested that no effect dose level of THR-221 is 1000 mg/kg/day and that of F 1 offspring is 300 mg/kg/day.

Animals↗
PubMed1988

[Antigenicity test of cefodizime sodium].

The antigenicity studies of a beta-lactam antibiotic, cefodizime sodium (THR-221), were examined in mice and guinea pigs and the following results were obtained. 1) In passive cutaneous anaphylaxis (PCA) with sera from BALB/c or C3H/He mice, a slight PCA reaction was observed only in BALB/c mice by using THR-221-ovalbumin (OVA) plus Freund's complete adjuvant (FCA) as the immunogen and THR-221 itself as the eliciting antigen. 2) Immunological cross-reactivity between THR-221 and CTX was present at the rat PCA reaction. 3) Antibodies against THR-221 were detected by PCA in guinea pigs. The anti-THR-221 antibodies gave PCA responses smaller than those of CMZ by using antibiotic plus FCA as the immunogen and the antibiotic-bovine serum albumin (BSA) as the eliciting antigen. 4) In the observation of active systemic anaphylaxis (ASA), no symptoms were observed in guinea pigs sensitized with THR-221 and provoked with THR-221-BSA. On the other hand, guinea pigs sensitized with THR-221 plus FCA by injecting THR-221-BSA showed fetal anaphylactic reactions. 5) The results of passive hemagglutination (PHA) also indicated that the PHA titer of THR-221 was lower than that of CMZ. 6) Protein binding property of THR-221 with human serum albumin was lower than other beta-lactam antibiotics. 7) Antibodies against THR-221-OVA by using THR-221-BSA as the eliciting antigen were detected in any tests above mentioned. It is concluded from these results that immunological activity of THR-221 was equivalent to the other beta-lactam antibiotics.

Anaphylaxis↗
PubMed1988

Mutagenicity test of cefodizime sodium.

The mutagenicity of cefodizime sodium (THR-221) was investigated by the reverse mutation test using seven bacterial strains (Salmonella typhimurium strains TA100, TA98, TA1535, TA1537 and TA1538, and Escherichia coli strains WP2 and WP2uvrA) and the chromosomal aberration test with cultured Chinese hamster lung (CHL) cells. The reverse mutation test was carried out in dose range from 0.0025 to 5.0 micrograms/plate in the absence and presence of mammalian metabolic activation system. Antibacterial effects were observed at concentrations more than 0.25 microgram/plate, and no significant increases in the number of revertants were observed at the dose levels where antibacterial effects were not detected. THR-221 caused no increases in the number of chromosomal aberrants at dose levels of 0.75, 1.5, 3.0 and 6.0 mg/ml in the absence and presence of the metabolic activation. These results indicate that THR-221 has no mutagenic activity.

Animals↗
PubMed1988

[Local irritation studies of cefodizime sodium].

Four local irritation studies of cefodizime sodium (THR-221), a new developed cephem-type antibiotics, were carried out with NZW rabbits. 1. In eye irritation test, 25% THR-221 water solution had no irritancy on eye mucosa in rabbits. 2. In single injective intramuscular irritation study, regardless of solvents (water or 0.5% lidocaine), 25% THR-221 solution had irritancy equal to 0.75% acetic acid. But recovery process of the muscle injured with THR-221 was faster and better than with 0.75% acetic acid. 3. In five days injective muscular irritation study, the irritancy of 25% THR-221 water solution on the muscle was milder than that of CTT or CET. Histopathological damage with THR-221, necrosis/degeneration of muscle fibers and edema/hemorrhage in interstitium etc., were well recovered. 4. In vessel irritation study, 10% or more THR-221 water solution had irritancy on ear vessel. THR-221, as same as CTT, caused organized thrombi and inflammation at the surrounding area. The degree of irritation of 20% THR-221 solution was slightly stronger than that of 20% CET, but weaker than that of 20% CTT. 5. In a clinical phase, it is to be desired that THR-221 like as CTT or CET shall be avoided repeated intramuscular or intravenous injections at the same site.

Animals↗