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Biomedical subjects

M Takano

Publications and source records attributed to M Takano.

At least 145 records · Page 8Linked to original sources

Veins of the lumbar spinal ganglia in human adults and fetuses.

To obtain a fundamental knowledge of the morphological relationship between nerve root symptoms and circulatory disorders, the distribution pattern of the veins in the lumbar spinal ganglia from the first to fifth vertebrae was investigated in 5 adult human cadavers (mean age 69.6 years) and 5 human fetuses (mean age 6.6 months). The following results were obtained: 1) In the adults the veins perforating from the outer surface of the fifth lumbar spinal ganglion were smaller in number than those perforating from the first to fourth ganglia. In contrast, in the fetuses the number of such veins was increased in the lower lumbar spinal ganglia. In each of the ganglia, the number of veins emerging through the dorsal side was much higher than the number perforating from the outer surface of the ventral sides. The veins perforating through the outer surface of the ganglion formed weak venous networks (periganglionic venous plexus) surrounding the dorsal ramus of the spinal nerve. 2) The veins communicating with the tributaries from the periganglionic venous plexus were classified into three types. Type 1 veins flowed into the intervertebral veins (the frequency ranged from 9.2 to 18.2 in the adults and from 22.4 to 37.0 in the fetuses). Type 2 veins coursed in the spinal cord along the dorsal root fibers and penetrated the dura mater on the way (the frequency ranged from 0.4 to 4.8 in the adults and from 1.2 to 2.2 in the fetuses). Type 3 veins opened directly into the internal vertebral plexus (the frequency ranged from 0.4 to 1.8 in the adults and from 0 to 0.4 in the fetuses). Type 1 veins were the most frequent among the three types of veins in both adults and fetuses. Few type 3 veins were observed in either group. 3) In the first and second lumbar vertebrae in the adults, three-quarters of each spinal ganglion was situated in the vertebral canal. In the lower lumbar region (L3-L5), three quarters of each spinal ganglion lay on the outside of the vertebral canal. In the fetuses, approximately one half to three-quarters of each lumbar spinal ganglion was located in the vertebral canal.

Aged↗

Dibutyryl cyclic adenosine monophosphate protects mice against tumor necrosis factor-alpha-induced hepatocyte apoptosis accompanied by increased heat shock protein 70 expression.

Liver injury accompanied by apoptosis of hepatocytes was provoked in mice by an intravenous injection of recombinant tumor necrosis factor-alpha (rTNF-alpha) (1.0 microg/kg) together with an intraperitoneal injection of D-galactosamine (D-gal) (500 mg/kg). Injection of various doses of dibutyryl cAMP (DBcAMP) protected mice from TNF-alpha/D-gal-induced liver injury as assessed by serum alanine aminotransferase (ALT) levels, histological examination and DNA fragmentation. DBcAMP significantly enhanced the Hsp70 expression in the hepatocytes of D-gal/TNF-alpha-injected mice in close correlation with suppression of liver injury. DBcAMP induced Hsp70 expression in the hepatocyte in vitro. These results suggest that increase in Hsp70 expression by DBcAMP is involved in protective mechanisms by DBcAMP against TNF-alpha-induced liver injury in D-gal-sensitized mice.

Animals↗

Clinical and neuroimaging features of Chiari type I malformations with and without associated syringomyelia.

The clinical and neuroimaging characteristics of 22 consecutive patients with Chiari type I malformations were evaluated to investigate the pathogenesis of syrinx formation. All patients underwent magnetic resonance imaging and x-ray tomography before surgery. The electric manometric Queckenstedt test was performed on 16 patients pre- and postoperatively. Syringomyelia was present in 17 patients and absent in five patients. All patients without syringomyelia suffered from foramen magnum compression syndrome, with a wider basal angle, more acute clivo-axial angle, shorter clivus, and more prominent tonsillar ectopia than patients with syringomyelia. Low brain stem position, basilar impression, and beaking of the cervicomedullary junction were also more prominent in patients without syringomyelia. Marked to complete block with the neck in flexed position by Queckenstedt test was present in all patients except one. Patients with Chiari malformation not associated with syringomyelia have more pronounced compression of the brain stem at the foramen magnum. Therefore, despite a block of the cerebrospinal fluid pathway at the foramen magnum, syrinx formation may be prevented by severe compression.

Adolescent↗

Clinical features of ovarian cancer in Japanese women with germ-line mutations of BRCA1.

We analyzed the clinical features of 25 ovarian cancer patients who were associated with germ-line mutations of BRCA1 from four site-specific ovarian cancer families and seven breast-ovarian cancer families in Japan. The average age at diagnosis was 51.1 years (range, 38-77 years). Histological examination revealed 24 serous cyst adenocarcinomas in 25 patients. In 23 patients with clear clinical records, 3 patients had stage I disease, 17 had stage III disease, and 3 had stage IV disease. Thirteen patients with stage III disease who were treated with cisplatin-containing chemotherapy following tumor reduction surgery showed more favorable outcomes in both the survival rate and disease-free intervals, compared with age- and treatment course-matched controls (5-year survival rate, 0.786 versus 0.303; median disease-free interval, 91.43 versus 40.92 months; P < 0.05 for both, by logarithmic rank test). Our statistical model for the inheritance of susceptibility to ovarian cancer was derived from the analysis of 26 patients and 19 healthy carriers of 12 families. The expected lifetime risk of ovarian cancer is about 80% for women with mutations of BRCA1. These results suggest that the clinical outcome of ovarian cancer with germ-line mutations of BRCA1 appears to be more favorable than that with sporadic cases and that the disease penetrance among pedigrees with germ-line mutations of the BRCA1 gene is substantially high.

Adult↗

Efflux of intracellular alpha-ketoglutarate via p-aminohippurate/dicarboxylate exchange in OK kidney epithelial cells.

The involvement of intracellular alpha-ketoglutarate (alpha-KG) in p-aminohippurate (PAH) transport was investigated in OK kidney epithelial cells. Efflux of intracellular alpha-KG from the OK cells to the basolateral side was increased by applying PAH to the basolateral side of the cells. In contrast, the intracellular alpha-KG concentration was not influenced by the addition of PAH. The alpha-KG efflux across the basolateral membrane induced by PAH was higher than that across the apical membrane. Probenecid inhibited the PAH-dependent alpha-KG efflux. The alpha-KG efflux to the basolateral side was saturable with increasing concentration of PAH in the basolateral medium. Antimycin A, a metabolic inhibitor, inhibited [14C]PAH uptake across the basolateral membrane of OK cells in a dose-dependent manner. In addition, both the alpha-KG efflux induced by PAH and the intracellular alpha-KG concentration were decreased by antimycin A dose-dependently. These results directly show that alpha-KG generated by intracellular metabolism is effluxed via PAH/dicarboxylate exchange in the basolateral membrane of OK cells.

Antimycin A↗

Distinct characteristics of transcellular transport between nicotine and tetraethylammonium in LLC-PK1 cells.

To clarify the mechanisms of the renal tubular secretion of nicotine, we studied transport of nicotine in the kidney epithelial cell line LLC-PK1. The transcellular transport of nicotine from the basolateral side to the apical side of the LLC-PK1 monolayers grown on membrane filters was much greater than that of tetraethylammonium. The basolateral-to-apical transport of nicotine was stimulated by lowering the pH of the apical side, accompanied by a decrease in the accumulation of nicotine. The accumulation of nicotine from the basolateral side was inhibited by unlabeled nicotine, cotinine, tetraethylammonium, cimetidine and quinidine. The uptake of nicotine across the apical membrane was inhibited by unlabeled nicotine and quinidine but not by tetraethylammonium or cimetidine. Pretreatment with p-chloromercuribenzene sulfonate caused a decrease in the transcellular transport of tetraethylammonium but not of nicotine. These results suggest that nicotine undergoes vectorial transport from basolateral side to the apical side of LLC-PK1 monolayers in a H+ gradient-dependent manner, corresponding to the secretion in the renal tubules. Nicotine transport in LLC-PK1 cells could be mediated by a transport system that is distinct from the transport system for tetraethylammonium.

4-Chloromercuribenzenesulfonate↗

[Effect of CDDP/5'-DFUR combination chemotherapy for advanced or recurrent gastric cancer].

CDDP/5'-DFUR combination chemotherapy was performed on 17 patients with non-resected and recurrent gastric cancer (clinical stage were IVb in all patients). They were treated with 1,400 mg/m2 of 5'-DFUR on days 1-4 orally following by withdrawal 10 days, every 2 weeks repeatedly and 80 mg/m2 of CDDP (c. i. v., on day 5, every 4 weeks). This chemotherapy was performed for at least 2 courses on all patients. Eight of 17 patients achieved a partial response and the overall response rate was 47.1% (differentiated type 57.1%, undifferentiated type 45.5%). Response rates of each lesion were as follows: primary foci 42.9%, abdominal lymph nodes 57.1%, hepatic metastasis 60.0% and ascites 33.3%, respectively. Improvement of performance status was seen in 12 of 17 patients (70.6%). The overall median survival time was 227 days. The median outpatient period was 113 days. There was no high-grade toxicity over grade 2. Therapeutic toxicity of grade 2 was manifested as renal dysfunction (23.5%), nausea/vomiting (17.6%), leukopenia (5.9%) and anemia (5.9%). We evaluated the therapeutic effect by visual examination after completion of the second course. However, poor effect and high incidence of renal dysfunction were found in patients treated with this therapy over four times. Therefore, the maximum effect seemed to be revealed after completion of the fourth course. From the present study, CDDP/5'-DFUR combination chemotherapy seems to be effective for patients with high-grade advanced gastric cancer and improved their quality of life.

Adenocarcinoma↗

[Exercises on a bicycle ergometer in a family of diabetes mellitus associated with a mutation of mitochondrial DNA].

The serum pyruvate and lactate levels were studied after exercise on a bicycle ergometer in a family of diabetes mellitus (DM) associated with a mutation at nucleotide 3243 in the mitochondrial gene. A 56-year-old Japanese woman with the mutation at a percentage of 5% in the blood had insulin-dependent DM and sensory hearing loss without muscle symptoms. Her serum lactate and pyruvate levels increased markedly during and after exercise on a bicycle ergometer. Two of her sons were found to have the same mutation at a percentage of 17% and 18%, respectively. Her 26-year-old son was found to have borderline DM after oral glucose loading, although he showed no abnormalities of the metabolism of pyruvate and lactate. Her 31-year-old son showed no abnormalities after oral glucose loading and after exercise on a bicycle ergometer. Although the same mutation causes more severe MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), little is known about whether these diabetic patients are subclinically involved with myopathy. The noninvasive ergometer exercise with determination of serum pyruvate and lactate may be useful in evaluating the severity of myopathy in these patients.

Adult↗

Myocardial ischemia induces differential regulation of KATP channel gene expression in rat hearts.

The cardiac ATP-sensitive potassium (KATP) channel is thought to be a complex composed of an inward rectifier potassium channel (Kir6.1 and/or Kir6.2) subunit and the sulfonylurea receptor (SUR2). This channel is activated during myocardial ischemia and protects the heart from ischemic injury. We examined the transcriptional expression of these genes in rats with myocardial ischemia. 60 min of myocardial regional ischemia followed by 24-72 h, but not 3-6 h, of reperfusion specifically upregulated Kir6.1 mRNA not only in the ischemic (approximately 2.7-3.1-fold) but also in the nonischemic (approximately 2.0-2.6-fold) region of the left ventricle. 24 h of continuous ischemia without reperfusion also induced an increase in Kir6.1 mRNA in both regions, whereas 15-30 min of ischemia followed by 24 h of reperfusion did not induce such expression. In contrast, mRNAs for Kir6.2 and SUR2 remained unchanged under these ischemic procedures. Western blotting demonstrated similar increases in the Kir6.1 protein level both in the ischemic (2.4-fold) and the nonischemic (2.2-fold) region of rat hearts subjected to 60 min of ischemia followed by 24 h of reperfusion. Thus, prolonged myocardial ischemia rather than reperfusion induces delayed and differential regulation of cardiac KATP channel gene expression.

ATP-Binding Cassette Transporters↗

Molecular cloning of cDNAs for mouse low-molecular-weight and high-molecular-weight prekininogens.

We isolated cDNAs encoding low-molecular-weight (L-) and high-molecular-weight (H-) prekininogens from a mouse liver cDNA library using rat T-kininogen cDNA and rat H-kininogen cDNA respectively, as probes. The signal peptide, the heavy chain, and the bradykinin moiety, which are common between the two prekininogens, consist of 20, 359, and 9 amino acids, respectively, while the light chains of the L- and H-prekininogens are composed of 44 and 273 amino acids, respectively. All 19 cysteine residues present in both mouse prekininogens are located at the same positions relative to those of human origin. The light chain of H-prekininogen contains a characteristic 15-repeated His-Gly sequence and a conserved sequence for binding prekallikrein or factor XI. Northern blotting or reverse transcription-polymerase chain reaction followed by Southern blotting using mouse L- and H-kininogen cDNAs demonstrated that both L- and H-kininogens are predominantly expressed in the liver and kidney. L-Kininogen mRNA was also expressed in other tissues, such as the adrenal gland, brain, spinal cord, testis, lung, heart, and skin, while levels of H-kininogen mRNA in these tissues were too low to detect, suggesting that L-kininogen is synthesized in various tissues of mouse, while H-kininogen is exclusively synthesized in the liver and kidney. A genomic Southern blot using H-prekininogen cDNA revealed that the L- and H-prekininogen mRNAs in mouse are probably encoded by a single gene, as is the case in both human and bovine.

Amino Acid Sequence↗

Characterization of Bacillus subtilis mutants resistant to cold shock-induced autolysis.

Bacillus subtilis vegetative cells undergo autolysis when exposed to cold shock treatment. A mutant (CA1) resistant to cold shock was isolated, and its DNA was used for the transformation of B. subtilis 168AR. The transformant (TR1) and CA1 had almost completely lost major vegetative autolysins (Cw1B and Cw1G) and motility, and showed a filamentous cell morphology during the exponential phase. Expression of the sigD-lacZ fusion was reduced in TR1. But the introduction of a SigD overproducing plasmid, pHYSigD, into TR1 led to a considerable increase in the amount of autolysin, a normal cell morphology (short rod), and the cold shock-sensitive phenotype. However, motility was not restored in the transformant. The roles of pleiotropic genes in cold shock-induced autolysis are discussed.

Bacillus subtilis↗

High Critical-Current Density in the Heavily Pb-Doped Bi2Sr2CaCu2O8+delta Superconductor: Generation of Efficient Pinning Centers

Critical-current density (Jc) is a parameter of primary importance for potential applications of high-temperature copper oxide superconductors. It is limited principally by the breakdown of zero-resistive current due to thermally activated flux flow at high temperatures and high magnetic fields. One promising method to overcome this limitation is to introduce efficient pinning centers into crystals that can suppress the flux flow. A marked increase in Jc was observed in Bi2Sr2CaCu2O8+delta (Bi-2212) single crystals doped with a large amount of Pb. By electron microscopy, characteristic microstructures were revealed that probably underlie the observed enhancement in Jc: thin (10 to 50 nanometers), platelike domains having a modulation-free structure appeared with spacings of 50 to 100 nanometers along the b axis.

Journal Article↗

Relationship between expression level of P-glycoprotein and daunorubicin transport in LLC-PK1 cells transfected with human MDR1 gene.

P-Glycoprotein-mediated transcellular transport and intracellular accumulation of [3H]daunorubicin were examined in cell monolayers with different levels of P-glycoprotein. The porcine kidney epithelial cell line LLC-PK1 was transfected with MDR1 cDNA, and four sublines, LLC-GA5, LLC-GA5-VLB4, LLC-GA5-COL10, and LLC-GA5-COL150, were obtained by culturing the cells in the absence or in the presence of 4 ng/mL vinblastine, 10 ng/mL colchicine, and 150 ng/mL colchicine, respectively. Western blot analysis showed a large difference in P-glycoprotein expression within these sublines. The degree of drug resistance was dependent on the expression level of P-glycoprotein. The amount of the unidirectional transport of [3H]daunorubicin by P-glycoprotein corresponded to the expression level of P-glycoprotein, which was followed by the decrease in intracellular accumulation of the agent. The concentration of cyclosporin A required for the inhibition of P-glycoprotein-mediated transport of [3H]daunorubicin was higher in cells with a high expression of P-glycoprotein. These findings suggest that the transport of daunorubicin by P-glycoprotein and its inhibition by cyclosporin A correspond to the expression level of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Species-specific B-cell epitope on the C-terminal region of the alpha antigen from Mycobacterium scrofulaceum.

In the amino acid (AA) sequences of alpha antigen from mycobacteria, C-terminal regions were variable among a variety of mycobacterial species though the N-terminal regions were relatively conserved. These regions may possess some species-specific antigenic determinants of the alpha antigen from Mycobacterium scrofulaceum (S-alpha). AAs288-300 of S-alpha fused to beta-galactosidase was reactive with the antisera raised against S-alpha. The same fused peptide did not react with the antisera raised against the alpha antigen from Mycobacterium avium (A-alpha) and Mycobacterium bovis BCG (B-alpha). B-cell epitope mapping then was performed focusing on the C-terminal region of S-alpha using the synthetic peptides. Their reactivities with antisera raised against the alpha antigens of three different mycobacterial species were assessed by ELISA. AAs279-286 were a cross-reactive common immunodominant region among three mycobacterial species. This region may be one of the cross-reactive common epitopes in mycobacterial species. And AAs291-300 were reactive only with the antisera raised against S-alpha. This region may possess a species-specific epitope.

Amino Acid Sequence↗

Clinical investigation of colorectal cancer detected by follow-up colonoscopy after endoscopic polypectomy.

PURPOSE: We analyzed the results of a long-term follow-up surveillance of patients with colorectal polyps after endoscopic polypectomy in terms of the cumulative incidence of subsequent colorectal cancer and the clinicopathologic characteristics of carcinomas detected by colonoscopy. METHOD: The study cohort consisted of 6,715 patients who had received endoscopic resection of single or multiple colorectal polyps and then underwent periodic colonoscopy (or a combination of sigmoidoscopy and barium x-ray examination in some cases) during an average follow-up of six years (40,622 person-years in total). RESULTS: During the follow-up, 31 cases of colorectal cancer containing 15 submucosal invasive carcinomas (T1,N0,M0) and 16 advanced carcinomas were detected. The cumulative incidence of colorectal cancer was analyzed for four subgroups of the 6,715 patients classified according to the diameter, grade of dysplasia, and histologic features of polyps. Furthermore, the depth of invasion, macroscopic configuration of submucosal invasive cancer, and site of colorectal cancer observed in the 31 cases were compared with those of a reference group of 1,497 patients with colorectal cancer treated at Takano Hospital during the same period. Submucosal invasive cancer was the most common type among the colorectal carcinomas detected during follow-up. In terms of macroscopic configuration of submucosal cancer, the superficial type was significantly more common than the protruded type. The superficial submucosal cancer showed a significantly longer interval to detection than the protruded submucosal cancer. By site of lesion, proximal colon cancer was significantly more common. CONCLUSION: Follow-up colonoscopy appears to be useful in patients with larger polyps (>5 mm). Patients with severe dysplasia and those with malignant polyps should be followed-up carefully. Because submucosal cancer detected by follow-up examination after polypectomy showed higher rates of superficial-type cancer and proximal colon cancer, careful endoscopic examination of the entire colon is important.

Adenomatous Polyps↗

Development and status of proctology in Japan.

Formerly in Japan, the treatment of anal diseases was performed with techniques transmitted from Asian countries such as China and Korea using herbs, necrotizing agents, ligation, seton, and other methods. Before World War II, western medicine and techniques were brought in from Germany, including Whitehead's operation. After the war, new knowledge was introduced from the United Kingdom and the United States: ligation and excision for hemorrhoids, sphincter-preserving methods such as Hanley's and Parks' for fistulas, and sliding skin graft methods such as Carmels' for anal fissure. After their introduction, those methods were revised and improved in Japan. Unfortunately, however, the results of those improvements were not introduced to other countries in medical journals or in presentations at international conferences. At this time, I am honored to give an overview of proctology in Japan for this special Japanese issue.

Colonic Diseases↗

Follow-up studies of sphincter-preserving operations for anal fistulas.

PURPOSE: This study was designed to evaluate and to compare the outcome of anal fistula surgery using techniques involving minimal sphincter damage (sphincter-preserving) and conventional laying open techniques. PATIENTS AND METHODS: From January 1987 to December 1993, 2,242 patients with anal fistulas were treated surgically, of whom 1,070 had sphincter-preserving operations. These included 530 patients with low intersphincteric fistulas (II L), 116 patients with high intersphincteric fistulas (II H), 73 patients with combined high and low intersphincteric fistulas, 239 patients with transphincteric fistulas (III), and 112 patients with supralevator fistulas (IV). The open method of fistula surgery was used in 1,172 patients. RESULTS: Of 1,070 sphincter-preserving operations, delayed healing occurred in 49 patients (4.6 percent) and recurrent fistula occurred in 32 patients (3 percent). By using the open method in 1,172 patients, delayed healing occurred in 10 patients (0.9 percent) and recurrence of fistula occurred in 23 patients (2 percent). Failure rates increased with increasing depth and complexity of the fistula. CONCLUSION: Sphincter function is better with sphincter-preserving fistula surgery than with the open method, although healing was delayed more commonly in sphincter-preserving operations that with the open methods, and fistula recurrence was similar with the two methods. Choice of operation depends on depth of fistula, outcome by manometry, and history of former operations.

Anal Canal↗