Biomedical subjects

R Yoshida

Publications and source records attributed to R Yoshida.

At least 19 recordsLinked to original sources

PubMed1992

Positive inotropic and negative chronotropic effects of (-)-cis-diltiazem in rat isolated atria.

1. The cardiovascular effects of (-)-cis-diltiazem, an optical isomer of diltiazem, were studied in the isolated atrium and aortic strip. (-)-cis-Diltiazem (30 microM or more) increased the developed tension of the rat left atrium, while (+)-cis-diltiazem (1 microM or more) decreased it. 2. (-)-cis-Diltiazem (1 to 100 microM) decreased the rate of spontaneous beating in the right atrium as did (+)-cis-diltiazem. 3. The potency of the positive inotropic action of (-)-cis-diltiazem was almost the same as that of ouabain in the rat left atrium, but in the guinea-pig left atrium it was considerably weaker than that of ouabain. 4. In both endothelium-intact and endothelium-denuded aortic strips, (-)-cis-diltiazem relaxed the Ca(2+)-induced contraction. In the endothelium-intact rat aortic strip depolarized by 15 mM KCl, Bay K 8644, a calcium channel agonist, increased the contractile force, whereas (-)-cis-diltiazem did not. 5. These results indicate that (-)-cis-diltiazem has a positive inotropic action in isolated atria in rats and guinea-pigs, but the mode of positive inotropic action of (-)-cis-diltiazem is different from that of ouabain or Bay K 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1992

Surface-modulated skin layers of thermal responsive hydrogels as on-off switches: II. Drug permeation.

'On-off' regulation of drug permeation through membranes in response to external temperature change has already been achieved using thermosensitive copolymers of N-isopropyl acrylamide (IPAAm) with butyl methacrylate (BMA). Increasing temperature induced formation of a dehydrated polymeric surface skin layer that stopped drug permeation. In this study, to control 'on-off' permeability of a drug, the polymer surface shrinking process was regulated by changing the length of alkyl side chain of the copolymer methacrylate component. Permeation experiments with indomethacin were performed in response to stepwise temperature changes between 20 and 30 degrees C with copolymers of IPAAm with BMA, hexyl methacrylate (HMA), and lauryl methacrylate (LMA). Burst permeation was found at the initial stage of the second 'on' period for both poly(IPAAm-co-HMA) and poly(IPAAm-co-LMA). These results suggest that drug diffuses during 'off' periods to change the concentration profile in the polymer gel. Polymer surface skin formation maintains a localized high water content inside the polymer gel even if drug permeation stops. The length of the alkyl side chain is an important parameter to control 'on-off' permeability of drug.

Acrylic Resins↗

PubMed1992

Direct effect of thyroid hormone on left ventricular myocardial relaxation.

The left ventricular diastolic indices of the hyperthyroid (HTH) patients without cardiac disease (n = 31) were compared with those of the normal controls (NC) (n = 49) using echocardiography. The HTH group had a significantly shorter IIa-mitral valve opening time (IIa-MVO), and a significantly larger maximum descending rate of the left ventricular posterior wall (maxPWDR), peak E and peak A than the NC group. IIa-MVO, maxPWDR, peak E and E/A showed significant simple correlation with T3 in the HTH group. To elucidate spurious correlation among these indices and T3, partial correlation analysis among these indices and its influencing factors were calculated. IIa-MVO, maxPWDR and peak E showed significant partial correlation coefficients with T3, but peak E had a lesser partial correlation with T3 than with age and left ventricular end-diastolic volume. Fourteen of the hyperthyroid patients were reexamined after antithyroid treatment. Their diastolic indices were found to be normalized compared with pre-treatment values and showed no significant difference with those of NC group. Augmented myocardial relaxation in patients with hyperthyroidism correlated with the thyroid hormone level, and IIa-MVO and maxPWDR were more effective indices of left ventricular myocardial relaxation than peak E and E/A in hyperthyroidism.

Adult↗

PubMed1992

[Reproductive and developmental toxicity study of suplatast tosilate (IPD-1151T) (2)--Teratological study in rats by oral administration].

A teratological study of suplatast tosilate (IPD-1151T), a new anti-allergic agent which has a suppressive action on IgE antibody formation, was conducted with pregnant Wistar rats. Dosage levels of IPD-1151T 0, 300, 900 and 2700 mg/kg/day were administered to dams orally by gavage on days 7 through 17 of gestation. Two-thirds of dams per group was caesarean-sectioned on day 20 of gestation and their fetuses were removed for examination of external, visceral and skeletal anomalies. The remaining one-third was allowed to deliver naturally. F1 neonates were examined developmental, functional and behavioral parameters and reproductive abilities. The results were as follows: 1. Toxicities on F0 dams in the 2700 mg/kg/day group were salivation, piloerection, and decreases in body weight and food consumption. Seven animals (19.4%) showed severe toxicity and were dead. Toxicity in the 900 mg/kg/day group was a slight decrease in food consumption. The dosage level of 300 mg/kg/day was non-toxic. 2. Toxicities on F1 fetuses in the 2700 mg/kg/day group were a decrease in body weight and an increase in visceral anomalies (main one was ventricular septal defect that might be related to developmental retardation). No toxicities were seen in the 300 and 900 mg/kg/day. 3. In F1 neonates, suppressions of body weight were observed clearly in the male and female 2700 mg/kg/day and slightly in the male 900 mg/kg/day groups. But no changes in parameters of development, function, behavior or reproductive ability were seen in any dosed groups. It was suggested that no effective dose levels of IPD-1151T were 300 mg/kg/day for F0 dams and F1 neonates, and 900 mg/kg/day for F1 fetuses.

Abnormalities, Drug-Induced↗

PubMed1992

[Mutagenicity tests of suplatast tosilate (IPD-1151T)].

1. The reverse mutation test was carried out on suplatast tosilate (IPD-1151T) at dose range of 50-5000 micrograms/plate using Salmonella typhimurium strains TA100, TA1535, TA98 TA1538 and TA1537, and Escherichia coli strains WP2, WP2uvrA. In all tester strains no significant differences were observed in the number of revertant colonies as compared with solvent control in the absence or presence of mammalian metabolic activation system. 2. The chromosomal aberration test on IPD-1151T was carried out using cultured Chinese hamster lung cells (CHL). The cells were treated with IPD-1151T at the doses of 125, 250 and 500 micrograms/ml without S9 Mix and at the doses of 1250, 2500 and 5000 micrograms/ml with S9 Mix. The incidence of structural- and numeral-aberration was 0-4% in the absence or presence of mammalian metabolic activation system, no significant increases were observed in the incidence of chromosomal aberrations. 3. The micronucleus test using BDF1 male mice was conducted in order to evaluate the in vivo mutagenicity of IPD-1151T. IPD-1151T was orally administered at doses of 625, 1250, 2500 and 5000 mg/kg, with a sampling time of 24 hr. The frequency of polychromatic erythrocytes with micronuclei (MNPCE) was 0.23% in the lowest dose (625mg/kg) of IPD-1151T, but the frequency of MNPCE was 0.03-0.13% in the groups treated with 1250-5000 mg/kg of IPD-1151T and no significant increases were observed with dose dependence. The results indicated that IPD-1151T was negative, even in the assessment standard using our background data. 4. The present study indicates that IPD-1151T has no in vitro and in vivo mutagenic potential.

Administration, Oral↗

PubMed1992

[Antigenicity tests of suplatast tosilate (IPD-1151T)].

Antigenicity of suplatast tosilate (IPD-1151T) was investigated in guinea pigs and mice. The results were as follows: 1. Homologous passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA), active cutaneous anaphylaxis (ACA) and Schultz-Dale reaction tests were carried out using guinea pigs which were immunized orally with IPD-1151T alone or subcutaneously with IPD-1151T and Freund's complete adjuvants (CFA). Positive reactions in these tests were not produced by eliciting injection of IPD-1151T or its metabolite, M-1. On the other hand, the sensitization of ovalbumin (OVA) with CFA produced positive reactions in all of PCA, ASA, ACA and Schultz-Dale tests. 2. Heterologous passive cutaneous anaphylaxis (PCA) test using rats was carried out using two strains of mice (C3H/He and BALB/c) which were immunized orally with IPD-1151T alone or intraperitoneally with IPD-1151T and aluminum hydroxide gel (Alum) as an adjuvant. No animals showed positive reaction to both eliciting antigens, IPD-1151T and M-1. On the other hand, a positive reaction in PCA test to eliciting antigen, OVA, was obtained in rats treated with sera of mice sensitized with OVA plus Alum. 3. These findings showed that IPD-1151T had no antigenicity in guinea pigs and mice.

Administration, Oral↗

PubMed1992

[Reproductive and developmental toxicity studies of FUT-187. (I)--Fertility study in rats with oral administration of FUT-187].

FUT-187 was given orally at 20, 120 and 720 mg/kg during the pre-pairing period (63 days prior to pairing in males and 14 days prior to pairing in females) and the pairing period to male and female rats and in the early stage of pregnancy (days 0 through 7 of gestation) to female rats, and the effects of the test compound on male and female reproductive performance and fetal development were evaluated. One male of the 720 mg/kg group died due to treatment. Temporary salivation was observed in males and females in the 20 mg/kg or more groups. In males, increases in the weight of the pancreas in the 120 mg/kg or more groups and the adrenals in the 720 mg/kg group, a depression of body weight gain and decreases in food intake and weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. In females, an increase in the weight of the pancreas in the 120 mg/kg or more groups, a slight depression of body weight gain during the early stage of pregnancy and a decrease in the food intake, and a decrease in the weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. No dose-related changes were found in the estrus, copulation, insemination and fertility indices. In fetuses, decreased numbers of corpora lutea, implantation and live fetuses were observed in the 720 mg/kg group. There were no treatment-related abnormalities in fetal mortality, sex ratio, weights of fetuses and placenta, and external and visceral examinations. Based on these results, it is concluded that the no-effect-dose levels of FUT-187 are less than 20 mg/kg for the parents, 720 mg/kg for reproductive performance and 120 mg/kg for fetal development.

Administration, Oral↗

PubMed1992

[Reproductive and developmental toxicity studies of FUT-187. (V)--Perinatal and postnatal study in rats with oral administration of FUT-187].

FUT-187 was given orally at 20, 120 and 720 mg/kg to female rats during the perinatal and postnatal periods and the effect on dams and offspring were evaluated. One dam during the terminal period of gestation and 3 dams after delivery in the 720 mg/kg group died due to FUT-187. In dams, an increased pancreas weight in the 20 mg/kg or more groups, temporary salivation after dosing in the 120 mg/kg or more groups, and a depression of body weight gain and decreased food intake and weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. In offspring, postnatal death rate in the 720 mg/kg group tended to increased. Decreased body weight gain and delayed appearance of abdominal hair and descent of testis in the 720 mg/kg group were statistically significant in comparison with controls. There were no treatment-related abnormalities in visceral examination, organ weight, skeletal examination, sensory function, behavioral function, learning ability or reproductive function. Based on these results, it is concluded that the no-effect-dose levels of FUT-187 are less than 20 mg/kg for dams, and 120 mg/kg for reproductive performance of dams and offspring development.

Abnormalities, Drug-Induced↗

PubMed1992

Portal hepatic venous shunt via an intrahepatic portal vein aneurysm.

A rare case of portal hepatic venous shunt (PHVS) via an intrahepatic portal vein aneurysm (PVA) is presented. A 66-year-old man was admitted for examination of a mass in the liver. Ultrasonography demonstrated a cystic lesion (15 mm in diameter) at the posterior superior segment of the right hepatic lobe which communicated with the right portal vein (RPV) and right hepatic vein (RHV). Superior mesenteric portography showed a biloculate aneurysm in RPV and PHVS. Color doppler ultrasonography indicated that flow in the tracts entered the aneurysmal cavity from RPV and drained into RHV.

Aged↗

PubMed1992

[EEG findings in hip fracture of the elderly].

Twenty three patients with hip fractures, over 70 years old of age, who had surgical treatment and medical rehabilitation in the Yokufukai Geriatric Hospital were studied to evaluate changes of EEG findings at the time of hip fracture. In all cases, the pre-fracture ambulation status were independent. EEG findings were graded as normal, abnormal (minor degree, moderate-to-severe degree) and states of ambulation after hip fracture were graded good or poor. Good ambulation was defined as total independence and poor ambulation was defined as dependent on assistance or bedridden. In 11 cases of good ambulation, nine had an EEG which was normal or abnormal to a minor degree during pre- and post-fracture periods. In 12 cases of poor ambulation, seven had an EEG which was normal or abnormal to a minor degree in the pre-fracture period, but in the post-fracture period, only two of them were in the same grade and five showed moderate-to-severe abnormal EEG findings. Five out of 12 cases of poor ambulation demonstrated moderate-to-severe EEG abnormality in pre- and post-fracture periods. The present study suggests that the response to hip fractures in the elderly are divided into two types based on their brain functions. One group can maintain good brain function immediately after hip fractures, while the other can not maintain sufficient brain function and lose their ambulatory ability.

Aged↗

PubMed1992

[Clinicopathological study on progressive hereditary nephritis: observations of ultrastructural lesions in the glomerular basement membrane].

Four boys and six girls with progressive hereditary nephritis were studied clinicopathologically. Renal biopsy was performed 16 times in ten cases. Mean age at renal biopsy was 7.3 years old (range 2 to 14 years old). The obtained results were as follows: (1) Montages of electron micrographs were prepared to complete one whole glomerulus. The length of the glomerular basement membrane (GBM) with the characteristic splitting of the lamina densa (Reticulation) was measured and expressed as a percentage of the total length of the GBM. The range of the percentage of the GBM with Reticulation was from 2 to 43% (13.4 +/- 10.0%, mean +/- SD, n = 16). In 4 cases of the 5 cases performed serial renal biopsy, the percentage of the GBM with Reticulation at the 2nd biopsy increased compared with the 1st one. (2) Protein excretion in the urine, serum albumin, alpha 2-globulin, fibrinogen and total cholesterol showed the correlation with the percentage of the GBM with Reticulation. (3) Incomplete ruptures (deep invasion of the epithelial cells into the thickened GBM with Reticulation) were observed. Those suggested that the GBM became fragile associated with the expansion of Reticulation and finally ruptured. Gaps of the GBM were observed 0 to 3 per in one glomerulus (0 to 1.87 per 1mm GBM) and the serial biopsies showed an increase in the number of the gaps as time passed. (4) This study showed the increase in factors activating the blood coagulation such as total cholesterol and fibrinogen, with the expansion of the GBM with Reticulation. And in a nephrotic case, fibrin strands were observed in the glomerular capillary loops and in the GBM. These findings suggest that the activation of the blood coagulation plays a role for the damage of the glomeruli in progressive hereditary nephritis.

Adolescent↗

PubMed1992

[A case of renal vein thrombosis].

A case of renal vein thrombosis in a seventy-five year old female was reported. She complained of severe left flank pain. The symptoms and signs resembled obstruction from a ureteral calculus. The kidney-ureter-bladder X-ray showed a calcification in the pelvic cavity. She was admitted under the initial diagnosis of left ureteral stone. The venous phase of renal arteriography revealed venous collaterals (ureteric vein and gonadal vein). Selective renal phlebography demonstrated a radiolucent area. Warfarin, 6 mg orally daily, has been administered for a year. It has effectively prevented subsequent emboli. This was a rare case of renal vein thrombosis in an old patient, because it was not associated with nephrotic syndrome or thromboembolic state and because it presented as sudden onset.

Aged↗

PubMed1992

[Yolk sac tumor of the testis in children: report of two cases].

Two cases of yolk sac tumor of the testis are presented. The patients were 17 months and 24 months old. The children were inflicted with painless swelling of their left scrotal content. alpha-Fetoprotein levels were elevated at presentation but decreased within normal limits after orchiectomy. Chest X-rays and CT scans were negative. The cases were diagnosed as stage I. Fifty six cases of testicular yolk sac tumor in children have been reported in Japan since 1981. There were no recurrent stage I cases. One patient with stage II and 3 patients with stage III died despite chemotherapy, while three children with stage II or stage III disease survived more than 36 months after a positive response to chemotherapy. We conclude that prepubertal stage I yolk sac tumor is treated best initially by orchiectomy alone. Aggressive chemotherapy has a major role in salvage of stage II or stage III patients.

Child, Preschool↗

PubMed1991

Cloning and expression of a cDNA encoding mouse indoleamine 2,3-dioxygenase.

The depletion of an essential amino acid (aa), tryptophan, caused by interferon-gamma (IFN-gamma)-mediated induction of indoleamine 2,3-dioxygenase (IDO) in mouse allografted tumor cells, has been suggested as a reason for the allograft rejection. To elucidate the mechanism of this IDO induction, attempts were made to isolate cDNA clones encoding mouse IDO. In seven of 25 mouse cell lines, IDO was induced by IFN-gamma, and the highest IDO induction was observed in the case of rectal cancer (CMT-93) cells, which were further stimulated two- to threefold by the simultaneous addition of dibutyryl cyclic AMP (Bt2cAMP). A cDNA library was prepared from poly(A)+ RNA isolated from CMT-93 cells treated with IFN-gamma/Bt2cAMP. The cDNA clones were isolated using the cDNA encoding human IDO as a probe. The mouse IDO cDNA encodes a 407-aa protein with an Mr of 45,639. The deduced aa sequence agreed with partial aa sequences derived from endopeptidase digestion of purified mouse IDO and revealed 61% homology with that of human IDO. Transient expression of the mouse IDO cDNA in COS-7 cells yielded a high level of IDO activity in the cells. Northern hybridization analysis of RNA in CMT-93 cells indicated that IFN-gamma induced the IDO mRNA, and that the level of RNA was increased by simultaneous addition of Bt2cAMP, while Bt2cAMP itself had no effect on mRNA induction.

Amino Acid Sequence↗

PubMed1991

Mononuclear phagocytes: a major population of effector cells responsible for rejection of allografted tumor cells in mice.

To understand the in situ mechanism of immunological response of recipient animals to allografted tumor cells, the types of cells that infiltrated into the rejection site were examined. When Meth A cells (H-2d) were given i.p. to an allogeneic [C57BL/6 (H-2b)] strain of mouse, the tumor cells ceased to grow on the 6th day, accompanied by an i.p. infiltration of leukocytes. The tumor cells were totally eliminated from the peritoneal cavity around the 12th day. The highest cytotoxic activity against Meth A cells was obtained with the peritoneal exudate cells harvested on day 8. On this day, the exudate cells consisted of three populations when examined by flow cytometry, and each was isolated by sorting. Each of them appeared to be homogeneous, and they were morphologically identified as lymphocytes; granulocytes; and medium-sized, mononuclear, less-granular cells. The cytotoxic activity was confined exclusively to the last population. The effector cells (H-2b) were cytotoxic against not only Meth A cells (H-2d) but also concanavalin A-stimulated allogeneic spleen cells [C3H/He (H-2k), CBA/N (H-2k), A/J (H-2a), BALB/c (H-2d), and DBA/2 (H-2d) strains of mouse]. The effector cells were totally inert against concanavalin A-activated syngeneic spleen cells [C57BL/6 (H-2b) and C57BL/10 (H-2b) strains of mouse]. The effector cells were phenotypically (Thy-1.2- CD3- Lyt-1- Lyt-2- L3T4- immunoglobulin- asialo GM1-), morphologically, and functionally distinct from cytotoxic T cells, natural killer cells, and lymphokine-activated killer cells but were adherent mononuclear phagocytes.

Animals↗

PubMed1991

Induction of indoleamine 2,3-dioxygenase in tumor cells transplanted into allogeneic mouse: interferon-gamma is the inducer.

Tryptophan depletion observed during induction of indoleamine 2,3-dioxygenase (IDO) in cultured cells has been suggested to involve a mechanism identical to that employed in self-defense against inhaled microorganisms and tumor growth. We recently reported that a dramatic induction of IDO occurred in i.p. transplanted tumor (Meth-A) cells undergoing rejection from allogeneic mice (C57BL/6), and that soluble factor(s) released from infiltrated host cells was responsible for the IDO induction. Here we report on the characterization of the soluble factor. To assay the factor, we used a 35 mm special culture dish (Transwell), which consisted of two wells divided vertically with a membrane (0.4 micron pore). Host cells (mainly lymphocytes) that infiltrated into the transplantation loci were cultured in the upper well, and untreated Meth-A cells in the lower well. With this in vitro system, the membrane-permeable factor, released by the host cells (upper well), induced IDO in the tumor cells (lower well). The culture superna tants, obtained by centrifuging the culture media from the upper and lower wells, contained the IDO inducer. The inducer activity was completely neutralized by the addition of antibody against interferon-gamma (IFN-gamma) but not by antibody against IFN-alpha/beta. The concentration of IFN-gamma in the medium after 1-day culture with a Transwell culture dish was found to be 2-3 U/ml based on the neutralization curve with the antibody. At this concentration, recombinant IFN-gamma induced IDO in Meth-A cells to the same extent as the inducer in the culture medium. These observations indicate that the in vivo factor for IDO induction in the allografted tumor cells is IFN-gamma.

Animals↗

PubMed1991

C3 deposition in IgA nephropathy in children and adolescents.

The aim of this study was to assess the significance of C3 deposition in IgA nephropathy in children and adolescents. One hundred and two patients aged 5-21 years (57 male and 45 female) were studied. The findings of C3 deposition were classified into 8 groups by immunofluorescent (IF) pattern and intensity as follows: group MC3+ (N = 12): mesangiocapillary pattern and 3+ in intensity; group MC2+ (N = 13): mesangiocapillary and 2+; group MC1+ (N = 4): mesangiocapillary and 1+; group M3+ (N = 11): mesangial and 3+; group M2+ (N = 24): mesangial and 2+; group M1+ (N = 18): mesangial 1+; group S (N = 12): only segmentally positive; and group N (N = 8): negative. Histological changes were scored semiquantitatively as an activity index (cellular proliferation, necrosis, interstitial cell infiltration, and cellular crescents) and a chronicity index (mesangial sclerosis, segmental and global glomerular sclerosis, fibrous crescents, adhesion and tubulo-interstitial change). IF findings were scored semiquantitatively and laboratory findings were also studied. The following results were obtained: 1) The scores of total activity index in MC groups were higher than in the M, S or N groups, and the greater the degree of C3 deposition, the higher the score; 2) Such result was not evident in the chronicity index; 3) High IF scores of IgG and IgM were found in the MC3+ and MC2+ groups; 4) Hematuria was more severe in MC3+ and MC2+ than in other groups, and proteinuria was more prominent in the MC than other groups. Thus the degree of C3 deposition was parallel with histological activity and urinary findings.

Adolescent↗

PubMed1991

C3 deposition in serially biopsied children with IgA nephropathy.

Twenty-five children with IgA nephropathy were studied by serial renal biopsy to investigate C3 deposition. The children were classified into three groups according to the immunofluorescent (IF) course of C3 deposition: group I (N = 9): unchanged or slightly decreased; group II (N = 4): changed to segmental deposition; and group III (N = 12): changed to negative deposition. Histological changes were scored semiquantitatively as an activity index (cellular proliferation, necrosis, interstitial cell infiltration and cellular crescents) and a chronicity index (mesangial sclerosis, segmental and global glomerular sclerosis, adhesion, fibrous crescents and tubulo-interstitial change). The IF findings were scored semiquantitatively and laboratory data were also studied. The following results were obtained: 1. Normal urinalysis was often observed in group III; 2. The IF scores of IgA and IgG were decreased at the second biopsy in all groups, most notably in group III; 3. The activity indices at second biopsies were decreased in all groups, most notably in groups II and III, consistently with our previous study which showed that C3 deposition increases in accordance with histological activity; 4. The chronicity index was unchanged in all groups and C3 deposition did not reflect histological chronicity. Thus, this study indicates that C3 deposition occurs as the disease progresses and reflects histological activity.

Adolescent↗