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Biomedical subjects

M Kanzaki

Publications and source records attributed to M Kanzaki.

At least 37 records · Page 2Linked to original sources

Nitinol stent for the treatment of tracheobronchial stenosis.

OBJECTIVE: The purpose of this study was to evaluate the potential utility of implantation of a nickel-titanium alloy (nitinol) stent for the treatment of malignant or benign tracheobronchial stenosis. METHODS: We evaluated 18 patients (14 men and 4 women) who received 24 nitinol stents, between November 1997 and May 2000. All 18 patients had severe dyspnea caused by tracheobronchial stenosis. The underlying condition was malignant disease in 15 patients, and benign tracheal collapse in the other 3 patients. RESULTS: Implantation of the stent was successfully performed in all patients. Seventeen patients experienced immediate clinical improvement in respiratory symptoms. The remaining 1 patient with a bronchial fistule after lobectomy did not benefit, and died of pneumonia at 16 days after the implantation. In 15 patients, the procedure was performed using a flexible bronchoscope under local anesthesia alone, while the remaining 3 patients needed intravenous sedation. There was no complication resulting from the stent implantation. Among the 3 patients with benign tracheal collapse, 2 patients were alive at 746 and at 401 days after the stent implantation, at the time of this report. One patient with cicatricial stenosis after intubation died of heart failure due to previous myocardial infarction. Among the 15 patients with malignant disease, 4 patients have survived for 177 to 305 days to date, while the other 11 patients have died of primary malignancy with a mean survival duration of 60.2 days. CONCLUSION: The nitinol stent was effective in treating malignant or benign tracheobronchial stenosis, and had some remarkable advantages compared with other tracheobronchial stents. In stenting, most procedures can be performed using flexible bronchoscope under local anesthesia.

Adult↗

Y-chromosome microdeletion and phenotype in cytogenetically normal men with idiopathic azoospermia.

OBJECTIVE: To determine the prevalence of microdeletions of the long arm of chromosome Y within the AZFa, AZFb, and AZFc subregions in patients with idiopathic azoospermia, and then correlate the microdeletions with clinical phenotypes to determine the most important subregion for screening. DESIGN: Controlled clinical study. SETTING: Male infertility clinic, Kobe University Hospital. PATIENT(S): Among 89 consecutive azoospermic patients, those whose infertility was related to known hereditary, endocrine, or obstructive causes or a cytogenetic abnormality were excluded; 54 remaining patients were studied using a polymerase chain reaction (PCR). Of these patients, 33 had Sertoli cell only syndrome, 10 had maturation arrest, and 11 had hypospermatogenesis. INTERVENTION(S): Blood and semen samples and testicular biopsies were obtained from all of the participants. MAIN OUTCOME MEASURE(S): We performed semen analysis, polymerase chain amplification of 28 DNA loci on the long arm of the Y chromosome involving the DAZ (deleted in azoospermia), and measured the plasma FSH, LH, testosterone, prolactin, and estradiol levels. RESULT(S): Microdeletions were detected in 14 of the 54 patients (nine with Sertoli cell only, three with maturation arrest, and two with hypospermatogenesis). Most microdeletions involved AZFb or AZFc. Patients with hypospermatogenesis or maturation arrest showed deletion only in AZFc. The DAZ gene was deleted in four patients with Sertoli cell only and one patient with maturation arrest. The RBM gene was deleted in two patients with Sertoli cell only who had particularly large deletions, but in no patients with arrest or hypospermatogenesis. CONCLUSION(S): Cytogenetically azoospermic patients should be examined for microdeletions before undertaking assisted reproduction. AZFc may be the most important subregion to screen. In addition, intact AZFa and AZFb subregions may be important for the presence of germ cells.

Adult↗

Significance of serum inhibin B concentration for evaluating improvement in spermatogenesis after varicocelectomy.

BACKGROUND: The study aim was to clarify the relationship of serum inhibin B concentrations to recovery of spermatogenic function after varicocelectomy, both as a predictor of improvement in the seminogram and as a means of monitoring hormonal function after surgery. METHODS: Fifty-two varicocele patients, including five with normal sperm concentrations, were studied. Changes in the seminogram, serum hormone concentrations and serum inhibin B were evaluated in the 47 oligozoospermic patients after surgery. Preoperative inhibin B concentrations correlated significantly with serum concentrations of FSH (r = 0.598, P < 0.0001) and testosterone (r = 0.380, P < 0.02). Inhibin B concentrations also correlated significantly with sperm concentration (r = 0.351, P < 0.02) and total testicular volume (r = 0.578, P < 0.0001). No significant correlation was seen between inhibin B and the Johnsen score. Preoperative concentrations of inhibin B were higher in patients who increased their sperm concentration after surgery (responders) than in those without improved concentrations (non-responders). No significant difference was observed between pre- and postoperative inhibin B concentrations in responders or non-responders. However, 15 of 25 (60%) patients with increased inhibin B showed improvement of the seminogram, while only five of 22 (23%) patients with no change or a decrease in inhibin B had any improvement (P < 0.05). CONCLUSIONS: Preoperative serum inhibin B concentration could not reliably predict a response to varicocelectomy. However, a change in serum inhibin B concentration after varicocelectomy might be helpful to evaluate the improvement of testicular function after varicocelectomy.

Adult↗

Signal integration and the specificity of insulin action.

Insulin is a potent metabolic hormone essential for the maintenance of normal circulating blood glucose level in mammals. The physiologic control of glucose homeostasis results from a balance between hepatic glucose release (glycogenolysis and gluconeogenesis) and dietary glucose absorption versus skeletal muscle and adipose tissue glucose uptake and disposal. Disruption of this delicate balance either through defects in insulin secretion, liver glucose output, or peripheral tissue glucose uptake results in pathophysiological states of insulin resistance and diabetes. In particular, glucose transport into skeletal muscle and adipose tissue is the rate-limiting step in glucose metabolism and reduction in the efficiency of this process (insulin resistance) is one of the earliest predictors for the development of Type II diabetes. Importantly, recent studies have directly implicated an impairment in insulin receptor signal transduction as the prime mechanism for peripheral tissue insulin resistance. In this review, we have focused on recent developments in our understanding of the molecular mechanisms and signal transduction pathways that insulin utilizes to specifically regulate glucose uptake. The detailed understanding of these events will provide a conceptual framework for the development of new therapeutic targets to treat this chronic and debilitating disease process.

Adipose Tissue↗

Effects of suspension of air-conditioning on airtight-type racks.

Although isolation racks are superior to open-type racks in terms of securing breeding conditions for laboratory animals, the contingency-proofing capability of the former has yet to be determined. Therefore, from the view of risk management, we studied the environmental change in isolation racks by forcibly suspending ventilation and air-conditioning and confirming the maximal time length for complete recovery to the original condition after restarting their operations. The isolation racks were placed in a room that was equipped with an independent air-conditioning system. When the inside condition of the racks reached 22-24 degrees C and 59-64% of relative humidity, the air-conditioning and ventilation were forcibly suspended and the subsequent temperature, relative humidity, ammonium and CO2 concentrations in the racks were measured over time. We found that after suspending the air-conditioning and ventilation, it took 40-60 min for temperature, and about 10 min for relative humidity to exceed the maximum values (temperature and relative humidity) referred to in the Showa 58 Nenban Guideline Jikken Doubutsu Shisetsu no Kenchiku oyobi Setsubi (Guidelines of buildings and facilities for experimental animals in Japan; Year 1983 edition). After 17 hr 25 min of the suspension of air-conditioning and ventilation, two rats were found dead. Then, the air-conditioning and ventilation were restarted. It took about 2 hr for temperature, and 50 min for relative humidity to regain the guideline values. The ammonium concentration stayed within the guideline value with a maximum concentration of 2 ppm in the experimental period, whereas the CO2 concentration was found to exceed 9% at the time of animal death.

Air Conditioning↗

CAP defines a second signalling pathway required for insulin-stimulated glucose transport.

Insulin stimulates the transport of glucose into fat and muscle cells. Although the precise molecular mechanisms involved in this process remain uncertain, insulin initiates its actions by binding to its tyrosine kinase receptor, leading to the phosphorylation of intracellular substrates. One such substrate is the Cbl proto-oncogene product. Cbl is recruited to the insulin receptor by interaction with the adapter protein CAP, through one of three adjacent SH3 domains in the carboxy terminus of CAP. Upon phosphorylation of Cbl, the CAP-Cbl complex dissociates from the insulin receptor and moves to a caveolin-enriched, triton-insoluble membrane fraction. Here, to identify a molecular mechanism underlying this subcellular redistribution, we screened a yeast two-hybrid library using the amino-terminal region of CAP and identified the caveolar protein flotillin. Flotillin forms a ternary complex with CAP and Cbl, directing the localization of the CAP-Cbl complex to a lipid raft subdomain of the plasma membrane. Expression of the N-terminal domain of CAP in 3T3-L1 adipocytes blocks the stimulation of glucose transport by insulin, without affecting signalling events that depend on phosphatidylinositol-3-OH kinase. Thus, localization of the Cbl-CAP complex to lipid rafts generates a pathway that is crucial in the regulation of glucose uptake.

3T3 Cells↗

The trimeric GTP-binding protein (G(q)/G(11)) alpha subunit is required for insulin-stimulated GLUT4 translocation in 3T3L1 adipocytes.

To investigate the potential role of trimeric GTP-binding proteins regulating GLUT4 translocation in adipocytes, wild type and constitutively active G(q) (G(q)/Q209L), G(i) (G(i)/Q205L), and G(s) (G(s)/Q227L) alpha subunit mutants were expressed in 3T3L1 adipocytes. Although expression of neither the wild type nor G(i)/Q205L and G(s)/Q227L alpha subunit mutants had any effect on the basal or insulin-stimulated translocation of a co-expressed GLUT4-enhanced green fluorescent protein (EGFP) fusion protein, expression of G(q)/Q209L resulted in GLUT4-EGFP translocation in the absence of insulin. In contrast, microinjection of an inhibitory G(q)/G(11) alpha subunit-specific antibody but not a G(i) or G(s) alpha subunit antibody prevented insulin-stimulated endogenous GLUT4 translocation. Consistent with a required role for GTP-bound G(q)/G(11), expression of the regulators of G protein signaling (RGS4 and RGS16) also attenuated insulin-stimulated GLUT4-EGFP translocation. To assess the relationship between G(q)/G(11) function with the phosphatidylinositol 3-kinase dependent pathway, expression of a dominant-interfering p85 regulatory subunit, as well as wortmannin treatment inhibited insulin-stimulated but not G(q)/Q209L-stimulated GLUT4-EGFP translocation. Furthermore, G(q)/Q209L did not induce the in vivo accumulation of phosphatidylinositol-3,4,5-trisphosphate (PIP(3)), whereas expression of the RGS proteins did not prevent the insulin-stimulated accumulation of PIP(3). Together, these data demonstrate that insulin stimulation of GLUT4 translocation requires at least two independent signal transduction pathways, one mediated through the phosphatidylinositol 3-kinase and another through the trimeric GTP-binding proteins G(q) and/or G(11).

3T3 Cells↗

Nitric oxide production of rat Leydig and Sertoli cells is stimulated by round spermatid factor(s).

In this study, we provide evidence of cell-to-cell interaction between rat germ cells and Leydig or Sertoli cells in relation to nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) expression. As a result of being cultured in a round spermatid-conditioned medium (RSd-CM), NO production in both Leydig and Sertoli cells increased in proportion to the length of the culture period. iNOS mRNA expression in both types of cells also increased in a dose-dependent manner as a result of being cultured with RSd-CM. This increase was detected as early as 3 h and was maintained up to 24 h. In contrast, neither NO production nor iNOS mRNA increased in either type of cell following culture in a pachytene spermatocyte-conditioned medium (PS-CM). Our findings suggest that RSd may control NO production of Leydig and Sertoli cells. This cell-to-cell interaction may be an important mechanism of regulation of testicular function.

Animals↗

Combined thoracic aortic or upper digestive tract resection for lung cancer and malignant mediastinal tumor.

OBJECTIVE: We studied possible indications and combined resection in patients with lung cancer and mediastinal tumors requiring combined thoracic aortic or upper digestive tract resection. METHODS: Ten patients with lung cancer and malignant mediastinal tumors (9 men and 1 woman aged 39 to 72 years; mean: 60.5) underwent combined aortic or upper digestive tract resection. RESULTS: Five--3 [corrected] with primary lung cancer, 1 with thymic cancer, and 1 with liposarcoma--, underwent combined aortic resection. In 2 each, lung cancer and malignant mediastinal tumor had infiltrated the thoracic aorta. The remaining case of lung cancer was complicated by aortic aneurysm in the distal arch. Cardiopulmonary bypass was conducted in 4, and selective cerebral perfusion in 2. Three patients are alive after 11, 22, and 61 months without disease recurrence. Those undergoing combined upper digestive tract resection all had lung cancer, with 4 having tumors infiltrating the esophagus or corpus ventriculi. The remaining patient had both lung and esophageal cancer. The patient treated with combined corpus ventriculi resection has survived 24 months and the patient treated with combined esophageal resection has survived 12 months without disease recurrence. The 1-year survival rate was 60%, 2-year 23%, and 3-year 23%. Prognosis was generally poor with the longest survival 13 months with N2 lung cancer. CONCLUSIONS: In combined resection due to malignant mediastinal tumor, T4N0-1 lung cancer, or diseases such as aortic aneurysm, prognosis can be expected to improve. Despite the often poor prognosis in T4N2 lung cancer, surgical intervention may be indicated to avoid complications due to tumor invasion and to lengthen survival and improve quality of life.

Adult↗

Clinical assessment of unilateral pulmonary artery occlusion test with dobutamine infusion. Expansion of surgical indications in patients with primary lung cancer and impaired cardiopulmonary functions.

OBJECTIVES: We evaluated the possibility of expanding indications for pulmonary resection based on an assessment of the pressure-flow relationship in pulmonary circulation. METHODS: In 6 of 28 lung cancer patients whose total pulmonary vascular resistance index exceeded the threshold during unilateral pulmonary artery occlusion testing, we conducted unilateral pulmonary artery occlusion testing with dobutamine administration, followed by lung resection. We studied hemodynamics during testing and derived a new indication for pulmonary resection from the postoperative course. RESULTS: Cardiac output was 3.82 +/- 0.74 l/min before testing, 3.66 +/- 0.76 l/min during pulmonary artery occlusion testing, and 5.92 +/- 1.78 l/min during unilateral pulmonary artery occlusion testing with dobutamine infusion. The total pulmonary vascular resistance index was 890 +/- 350 dyne.sec.cm-5.m2 before testing, 1170 +/- 320 dyne.sec.cm-5.m2 during testing, and 800 +/- 160 dyne.sec.cm-5.m2 during testing with dobutamine infusion. Cardiac output increased (p = 0.014) during unilateral pulmonary artery occlusion testing with dobutamine infusion, and the total pulmonary vascular resistance index significantly decreased (p = 0.034). Of the 4 patients eligible for lobectomy, 2 underwent the procedure--one undergoing segmentectomy in which pulmonary metastasis was found during surgery and the other undergoing radiotherapy for cN2 disease with chest wall invasion. Of the 2 initially ineligible for lobectomy, one underwent partial pulmonary resection and the other underwent lobectomy because the total pulmonary vascular resistance index was less than 800 dyne.sec.cm-5.m2 during selective pulmonary artery occlusion testing with dobutamine infusion, indicating eligibility for lobectomy. No severe complications of cardiopulmonary function failure after surgery occurred in any of the 5 cases. CONCLUSIONS: Unilateral pulmonary artery occlusion testing with dobutamine infusion is useful in determining patient eligibility for pulmonary resection.

Aged↗

An ab initio calculation of 17O and 29Si NMR parameters for SiO2 polymorphs.

Ab initio molecular orbital calculations (Hartree-Fock, HF and density functional theories, DFTs) have been carried out for SiO2 polymorphs coesite, low cristobalite, and alpha-quartz, in order to investigate the reliability of this method for predicting 29Si and 17O nuclear magnetic resonance (NMR) properties of silicates. Oxygen- and silicon-centered clusters consisting of one (1T) to three tetrahedral (3T) shells (one to four atomic shells), taken from real crystal structure, have been investigated. It is found that for reasonable predication of both the 29Si and 17O chemical shifts (deltaSi and delta(i)O), the minimum cluster is one that gives the correct second neighbors to the nucleus of interest. Both the delta(i)Si and delta(i)O have reached convergence with respect to cluster size at the OH-terminated two tetrahedral (2T) shell (three atomic shells around Si and four atomic shells around O) model. At convergence, the calculated delta(i)Si values agree well (within +/- 1 ppm) with experimental data. The calculated 17O electric field gradient (EFG)-related parameters also agree with experimental data within experimental uncertainties. The calculation also reproduces small differences in delta(i)O for O sites with similar tetrahedral connectivities, but shows deviations up to about 10 ppm in relative difference for O sites with different tetrahedral connectivities. The poor performance for the latter is mainly due to the approximations of the HF method. Our study thus suggests that the ab initio calculation method is a reliable mean for predicting 29Si and 17O NMR parameters for silicates. Such an approach should find application not only to well-ordered crystalline phases, but also to disordered materials, by combining with other techniques, such as the molecular dynamics simulation method.

Crystallization↗

Inhibition of apoptosis in cultured immature rat Leydig cells by human chorionic gonadotropin associated with Bcl-2 mRNA expression.

Bcl-2 is the first identified negative regulator of apoptotic cell death. When the level of Bcl-2 mRNA in rat whole testes was examined in the present study, it gradually decreased in rats from 2.5 to 9 weeks old. We also examined the effect of human chorionic gonadotropin (hCG) on apoptosis and the level of Bcl-2 mRNA expression in immature Leydig cells in vitro. When the cells were cultured with serum free media (SFM), Bcl-2 mRNA levels gradually decreased. On the other hand, the level of Bcl-2 mRNA in cells treated with 50 ng/ml of hCG decreased at 6 h, but increased after 12 h. At 24 h, the level of Bcl-2 mRNA in the treated cells was almost the same as that of control cells (time = 0). At 12 h after the addition of various concentrations (from 0.1-1000 ng/ml) of hCG, Bcl-2 mRNA levels increased in a dose-dependent manner. An analysis of DNA fragmentation showed that treatment with hCG prevents the apoptosis of immature Leydig cells. Our findings suggest that Bcl-2 mRNA may be related to the programmed cell death of immature rat Leydig cells in vitro, which are inhibited by hCG.

Animals↗

Munc18c function is required for insulin-stimulated plasma membrane fusion of GLUT4 and insulin-responsive amino peptidase storage vesicles.

To examine the functional role of the interaction between Munc18c and syntaxin 4 in the regulation of GLUT4 translocation in 3T3L1 adipocytes, we assessed the effects of introducing three different peptide fragments (20 to 24 amino acids) of Munc18c from evolutionarily conserved regions of the Sec1 protein family predicted to be solvent exposed. One peptide, termed 18c/pep3, inhibited the binding of full-length Munc18c to syntaxin 4, whereas expression of the other two peptides had no effect. In parallel, microinjection of 18c/pep3 but not a control peptide inhibited the insulin-stimulated translocation of endogenous GLUT4 and insulin-responsive amino peptidase (IRAP) to the plasma membrane. In addition, expression of 18c/pep3 prevented the insulin-stimulated fusion of endogenous and enhanced green fluorescent protein epitope-tagged GLUT4- and IRAP-containing vesicles into the plasma membrane, as assessed by intact cell immunofluorescence. However, unlike the pattern of inhibition seen with full-length Munc18c expression, cells expressing 18c/pep3 displayed discrete clusters of GLUT4 abd IRAP storage vesicles at the cell surface which were not contiguous with the plasma membrane. Together, these data suggest that the interaction between Munc18c and syntaxin 4 is required for the integration of GLUT4 and IRAP storage vesicles into the plasma membrane but is not necessary for the insulin-stimulated trafficking to and association with the cell surface.

Adipocytes↗

[Recent advances in colorectal cancer surgery].

Recent advances in colorectal cancer surgery have been made in improving the cure rate after surgery, the preservation of postoperative function, and the development of minimally invasive procedures. Indication for wide lymph node dissection in rectal cancer surgery is now limited to a smaller number of cases. Functional outcome is being improved thanks to the introduction of autonomic nerve preserving operations as well as the increasing number of sphincter preserving operations. Laparoscopic colectomy for cancer has been practiced for 7-8 years, and the advantages and disadvantages of this procedure are being clarified. Transanal endoscopic microsurgery (TEM) is a minimally invasive surgery for rectal tumors in early stages. The procedure is now overtaking the posterior surgical approach, which is used less and less in recent years. Future goals in colorectal cancer surgery are further improvements in the cure rate and the functional results. Minimally invasive surgery may become the established procedure after a careful assessment of its cure rate compared to the open surgical procedure.

Colorectal Neoplasms↗

[Laparoscopic colectomy for colorectal carcinoma].

Laparoscopic-assisted colectomy is considered to be a less invasive technique, and patients experience less pain and more rapid postoperative recovery. This operation has been indicated for large sessile adenomas or for early invasive carcinomas in Japan. The indications for this procedure in more advanced colorectal carcinomas is controversial. However, based on our experience with 130 cases, laparoscopic-assisted colectomy can be as curative as open colectomy provided that the patients are properly selected. In this review, the technical difficulties of this procedure are also discussed.

Colectomy↗

[Results of surgical treatment for pulmonary aspergilloma in postlobectomy patients].

The purpose of this study was to evaluate the results of surgical treatment of postlobectomy pulmonary aspergilloma. Between January 1986 and September 1999, six patients were surgically treated. Aspergilloma were diagnosed on the basis of the clinical and radiographic findings in all cases. All patients were poor pulmonary function. Space-reducing surgery was performed in 5 patients, completion pneumonectomy was performed in 1 patient. The reoperation was only one, the clinical impression of the cause was too difficult direct closure of the bronchial fistula due to formation of marginal fistula. We believe that space-reducing surgery for postlobectomy patients with pulmonary aspergilloma is useful and benefit treatment.

Aged↗

Molecular identification of a eukaryotic, stretch-activated nonselective cation channel.

Calcium-permeable, stretch-activated nonselective cation (SA Cat) channels mediate cellular responses to mechanical stimuli. However, genes encoding such channels have not been identified in eukaryotes. The yeast MID1 gene product (Mid1) is required for calcium influx in the yeast Saccharomyces cerevisiae. Functional expression of Mid1 in Chinese hamster ovary cells conferred sensitivity to mechanical stress that resulted in increases in both calcium conductance and the concentration of cytosolic free calcium. These increases were dependent on the presence of extracellular calcium and were reduced by gadolinium, a blocker of SA Cat channels. Single-channel analyses with cell-attached patches revealed that Mid1 acts as a calcium-permeable, cation-selective stretch-activated channel with a conductance of 32 picosiemens at 150 millimolar cesium chloride in the pipette. Thus, Mid1 appears to be a eukaryotic, SA Cat channel.

Amino Acid Sequence↗