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Biomedical subjects

Y Oka

Publications and source records attributed to Y Oka.

At least 91 records · Page 5Linked to original sources
PubMed2000

Incidence of malignant tumors in patients with acromegaly.

Neoplasms may be one of the systemic complications to which we attribute high mortality in acromegaly. The present study was designed to investigate the incidence of malignant tumors in patients with acromegaly in the Japanese population. In this report, 44 patients (25 men and 19 women) with biochemically proven acromegaly were studied retrospectively and had a total 670 patient years of the duration of acromegaly. We investigated the incidence of malignant tumors. There were 5 patients with malignant tumors (5 in men) in this study (11%). Male patients with acromegaly had nearly a 3.5 times higher ratio of malignancy than expected and this increased cancer incidence was considered significant (P=0.01). There was no significant increase in cancer incidence of either the total patient population or female patients. The malignant tumors were two thyroid cancers and one colon, one gastric and one bladder cancer. It is of note that the colon cancer of one patient was diagnosed 2 years after transsphenoidal surgery even though the levels of serum GH and insulin-like growth factor (IGF-1) were reduced to normal after operation. This preliminary study has suggested that male patients with acromegaly might have a high risk of malignancy and that careful screening for tumors is needed both before and after surgical and medical treatment, even in patients with normalized serum GH and IGF-1 levels.

Acromegaly↗
PubMed2000

Creation and use of a composite polyurethane-expanded polytetrafluoroethylene graft for hemodialysis access.

The Thoratec (Vectra) polyurethane vascular access graft (TPVA) is among the most recent additions to the list of materials used to construct prosthetic grafts for vascular access during hemodialysis. We give the TPVA very high marks, and recognize the utility of such a graft for use in hemodialysis. However, the strong elasticity of this graft can lead to unexpected complications after suturing. We devised a new surgical method using a TPVA-ePTFE (expanded polytetrafluoroethylene) composite graft, substituting the anastomosis section of the TPVA with a portion of ePTFE graft material, and have been able to overcome most of the TPVA's potential problems. We herein describe the technique.

Aged↗
PubMed2000

Transvenous embolization of carotid-cavernous sinus fistula associated with a primitive trigeminal artery--case report.

A 58-year-old female presented with right conjunctival chemosis and right abducens nerve paresis. Cerebral angiography demonstrated a right carotid-cavernous sinus fistula associated with persistent primitive trigeminal artery. The fistula was treated by introducing detachable coils through the transvenous approach, as the detachable balloon was not available. Follow-up angiography performed 14 days after the embolization revealed complete disappearance of the carotid-cavernous sinus fistula due to thrombosis, which was presumably accelerated by the coils. Transvenous coil embolization should be considered as an alternative treatment for high-flow carotid-cavernous sinus fistula, but only if transarterial balloon embolization is not successful or unavailable.

Arteries↗
PubMed2000

Light-sensitive voltage responses in the neurons of the cerebral ganglion of Ciona savignyi (Chordata: Ascidiacea).

Light-responsive behaviors such as siphon contraction (1), phototropism (2), and gamete release (3, 4) have been described in several ascidian species. The pigmented spots around the siphon openers (5), the epithelial cells of the sperm duct (6, 7), and the cerebral ganglion (8) have been suggested to be the photoreceptor candidates underlying these behaviors. However, these arguments have not yet been settled because no direct electrophysiological recordings of light-induced receptor potentials have been reported. In this study, we focused on the cerebral ganglion and performed intracellular recordings from the neurons in the ventral side of the cerebral ganglion in an isolated in vitro preparation of the neural complex in Ciona savignyi. We found that 24% (n = 115) of the recorded neurons showed various types of voltage responses to light stimuli. Almost all (27/28) of the recorded voltage responses were "on" responses that included hyperpolarizing and depolarizing responses and could be categorized into five types, except for a complex response recorded in one cell; the remaining one (1/28) was a depolarizing "off" response. This is the first report of electrophysiological recordings of light-sensitive voltage responses from ascidian cerebral ganglion neurons.

Animals↗
PubMed2000

Genetic analysis of Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy: nucleotide-binding fold-2 mutation impairs cooperative binding of adenine nucleotides to sulfonylurea receptor 1.

To elucidate the genetic etiology of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in the Japanese population, we conducted a polymerase chain reaction-single-strand conformation polymorphism analysis of the sulfonylurea receptor 1 (SUR1) and Kir6.2 genes in 17 Japanese PHHI patients, including a pair of siblings from a consanguineous family. We also analyzed the glutamate dehydrogenase gene for the exons encoding an allosteric regulatory domain of the enzyme. In the SUR1 gene, we identified one frameshift (I446fsdelT) and two missense (R1420C, R1436Q) mutations. None of these mutations were found in control Japanese subjects. Siblings homozygous for the R1420C mutation had a mild form, whereas two patients heterozygous for the I446fsdelT and R1436Q mutations, respectively, exhibited a severe form of PHHI. Functional consequences of these mutations on K(ATP) function were evaluated using 86Rb+ efflux studies in COS-7 cells. SUR1-446fsdelT and SUR1-1436Q did not form a functional K(ATP). Western blot analysis after transient expression in COS-7 cells revealed the expression of SUR1-1436Q protein to be markedly reduced, suggesting SUR1-1436Q to be unstable in these cells. K(ATP)(SUR1-1420C) showed reduced responses to metabolic inhibition by oligomycin and 2-deoxyglucose. K(ATP) channels are under complex regulation by intracellular ATP and ADP. ATP both inhibits and activates these channels. The inhibition is probably mediated through direct ATP interaction with a pore-forming subunit Kir6.2, whereas the activation is likely to be through a regulatory subunit SUR1. There is a cooperative regulation of ATP and ADP binding to SUR1, and this cooperativity may be involved in regulating the K(ATP) channel. In SUR1-1420C, high-affinity binding of ATP to the nucleotide-binding fold (NBF)-1 was indistinguishable from that of wild-type SUR1. However, stabilization of ATP binding to NBF-1 by MgATP or MgADP was impaired, suggesting that this defect may account for impaired K(ATP)(SUR1-1420C) function. This is the first direct biochemical evidence that the cooperativity of nucleotide binding to SUR1 is impaired in a SUR1 mutant causing PHHI. No mutations were identified in the Kir6.2 and glutamate dehydrogenase genes. The genetic etiology of PHHI appears to be heterogeneous. SUR1 mutations may account for no more than 20% of PHHI cases in Japanese patients. Mutations of Kir6.2 and glutamate dehydrogenase genes are likely to be even less common.

ATP-Binding Cassette Transporters↗
PubMed2000

Dexamethasone-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than insulin signal transduction.

Glucocorticoids reportedly induce insulin resistance. In this study, we investigated the mechanism of glucocorticoid-induced insulin resistance using 3T3-L1 adipocytes in which treatment with dexamethasone has been shown to impair the insulin-induced increase in glucose uptake. In 3T3-L1 adipocytes treated with dexamethasone, the GLUT1 protein expression level was decreased by 30%, which possibly caused decreased basal glucose uptake. On the other hand, dexamethasone treatment did not alter the amount of GLUT4 protein in total cell lysates but decreased the insulin-stimulated GLUT4 translocation to the plasma membrane, which possibly caused decreased insulin-stimulated glucose uptake. Dexamethasone did not alter tyrosine phosphorylation of insulin receptors, and it significantly decreased protein expression and tyrosine phosphorylation of insulin receptor substrate (IRS)-1. Interestingly, however, protein expression and tyrosine phosphorylation of IRS-2 were increased. To investigate whether the reduced IRS-1 content is involved in insulin resistance, IRS-1 was overexpressed in dexamethasone-treated 3T3-L1 adipocytes using an adenovirus transfection system. Despite protein expression and phosphorylation levels of IRS-1 being normalized, insulin-induced 2-deoxy-D-[3H]glucose uptake impaired by dexamethasone showed no significant improvement. Subsequently, we examined the effect of dexamethasone on the glucose uptake increase induced by overexpression of GLUT2-tagged p110alpha, constitutively active Akt (myristoylated Akt), oxidative stress (30 mU glucose oxidase for 2 h), 2 mmol/l 5-aminoimidazole-4-carboxamide ribonucleoside for 30 min, and osmotic shock (600 mmol/l sorbitol for 30 min). Dexamethasone treatment clearly inhibited the increases in glucose uptake produced by these agents. Thus, in conclusion, the GLUT1 decrease may be involved in the dexamethasone-induced decrease in basal glucose transport activity, and the mechanism of dexamethasone-induced insulin resistance in glucose transport activity (rather than the inhibition of phosphatidylinositol 3-kinase activation resulting from a decreased IRS-1 content) is likely to underlie impaired glucose transporter regulation.

3T3 Cells↗
PubMed2000

[Insulin resistance and glucose transporter].

Insulin stimulates glucose transport in muscle and adipose tissue by promoting the appearance of GLUT4, the main glucose transporter isoform in these tissues, on the cell surface. Insulin resistance is instrumental in pathogenesis of type 2 diabetes mellitus and involves decreased glucose transport activity in these tissues. No significant differences are observed between the diabetic and non-diabetic subjects in muscle GLUT4 levels. Polymorphism in the GLUT4 gene, which is very rare, has the same prevalence between subjects with type 2 diabetes mellitus and the non-diabetic subjects. The most likely explanation for the insulin resistance is a defect in insulin signaling pathways or GLUT4 intracellular trafficking pathways.

Adipocytes↗
PubMed2000

[Rosiglitazone (BRL-49653)].

Rosiglitazone, a thiazolidinedion antidiabetic agent, improves insulin resistance in patients with type 2 diabetes mellitus. Rosiglitazone binds to PPAR-gamma with high affinity and the in vivo antidiabetic potency of rosiglitazone is correlated with its high biding affinity. In animal models of insulin resistence, rosiglitazone decreased plasma glucose, triglyceride and insulin levels and also prevented diabetic nephropathy and pancreatic islet cell degeneration. In clinical trials in patients with type 2 diabetes mellitus, rosiglitazone, 2 to 12 mg/day (as a single daily dose or 2 divided daily doses), improved glycemic control as demonstrated, by decreases in fasting plasma glucose and HbA1C levels. Rosiglitazone did not appear to increase the risk of hypoglycemia and there was no evidence of hepatotoxicity in pre-clinical trials.

Animals↗
PubMed2000

[Evaluation of hemodynamics in cerebral infarction using MRI with FAIR sequence].

In comparison with 99mTc-ECD SPECT, the usefulness for evaluation of cerebral blood flow by the perfusion images using MRI with FAIR sequence was studied in ischemic stroke patients. Among 27 cases, 15 patients showed lacunar infarctions and 12 patients showed cortical infarctions determined by T2 weighted MR images. FAIR images were obtained as single images at the slice position running through the basal ganglia or corona radiata. The inversion times(TI) were varied, ranging from 800 to 1,400 msec. In 15 patients without definite low perfusions in the SPECT study, FAIR images showed sequentially proxymal arterial branches in early phase and distal arterial branches or capillary beds in the cortical tissues in a late phase as the TI was elongated. Nine of the 12 patients with low cerebral perfusions in the SPECT study showed perfusion defects in FAIR imaging. Five of the 12 patients with a small low cerebral perfusion area in the SPECT study showed a delay of the depiction of cortical arteries along with TI elongation. In 3 patients, ischemic lesions demonstrated by the SPECT study was not shown in the MRI study because of motion artifacts. In conclusion, FAIR imagings are considered to be useful in the evaluation of cerebral flow dynamics in the ischemic stroke patients.

Aged↗
PubMed2000

Constitutively active STAT5A and STAT5B in vitro and in vivo: mutation of STAT5 is not a frequent cause of leukemogenesis.

We recently identified several constitutively active forms of signal transducers and activators of transcription 5 (STAT5) using polymerase chain reaction-driven random mutagenesis followed by retrovirus-mediated expression screening. All constitutively active STAT5 showed constitutive phosphorylation on their tyrosine residues and induced factor-independent growth in a mouse interleukin-3-dependent cell line, Ba/F3. Sequence analysis of these active STAT5 revealed two important mutations: S710F and N642H. The N642H mutation localized in the SH2 domain was able to induce autonomous growth of Ba/F3 cells by itself, whereas S710F in the effector domain was able to induce autonomous growth of Ba/F3 cells in concert with a second mutation including H298R and E150G. Recently, constitutive activation of STAT5 has been reported in patients' leukemic cells and is implicated in leukemogenesis. We attempted to clarify whether leukemic cells harbored activating mutations primarily in STAT5 proteins, and analyzed the sequence of STAT5 derived from 49 leukemic patients. No mutations were found, however, in the regions surrounding S710 and N642 of STAT5A and corresponding residues of STAT5B. We also cloned full-length cDNAs for STAT5s from three patients whose leukemic cells exhibited constitutive tyrosine phosphorylation of the STAT5 protein and expressed the derived STAT5 proteins in Ba/F3 cells. However, none of these clones exhibited constitutive tyrosine phosphorylation or gave rise to FI proliferation of Ba/F3 cells. These results indicate that constitutive activation of STAT5 is a secondary event in most leukemias.

Animals↗
PubMed2000

[A case of adult moyamoya disease progressed after vascular reconstructive surgery].

We report an adult onset patient with moyamoya disease showing acute progress after contralateral vascular reconstructive surgery. A 47-year-old female developed cerebral infarction in the left corona radiata. A magnetic resonance (MR) angiography and a cerebral angiogram revealed severe stenosis extending from the terminal portion of left internal carotid artery (ICA) to the M1 portion. The right ICA showed slight stenosis. We performed direct bypass surgery (STA-MCA anastomosis) on the affected left side. MR angiography 1 month after surgery revealed the progressive stenosis of the C1 portion of the right ICA. While measurement of cerebral blood flow (CBF) showed a slight impairment of vascular reactivity to acetazolamide loading in the region of the right MCA, we continued without vascular reconstructive surgery for the right side because there was no ischemic attack. The patient had a transient sensory disturbance of the left upper extremity 16 months after surgery. MR angiography and a cerebral angiogram revealed more progressive stenosis extending from the right ICA to the M1 portion. CBF study showed a low CBF at rest and a negative response to acetazolamide loading in the region of the right MCA. Direct bypass surgery was performed on the right hemisphere. Follow-up study revealed an increment of rest CBF and improvement of vascular reactivity. We underlined the necessity for careful postoperation observation of progressive contralateral arterial stenosis using MR angiography and CBF study in adult onset patients with moyamoya disease.

Cerebral Angiography↗
PubMed2000

Silastic interposition arthroplasty for osteoarthrosis of the carpometacarpal joint of the thumb.

We performed Ashworth's (1977) silastic interposition arthroplasty for painful osteoarthrosis of the carpometacarpal (CM) joint of the thumb. Recently, however, some unsuccessful cases treated by this method have been reported. We therefore reviewed the results of patients treated by Ashworth's method. We reviewed 16 patients operated on according to the original Ashworth method for osteoarthrosis of the first CM joint. The cases consisted of 8 males and 8 females, ranging in age from 32 to 76 years (average, 59.6 years). The patients were grouped according to Eaton's classification as follows: 1 patient was stage II, 6 were stage III, and 9 were stage IV. All patients were followed postoperatively for 1 to 12.5 years (average, 4.5 years). Twelve patients did not complain of any pain but 3 patients felt slight pain when moving their thumb. However, the degree of pain was much less than that experienced preoperatively. Only one patient complained of severe pain 2 years after the first operation. Her implant ruptured and required additional surgery. All except one showed either an increase or no change in grip strength. The range of motion (ROM) was full in all patients. Implants showed sinking in 3 patients, a partial rupture of the implant edge in 5 patients and a whole body failure in only 1 implant, roentogenographically. In spite of these troubles, only 3 patients complained of an unpleasant feeling and 2 reported slight pain. Implant trouble did not always cause the symptoms. The clinical results of this method were mostly satisfactory.

Adult↗
PubMed2000

Reconstruction of the flexor pollicis longus tendon ruptured, but untreated, during infancy.

We treated 3 patients who had ruptured the flexor pollicis longus (FPL) tendon during infancy and which had not been repaired. A two-stage surgical procedure, using a silicone rod, was performed to reconstruct the tendon, and favorable thumb flexion was obtained. A favorable outcome was obtained, even if the gliding of the silicone rod had been poor after the first stage procedure. When the scar of the tendon sheath is available, it should be used as a pulley. When the tendon sheath has completely disappeared, it should be reconstructed. At the second stage of surgery, the flexor digitorum superficialis muscle of the injured finger can be used as a motor source when the muscle is conserved in good condition because its distal stump adheres to the bone. If the muscle is not in good condition, transfer of the flexor digitorum superficialis muscle of the ring finger should be performed.

Adolescent↗
PubMed2000

[Glucagon].

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Glucagon↗
PubMed2000

[A preliminary study on dihydropyrimidine dehydrogenase activity in breast cancer].

We studied dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS), key enzymes in regulating the pharmacokinetics and chemosensitivity to 5-FU, in 36 breast cancer patients as a control group and 18 patients as a 5-FU group, in which 5-FU was given orally for 2 weeks before surgery at a dose of 200 mg/day. Cancer tissues with adjacent normal tissue were sampled and stored until the assay. The DPD activity and TS amount were determined according to the radio-enzymatic assay and radiobinding assay, respectively. The DPD activity was significantly higher in breast cancer than in the adjacent breast tissue. This finding was observed in T1 and T2, node negative and ER positive breast cancers in the control group as well as in the 5-FU group. The DPD activity in T3 was significantly lower than in T1, and that of the adjacent breast tissue in T3 was significantly higher than in T1; therefore, the tumoral/non-tumoral ratio of DPD activity was significantly lower in T3 than T1. TS was significantly elevated in both groups, without significant differences. The clinical implication of elevated DPD activity in T1, T2, node negative or ER positive breast cancer compared to the respective normal breast tissue activity remains to be studied, because it is still unclear whether or not the tumoral DPD activity regulates the local concentration of 5-FU within the tumor. The amount of TS and DPD activity was not influenced by the oral administration of 5-FU for 2 weeks at the dose of 200 mg/day.

Antimetabolites, Antineoplastic↗
PubMed2000

[Positional cloning of the gene(WFS1) for Wolfram syndrome].

Wolfram syndrome(DIDMOAD syndrome) is an autosomal recessive neurodegenerative disorder characterized by juvenile-onset, insulin-requiring diabetes mellitus and optic atrophy. Other symptoms including diabetes insipidus, neurosensory deafness, urinary tract and neurological abnormalities are often accompanied. In patients, beta-cells are selectively lost from their pancreatic islets of Langerhans. The gene was previously mapped to 4p16.1. By haplotype analysis and recombination mapping in 5 families, we localized the gene within a region less than 250 kb on chromosome 6p. In the region, we identified a novel gene(WFS1) encoding a putative transmembrane protein. Mutations were identified in all affected members of the families and these mutations were associated with disease phenotype. This finding was further confirmed by other investigators and to date, more than 50 mutations were identified in the WFS1 gene from the patients with Wolfram syndrome. The WFS1 gene encodes a protein of 100.3 kDa with 9 to 10 putative transmembrane domains. The protein appears to be important in the survival and maintenance of normal pancreatic beta-cells and neurons. Physiological function of the WFS1 protein and mechanisms by which defective WFS1 lead to the development of Wolfram syndrome need to be clarified.

Cell Survival↗