Biomedical subjects

S Uchino

Publications and source records attributed to S Uchino.

At least 19 recordsLinked to original sources

PubMed1999

Citron, a Rho-target, interacts with PSD-95/SAP-90 at glutamatergic synapses in the thalamus.

Proteins of the membrane-associated guanylate kinase family play an important role in the anchoring and clustering of neurotransmitter receptors in the postsynaptic density (PSD) at many central synapses. However, relatively little is known about how these multifunctional scaffold proteins might provide a privileged site for activity- and cell type-dependent specification of the postsynaptic signaling machinery. Rho signaling pathway has classically been implicated in mechanisms of axonal outgrowth, dendrogenesis, and cell migration during neural development, but its contribution remains unclear at the synapses in the mature CNS. Here, we present evidence that Citron, a Rho-effector in the brain, is enriched in the PSD fraction and interacts with PSD-95/synapse-associated protein (SAP)-90 both in vivo and in vitro. Citron colocalization with PSD-95 occurred, not exclusively but certainly, at glutamatergic synapses in a limited set of neurons, such as the thalamic excitatory neurons; Citron expression, however, could not be detected in the principal neurons of the hippocampus and the cerebellum in the adult mouse brain. In a heterologous system, Citron was shown to form a heteromeric complex not only with PSD-95 but also with NMDA receptors. Thus, Citron-PSD-95/SAP-90 interaction may provide a region- and cell type-specific link between the Rho signaling cascade and the synaptic NMDA receptor complex.

Animals↗

PubMed1999

Postoperative tetany in Graves disease: important role of vitamin D metabolites.

OBJECTIVE: To test the authors' hypothesis of the causal mechanism(s) of postoperative tetany in patients with Graves disease. SUMMARY BACKGROUND DATA: Previous studies by the authors suggested that postoperative tetany in patients with Graves disease occurs during the period of bone restoration and resulted from continuation of a calcium flux into bone concomitant with transient hypoparathyroidism induced by surgery. PATIENTS AND METHODS: A prospective study was carried out to investigate sequential changes in serum levels of intact parathyroid hormone (iPTH), calcium and other electrolytes, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and bone metabolic markers in 109 consecutive patients with Graves disease who underwent subtotal thyroidectomy. RESULTS: Preoperative serum iPTH levels negatively correlated with ionized calcium levels and positively correlated with 1,25(OH)2D or 1,25(OH)2D/25OHD. After the operation, there was a significant decline in levels of ionized calcium, magnesium, and iPTH. Serum iPTH was not detected in 15 patients after surgery. Four of these 15 patients, and 1 patient whose iPTH level was below normal, developed tetany. Preoperative serum ionized calcium levels were significantly lower, and iPTH levels were higher, in the 5 patients with tetany than in the 11 patients who did not develop tetany despite undetectable iPTH levels. The tetany group had significantly lower serum 25OHD levels and higher 1,25(OH)2D levels, and had increased 1,25(OH)2D/25OHD as an index of the renal 25OHD-1-hydroxylase activity than those in the nontetany group. These results suggest that patients with a high serum level of iPTH as a result of low serum calcium levels (secondary hyperparathyroidism) are susceptible to tetany under conditions of hypoparathyroid function after surgery. CONCLUSIONS: Postoperative tetany occurs in patients with secondary hyperparathyroidism caused by a relative deficiency in calcium and vitamin D because of their increased demand for bone restoration after preoperative medical therapy concomitant with transient hypoparathyroidism after surgery. Calcium and vitamin D supplements may be recommended before and/or after surgery for patients in whom postoperative tetany is expected to develop.

Adolescent↗

PubMed1998

Changing trends and prognoses for patients with papillary thyroid cancer.

OBJECTIVE: To analyze differences in the demographic backgrounds, and in treatments, prognosis, and risk factors of patients with papillary thyroid cancer operated on from 1965 to 1990, by dividing them into 3 chronological groups. DESIGN: Retrospective cohort study of 2423 patients with papillary thyroid cancer (tumor size, > or = 10 mm) who underwent curative surgery at the Noguchi Thyroid Clinic, Oita, Japan. SETTING: A center for the treatment of thyroid disease, at which about 1400 thyroid operations are performed per year. PATIENTS: There were 596 patients treated during from January 1, 1965, to December 31, 1973; 964 patients treated from January 1, 1974, to December 31, 1982; and 959 patients treated from January 1, 1983, to December 31, 1990. RESULTS: Of the 2519 patients treated, 96 were excluded from the study because they had undergone noncurative surgery. Therefore, the analyses are based on data for 2423 patients who underwent curative surgery. Three groups were defined as follows: group 1, underwent surgery during the period 1965-1973 (n = 577); group 2, underwent surgery during the period 1974-1982 (n = 924); and group 3, underwent surgery during the period 1983-1990 (n = 922). The mean age of the patients in group 1 was 42.4 years, in group 2, 45.0 years, and in group 3, 47.8 years. The mean tumor size was 30.4 mm, 26.5 mm, and 24.6 mm, respectively, for groups 1, 2, and 3. The 10- and 20-year disease-specific survival rates were significantly improved from group 1 (95.5% and 90.3%, respectively) to group 2 (97.8% and 93.9%, respectively), and the 10-year rate was significantly improved for group 3 (98.2%). In the multivariate analysis, age, sex, tumor size, and gross nodal metastasis were significant predictors of survival for group 1; however, only age and gross nodal metastasis were significant for group 3. CONCLUSIONS: Over time, papillary thyroid cancer has become diagnosed at an earlier stage, but the age of the patients at diagnosis is older. The disease-specific survival rate was significantly improved, mainly owing to earlier treatment, and the change in the risk factor profile for cancer mortality may be due to the changes in the demographic backgrounds and diagnostic and therapeutic modalities. These considerations derived from risk factor analysis should be considered for treating the patient and for the prediction of patient survival.

Adolescent↗

PubMed1998

Gallbladder contraction in biliary atresia: a pitfall of ultrasound diagnosis.

In 3 (9 %) of 34 children with biliary atresia, US revealed gallbladder contraction following an oral feed, given on admission, but not with subsequent feeds. Surgery revealed a Kasai type IIIa biliary atresia with a patent communication between the gallbladder and duodenum. We propose that the bile ducts may initially have been patent, but then gradually became obliterated secondary to inflammation. These cases may explain the development of one type of biliary atresia.

Biliary Atresia↗

PubMed1998

Transiliac catheterization of the inferior vena cava for long-term venous access in children.

In infants and children requiring prolonged, multiple central venous (CV) catheterizations, the superior (SVC) and inferior vena cava may become thrombosed or stenotic, making CV access a difficult problem. Use of the iliac vein may be an acceptable alternative. We report a patient with thrombosis of the SVC in whom the external iliac vein was accessed through a retroperitoneal approach for placement of an implantable port. This technique is easy to perform, and there are no special materials or patient positioning required.

Catheterization, Central Venous↗

PubMed1998

Chronic thyroiditis as a favorable prognostic factor in papillary thyroid carcinoma.

A subgroup of patients with papillary thyroid carcinoma (PTC) also has chronic thyroiditis (CT) as an associated disease of the thyroid. To assess the prognostic value of CT in patients with PTC, we reviewed the histological slides of 2225 patients with PTC who had undergone surgery between 1971 and 1992. Of the 2225 patients, 692 were excluded from the analysis because regional lymph nodes and/or nonneoplastic thyroid tissues were unavailable for histological assessment. The series included 281 patients with CT in nonneoplastic thyroid tissue and 1252 without CT. We performed statistical analyzes by the log-rank test and Cox's proportional-hazard method. Sixty-two (5.0%) of the 1252 patients without CT died of metastatic disease during the follow-up period and the relapse-free 10-year survival rate was 85%. By contrast, only 2 (<1.0%) of the 281 patients with CT died, and their relapse-free 10-year survival rate was 95%. The difference between patients with CT and those without CT in terms of relapse-free and overall survival was statistically significant (p < 0.0001). Risk factors for unfavorable outcome were age 45 years or more, absence of psammoma bodies, and absence of CT (p < 0.0001), followed by vascular invasion (p = 0.0007), male sex (p = 0.0013), and metastasis to regional lymph nodes (p = 0.047). Multivariate analysis indicated that all of these factors with the exception of gender were independent factors in the final model for overall survival. Chronic thyroiditis in the nonneoplastic thyroid of patients with PTC is a powerful prognostic factor for both relapse-free and overall survival.

Adult↗

PubMed1998

Novel point mutations and allele loss at the RET locus in sporadic medullary thyroid carcinomas.

Germline mutations in the RET proto-oncogene have been shown to be the underlying cause of multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Some cases of sporadic medullary thyroid carcinoma (sporadic MTC) are reported to have specific codon 918, 883 and 768 mutations of the RET gene in tumor tissues. We examined RET gene mutations in 40 Japanese cases who had previously undergone surgery for sporadic MTC. DNA extracted from formalin-fixed tumor tissues and corresponding normal thyroid tissues or peripheral blood leukocytes was analyzed for mutations of exon 10, 11, 13, 14 and 16 of the RET gene by DNA sequencing and by mutation-specific restriction enzyme analysis. Germline RET point mutations were found in six of 40 cases (15%), cysteine residues at codon 618 in two, codon 634 in three and valine residue at codon 804 in one, and were newly identified as heritable MTC. Of the remaining 34 sporadic MTC cases, four (12%) had tumor-specific RET point mutations. Two were found in exon 16; one case showed an ATG to ACG (Met to Thr) mutation at codon 918, and the other showed two point mutations, ATG to ACG (Met to Thr) at codon 918 and GCA to GTA (Ala to Val) at codon 919 with loss of the wild-type allele, suggesting that both alleles at the RET locus were altered. The other two were found in exon 13; one case showed a CCG to TCG (Pro to Ser) mutation at codon 766 and the other showed a silent mutation, GTC to GTT (Val) at codon 778 with loss of the wild-type allele. There was no association of sporadic mutations with recurrence or prognosis in patients with sporadic MTC. The low rate of somatic RET mutation at codon 918 in our sporadic MTC suggests that as yet unknown factors may be involved. Genetic alterations in both alleles may have an important role in small fraction of sporadic MTCs.

Adult↗

PubMed1998

[Prognostic effect of PyNPase (pyrimidine nucleoside phosphorylase) activity in breast cancer].

To clarify the clinical significance of PyNPase (Pyrimidine Nucleoside Phosphorylase)/ PD-ECGF activity in breast cancer, we examined the possible correlation of PyNPase activity to clinicopathological features and prognosis in 195 patients with primary breast cancer between January 1992 through December 1993. The mean PyNPase activity of primary breast cancer, assayed by ELISA method, was 140.6 U/ml, which was between that of benign breast disease (18.2) and recurrent tumors (270.9). In histological type of breast cancer, tumors with solid-tubular carcinoma had significantly higher levels of PyNPase activity. The activity of ER negative or aneuploid tumors was higher than that of ER positive or diploid tumors, respectively. And there was a significant relationship between PyNPase activity and proliferative activity determined by S-phase fraction (SPF) or DNA polymerase alpha. These findings suggested that PyNPase activity was associated with the degree of malignancy. As regards prognosis, in lower SPF (< 16%) group, patients with higher PyNPase activity had significantly lower disease--free survival rates, whereas those with higher activity had a favorable prognosis in the higher SPF (> or = 16%) group. The contradiction might be explained by the possibility that 5-FU derivatives were effective only in patients with high SPF and PyNPase activity, as all patients were treated by a regimen containing 5-FU derivatives. We suggest that PyNPase activity is associated with progression and proliferation of breast cancer, and that it may be useful for prediction of prognosis and therapeutic efficacy of 5-FU derivatives.

Adult↗

PubMed1998

Loss of heterozygosity on chromosome 18q in cohesive-type gastric cancer is associated with tumor progression and poor prognosis.

Although loss of heterozygosity (LOH) on chromosome 18q is frequently found in gastric cancer, the clinical significance of this abnormality has not been well documented. We examined LOH on chromosome 18q22-23 in DNA extracted from the tissues of gastric cancer patients using the PCR-based dinucleotide repeat assay with two microsatellite markers, D18S61 and D18S58. We investigated LOH in 100 samples of DNA extracted from formalin-fixed, paraffin-embedded tissues of cohesive-type gastric cancer patients operated on between 1984 and 1993. Thirty-two of 83 informative cases (39%) showed LOH on chromosome 18q22-23 at one or two loci. The LOH correlated significantly with serosal invasion of the tumor (P = 0.004) and hematogenous recurrence (P = 0.035). In 60 cases who were cured, the 5-year survival rate in patients with LOH (54%) was lower than that in patients without LOH (81%; P = 0.019). These results suggest that 18q22-23 LOH in cohesive gastric cancer is associated with tumor progression and a patient's poor prognosis.

Aged↗

PubMed1997

Organization of the blood and lymphatic microvasculature of the gallbladder in the guinea pig: a scanning electron microscopic study.

The organization of the blood and lymphatic microvessels of the gallbladder in the guinea pig is demonstrated by scanning electron microscopy (SEM) of vascular corrosion casts, and SEM of KOH-macerated tissues. In the lamina propria of the gallbladder, there is a dense network of subepithelial capillaries. The network is supplied by the arterioles that come off the arterial plexus located deep in the lamina propria. The network gathers into the postcapillary venules continuous with the collecting venular plexus located immediately below the subepithelial capillary network. The precapillary arterioles are sparsely surrounded by a single layer of circularly oriented extensions of smooth muscle cells. The terminal arterioles are endowed with circularly oriented fusiform smooth muscle cells. The nervous plexus is also noticed along the terminal arterioles. The capillaries are embraced by flat prolongations of pericytes. The postcapillary venules are sparsely surrounded by stellate pericytes and the collecting venules are sparsely surrounded by elongated or branched spindle-shaped, primitive smooth muscle cells which extend their long process in various directions along the vascular wall. The lymphatics are mostly located in the subserosal layer. The tips of the initial lymphatics are closed by endothelial cells, although there are frequently some gaps between them. The thin flaps of the lymphatic endothelial cells overlap or interdigitate with each other. The luminar surfaces of the lymphatics show oval nuclear protrusions, while the abluminal surfaces showed numerous microfolds except for the oval and flat nuclear portions. The lymphatics possess neither smooth muscle cells nor pericytes.

Animals↗

PubMed1997

Male to male transmission of supernumerary nipples.

We report on a father and his son with supernumerary nipples. No male-to-male transmission has previously been described with this trait. This observation confirms that this trait is inherited in an autosomal dominant fashion.

Child, Preschool↗

PubMed1997

Analysis of the glycine binding domain of the NMDA receptor channel zeta 1 subunit.

In an attempt to examine glycine binding domain of the zeta 1 subunit of the mouse N-methyl-D-aspartate (NMDA) receptor channel, we constructed N-terminal or C-terminal deletion mutants of the zeta 1 subunit cDNA and expressed them in Spodoptera frugiperda cells using a baculovirus system. Analysis of binding of a glycine binding site antagonist, 5,7-[3(-3)H]dichlorokynurenate ([3H]DCKA) to the deleted zeta 1 mutants provided the first direct experimental evidence that the regions of N-terminal 282 and C-terminal 102 amino acid residues do not significantly affect glycine binding, and that both the region of approximately 260 amino acid residues preceding the putative transmembrane segment M1 and the region between the segments M3 and M4 are required to form the glycine binding domain.

Animals↗

PubMed1997

Thyroid cancer associated with adenomatous goiter: an analysis of the incidence and clinical factors.

We evaluated the incidence of thyroid cancer in patients with adenomatous goiter and investigated the clinical factors distinguishing patients with occult thyroid cancer, defined as a tumor size smaller than or equal to 10 mm, from those with clinical thyroid cancer, defined as a tumor size larger than 10 mm. Of 835 patients with histologically confirmed adenomatous goiter, 256 (30.7%) also had thyroid cancer, being occult in 137 patients and clinical in 119 patients. There was no correlation between the maximum size of the thyroid cancer tumor and the age of the patient, and the percentage of patients with thyroid cancer in each group was not influenced by age. There were no significant differences in age, sex, the serum concentrations of free triiodothyronine, free thyroxine, thyrotropin, and thyroglobulin, or the urinary iodine creatinine ratio. The frequency of calcified lesions being detected by ultrasonography (US) and/or neck X-ray in the patients with clinical thyroid cancer was significantly greater than that in those with occult cancer at 83% vs 57%, respectively (P < 0.0001). This study disclosed a high prevalence of thyroid cancer associated with adenomatous goiter, and the results suggest that a considerable number of associated carcinomas remain occult. The detection of calcification in the thyroid gland is one of the surgical indications for patients with adenomatous goiter.

Adenocarcinoma, Follicular↗

PubMed1997

Inducible expression of N-methyl-D-aspartate (NMDA) receptor channels from cloned cDNAs in CHO cells.

To develop a drug screening system, we introduced expression vectors carrying the mouse N-methyl-D-aspartate (NMDA) receptor channel epsilon1 and zeta1 subunit cDNAs under the promoter of the Drosophila heat shock protein hsp70 into Chinese hamster ovary (CHO) cells. We selected clonal cell lines by means of RNA blot hybridization and fura-2 fluorometry. One of these cell lines, ZE1-1, optimally expressed the epsilon1 and zeta1 subunit mRNAs when induced by an incubation at 43 degrees C for 2 h. Heated ZE1-1 cells exhibited the NMDA-induced intracellular Ca2+ elevation, whereas unheated they showed no such response. NMDA and L-glutamate, but not alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate, induced an increase in the intracellular Ca2+ concentration. The response to the agonists was marginal in the absence of glycine, and diminished by Mg2+ and NMDA receptor antagonists. Furthermore, exposure to agonists of ZE1-1 cells expressing the epsilon1/zeta1 NMDA receptor channel resulted in the release of lactate dehydrogenase (LDH) activity in the culture medium indicating agonist-induced cell death. NMDA receptor antagonists inhibited the LDH activity release. These results suggest that ZE1-1 cells will provide a useful screening system for novel drugs acting on the epsilon1/zeta1 NMDA receptor channel.

Animals↗

PubMed1997

Arginine-481 mutation abolishes ligand-binding of the AMPA-selective glutamate receptor channel alpha1-subunit.

Arginine-481 is located in the putative agonist-binding region preceding the putative transmembrane segment M1 of the alpha1-subunit of the AMPA-selective glutamate receptor (GluR) channel. This amino acid is completely conserved among GluR proteins. A site-directed mutagenesis study using a baculovirus expression system showed that substitution of glutamate, glutamine and lysine for arginine-481 of the recombinant alpha1-subunit protein abolishes binding to [3H]AMPA completely. The present study provides the first direct experimental evidence that the conserved charged arginine-481 residue is essential, directly or indirectly, for the acquisition of ligand-binding activity by the receptor protein.

Animals↗

PubMed1997

Postoperative tetany in patients with Graves' disease: a risk factor analysis.

OBJECTIVE: There is little information regarding the clinical risk factors for postoperative tetany in patients with Graves' disease. We analysed the risk factors responsible for postoperative tetany by univariate and multivariate analysis in thyroidectomized patients with Graves' disease, and we discuss the mechanisms of hypocalcaemia and tetany after surgery. PATIENTS: The subjects were 1742 consecutive patients with Graves' disease who underwent subtotal thyroidectomy between 1992 and 1994. RESULTS: Univariate analysis of 15 possible risk factors demonstrated that 10 were significant: sex, required operation time, blood loss, preoperative serum calcium level, estimated weight of thyroid remnant, size of goitre, amount of excised thyroid tissue, serum alkaline phosphatase concentration, age at operation and TSH-binding inhibitory immunoglobin (TBII). In multivariate analysis in female patients, the risk factors were: preoperative lower serum calcium level, younger age, higher serum alkaline phosphatase concentration, larger size of goitre and higher value of TBII, in order of decreasing probability of significance. CONCLUSION: These results, combined with previous observations in which a significant decline in serum parathyroid hormone level was found in patients with Graves' disease who suffered postoperative tetany, suggests that postoperative tetany may occur during the period of bone restoration due to antithyroid drug therapy and be due to continuation of a calcium flux bone concomitant with transient hypoparathyroidism induced by surgery. Calcium supplements during preoperative period and/or after surgery may be appropriate for patients who are anticipated to develop postoperative tetany based on these risk factors.

Adolescent↗

PubMed1997

[Bilateral leg ulcers with pathologic evidence of small vessel vasculitis by skin biopsy during hydroxyurea therapy of chronic myelogenous leukemia].

We report a 45-year-old male with chronic myelogenous leukemia (CML) who experienced skin ulcers of the left lateral malleolus and dorsum of both feet. He had been treated with hydroxyurea (HU) for 2 years. His leg ulcers improved after HU was discontinued. Skin biopsy of the ulcerated lesion revealed that the lesion is compatible with small vessel vasculitis, but circulating immune complexes (C1q, anti-C3d antibody) were negative. Although the precise mechanism of the skin ulcer is unknown, we must take into consideration the skin changes were secondary to hydroxyurea therapy in myeloproliferative disorders.

Antineoplastic Agents↗

PubMed1996

Resolution of cirrhosis-related pulmonary shunting in two children with a transplanted liver.

We treated two children with hypoxemia caused by intrapulmonary shunting associated with cirrhosis secondary to extrahepatic biliary atresia. Following orthotopic liver transplantation, digital clubbing and intrapulmonary shunting were resolved, as demonstrated by normalization of room air arterial blood gases, reduction in shunt fraction, and perfusion lung scanning with 99mTc-labeled macroaggregates of albumin. We recommend that early liver transplantation be considered for young subjects with a severe hepatopulmonary syndrome.

Biliary Atresia↗