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Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 163 records · Page 9Linked to original sources
PubMed2000

Experience with freeze-dried PGLA/HA/rhBMP-2 as a bone graft substitute.

We investigated bone induction by recombinant human bone morphogenetic protein-2 in rodents. The purpose of this study was to evaluate the osteoinductive potential of a resorbable bone substitute fabricated from freeze-dried poly(glycolic acid-co-lactic acid) (PGLA) mixed with hydroxyapatite particles incorporated with bone morphogenetic protein-2 in skull defects of rats (FD-PGLA/HA/rhBMP-2). The FD-PGLA/HA/rhBMP-2 composite or as a control, the FD-PGLA/HA by itself were implanted in skull defects (psi 8 mm) of rats. The samples were harvested at 2 or 4 weeks postoperatively and were studied radiographically and histologically. Four weeks after implantation, the FD-PGLA/HA/rhBMP-2 discs were completely replaced by newly-formed bone possessing bone marrow. In contrast, the defects implanted with FD-PGLA/HA were filled only with fibrous connective tissue. The results suggest that the FD-PGLA/HA/rhBMP-2 composite could be an optimum bone substitute with osteoinductive potential and could function as an alternative bone graft material for autogenous bone in humans.

Absorbable Implants↗
PubMed2000

Management of orbital lymphangioma using intralesional injection of OK-432.

AIM: To treat orbital lymphangioma with an intralesional injection of OK-432 (group A Streptococcus pyogenes of human origin). METHOD: A 14 year old boy had a right orbital cystic lymphangioma. The visual acuity in the eye was 20/28. In an initial treatment, 0.02 mg of OK-432, was injected into the tumour after aspiration of the fluid contents, but no effect was seen. The second treatment was performed with 0.04 mg of OK-432. RESULT: 4 months later, the lesion had totally shrunk to fibrous tissue. The side effects were fever, a local inflammatory reaction lasting 3 days, and increased intraocular pressure, which was managed by draining the fluid contents. Visual acuity improved to 20/15, and the visual field defect and restriction of eye movement seen before treatment disappeared. No recurrence was noted 1 year after treatment. CONCLUSION: An intralesional injection of OK-432 shrunk the lymphangioma without functional disturbance and scar in the facial skin. OK-432 may be useful for orbital lymphangioma, but further studies are still warranted to determine efficacy, complications, and the optimal dose for safe treatment.

Adolescent↗
PubMed2000

A K(ATP) channel deficiency affects resting tension, not contractile force, during fatigue in skeletal muscle.

The objective of this study was to determine how an ATP-sensitive K(+) (K(ATP)) channel deficiency affects the contractile and fatigue characteristics of extensor digitorum longus (EDL) and soleus muscle of 2- to 3-mo-old and 1-yr-old mice. K(ATP) channel-deficient mice were obtained by disrupting the Kir6.2 gene that encodes for the protein forming the pore of the channel. At 2-3 mo of age, the force-frequency curve, the twitch, and the tetanic force of EDL and soleus muscle of K(ATP) channel-deficient mice were not significantly different from those in wild-type mice. However, the tetanic force and maximum rate of force development decreased with aging to a greater extent in EDL and soleus muscle of K(ATP) channel-deficient mice (24-40%) than in muscle of wild-type mice (7-17%). During fatigue, the K(ATP) channel deficiency had no effect on the decrease in tetanic force in EDL and soleus muscle, whereas it caused a significantly greater increase in resting tension when compared with muscle of wild-type mice. The recovery of tetanic force after fatigue was not affected by the deficiency in 2- to 3-mo-old mice, whereas in 1-yr-old mice, force recovery was significantly less in muscle of K(ATP) channel-deficient than wild-type mice. It is suggested that the major function of the K(ATP) channel during fatigue is to reduce the development of a resting tension and not to contribute to the decrease in force. It is also suggested that the K(ATP) channel plays an important role in protecting muscle function in older mice.

Animals↗
PubMed2000

Insulin secretion and differential gene expression in glucose-responsive and -unresponsive MIN6 sublines.

We have established two sublines derived from the insulin-secreting mouse pancreatic beta-cell line MIN6, designated m9 and m14. m9 Cells exhibit glucose-induced insulin secretion in a concentration-dependent manner, whereas m14 cells respond poorly to glucose. In m14 cells, glucose consumption and lactate production are enhanced, and ATP production is largely through nonoxidative pathways. Moreover, lactate dehydrogenase activity is increased, and hexokinase replaces glucokinase as a glucose-phosphorylating enzyme. The ATP-sensitive K(+) channel activity and voltage-dependent calcium channel activity in m14 cells are reduced, and the resting membrane potential is significantly higher than in m9 cells. Thus, in contrast to m9, a model for beta-cells with normal insulin response, m14 is a model for beta-cells with impaired glucose-induced insulin secretion. By mRNA differential display of these sublines, we found 10 genes to be expressed at markedly different levels. These newly established MIN6 cell sublines should be useful tools in the analysis of the genetic and molecular basis of impaired glucose-induced insulin secretion.

ATP-Binding Cassette Transporters↗
PubMed2000

HLA-DRB genotypes in Japanese patients with renal cell carcinoma.

OBJECTIVES: Several clinical features, such as the spontaneous regression of some renal cell carcinoma (RCC) metastases after nephrectomy, suggest immune involvement in tumor destruction. PATIENTS AND METHODS: We investigated the role of genetic variation at the HLA class II loci in RCC by analyzing the HLA-DR antigen and HLA-DRB1, DRB3, DRB4 and DRB5 alleles in 55 patients using the polymerase chain rection. RESULTS: No statistically significant differences were observed in the frequency of the HLA-DR antigen or HLA-DRB3, DRB4, or DRB5 genes between the patients and a healthy control group. On the other hand, the HLA-DRB1*0403 and *1202 alleles were significantly more frequent in the patients than in the controls (p < 0.001 and p < 0.01, respectively). CONCLUSION: RCC might be linked to these two alleles in Japanese patients.

Adult↗
PubMed2000

Doppler resistive index in benign prostatic hyperplasia: correlation with ultrasonic appearance of the prostate and infravesical obstruction.

OBJECTIVE: This study was designed to characterize the resistive index (RI) of prostatic blood flows obtained by transrectal power Doppler sonography (TRPDS) in benign prostatic hyperplasia (BPH). METHOD: In 140 patients with lower urinary tract symptoms, the RI was measured using TRPDS and compared with age and planimetric parameters of the prostate obtained by conventional transrectal sonography. In addition, the RI was related with pressure flow studies. RESULTS: The RI was significantly higher in patients with BPH (0.72+/-0.06, p<0.0001) than those with a normal prostate (0. 64+/-0.04). Although the RI correlated significantly with age and all prostatic planimetric parameters, multiple regression analysis revealed that age and presumed circle area ratio were independent predictors for RI. The RI was also higher in patients with infravesical obstruction than those without (0.74+/-0.06 vs. 0. 70+/-0.05, p<0.005). There was a significant correlation between RI and urodynamic parameters obtained in pressure flow studies. Out of 33 patients with obstruction, 28 (85%) had an RI of 0.7 or more, while 11 out of 24 patients (46%) without obstruction had an RI less than 0.7. CONCLUSION: The RI is promising as a new parameter to estimate the intraprostatic pressure to investigate BPH. Its value to represent urodynamic information during voiding remains to be studied.

Aged↗
PubMed2000

Transition zone biopsy in the detection of prostate cancer.

OBJECTIVE: About 25% of all prostate cancers occur in the transition zone (TZ). We analyzed the impact of 4 systematic TZ and 2 systematic apex (AP) biopsies in addition to systematic sextant biopsies in an effort to establish the diagnostic importance of early prostate cancer. METHODS: One hundred and thirty patients underwent systematic transperineal multipoint prostate biopsy (biopsy of 12 sites, including 4 TZ and 2 AP biopsies). RESULTS: Forty-one of 130 men (31.5%) had biopsy specimens positive for cancer, and cancer originated in the TZ alone in 4 of these 41 patients (9.8%). Fourteen patients underwent radical retropubic prostatectomy. We compare the pathological findings of radical prostatectomy specimens and biopsy results. Prostate cancers predicted to be stage T(2c) by TZ biopsy were all classified as pT(2c) or greater. CONCLUSIONS: Routine TZ biopsy does not substantially increase the prostate cancer detection rate; however, it can be useful in patients who require repeat biopsy.

Aged↗
PubMed2000

Acupuncture on clinical symptoms and urodynamic measurements in spinal-cord-injured patients with detrusor hyperreflexia.

OBJECTIVES: We investigated the possible use of acupuncture for the treatment of urinary incontinence caused by detrusor hyperreflexia in patients with chronic spinal cord injuries. METHODS: A total of 13 patients (11 males, 2 females) suffering from urinary incontinence due to spinal cord injuries were treated by acupuncture, which was carried out with disposable stainless steel needles inserted into the bilateral BL-33 (Zhongliao) points on the skin of the third posterior sacral foramina. Urodynamic studies were also performed before acupuncture, immediately after the 1st acupuncture and 1 week after the 4th acupuncture. In 6 patients, these urodynamic studies were performed again 1 month after the 4th acupuncture. RESULTS: No side effects were recognized throughout the treatment period. Of the 13 patients, incontinence disappeared in 2 (15%) and decreased to 50% or less compared to baseline in a further 6 (46%). Maximum cystometric bladder capacity increased significantly from 76.2 +/- 62.3 to 148.1 +/- 81.5 ml 1 week after the 4th acupuncture (p < 0.01). In the 6 patients in whom cystometry was repeated 1 month after the 4th acupuncture, bladder capacity decreased from 187.5 +/- 90.4 ml 1 week after the 4th acupuncture to 128.3 +/- 93.4 ml. CONCLUSION: In spinal cord injury patients acupuncture could represent another valuable therapeutic alternative to the treatment of urinary incontinence caused by detrusor hyperreflexia.

Acupuncture Therapy↗
PubMed2000

Deletion polymorphism of ACE gene is associated with higher blood pressure after hospitalization in normotensive subjects.

Blood pressure has been shown to decrease in response to hospital admission. Several parameters including the decline of sympathetic nervous activity and negative sodium balance have been shown to be involved in this phenomenon. We investigated genetic influence on office BP and BP after hospitalization. One hundred and sixty-three men from the general population, free from antihypertensive medication, were enrolled in the present study. They stayed at the hospital for general medical check-up. BP was measured on the day of admission, and again the following day. Mean systolic blood pressure was significantly decreased after hospitalization from 117.3 +/- 9.9 mmHg to 115.3 +/- 12.8 mmHg (p=0.042). Subjects with DD+ID genotype showed a significantly higher systolic blood pressure after hospitalization than that of subjects with genotype II. There were no genotype specific differences in diastolic blood pressure or changes in blood pressure by the administration. In summary, systolic blood pressure after hospitalization was significantly higher in normotensive male subjects who possessed the D allele of ACE I/D polymorphism.

Alleles↗
PubMed2000

Characterization of genes encoding the pancreatic beta-cell ATP-sensitive K+ channel in persistent hyperinsulinemic hypoglycemia of infancy in Japanese patients.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a genetic disorder characterized by unregulated insulin secretion and profound hypoglycemia. Recently, mutations of SUR1 and Kir6.2, which constitute the pancreatic beta-cell ATP-sensitive potassium (K(ATP)) channel, have been shown to be associated with familial PHHI in certain ethnic groups. In the present study, we examined clinical symptoms, therapy, and variations in the SUR1 and Kir6.2 genes in eight Japanese patients with PHHI. Four patients were being treated with pharmacological agents and the other four had required pancreatectomy to normalize glucose levels. There was no difference in timing of the onset of hypoglycemia between the groups. There also was no difference in severity between the two groups, as assessed by blood glucose levels, plasma insulin levels, and birth weight. However, all of the pancreatectomized patients and none of the medically treated group had presented with seizures. By genetic screening, we found eleven nucleotide substitutions in the SUR1 gene, three of which result in amino acid changes, and three nucleotide substitutions in the Kir6.2 gene, two of which result in amino acid changes, but all of these genetic variants had been previously reported in normal subjects. These results indicate that the mechanism of hypoglycemia in these patients is different from those previously reported in PHHI patients, giving further support to the view that PHHI is a heterogeneous disorder.

ATP-Binding Cassette Transporters↗
PubMed2000

Endothelium-dependent coronary response is impaired in the myocardium at an early phase of post-infarct remodeling.

The aim of the present study was to characterize endothelium-dependent and -independent coronary functions in remodeling hearts after infarction. First, echocardiography showed that the left ventricular diastolic dimension and thickness of the non-ischemic region were increased by 25% and 20%, respectively, at 2 weeks after coronary ligation in the rabbit heart. In the second series of experiments, 2 weeks after coronary ligation or a sham operation, the heart was isolated and perfused with modified Krebs-Henseleit buffer at 75 mmHg, and effluent from the pulmonary artery was measured as total coronary flow (CF). Regional CF analysis by microspheres indicated that flow to the infarcted region as a percentage of total CF is negligibly small. There was no significant difference between CF responses to sodium nitroprusside (10(-9)-10(-5) mole/l) in the sham-operated and remodeling hearts. However, the increase in CF after acetylcholine (ACh: 10(-8)-10(-5) mole/l) injection was significantly reduced by approximately 50% in the remodeling hearts compared to that in the sham-operated hearts. Furthermore, the percent increase in CF by ACh (10(-5) mole/l) was inversely correlated with weight of the remodeling myocardium (r = -0.630, p < 0.05). These results suggest that endothelium-dependent vasodilatory function is impaired in the myocardium at the early stage of post-infarct remodeling and that this endothelial dysfunction is closely related to the degree of hypertrophy of the remodeling myocardium.

Acetylcholine↗
PubMed2000

Diverse roles of K(ATP) channels learned from Kir6.2 genetically engineered mice.

The regulation of insulin secretion from pancreatic beta-cells depends critically on the activities of their plasma membrane ion channels. ATP-sensitive K+ channels (K(ATP) channels) are present in many cells and regulate a variety of cellular functions by coupling cell metabolism with membrane potential. The activity of the K(ATP) channels in pancreatic beta-cells is regulated by changes in the ATP and ADP concentrations (ATP/ADP ratio) caused by glucose metabolism. Thus, the K(ATP) channels are the ATP and ADP sensors in the regulation of glucose-induced insulin secretion. K(ATP) channels are also the target of sulfonylureas, which are widely used in the treatment of type 2 diabetes. Molecular cloning of the two subunits of the pancreatic beta-cell K(ATP) channel, Kir6.2 (an inward rectifier K+ channel member) and SUR1 (a receptor for sulfonylureas), has provided great insight into its structure and function. Kir6.2 subunits form the K+ ion-permeable pore and primarily confer inhibition of the channels by ATP, while SUR1 subunits confer activation of the channels by MgADP and K+ channel openers, such as diazoxide, as well as inhibition by sulfonylureas. The SUR1 subunits also enhance the sensitivity of the channels to ATP. To determine the physiological roles of K(ATP) channels directly, we have generated two kinds of genetically engineered mice: mice expressing a dominant-negative form of Kir6.2 specifically in the pancreatic beta-cells (Kir6.2G132S Tg mice) and mice lacking Kir6.2 (Kir6.2 knockout mice). Studies of these mice elucidated various roles of the K(ATP) channels in endocrine pancreatic function: 1) the K(ATP) channels are the major determinant of the resting membrane potential of pancreatic beta-cells, 2) both glucose- and sulfonylurea-induced membrane depolarization of beta-cells require closure of the K(ATP) channels, 3) both glucose- and sulfonylurea-induced rises in intracellular calcium concentration in beta-cells require closure of the K(ATP) channels, 4) both glucose- and sulfonylurea-induced insulin secretions are mediated principally by the K(ATP) channel-dependent pathway, 5) the K(ATP) channels are important for beta-cell survival and architecture of the islets, 6) the K(ATP) channels are important in the differentiation of islet cells, and 7) the K(ATP) channels in glucose-responsive cells generally participate in coupling glucose sensing with cell excitability. Interestingly, despite the severe defect in glucose-induced insulin secretion, Kir6.2 knockout mice show only a very mild impairment in glucose tolerance. However, when the knockout mice become obese with age, they develop fasting hyperglycemia and glucose intolerance, while neither fasting hyperglycemia nor glucose intolerance is evident in the aged knockout mice without obesity, suggesting that both the genetic defect in glucose-induced insulin secretion and the acquired insulin resistance due to environmental factors are necessary to develop diabetes in Kir6.2 knockout mice. Thus, Kir6.2G132S Tg mice and Kir6.2 knockout mice provide a model of type 2 diabetes and clarify the various roles of K(ATP) channels in endocrine pancreatic function.

Adenosine Triphosphate↗
PubMed2000

Sympathetic fibers innervating the extraocular muscles: cells of origin in the cat superior cervical ganglion.

Cells of origin of sympathetic fibers innervating the extraocular muscles were demonstrated in the cat superior cervical ganglion (SCG) using the horseradish peroxidase (HRP) technique. Each injection of HRP into the muscles was confirmed by labeling in the oculomotor, trochlear and abducens nuclei. In all cases retrogradely labeled neurons were found to be distributed widely to the ipsilateral SCG. Labeled neurons were round or oval in shape and majority of these were medium in size. There were some large-sized neurons which frequently showed to have long dendrites expanding rostrocaudally. The labeling was characterized by localization in the rostral two-thirds of the SCG after HRP injections into the medial, lateral and inferior and superior oblique muscles. However, the labeling was found in the whole of the SCG after HRP injections into the superior rectus and inferior oblique muscles. Compared with our previous studies demonstrating cells of origin of the sympathetic fibers in the facial and hypoglossal nerves, the present experiments showed quite different pattern of distribution of labeled neurons in the SCG.

Adrenergic Fibers↗
PubMed2000

[A very elderly autopsy case of cecal cancer with pulmonary lymphangitis carcinomatosa].

A 91-year-old man was admitted with colliquative diarrhea, anorexia and weight loss. He had a history of healed tuberculosis, hypertension and atherosclerotic abdominal aortic aneurysms. On admission, shortness of breath without cough, exertional dyspnea, and ascites were also noticed. His chest X-ray and CT showed almost normal findings in the lung fields except for calcified old pleurisy. Since laboratory tests revealed thrombocytopenia, low fibrinogen, and increased CA19-9. DIC induced by an unknown cancer was diagnosed. He died on the eighth day due to progressive respiratory failure which did not respond to oxygen therapy. Autopsy revealed that he had a poorly differentiated adenocarcinoma in the cecum complicated with pulmonary lymphangitis carcinomatosa. Lymphangitis should be considered in the case of unexplained progressive respiratory failure developing in patient with cancer, even in the absence of X-ray findings.

Adenocarcinoma↗
PubMed2000

[An autopsy case of anaplastic thyroid carcinoma that transformed from papillary carcinoma within 5 years from initial diagnosis].

An 84-year-old man was admitted to our hospital with right shoulder pain. He had been suffering from well-differentiated papillary thyroid carcinoma since 1994, and had undergone surgery three times, including procedures due to recurrence. Since CT showed a right cervical tumor, recurrence of thyroid carcinoma was diagnosed. He died in September 1999 due to progressive respiratory failure. Autopsy was performed and pathological examination revealed the recurrent tumor and metastatic lesions had totally transformed to anaplastic thyroid carcinoma. Since anaplastic carcinoma is characterized by exceptionally rapid progression with dire prognosis, physicians should be aware of the major risk factors of anaplastic transformation in elderly males aged over 60 years old, with repeated relapses of differentiated carcinoma, and a history of tumor irradiation.

Adenocarcinoma, Papillary↗
PubMed2000

Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice.

Lung cancer is commonly associated with multiorgan metastasis, and bone is a frequent metastatic site for lung cancer. Nevertheless, no bone metastasis model of lung cancer with multiorgan dissemination is available, which could provide opportunity to study the molecular pathogenesis. We examined the abilities of eight human lung cancer cell lines injected intravenously into natural killer (NK) cell-depleted SCID mice to generate metastatic nodules in bone and multiple organs, and explored the correlation of the parathyroid hormone-related protein (PTHrP) with the bone metastasis. Although all the small-cell carcinoma cell lines (SBC-5, SBC-3, SBC-3/ADM, H69, H69/VP) formed metastatic nodules in multiple organs (liver, kidney, and lymph nodes), only SBC-5 cells reproducibly developed bone metastases. Squamous cell carcinoma (RERF-LC-AI) cells metastasized mainly into the liver and kidneys, whereas adenocarcinoma (PC-14, A549) mainly produced colonies in the lungs. As assessed by X-ray photography, the osteolytic bone metastases produced by SBC-5 cells were detected as early as on day 28, and all recipient mice developed bone metastasis by day 35. The expression of PTHrP in eight cell lines was directly correlated with the formation of bone metastasis. No correlation was observed between the formation of bone metastasis and the expression of other metastasis-related cytokines (IL-1, IL-6, IL-8, IL-10, IL-11, TNF-alpha, VEGF, M-CSF). Consistent with the formation of bone metastasis by SBC-5 cells, the levels of PTHrP and calcium in the mouse serum were increased in a time-dependent manner, suggesting that PTHrP produced by human lung cancer may play a crucial role in the formation of bone metastasis and hypercalcemia. These findings indicate that a bone metastasis model of SBC-5 cells may be useful for clarifying the molecular aspects of the metastatic processes in different organ microenvironments and the development of therapeutic modalities for lung cancer patients with bone metastases.

Animals↗