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Biomedical subjects

H Kuroda

Publications and source records attributed to H Kuroda.

At least 19 recordsLinked to original sources

[Identification of a 3' splice site mutation in the thyroglobulin gene in a case of congenital familial goiter].

A case of congenital familial goiter with impaired thyroglobulin (Tg) synthesis has been reported. The patient is the fifth in a family of six children, three of whom have a goiter. The parents are cousins. The patient's thyroid function tests showed low T4 (1.0 microgram g/dl) and free T4 (0.2 ng/dl), normal or slightly increased T3 (1.8 ng/ml) and free T3 (7.4 pg/ml), and high TSH (57 micrograms U/ml). Serum Tg was 5.1 ng/ml (normal less than 30). The thyroidal 123I-uptake was 59.8% before and 54.5% after perchlorate test. Gel filtration with Bio-Gel A 5m demonstrated the presence of albumin-like protein probably iodinated as a major protein in the thyroid and very low content of Tg which was smaller than the normal 19S Tg. Histologically microfollicular adenoma and negative Tg immunostaining were the dominant findings. Segregation of Tg alleles in the family was studied by Southern blotting with a probe revealing a diallelic RFLP. The results demonstrated that the affected siblings had received the same alleles from both parents and were homozygous for the RFLP. Northern blotting analysis of the goiter RNA with a Tg probe revealed that, whereas the amount of Tg mRNA was normal, its size seemed slightly reduced. PCR amplification of Tg mRNA as six overlapping cDNA fragments demonstrated that a 200bp fragment was missing from the 5' region of the goiter mRNA. Subcloning and sequencing of the cDNA fragments, and of the patient's genomic DNA amplified from this region, revealed that this aberrant splicing is due to a cytosine to guanine transversion at position minus 3 in the acceptor splice site of intron 3. The presence in exon 4 of a putative donor tyrosine residue (tyr 130) involved in thyroid hormone formation provides a coherent explanation of the hypothyroid status of the patient. To our knowledge, this is the first identified mutation responsible for congenital familial goiter in humans.

Adult

The effect of dopamine on rat gastric motility.

The inhibitory mechanism of dopamine (DA) on rat gastric motility was investigated in association with DA receptors. Gastric movement was assessed according to the method of Jacoby et al and was expressed with the system of Ludwick et al. (1968). DA inhibited gastric movement in both the corpus and antrum in a dose-dependent manner. Domperidone, a specific antagonist of DA2 receptor, suppressed DA-induced inhibition of gastric movement in a dose-dependent manner. SCH23390, a specific antagonist of DA1 receptor did not affect DA-induced inhibition of gastric movement. LY171555, a specific agonist of DA2 receptor, inhibited gastric movement in both the corpus and antrum in a dose-dependent manner. SKF38393, a specific agonist of DA1 receptor, did not affect gastric movement. These results indicate that DA plays an important role in the inhibitory regulation of gastric motility, through DA2 receptor but not DA1 receptor.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Possible involvement of Na(+)-H+ exchange in the early phase of reperfusion in myocardial stunning.

Calcium overload during reperfusion after prolonged ischemia has been associated with the Na(+)-Ca2+ exchange system. It has been proposed that the promotion of Na(+)-Ca2+ exchange at reperfusion may be mediated by Na(+)-H+ exchange. To evaluate whether this hypothesis is applicable for stunned myocardium, we examined the influence of temporary suppression of Na(+)-H+ and/or Na(+)-Ca2+ exchange during early reperfusion in isolated rat hearts. Myocardial stunning was produced by global ischemia for 15 min at 37 degrees C. The initial reperfusate was given during the subsequent 10 min after ischemia, and followed by reperfusion with normal Krebs-Henseleit buffer solution for 40 min. Hemodynamic indices, creatine kinase in coronary effluent, and myocardial water content were measured during reperfusion. The functional recovery of stunned myocardium was improved with higher extracellular Na+ concentration and/or lower Ca2+ concentration of the initial reperfusate. Aortic flow recovery of group II (135 mM Na(+)-0.5 mM Ca2+) was 77.0 +/- 3.4%, which was substantially greater (P < 0.05) than that of other groups: group I (control, 135 mM Na(+)-1.5 mM Ca2+), 68.2 +/- 2.4%; group III (25 mM Na(+)-0.5 mM Ca2+), 48.7 +/- 2.9%; group IV (25 mM Na(+)-1.5 mM Ca2+), 21.6 +/- 1.5%. Administration of amiloride, an inhibitor of Na(+)-H+ exchange, in the initial reperfusate ameliorates cardiac damage and improved aortic flow recovery in a dose-dependent manner (10(-6) M, 70.1 +/- 3.7%; 10(-5) M, 77.3 +/- 1.7%; 10(-4) M, 82.0 +/- 2.1% vs control 68.2 +/- 2.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride

Sequence analysis of the 3'-terminal halves of RNA 1 of two strains of barley mild mosaic virus.

DNA complementary to the 3'-terminal halves of RNA 1 of two strains of barley mild mosaic virus (BaMMV) from Japan, BaMMV-Ka1 and BaMMV-Na1, was cloned and sequenced. The sequences start within a single long open reading frame (ORF), and are followed by 337 and 338 3' non-coding nucleotides, for BaMMV-Ka1 and BaMMV-Na1 respectively. The two strains have 88% nucleotide identity in the ORFs and 92% identity in the non-coding regions. The putative ORF products contain the capsid proteins at the C termini, as indicated by amino acid sequence analysis, and two putative non-structural proteins are arranged in the same manner as in RNA 1 of barley yellow mosaic virus (BaYMV). The deduced capsid proteins of BaMMV-Ka1 and BaMMV-Na1 each contain 251 amino acids and have 94% sequence identity, which is compatible with their close serological relationship. Most of the sequence differences between the two capsid proteins are found in the N-terminal region, and might explain their serological differences. Significant sequence similarities of the capsid proteins of the two BaMMV strains (37 and 35% respectively) with that of BaYMV, and their marginal similarities (21 to 26%) to the capsid proteins of aphid-borne or mite-borne potyviruses support the classification of BaMMV and BaYMV as distinct members of the same virus group, which is separate from the group(s) containing aphidborne or mite-borne potyviruses.

Amino Acid Sequence

Unexpected racemization of proline or hydroxy-proline phenacyl ester during coupling reactions with Boc-amino acids.

When L-proline or O-benzyl-trans-4-hydroxy-L-proline phenacyl ester was coupled with Boc-amino acids in dimethylformamide using water-soluble carbodiimide (WSCI) in the presence of anhydrous 1-hydroxybenzotriazole (HOBt) as coupling reagents, extensive racemization was observed at the C alpha of the proline or hydroxy-proline residue. The extent of racemization was measured by HPLC after the coupling with Boc-L-Leu-OH in the presence or absence of HOBt. The extent of racemization increased when HOBt was added to the reaction mixture, but greatly decreased when it was not, indicating that HOBt was needed for inducing racemization. Almost no racemization was observed when the coupling reaction was carried out by the mixed anhydride procedure in tetrahydrofuran or by the carbodiimide method in dichloromethane without using HOBt. In the case of coupling reactions with ordinary L-amino acid phenacyl esters, no racemization was observed. Examination of some model systems yielded sufficient evidence to prove that HOBt is an efficient catalyst for racemizing proline or hydroxy-proline phenacyl ester not only in the stage of cyclic intermediate formation but also in the opening of the ring structure. Thus, the racemization reaction was found to be closely related to the formation of the cyclic carbinol-amine derivative.

Acetophenones

[Retroperitoneal giant malignant fibrous histiocytoma: report of a case].

A case of histiocytoma in a 63-year-old woman with general fatigue is described. Ultrasonography and radiological examination revealed a large mass at the retroperitoneum displacing the right kidney to medial anterior abdomen. Exploration of the tumor with right kidney was done via a transperitoneal approach because the tumor had invaded the hilar fat tissue of the right kidney. The total resected weight was 3,200 g. Histological study showed malignant fibrous histiocytoma, storiform-pleomorphic type. Post-operative chemotherapy consisting of cyclophosphamide, vincristine, adriamycin, dimethyl triazeno-imidazole carboxamide (CYVADIC) was performed and the patient is doing well without any evidence of recurrence or metastasis.

Antineoplastic Combined Chemotherapy Protocols

[Mitral valve surgery for patients after undergoing percutaneous transvenous mitral commissurotomy (PTMC)--investigation on indication of PTMC based on the intraoperative findings].

Ten patients underwent open heart surgery for mitral valve after PTMC because of post PTMC MS (n = 4) and MR (n = 6) out of 150 patients undergoing PTMC in our hospital between June 1987 and October 1991. Intraoperative findings of 4 patients with residual mitral stenosis included severe thickening, stiffening and calcification on anterior and posterior leaflets, commissures and subvalvular apparatus. Mitral valve repair was possible in 2 and mitral valve replacement (MVR) was necessary in the other 2. In all 6 cases who massive mitral regurgitation after PTMC, in repairable tears in the mitral leaflets necessitated MVR. Since in these cases changes in the leaflets were less severe than those of the commissures or subvalvular apparatus, surgical repair could have been possible if open mitral commissurotomy (OMC) was done primarily. Patients selection for PTMC versus OMC based on precise morphological evaluation of mitral valve would reduce occurrence of massive MR resulting in surgical replacement.

Adult

[Development of constrictive pericarditis 20 years after closed mitral commissurotomy--a case report].

Pericardial constriction has emerged as an infrequent but well documented late complication of cardiac surgery. A rare case of constrictive pericarditis developed 20 years after closed mitral commissurotomy was observed. The patient had been treated for the poorly controlled ascites of unknown origin associated with crural edema and mild congestive liver cirrhosis. The long interval between the previous cardiac operation and the clinical manifestation of constriction made it difficult to establish the diagnosis. Extensive resection of the calcified pericardium through a median sternotomy with cardiopulmonary bypass standby relieved the ascites and crural edema.

Female

[Initial and follow-up results of PTCA and PTMC].

On the bases of the initial and follow-up results of patients who underwent percutaneous transluminal coronary angioplasty (PTCA) and percutaneous transvenous mitral commissurotomy (PTMC), the proper applications of these interventional therapies were discussed. The efficacy of PTMC on valvotomy was comparable to open mitral commissurotomy and the procedural safety was noticed. Our results supported the use of PTMC for patients with plicable mitral valve. Despite the good and acceptable results of elective PTCA, low initial success rate and high incidence of major cardiac events including mortality was noted in the group of urgent PTCA for patients with multivessel lesions. The urgent use of PTCA for refractory unstable angina should be restricted to selected patients without high-risk multivessel lesions.

Angioplasty, Balloon, Coronary

Long-term cultured neurons from rat suprachiasmatic nucleus retain the capacity for circadian oscillation of vasopressin release.

We have developed a dissociated suprachiasmatic nucleus (SCN) cell culture system in order to begin a cellular analysis of the mammalian circadian oscillator. Monolayer-cultured neurons prepared from the SCN regions of 1-day-old rats were maintained in serum-free culture medium for 3-4 weeks and then perfused. In 12 out of 40 wells, a circadian oscillation of vasopressin release persisted for at least 4-5 cycles until the end of the perfusion period with no damping of the amplitude. This finding suggests that cultured SCN neurons retain the capacity for circadian oscillation for a long time, and should provide a useful model for the analysis of a mammalian circadian system at the cellular level.

Animals

Different drug sensitivity in two neuroblastoma cell lines established from the same patient before and after chemotherapy.

Drug resistance is one of the major impediments to the treatment of advanced neuroblastoma. Two neuroblastoma cell lines established from the same patient before (KP-N-AY) and after (KP-N-AYR) chemotherapy are described. Both cell lines were established from bone-marrow metastases of a 2 1/2-year-old patient with stage IV neuroblastoma. Chromosomal analysis, catecholamine assessment and the surface membrane phenotype of these cell lines confirmed that the tumors were of neuroblastoma origin. Compared with the KP-N-AY cell line, the KP-N-AYR line had decreased N-myc amplification but increased N-myc expression. An in vitro sensitivity test using a clonogenic assay showed the KP-N-AYR cell line to be 3.0-fold resistant to adriamycin and 2.7-fold resistant to cis-platinum as compared with the KP-N-AY cell line. The expression of the multi-drug-resistance gene (MDR1) was not observed in either cell line by the ribonuclease protection assay. The KP-N-AY cell line revealed only faint MDR1 RNA by the polymerase chain reaction, whereas the KP-N-AYR cell line had no expression of the MDR1 gene. The level of glutathione-S-transferase-pi was significantly higher in the KP-N-AYR cell line than in the KP-N-AY cell line. These findings suggest that the development of clinical drug resistance may be associated with the enhanced glutathione-S-transferase-pi activity but not with MDR1 gene expression.

Antigens, Surface

The cystine-stabilized alpha-helix: a common structural motif of ion-channel blocking neurotoxic peptides.

Neurotoxic peptides from venoms of scorpions and honey bees exhibit a consensus pattern in the two disulfide bridgings related to the sequence portions Cys-X-Cys and Cys-X-X-X-Cys. A revised three-dimensional structure of charybdotoxin, as determined by two-dimensional nmr spectroscopy, confirms that the consensus cystine dislocation generates in all these toxins a common structural element, i.e., the cystine-stabilized alpha-helical (CSH) motif, which may be correlated with their common ion channel blocking activity.

Amino Acid Sequence

Rapid reentrainment of the circadian clock itself, but not the measurable activity rhythms to a new light-dark cycle in the rat.

Experiments were performed to determine if the circadian clock reentrains more quickly to an 8-hour phase shift in light-dark (LD) cycles than does the overt rhythm of activity. To investigate the reentrainment of the clock itself to an 8-hour advance or delay in the LD cycle, the rats were released into constant darkness only two or three days after a shift in LD cycle, and the amount of the phase shift of the clock itself was estimated from where free-running rhythm started by backward extrapolation. If the circadian clock could rapidly reset itself to the new LD cycle, it was predicted that the free-running rhythm of activity would start from near the dark period of the new LD cycle rather than the preceding one. When rats were released into constant darkness three days after the LD cycle was advanced by 8 hours, the activity of the free-running rhythm started near time of dark period of the new LD cycle in all rats (n = 16). When rats (n = 24) were released into constant darkness two days after the LD cycle was advanced by 8 hours, 12 rats started the activity near time of dark period of the new LD cycle, while 9 rats started the activity near time of dark period of the preceding LD cycle. The remaining 3 rats showed the activity of the free-running rhythm near intermediate phase (transient phase). On the other hand, when the rats were not released into constant darkness after LD cycle was advanced by 8 hours, it took 6.4 days for activity rhythm to reentrain to the advanced LD cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Long-term effects of mass screening for neuroblastoma in infancy.

Eighty-four neuroblastoma patients were treated at the Department of Pediatrics, Kyoto Prefectural University of Medicine, during the 27 years from 1962 to 1988. They were divided into three groups: 35 cases in phase 1, the 12 years before mass screening from 1962 to 1974; 22 in phase 2, the 8 years after the onset of mass screening by a qualitative vanillylmandelic acid (VMA) test from 1974 to 1982; and 27 in phase 3, the recent 6 years from 1983 to 1988, after the introduction of mass screening by quantitative assay for VMA and homovanillic acid using high performance liquid chromatography. The clinical findings of these patients were compared for each phase. In Kyoto, the number of annual neuroblastoma cases diagnosed under 1 year of age increased from 0.58 in phase 1 to 1.50 in phase 2 and 3.17 in phase 3. The number of cases over 2 years of age decreased from 2.00 in phase 1 to 0.88 in phase 2 and 1.00 in phase 3. Survival rates increased from 17.1% (six of 35) in phase 1 to 54.5% (12 of 22) in phase 2 and 85.2% (23 of 27) in phase 3. The annual number of neuroblastoma deaths decreased from 2.42 in phase 1 to 1.25 in phase 2 and 0.67 in phase 3. Mass screening for neuroblastoma in infancy has increased the long-term survival rates of neuroblastoma cases treated at this hospital.

Adrenal Gland Neoplasms

[Articulatory evaluation after mesopharyngeal reconstruction with the radial forearm flap].

Soft palate and tonsil (mesopharynx) play an important role on articulation and swallowing. We must take care not to restrict these physiological function when we reconstruct the mesopharyngeal defect after cancer ablation. In order not to restrict the postoperative function of mesopharynx, we take it the more important to preserve the function of the residual tissue rather than to rebuild the lost function. We took notice of pliable nature of the radial forearm flap and tried to reconstruct mesopharyngeal defect in five cases with this flap. We analyzed articulatory function and velopharyngeal closure in these cases, postoperatively. Articulatory function was assessed on the results of intelligibility test with 100 Japanese monosyllables. In four cases out of five, about 70% of syllables were accurately heard. According to the Hirose's standard of speech function after the operation of oral and/or oropharyngeal cancer, those four cases were evaluated also to be excellent. Whether the resection was done beyond the uvula or not, proved not to have anything to do with the postoperative speech intelligibility. Although speech intelligibility once went down immediately after the operation, it improved around six months later. The improvement might be due to the following facts; The forearm flap was cicatrized postoperatively, disturbing the mobility. After the softening of the cicatrix began, the flap gradually recovered flexibility, which enabled surrounding structure to move more smoothly. Articulatory dysfunction was characterized as plosives tend to be misunderstood as nasals or affricates. Concerning nasality, the velopharyngeal closure was examined by fiberscope. Perfect closure was seen in two cases, near-perfect in two cases, and insufficient in one case.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Abnormal structure of the canine oncogene, related to the human c-yes-1 oncogene, in canine mammary tumor tissue.

Cellular oncogenes of genomic DNA in 6 canine primary mammary tumors were screened by Southern blot analysis, using 7 oncogene probes. A canine genomic oncogene related to the human c-yes-1 oncogene was detected as abnormal bands in solid carcinoma genomic DNA digested with EcoRI, HindIII, HindIII-EcoRI, or HindIII-BamHI. Comparison was made between other tumor specimens and control specimens obtained from 4 clinically normal dogs--1 mixed breed and 3 Shiba Inu dogs (the same breed as the dog from which the solid carcinoma was obtained). These abnormal bands were 0.1 to 1 kilobase shorter than the normal gene. However, digestion of genomic DNA obtained from normal WBC of this dog also produced all of the abnormal bands as observed in digested DNA from the solid carcinoma tissue. Therefore, in this dog, the genomic DNA of all somatic cells from the ontogenic stage still had the abnormal sequences related to the human c-yes-1 oncogene, and it is possible that this abnormal structure may have some role (eg, as an initiator) in tumorigenesis or the progression of this tumor.

Animals

[Prospective controlled study of elective sclerotherapy plus oral propranolol for prevention of recurrent bleeding in cirrhotics with recent variceal hemorrhage].

In a prospective, randomized controlled trial, 43 patients with cirrhosis and variceal hemorrhage were allocated after control of the bleeding to treat by elective sclerotherapy alone (n = 23) or by oral propranolol after elective sclerotherapy (n = 20). The dose of oral propranolol was based on a reduction of the resting pulse rate by 25%. The end points of the study were rebleeding or death. Both treatment groups were comparable with respect to origin and severity of liver disease, size of esophageal varices and portal pressure at entry. The mean follow up was 27 +/- 19 months for all patients. Patients treated sclerotherapy alone had more rebleeding (n = 11) did than those in the sclerotherapy plus propranolol (n = 3). The cumulative percentages of patients free of rebleeding 1 and 2 years after inclusion were 77 and 66% in sclerotherapy alone, and 100 and 85% in sclerotherapy plus propranolol; the difference between the two groups was significant. No statistically significant effect on mortality was seen. These data support that oral propranolol after sclerotherapy reduces the risk of recurrent bleeding in cirrhotics treated elective sclerotherapy.

Administration, Oral

[Clinical evaluation of the combination of carumonam and cefotiam in the treatment of complicated urinary tract infection].

The combination of carumonam (CRMN) and cefotiam (CTM), expected to have a broader spectrum of coverage in connection with urinary tract infections, was evaluated for its effectiveness and safety at the Department of Urology, Osaka University Hospital and 17 affiliated hospitals. CRMN and CTM were given together to 109 patients with complicated urinary tract infections (UTI), of whom 65 cases satisfied the "Criteria of UTI Committee for the Evaluation of Drug Efficacy in the UTI (3rd Ed.)", which was modified by adopting the midstream urine data for women. CRMN and CTM were administered by drip or one-shot infusion at a total daily dose of 4 g (equally mixed 1 g plus 1 g each, twice a day) for 5 consecutive days or longer. The overall clinical efficacy rate in the 65 cases of complicated UTI was 72%, estimated by the criteria cited above. The efficacy rate according to the infection type groupings was 72% for the 29 patients in the 1st group, 100% for the 1 patient in the 2nd group, 100% for the 7 patients in the 3rd group, 83% for the 6 patients in the 4th group, 50% for the 14 patients in the 5th group and 75% for the 8 patients in the 6th group. The disappearance rate of both urinary Gram positive cocci and Gram negative bacilli was 83.3%. Fifteen strains appeared after the treatment, only 4 of which were Gram positive cocci. Among the 109 patients treated with CRMN+CTM, no subjective side effects were recorded and the abnormalized laboratory findings observed were: eosinophilia in one patient, increases in both GPT and GOT in one patient, and lowered creatinine clearance in one patient. With a broader spectrum and safe regimen, the combination of CRMN/CTM is recommended as the first choice against complicated UTI.

Adult