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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 685 records · Page 38Linked to original sources

Effects of chronic, urea-induced osmotic diuresis on kidney weight and function in rats.

To study the effects of chronic osmotic diuresis which were not associated with hyperglycaemia on the rat kidney, osmotic diuresis was induced by i.v. infusion of urea. A 5 mol/l urea solution was continuously infused at a rate of 100 ml.kg-1 x day-1 on the basis of body weight on day 0. Duration of infusion was 2, 6, 10 or 14 days. Control rats received continuously infused Ringer's solution. Urea-treated groups developed osmotic diuresis (urine flow = about 0.04 ml.min-1 x 100 g body weight-1) comparable to that in rats with experimental diabetes mellitus induced by i.v. streptozotocin (55 mg/kg), however urea-induced osmotic diuresis was not associated with blood glucose level increases. Compared with their controls, rats receiving urea for 2-14 days had markedly increased kidney weight. Rats receiving urea for 10 days showed greatest kidney weight increase, 0.565 +/- 0.044 g/100 g body weight (mean +/- SD), representing a 53% increase compared with the control (0.369 +/- 0.034 g/100 g body weight). Kidney weight was associated with increases in kidney protein content. In contrast, none of control kidney weight values differed significantly from day 0 values (= normal rats; 0.387 +/- 0.028 g/100 g body weight). Creatinine clearance values in urea-treated groups were also higher than those in controls. The maximum value, 0.65 +/- 0.17.ml-min-1 x 100 g body weight-1, was recorded in the 14-day group and was significantly higher than the corresponding control value (0.34 +/- 0.07 ml.min-1 x 100 g body weight-1) (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Refined mapping of eight cosmid markers on human chromosome 22.

Eight cosmid clones were regionally assigned to small subregions of chromosome 22 by hybridization with a total of 22 somatic cell hybrids. One cosmid was localized to the proximal part of 22q which contained the region commonly deleted in the DiGeorge syndrome. Seven cosmids showing restriction fragment length polymorphisms were localized to the telomeric region distal to the MB locus, which was reported to be frequently deleted in sporadic meningioma. These cosmids, when finely mapped and ordered, are considered useful for the identification of genetic alterations on this chromosome arm.

Chromosome Mapping↗

Predictive factors for postoperative recurrence of hepatocellular carcinoma.

BACKGROUND/AIMS: The survival rate for hepatocellular carcinoma after hepatectomy remains unsatisfactorily low because of the high recurrence rate. The purpose of this study was to elucidate predictive factors for postoperative recurrence of hepatocellular carcinoma. METHODS: Univariate analysis and a multiple regression model were used to retrospectively determine the factors potentially related to recurrence in 98 patients with hepatocellular carcinoma who had undergone curative hepatic resection. RESULTS: DNA diploidy, absence of alcohol abuse, and absence of vascular invasion were determined to be independent favorable predictive factors using a multivariate analysis with Cox's proportional hazards model. A predictive index was developed using these three factors according to the following equation: 1.486 x (O = DNA diploidy or 1 = DNA aneuploidy) + 1.138 x (O = absence or 1 = presence of alcohol abuse) + 0.946 x (O = absence or 1 = presence of vascular invasion). This index was used to classify the patients into two groups with good or poor prognosis. The median time for disease recurrence for the two groups was 24.1 and 9.2 months, respectively (P < 0.001). CONCLUSIONS: The results may be useful in the determination of treatment strategies and postoperative follow-up schedules and in the design and analysis of future clinical trials of therapy for hepatocellular carcinoma.

Aged↗

Two-dimensional demonstration of myenteric nerve plexus: application for pseudo-Hirschsprung's disease.

The use of two-dimensional demonstration of myenteric nerve plexus for the morphological estimation of pseudo-Hirschsprung's disease is introduced. By fluorescent immunohistochemistry for S-100 protein on flat-mounted frozen sections, a decrease in the amount of ganglionic plexuses in the small intestinal segments in cases of pseudo-Hirschsprung's disease was able to be distinguished from normoganglionic plexuses in control cases. Moreover, a morphological difference between the two types of cases was clearly demonstrated. This method may be an indispensable tool in the reliable diagnosis of pseudo-Hirschsprung's disease.

Female↗

Structural requirements for the biological activity of enterostatin.

A series of enterostatin analogues were tested to investigate the minimal structure required for activity to suppress the intake of high-fat (HF) diets. The dose-response curve to intracerebroventricular (ICV) enterostatin was U-shaped (maximal inhibition at 1 nmol). Removal or modification of the N-terminal valine from enterostatin (Val-Pro-Asp-Pro-Arg) abolished activity, as did C-terminal amidation. The tripeptide (Pro-Asp-Pro) and the cyclo-diketopiperazine cyclo-Asp-Pro retained activity whereas the linear Asp-Pro dipeptide was inactive. In rats adapted to a three-choice macronutrient diet, cyclo-Asp-Pro specifically inhibited fat intake and had near maximal inhibition (50%) at the 0.03 nmol dose. The enterostatin inhibitory effect on fat intake may reside in the cyclo-diketopiperazine molecule, cyclo-Asp-Pro.

Amino Acid Sequence↗

In vitro mutagenesis of growth hormone receptor Asn-linked glycosylation sites.

Site-directed mutagenesis was used to replace asparagine (Asn) residues with glutamine (Gln) at the five potential N-linked glycosylation sites located at positions 28, 97, 138, 143, and 182 in the extracellular domain of the porcine growth hormone receptor (pGHR). These mutated pGHR cDNAs were stably expressed in mouse L cells. Single substitution of the Asn residues did not alter growth hormone binding when compared to cells which express native pGHR (KD approximately 1 nM). However, substitution of the five potential Asn-linked sites together (pGHR delta 5) resulted in a 20-fold reduced GH binding affinity (KD = 20 nM). Residues Asn97, Asn138, and Asn182 were apparently glycosylated and upon cross-linking with 125I-labeled pGH migrated as a molecular complex of approximately 130 kDa. Native pGHR and pGHR analogs with substitutions of N28Q and N143Q when cross-linked to 125I-labeled pGH, migrated with a Mr of 138 kDa. The fully deglycosylated cross-linked receptor, pGHR delta 5, migrated as a complex of 108 kDa. Therefore, each carbohydrate moiety contributed approximately 10 kDa to the total molecular mass of the pGHR, in sum contributing 30 kDa to the total Mr of the glycosylated pGHR. pGHR delta 5 was able to internalize nearly all the bound 125I-labeled pGH within 10 min, whereas native pGHR and individual Asn substituted pGHR analogs internalized 25% of bound 125I-labeled pGH at 10 min. Also, mutagenesis of the pGHR five potential Asn-linked glycosylation sites, either singly or together, did not alter the ability of GH to induce tyrosine phosphorylation of a 95-kDa protein. Together, the results indicate that three of the five pGHR Asn residues are apparently glycosylated and are necessary for maintenance of a high affinity GH binding site and for GH internalization. However, glycosylation of the pGHR is not critical for eliciting tyrosine phosphorylated proteins following the GH/GHR interaction.

Amino Acid Sequence↗

Delayed myelination in a patient with 18q- syndrome.

A Japanese boy with the typical manifestations of 18q-syndrome and delayed myelination on magnetic resonance imaging is described. Cytogenetic investigation revealed a deletion at 18q21.3. Three serial magnetic resonance images demonstrated that myelination in the central nervous system was delayed except for the corpus callosum and brainstem. This pattern of delayed myelination appears to be peculiar to the 18q- syndrome. Because the gene for myelin basic protein has been localized to the distal end of the long arm of chromosome 18, we speculate that the abnormal myelination in our patient was partly due to the failure of expression of the myelin basic protein gene.

Brain↗

Tumor detection by radioimaging of hepatic radiozinc--correlation with metallothionein content.

In order to determine if the radioimaging of the level of hepatic metallothionein (MT) is able to detect malignancy, we performed, using 45Zn, a trial to measure MT levels in the liver of experimental tumor-bearing mice and rats. The distribution of 65Zn in the livers of the mice and rats increased with s.c. transplantation of Ehrlich carcinoma and ascites hepatoma 7974F, respectively. A Sephadex G-75 elution profile of the cytosol fraction of the liver showed that the elevation of 65Zn level was due to elevation of the MT level. At 2 days after tumor transplantation in mice, the 65Zn-image demonstrated elevation of the hepatic MT level, while 67Ga-citrate, which is currently utilized, could not image the tumor at such an early period of growth. These results suggest that hepatic MT is a useful marker for the detection of malignancy at the early stage.

Animals↗

Diagnosis of pelvic endometriosis by magnetic resonance imaging using "fat-saturation" technique.

OBJECTIVE: To assess the usefulness of fat-saturated magnetic resonance (MR) imaging for detecting small endometrial implants. DESIGN: Prospective evaluation by conventional and fat-saturated MR imaging. SETTING: Shimane Medical University Hospital, Izumo, Japan. PATIENTS: Fifty-one consecutive patients with clinically suspected pelvic endometriosis. INTERVENTIONS: Magnetic resonance images < 2 weeks before laparoscopy or laparotomy. MAIN OUTCOME MEASURE: The location, number, and size of lesions. RESULTS: Surgery revealed a normal pelvis in 5 patients, endometriosis in 44 (42 with pigmented lesions and 2 with nonpigmented lesions and adhesions), and other cystic lesions in 2. With fat-saturated MR imaging, overall sensitivity, specificity, positive predictive value, and negative predictive value were 89%, 71%, 95%, and 50%, respectively. At surgery, 122 pigmented lesions of endometriosis were detected. Conventional MR images indicated lesions of endometriosis in 74. When fat-saturated images were used, 103 lesions were detected. With conventional MR images, only one of 34 small endometrial implants (2 to 3 mm in diameter) was detected. However, the addition of fat-saturated images increased the detection rate to 15 of 34, and all lesions > 4 mm in diameter. CONCLUSION: Conventional MR imaging for detecting small endometrial implants was improved by addition of the fat-saturation technique. Therefore, fat-saturation MR imaging is an acceptable for detecting small endometriomas.

Adipose Tissue↗

Human herpesvirus 7: another causal agent for roseola (exanthem subitum).

Human herpesvirus 7 (HHV-7) was isolated from peripheral blood mononuclear cells of two infants with typical exanthem subitum. The HindIII-, BamHI-, and EcoRI-digested DNA patterns of the isolated viruses were very similar to that of the prototype HHV-7 (RK strain), but different from that of human herpesvirus 6 (HHV-6). During the convalescent period of the first patient, the titer of antibody to HHV-7 rose from < 1:10 to 1:320 by an immunofluorescence antibody test, whereas the titer of antibody to HHV-6 remained < 1:10. In the second patient, who had two independent episodes of exanthem subitum during 2 months, both HHV-6 and HHV-7 were sequentially isolated; seroconversion to HHV-6 occurred during the first episode and to HHV-7 during the second episode. In addition, sera from another 15 children who had episodes of exanthem subitum were serologically tested for antibodies to HHV-6 and HHV-7 by immunofluorescence antibody test. Five of seven patients had seroconversion to HHV-7 just after having typical signs and symptoms of exanthem subitum. These results suggest that HHV-7 is one of the causative agents of exanthem subitum.

Child, Preschool↗

Superinfection of cats with feline immunodeficiency virus subtypes A and B.

The ability of feline immunodeficiency virus (FIV) isolates from subtypes A and B to superinfect cats and cell cultures was tested. Three specific pathogen-free (SPF) cats were first inoculated with 10 ID50 of subtype B virus (FIVBang) and 30 weeks later inoculated with 100 ID50 of subtype A virus (FIVPet). On the basis of subtype-specific PCR analysis, both FIV subtypes were detected in the peripheral blood lymphocytes (PBLs) of two of three cats from 9 to 30 weeks following the second inoculation. Only the first virus was detected in the bone marrow (BM) cells of these two cats until 30 weeks following the second inoculation, at which time the second virus was finally detected in their BM cells. Both cats developed significant virus-neutralizing (VN) antibodies to the second virus by 15 weeks following the second inoculation; but only one cat had high VN titers to the first virus, which remained at the same level even after the second inoculation. The two control cats inoculated with only the second virus developed VN titers specifically to the second virus and were consistently PCR positive for the virus in PBLs and BM cells starting 9 weeks postinoculation. Thus a delay in BM infection with the second virus was observed in the two superinfected cats. In contrast, one of three cats had neither VN antibodies to the second virus nor PCR signal of the second virus in its PBLs, BM, and lymph node throughout the 30 weeks of study and it appeared to be resistant to superinfection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Induction of free radicals and tumors in the kidneys of Wistar rats by ferric ethylenediamine-N,N'-diacetate.

An iron chelate, ferric ethylenediamine-N,N'-diacetate [Fe(III)-EDDA], was found to produce hydroxyl radicals with hydrogen peroxide, as determined by both a deoxyribose degradation test and electron spin resonance. Hydroxyl radical production was inhibited not only by adding hydroxyl radical scavengers and catalase, but also by adding superoxide dismutase to the reaction mixture, suggesting that superoxide anion may be involved in the hydroxyl radical production. A single injection of Fe(III)-EDDA (10 mg Fe/kg body wt) to Wistar rats induced thiobarbituric acid reactivity in the kidneys and liver. Repeated injections of Fe(III)-EDDA (10 mg Fe/kg body wt, twice weekly for 3 months) induced a 40% incidence of renal tumors, including renal adenocarcinoma and renal adenoma, 1 year later. These results suggest that Fe(III)-EDDA is an effective free radical producer in vitro and in vivo and that it may be useful in preparing animal models related to iron-dependent free radical damage. The results support our hypothesis that endogenous or exogenous iron, complexed with certain kinds of chelators, promotes free radical-dependent tissue damage and ultimately leads to carcinogenesis in the affected tissue.

Adenocarcinoma↗

Transvaginal ultrasound imaging, histopathology and endocrinopathy in patients with polycystic ovarian syndrome.

In order to investigate the pathological characteristics of polycystic ovaries diagnosed by transvaginal ultrasound (TVS) in patients with polycystic ovarian syndrome (PCOS) and to investigate the relationship between morphological and endocrine changes in the ovaries, 32 PCOS patients with bilateral polycystic ovaries (> 10 cysts) detected by TVS were studied; 20 ovulatory women served as controls. Ovarian tissues from wedge resection were examined histologically. A comparative histological and TVS study of ovarian morphology was made, and the relationship between the number of small cysts and the endocrine profile was examined. The position and size of small cysts on TVS agreed with those observed histologically. There was a significant correlation between the number of small cysts on TVS and the number of atretic follicles with hypertrophied and luteinized inner theca cells, and thickened ovarian capsules. Numerous atretic follicles and thickened ovarian capsules were observed in 97 and 64% of ovaries respectively, from PCOS patients. In patients with PCOS, a significant positive correlation was noted both between the number of small cysts and delta 4-androstenedione (ASD), and between ASD and the luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio. Furthermore, testosterone, ASD and the number of small cysts on TVS were significantly higher in PCOS patients with ovarian thickened tunica compared to PCOS patients without ovarian thickened tunica. TVS images of ovaries in patients with PCOS correlated with the histopathological and endocrine features. It is suggested that an increase in intra-ovarian small cysts leads to increased production of ovarian androgen, in turn influencing the secretion of gonadotrophin, and is correlated with ovarian capsular thickness.

Adult↗

Purification and characterization of galactocerebrosidase from human lymphocytes.

Galactocerebrosidase was purified about 22,600-fold using several hydrophobic column and gel filtration steps with a 4.8% recovery, from human lymphocytes. Its specific activity was 1.54 x 10(5) nmol/h/mg with tritium-labeled galactocerebroside as the substrate in the taurocholate system. The optimal pH for galactocerebroside was 4.2 in the taurocholate system and 4.6 in the cholate system. The Km values for galactocerebroside were 5 microM in the taurocholate system and 25 microM in the cholate system. The molecular weight of the purified enzyme was estimated to be 90 kDa by sodium dodecylsulfate polyacrylamide gel electrophoresis and gel filtration. However, 70, 50, 40, and 30 kDa bands were also recognized on SDS-PAGE. The N-terminal amino acid sequences of the 70 kDa molecule and the three 50 kDa molecules were the same as that of the 90 kDa molecule. The N-terminal amino acid sequences of the 40 and 30 kDa molecules were unique. A monoclonal antibody raised against the purified enzyme effectively immunoprecipitated galactocerebrosidase activity, and an affinity column prepared with this monoclonal antibody bound the 90 and 50 kDa proteins. These results suggest that this enzyme is probably processed from the 90 kDa protein.

Amino Acid Sequence↗

Central nervous system abnormalities in chromosome deletion at 11q23.

Two Japanese pediatric patients with terminal deletion of the long arm of chromosome 11 are described. Both had the morphological abnormalities of the 11q deletion syndrome, such as prominent epicanthal folds, broad flat nasal bridge with short, upturned nose, short philtrum with carp-shaped mouth, cardiac anomalies and nonprogressive moderate psychomotor developmental delay. Patient 1 is the first case to be reported with 11q deletion with serial magnetic resonance (MR) examinations of cerebral white matter. The initial MR imaging studies demonstrated multiple areas of T1 and T2 prolongation in the cerebral white matter in both patients at the ages of 2 5/12 and 2 1/12 years, respectively. A second MR imaging, performed 1 year after the first in Patient 1, demonstrated slight improvement of the lesions. Neither patient showed clinical deterioration. These results suggest that the lesions were caused by delayed myelination, rather than by demyelination. It is suggested that an unknown factor which is important for myelination is located on the long arm of chromosome 11: perhaps the neural cell adhesion molecule (NCAM).

Abnormalities, Multiple↗

[Microbiological and clinical studies of vancomycin resistant Leuconostoc spp. and Pediococcus spp. isolated from septicemia patients].

We described three septicemia cases in which blood cultures yielded gram-positive cocci identified as Leuconostoc spp. and Pediococcus spp. Patients were three male adults aged 63 to 71 years with severe underlying diseases, pancreatic cancer, esophageal cancer and diabetes mellitus with chronic renal failure. They had fever and chills at the onsets of septicemia with acute obstructive suppurative cholangitis, acute pneumonia, and infection complicated with invasion sites of esophageal cancer contagious to bronchus and subcutaneous tissue. Blood cultures yielded catalase and oxidase negative highly vancomycin-resistant (MIC: 1024 micrograms/ml <) gram-positive cocci showing alpha or gamma hemolysis on blood agar plates. Two cases were polymicrobial infections. In one case with esophageal cancer, clinical symptoms persisted after the start of antimicrobial chemotherapy and the patient died 10 days later associated with complications of esophageal cancer. Leuconostoc lactis, Leuconostoc mesenteroides subsp. dextranicum, and Pediococcus acidilactici wee identified by physiological reactions. These strains were also highly resistant to teicoplanin and fosfomycin, and tolerant to all rested beta-lactams such as benzylpenicillin. This is the first report in Japan to our knowledge on the identification of Leuconostoc spp. and Pediococcus spp. isolated from human infectious diseases.

Aged↗