Biomedical subjects

S Gotoh

Publications and source records attributed to S Gotoh.

At least 73 records · Page 4Linked to original sources

PubMed1993

An attempt to substitute the cell binding domain of human fibronectin in lambda phage J protein: computer design and expression.

We superimposed hydropathic indexes of the human fibronectin cell binding domain (CBD) on the lambda phage J protein by computer, and substituted 22 amino acids from the fibronectin CBD for a part of the lambda phage J protein. The fibronectin cell binding domain -Arg-Gly-Asp-Ser- (-RGDS-) localizes at the junction of hydrophobicity and hydrophilicity. We selected a similar hydrophobic-to-hydrophilic junction in the J protein region for substitution. This junction corresponds to 150 bp of the PstI fragment of J protein cDNA. We synthesized 150 bp of the relevant PstI fragment that includes the cell binding domain region. The region was then constructed by serial cloning as an expression vector, pJCBD. The vector pJCBD expressed the fused protein named JCBD (M(r) 32 kDa) in E coli XL1-BLUE. The expressed JCBD protein was identified by Western blot analysis in the extract of the pJCBD carrying bacterial lysate using both rabbit anti-lambda phage antiserum and anti-CBD of fibronectin antibody. The JCBD protein appeared to recognize retinoblast cell membrane RGDS-directed receptors, detected by enzyme-linked immuno-sorbent assay and also by binding competition assay with synthetic pentapeptides, Gly-Arg-Gly-Asp-Ser (GRGDS) and Gly-Arg-Gly-Glu-Ser (GRGES). The former competitor inhibited completely fibronectin CBD-dependent binding activity of JCBD, the latter had no inhibitory activity. These results suggest that certain functional proteins engineered by computer design between human fibronectin cell binding domain and lambda phage J protein can be produced.

Amino Acid Sequence↗

PubMed1993

Effects of the molecular weight of hyaluronic acid and its action mechanisms on experimental joint pain in rats.

OBJECTIVES: It has been shown previously that hyaluronic acid (HA) has an analgesic action on bradykinin induced pain in the knee joints of rats. This study further clarifies the effects of the molecular weight of HA and its mechanism of action in the same model using HA of molecular weight 800 to 2.3 x 10(6) daltons and a bradykinin antagonist. METHODS: Bradykinin and the test HA preparations were given to rats by intra-articular injection, and the severity of pain was evaluated by a change in the walking behaviour. RESULTS: HA with a molecular weight greater than 40 kilodaltons produces analgesic effects with a simultaneous or earlier injection. The ID50 values of HA with molecular weight 40, 310, 860, and 2300 kilodaltons were greater than 2.5, 0.6, 0.07, and 0.06 mg/joint respectively. The duration of the analgesic effect of 860 and 2300 kilodalton HA was 72 hours at 10 mg/ml, whereas that of 310 kilodalton HA was short, being undetectable after 24 hours. The analgesic action of HA of 860 kilodaltons was not changed by pretreatment with four saccharide HA and inhibited by pretreatment with HA larger than six to eight saccharides, capable of binding to HA receptors. Further, HA did not interfere with the analgesic action of the bradykinin antagonist, indicating that HA does not directly bind with bradykinin receptors. CONCLUSIONS: HA with a molecular weight of greater than 40 kilodaltons produced an analgesic effect, and HA of 860 and 2300 kilodaltons produced high and long-lasting analgesia. These effects of HA appear to be caused by the interaction between HA and HA receptors.

Animals↗

PubMed1993

[Intra-arterial CDDP and CDDP plus THP-ADM therapy for bladder cancer].

From 1983 to 1988, 20 patients (group A: 3 stage T1, 4 stage T2 and 13 stage T3-4 tumors) with bladder cancer were treated with single injection of CDDP (150-200 mg/body), and 28 patients (group B: 4 stage T1, 9 stage T2 and 15 stage T3-4 tumors) were treated twice with injection of CDDP (100 mg/m2) and THP-ADM (40 mg/m2) mixture from the internal iliac artery. As a rule, one half of the agents was equally given for the both sides, while 75% dose was given to the tumor side to the case with unilateral localized tumors. Then total or partial cystectomy was followed. When residual invasive cancer was pathologically present in operative specimens, patients underwent three to six courses of adjuvant chemotherapy including CDDP. Clinical response rate (CR+PR) to the intra-arterial chemotherapy in group A and B were 39% and 62%, respectively. Pathological response rate (grade 3 and grade 4 by Oboshi and Shimozato classification) were 17% in both group. After total cystectomy, the 2-year cancer specific survival rates of 17 patients in group A and 22 patients in group B were 75% and 59%, respectively. The 2-year cancer specific survival rates of 8 patients in group A and 10 patients in group B with pT3b were 63% and 54%, respectively. No cancer death occurred thereafter in the patients of group A during another three years. The 3-year cancer specific survival rate of 9 patients after partial cystectomy (3 in group A, 6 in group B) was 86%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Differential responsiveness of normal and simian virus 40-transformed human fibroblast cells to interferon-gamma.

The effect of interferon-gamma (IFN-gamma) on epidermal growth factor (EGF) receptor binding and the proliferation of normal and simian virus 40 (SV40)-transformed human fibroblast cells was compared under identical culture conditions. IFN-gamma induced an enhancement of EGF binding to normal cells, whereas it decreased the EGF binding to SV40-transformed cells. Half-maximal enhancement occurred at 72 h after the normal cells were exposed to 10 U/ml of IFN-gamma, and maximal stimulation was obtained at about 10(2) U/ml of IFN-gamma at 72 h. On the other hand, half-maximal reduction was observed for SV40-transformed cells at less than 10 U/ml of IFN-gamma at 72 h, and maximal reduction was obtained at around 10(3) U/ml of IFN-gamma at 72 h. Scatchard analysis indicated that the number of EGF binding sites of normal and SV40-transformed cells was calculated to be 1.6 x 10(5) and 0.88 x 10(5) per cell, respectively, and was little altered by IFN-gamma treatment. The dissociation constant (Kd) of normal cells, however, decreased from 4.5 nM (control) to 2.0 nM (IFN-gamma-treated), while the Kd of SV40-transformed cells increased from 3.6 nM (control) to 17.0 nM (IFN-gamma-treated). The immunoprecipitation of 125I-labeled EGF-bound EGF receptors with anti-receptor antiserum indicated that a 72-h IFN-gamma treatment did not induce a conformational alteration in the EGF receptors of both normal and transformed cells. The DNA synthesis of normal cells was enhanced by EGF, and IFN-gamma treatment potentiated the effect of EGF on DNA synthesis, probably due to the increased binding affinity of EGF to the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Transformation, Viral↗

PubMed1992

Comparison of Ki-ras gene mutation among simultaneously occurring multiple urethan-induced lung tumors in individual mice.

Mouse lung tumors were induced in C57BL/6J(female) x A/J(male) F1 mice by a single s.c. injection of urethan. About 6 months later, multiple small-sized lung tumors were detectable in almost all mice. After a further 6 months, some of these tumors became larger than the rest. We examined whether there were any mutational differences among multiple lung tumors in a single mouse. Direct DNA sequencing of a separately amplified Ki-ras gene by polymerase chain reaction (PCR) was carried out with 25 DNA samples from multiple tumors in four mice. Twenty-four of 25 tumors (96%) had mutations at the codon 61 of the Ki-ras gene. The major mutations involved were either AT to GC transition (44%) or AT to TA transversion (44%) at the second base of codon 61. We compared the types of these gene mutations among the tumors from each of two mice from two different groups of siblings and then compared the two groups. Interestingly, in the first group of siblings, we detected CTA in 5/6 tumors in the first mouse and again CTA in 4/6 tumors in the second one. In the second group of siblings, we detected CGA in 5/7 tumors in one mouse and CGA again in 3/5 tumors in the second mouse. These results show that the pattern of Ki-ras codon 61 mutations in urethan-induced lung tumors is similar in tumors developing in siblings, suggesting that host factors have an effect on the carcinogen-induced mutational pattern. There was no major mutational difference between small and large tumors. The results suggested that other event(s) in addition to the mutation of the Ki-ras gene might play a role during the development of large-sized tumors.

Amino Acid Sequence↗

PubMed1992

Accumulation of cardiac lipofuscin depends on metabolic rate of mammals.

The accumulation of lipofuscin, an important phenomenon during aging, suggests that the sexual maturity (puberty) of mammals is a starting point of the aging process. The rate of cardiac lipofuscin accumulation was not correlated linearly with maximum life span of mammals, but the correlation was a power function of the maximum life span. The rate of lipofuscin accumulation statistically correlated with the specific metabolic rate, and inversely correlated with the brain weight of mammals. The first appearance of lipofuscin showed a good correlation with the brain weight. However, the slope of the line was different between primates and domestic and laboratory animals. From these results, it is suggested that the accumulation of cardiac lipofuscin is dependent on the specific metabolic rate of mammals.

Aging↗

PubMed1992

Pediatric brain stem infarction caused by a basilar and vertebral artery occlusion: case report.

Basilar and right vertebral artery occlusion, which caused a brain stem infarction, occurred in an 11-year-old boy. There have been nine previous cases of basilar artery occlusion with steno-occlusive lesion in the vertebral artery. It is suspected that dissection of the vertebral artery at the atlantoaxial level and a gradual progression of arterial dissection to the basilar artery were the major causes of this infarction.

Brain Stem↗

PubMed1992

[Adjuvant chemotherapy for invasive bladder cancer. Multicenter study].

During 2 years and 10 months from November 1985 to September 1988, 50 patients with invasive bladder cancer (pT2-4, pN0-2, M0) were treated with total cystectomy followed by adjuvant combination chemotherapy including cis-platinum. In addition, so-called immunopotentiator (OK-432) and Kanpo (Juzentaihoto: TJ-48) were given to the patients in a random fashion to evaluate whether or not these agents had any significant effect on patients' prognosis. The 3- and 5-year survival rates for 48 evaluable patients were 71% and 67%, respectively. Histologic grade of primary tumors and number of cycles of adjuvant chemotherapy administered had a significant correlation to patients' survival: patients with grade 2 anaplasia had a better 3- and 5-year survival rates than those with grade 3 anaplasia, and patients receiving 3 or more cycles of chemotherapy had a better 3-year survival rate than those with 2 or less cycles. pT and pN categories also affected patients' survival, though not statistically significant. Administration of OK-432 or TJ-48 and pre-operative treatment such as irradiation and intra-arterial chemotherapy had no favourable effects on the survival. Side effects of the adjuvant chemotherapy were minimal to moderate and more than 70% of the patients tolerated at least 3 cycles of chemotherapy. It is likely that adjuvant chemotherapy, when given in a post-operative setting, should be repeated at least 3 cycles or more.

Adult↗

PubMed1992

Measurement of serum IgE antibodies against Japanese cedar pollen (Cryptomeria japonica) in Japanese monkeys (Macaca fuscata) with pollinosis.

IgE antibodies against allergens of Japanese cedar (Cryptomeria japonica, CJ) pollen in the serum of seven Japanese monkeys (Macaca fuscata) with pollinosis were measured by fluorometric indirect enzyme-linked immunosorbent assay (ELISA). All of the monkeys were found to have specific IgE to the crude pollen antigen. The specific IgE levels were well correlated with those determined by the Pharmacia CAP system. IgE antibodies were then assayed with two kinds of purified allergens (Cry j I and Cry j II) by the ELISA. We found that five monkeys had specific IgE to both allergens, although the other two had IgE only to Cry j I or Cry j II; there is different immune responsiveness to the two major allergens in the monkeys.

Allergens↗

PubMed1992

[A study of intraoperative rapid frozen section diagnosis focusing on accuracy and quality assessment].

Accuracy of frozen section (FS) diagnoses was investigated in a consecutive series of 1129 intraoperative consultations. In our series, the correct diagnosis including clinically not serious minor errors was made in 96.9% of the cases. Whereas the accuracy ratio of FS diagnosis for unknown pathologic process decreased to 92.2%. Among all the types of tissues, central nervous system was shown to be the most frequently handled for FS, followed by lung/bronchus, breast, liver/biliary tract, lymph node and so forth. The requesting ratio of FS, on the other hand, tended to be high in the following specialties; neurosurgery (46.5%), thoracic surgery (19.0%), general surgery, (10.0%). Deferred diagnosis with a provisional diagnosis and misinterpretations in histology typing without serious clinical problem accounted for 2.7% and 3.1% respectively. Causes of erroneous diagnoses seemed to be multifactorial, such as inappropriate sampling, diagnosis on poor quality histology sections, lack of clinical information, lack of enough experience in FS practice of pathologists, or a combination of more than two of them, though inevitable cases showing minimal cytological and structural atypia were included. Intraoperative consultation by FS diagnosis is now essential to serve a good quality medication to patients. It is thus necessary that to establish a tight peer review system and also to provide an education program with regard to practice in FS diagnosis particularly for young pathologists.

Frozen Sections↗

PubMed1992

[Usefulness and safety of bunazosin hydrochloride in neurogenic bladder after prolonged administration].

Bunazosin hydrochloride (Ea-0643), a selective alpha 1-blocker, was administered to 14 patients with neurogenic bladder over prolonged periods of time in order to determine its efficacy and safety. Subjective symptoms were classified into 4 grades, and their response assessed after 12 weeks of treatment. The proportion of patients showing improvement by at least one grade was 50.0% for retarded urination, 16.7% for prolonged urination, 25.0% for urinary stream condition, 25.0% for abdominal pressure at voiding, and 28.6% for residual urine. Objective symptoms were also assessed after 12 weeks of treatment, and a statistically significant improvement was recognized in the volume of spontaneously voided urine, the maximum and mean flow rates on uroflowmetry. It should be noted that both of those flow rates had improved significantly only 2 weeks into the treatment. The degree of improvement in subjective and objective symptoms and the degree of general improvement were all higher at week 12 than at week 2 of treatment. Current knowledge of the mechanism of action of this drug, coupled with the observations made in this study, suggests that, once it has improved the urodynamics, it exhibits a sustained effect for prolonged periods of treatment. However, further studies are warranted concerning the mechanisms of the pharmacological action of the drug from a pathological viewpoint. The proportion of patients in whom Ea-0643 was judged to be useful at 12 weeks of treatment was 41.7%, but when the assessment of 'slightly useful' was taken into consideration, the usefulness rate rose as high as 91.7%. Stomatitis was observed in only one case as a side effect of this drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1992

[Dilated cardiomyopathy following alpha interferon therapy of renal tumor with pulmonary metastases: a case report].

We report a case of renal cell carcinoma with pulmonary metastases treated with recombinant alpha interferon and subsequently presenting as congestive heart failure due to a dilated cardiomyopathy. A 66-year-old man presented himself to the department of internal medicine at our hospital with a complaint of persistent cough with sputum on August 27, 1988. Ultrasonogram, computed tomography and angiography showed a right renal cell carcinoma and chest x-ray films disclosed bilateral multiple nodular shadows, probably representing metastases of the renal tumor. After being transferred to our department, the patient underwent the ligation of the right renal artery and vein and the postoperative treatment with recombinant alpha interferon, achieving a complete response for pulmonary metastases and a partial response for the primary region. On February 14, 1990 the patient was admitted to our hospital with a complaint of dyspnea to be diagnosed as congestive heart failure due to dilated cardiomyopathy. The interferon therapy was suspected to have caused the heart disease, and four months after discontinuation of interferon therapy the heart failure symptoms had improved, but hypokinesis of the cardiac wall still persisted. To our knowledge, this may be the first case of alpha interferon-related cardiomyopathy in Japan.

Aged↗

PubMed1992

[Results of surgical repair by muscle flap closure for poststernotomy mediastinitis].

Between 1984 and 1991, 30 patients developed poststernotomy mediastinitis after cardiac or mediastinal operations. Sixteen of these patients were treated with debridement and open drainage or primary closure following mediastinal irrigation (drainage group). Fourteen patients were treated with debridement, and delayed or primary wound closure by the technique of pectoral or rectus abdominus muscle flap mobilization (muscle flap group). The purpose of this study was to compare the results of the different treatment of poststernotomy mediastinitis. Although the pre- and perioperative profile, complications and risk factors for mediastinal infection were the same, the mortality of muscle flap group was significantly lower than that of drainage group (Fisher exact probability test, p < 0.05). Pulmonary function of the patients who received muscle flap mobilization did not decrease from the function before surgery, despite the defect of sternal bony stabilization. We conclude that muscle flap mobilization may be a superior method as the treatment for poststernotomy mediastinitis after cardiac operations, and may not decrease respiratory function of the patients.

Abdominal Muscles↗

PubMed1992

[Adrenal catecholamine releases during hypotension with continuous administration of calcium entry blockers and nitroglycerin].

We investigated the effect of nicardipine and diltiazem on adrenal catecholamine releases, and compared it with the effect of nitroglycerin in dogs. A 35% reduction in mean arterial pressure was achieved and maintained for 45 minutes. The dogs were observed until 60 minutes after the discontinuation of drug infusions. Adrenal catecholamine releases increased during hypotension with continuous administration of nicardipine, diltiazem and nitroglycerin, but they showed no significant differences between each drug. There was no more increase in adrenal catecholamine releases in spite of additional nicardipine administration. These results suggest that Ca2+ antagonist such as nicardipine directly inhibits the catecholamine releases from the adrenal glands.

Adrenal Glands↗

PubMed1992

[Dissecting aneurysm of the posterior inferior cerebellar artery; a case report].

A case of a dissecting aneurysm of the left posterior inferior cerebellar artery caused by giant cell angiitis is presented. A 22-year-old woman was admitted on August 30, 1990, with sudden onset of severe occipital headache and vomiting. Neurological examination on admission only showed severe meningismus. CT scan demonstrated subarachnoid hemorrhage and a small hematoma in the 4th ventricle. A left vertebral angiogram demonstrated that the left posterior inferior cerebellar artery was occluded at the lateral medullary segment. We diagnosed subarachnoid hemorrhage from a dissecting aneurysm. On the day following admission, the patient underwent a left suboccipital craniectomy. The posterior inferior cerebellar artery was enlarged for a distance of about 8 mm and there was typical purplish-red appearance in the dissecting aneurysm. This aneurysm was excised after trapping. The histological diagnosis was primary localized giant cell angiitis without systemic involvement. The etiology of the intracranial dissecting aneurysm is obscure, but this report suggests that cerebral angiitis can be considered as an important factor.

Adult↗

PubMed1992

[A case of a primary neurofibroma of the left ventricle].

A neurogenic tumor of the heart is extremely rare, and previously only 8 cases of malignant schwannoma and 3 cases of neurilemmoma have been reported. The patient of this case was a seven year old boy and referred to our hospital by his school doctor for investigation of IRBBB on screening ECG. The chest-X-ray showed a bulging contour on left ventricular apex. Echocardiography and angiography showed a 4 x 4 cm solid mass in the anterior-lateral wall of the left ventricle near the apex. Thoracotomy was performed and during cardiopulmonary bypass the tumor was successfully removed without involvement of the endocardium. It was not encapsulated. The pathohistological findings of the specimen were compatible with neurofibroma, and S-100 protein was demonstrated immunohistochemically.

Child↗

PubMed1991

Down modulation of N-myc, heat-shock protein 70, and nucleolin during the differentiation of human neuroblastoma cells.

Cultured human neuroblastoma (GOTO) cells were induced to differentiate by dibutyryl cyclic AMP (Bt2cAMP) and/or retinoic acid (RA). A combination of Bt2cAMP (1 mM) and RA (1 microM) yielded the most significant networks of neurites after 3 to 4 days, this being associated with the reduction of N-myc mRNA levels. Next, we examined several cellular genes that were possibly linked with changes in N-myc gene expression under these conditions. Among the genes examined, both nucleolin and a major heat-shock protein (hsp70) mRNAs showed changes concomitant with those in N-myc mRNA levels when induced by Bt2cAMP and RA. Dibutyryl cAMP alone induced several short cellular processes and caused a marked decrease in N-myc mRNA within 2 days. RA alone induced a few long and straight neurites along the longitudinal axis of individual cells and a significant decrease in growth rate but showed neither network formation nor a decrease in N-myc gene expression. These results indicate differential effects of Bt2cAMP and RA on the regulatory mechanisms of both cell proliferation and differentiation and also indicate a possible association of expression of N-myc gene with those of hsp70 and nucleolin genes.

Bucladesine↗

PubMed1991

Immunological tolerance induced by liver grafting in the rat: splenic macrophages and T cells mediate distinct phases of immunosuppressive activity.

In the rat combination DA into PVG, liver grafts are not rejected but induce donor-specific transplantation tolerance. We have examined the immunosuppressive properties of spleen cells from PVG recipients of DA liver grafts at various times post-grafting. The results indicate the development of two phases of cell-mediated suppressor activity, which appear to be mediated by separate spleen cell populations. Mitomycin-C-treated spleen cells taken from animals between 5 and 28 days post-grafting were able to suppress rat mixed lymphocyte reactions (MLRs). These 'early' suppressor cells were glass adherent and absent from populations purified by passage through nylon wool or G10 Sephadex columns. Suppression of MLR by purified glass adherent cells was not specific for either stimulator or responder haplotypes and was blocked by indomethacin. Nylon wool purified T cells were not suppressive at this time. Spleen cell suppressor activity declined to background levels after 35 days post-grafting. However, spleen cells from long-term surviving liver graft recipients (20 weeks or more) were again able to suppress MLR; the 'late' suppressor cells were nylon wool non-adherent and suppression was specific for the donor (DA) MHC type. We conclude that liver grafting in this combination generates early and late phases of suppression among spleen cells, that the early phase is produced by macrophages and mediated by prostaglandins and that the late phase is dependent on allospecific suppressor T cells.

Animals↗