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Biomedical subjects

K Kitagawa

Publications and source records attributed to K Kitagawa.

At least 73 records · Page 4Linked to original sources

Active-oxygen involvement in canine NK-mediated cytotoxicity.

We examined the relationship between natural killer (NK) cell-mediated cytotoxicity, the produced active-oxygen and cytotoxic factor (CF) release in co-culturing canine NK cells with tumor cells (CL-1 target cells). In co-culturing, the adding of n-propyl gallate (active-oxide scavenger) removed the produced active-oxygen, which inhibited NK cell-mediated cytotoxicity and the CF release. Moreover, adding of this agent inhibited the tyrosine phosphorylation of NK intracellular protein which observed in co-culturing. Therefore, the active-oxygen produced from canine NK cells are thought to relate the signal transduction in NK-mediated cytotoxicity.

Animals↗

Malignant colonic obstruction due to extrinsic tumor: palliative treatment with a self-expanding nitinol stent.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of self-expanding nitinol stents for palliative treatment of malignant colorectal obstruction caused by unresectable extrinsic tumor, colorectal metastasis, or peritoneal seeding. SUBJECTS AND METHODS: One covered stent and 10 uncovered stents were deployed in eight patients with colorectal obstruction due to extrinsic tumor under fluoroscopic guidance. The sites of obstruction were located in the rectum (n = 5), in the rectosigmoid colon (n = 2), and from the transverse colon to the descending colon (n = 1). Clinical usefulness and complications were analyzed. RESULTS: Stents were placed successfully in all patients. Minor modifications of the delivery system were required in the tortuous rectosigmoid and lower rectum strictures. Symptoms of obstruction were initially resolved in all but one patient. In that patient, the presence of other points of obstruction was suspected. Bowel obstruction recurred in two patients: one obstruction was due to migration of a covered stent 4 days after the procedure, and the other obstruction was due to peritoneal seeding 33 days after the procedure. Both required colostomy or ileostomy. All patients died 12-111 days after stent placement (mean, 56 days). In five patients (63%), colonic obstruction was palliated by placing a stent until the patients' death between 39 and 111 days after stent placement (mean, 62 days). Six complications occurred in four patients and included stent migration (n = 1), anal bleeding (n = 2), anal pain that required analgesia (n = 1), and fever (n = 2). CONCLUSION; This self-expandable nitinol stent adequately palliated 63% of patients with colonic obstruction due to extrinsic tumor in this small series. Patient selection is very important to the success of this treatment.

Alloys↗

[A case of successful management of nonresectable advanced cholangiocellular carcinoma by intermittent hepatic arterial infusion at home].

An 82-year-old female was referred to our hospital because a 16 x 8 cm tumor detected in her liver by abdominal ultrasonography (echo, hereafter) and CT. The patient was diagnosed as having highly advanced cholangiocellular carcinoma (CCC) by abdominal angiography. Since excision of the tumor was impossible due to the patient's age, a reservoir was indwelled for intra-arterial injection into the liver. Continuous injection of 1,000 mg 5-FU over 24 hours was performed every 2 weeks using a portable disposable pump 70 times. The tumor has been markedly reduced since the start of chemotherapy, with a reduction rate (PR) of 98% over the 3 years until the present. Since the frequency of administration was low, only twice a month, the patient had few side effects despite her old age, and injections could be performed in the outpatient department. Usually, the prognosis for CCC is poor. However, the patient has maintained a good QOL with the periodic intra-arterial injection of the carcinostatic into the liver, and this treatment has had a strong antitumor effect. This chemotherapy is thus considered useful for CCC which can not be resected.

Aged↗

[Twenty-three cases of primary cornea guttata].

PURPOSE: To evaluate the clinical aspects of patients with primary cornea guttata and the morphology of their corneal endothelial cells. METHODS: Twenty-three patients who visited Kanazawa Medical University Hospital or related hospitals in Ishikawa or Fukui prefectures and were diagnosed as having primary cornea guttata by slit lamp microscopy and contact specular microscopy underwent an analysis of corneal endothelial cells as well as their clinical status. RESULTS: In 23 cases, the number of men and young people under 30 years of age was low, with 4 and 2 cases respectively. There was no visual impairment due to cornea guttata. In the specular microscopic findings, the size and density of dark areas varied according to each case and there was asymmetry in some cases. The parameters of the endothelial cells, comprising mean cell area, hexagonality, and the coefficient of variation, were almost within normal limits except for 1 eye of a 79-year-old man who was speculated to be at an early stage of Fuchs' endothelial corneal dystrophy. Three cases had received cataract surgery, but showed no statistical changes in endothelial morphology before or after the surgery. CONCLUSION: Cornea guttata is thought to be a disease which is not uncommon in Japanese people and which does not bring about visual impairment or abnormalities in corneal endothelial cell parameters except for a small number of patients. Such cases with remarkably decreased cell densities should be considered to be at an early stage of Fuchs' dystrophy.

Adult↗

Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and oral cavity cancer.

Both genetic and environmental factors are involved in the development of cancer. Oral cavity cancer has been reported to be epidemiologically associated with tobacco and alcohol consumption. We examined genetic polymorphisms of the glutathione-S-transferase (GST) M1/T1, cytochrome P-450 (CYP) 1A1/2E1 and aldehyde dehydrogenase 2 (ALDH2) genes in 92 Japanese patients with oral cavity cancer and 147 unrelated non-cancer Japanese controls. There was a significant association between cigarette smoking and cancer risk but no significant association between alcohol consumption and cancer risk. The frequency of the GSTM1 null genotype was significantly higher in cancers (58.7%) compared with controls (46. 3%). However, there were no significant differences between controls and patients with oral cavity cancer in the polymorphisms of the GSTT1, CYP1A1, CYP2E1 and ALDH2 genes. From statistical evaluation on various combinations of genotypes, we did not observe any gene combinations associated with cancer risk. There were also no genetic polymorphisms associated with increased risk of oral cavity cancer among smokers and drinkers. These results imply that the GSTM1 null genotype has a weak correlation, but another 4 genetic polymorphisms are unlikely to be associated, with oral cavity cancer among Japanese.

Adult↗

Deficiency of intercellular adhesion molecule 1 fails to mitigate selective neuronal death after transient global ischemia.

Recent studies have shown a crucial role of intercellular adhesion molecule 1 (ICAM-1) in expansion of infarction after focal cerebral ischemia. The purpose of the present study was to assess whether ICAM-1 is involved in selective neuronal vulnerability and reactive gliosis after transient forebrain ischemia. ICAM-1 knockout mice and wild-type mice were subjected to transient forebrain ischemia for 5, 10 or 15 min, and the hippocampus and caudoputamen were examined 7 days later with conventional histological and immunohistochemical methods. Bilateral common carotid artery occlusion with less than 10% of baseline cortical microperfusion for 10 or 15 min resulted in ischemic neuronal damage in the hippocampus and caudoputamen. The frequency and the severity of neuronal damage were similar in wild-type and knockout mice. Proliferation of reactive astrocytes in the hippocampus was also similar in both types of mice. Therefore, it is highly unlikely that ICAM-1 plays a key role in delayed neuronal death after transient global ischemia or in astroglial responses after ischemic neuronal injury.

Animals↗

The significance of the homozygous CYP2A6 deletion on nicotine metabolism: a new genotyping method of CYP2A6 using a single PCR-RFLP.

A convenient and specific CYP2A6 genotyping method was developed in this study. This method consisting of a single PCR-RFLP is capable of resolving the genotype into either CYP2A6*1 (wild type), CYP2A6*2, or CYP2A6*3. Among 252 Japanese persons genotyped, 241 were genotyped as the wild type, 1 as an unknown variant, and none as either CYP2A6*2 or CYP2A6*3. A homozygous deletion was found in the 10 remaining subjects. To clarify the metabolic significance of this deletion in the whole human body, urinary cotinine, the principal metabolite of nicotine, was analyzed subsequent to smoking. Cumulated urinary cotinine excretion in the homozygously CYP2A6-deleted individuals was about one-seventh compared to the control group (wild type). This study provides a firm experimental basis for correlating genotypic characterization of CYP2A6 with phenotypic expression of nicotine metabolism.

Alleles↗

Lithium decreases Cl--ATPase activity and increases intracellular Cl- concentration in cultured rat hippocampal neurons.

Under the conditions of stimulated phosphatidylinositol turnover (0. 1 mM carbachol plus 20 mM KCl), LiCl (0.1-10 mM) reduced the activity of Cl--ATPase in cultured rat hippocampal neurons without affecting Na+/K+- or anion-insensitive Mg2+-ATPase. This inhibition of Cl--ATPase was attenuated by the addition of 0.5 mM inositol to culture media. The intracellular Cl- concentrations of the LiCl-treated neurons increased in an inositol-sensitive manner.

Adenosine Triphosphatases↗

Species differences in fodrin proteolysis in the ischemic brain.

There has been growing evidence that the breakdown of cytoskeletal proteins is an important biochemical change leading to ischemic neuronal death. In the present study, we investigated species differences in the susceptibility of fodrin to calpain activation induced by cerebral ischemia in gerbils, rats, and mice. In vivo fodrin proteolysis and degradation of microtubule-associated protein 2 after complete ischemia occurred more rapidly in the hippocampus and cerebral cortex of the gerbil brain than in the corresponding area of the rat and mouse brain. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 injected intraperitoneally before ischemia did not diminish fodrin degradation in the gerbil hippocampus. In vivo fodrin proteolysis was inhibited at 33 degrees C and enhanced at 41 degrees C compared with proteolysis at 37 degrees C during ischemia. However, in vitro fodrin proteolysis after addition of Ca2+ into the crude membrane fraction did not show any differences among three species. Although it is highly unlikely that the difference in the sensitivity of NMDA receptor or the sensitivity of calpain activation to calcium was the crucial determinant of susceptibility of fodrin degradation in the gerbil brain, the present study clearly demonstrated that fodrin in the gerbil brain was more susceptible to calpain activation induced by ischemia than that in the rat and mouse brains. Enhanced proteolysis may be one of the reasons neurons in the gerbil brain are highly vulnerable to ischemia.

Animals↗

DNA cleavage and proteolysis of microtubule-associated protein 2 after cerebral ischemia of different severity.

We report temporal profiles of cytoplasmic proteolysis and genomic DNA cleavage after cerebral ischemia of different severity in gerbils. Global forebrain ischemia by bilateral common carotid artery occlusion for 5 min with reperfusion, severe unilateral hemispheric ischemia by unilateral common carotid artery occlusion for 30 min with reperfusion, and complete ischemia by decapitation were used. The hippocampus was examined for proteolysis by using immunohistochemistry for microtubule-associated protein 2, DNA cleavage by using in situ nick-end labelling, and nuclear morphology by Hematoxylin staining. During evolution of delayed neuronal death after transient forebrain ischemia, loss of the immunoreaction for microtubule-associated protein 2 occurred almost in parallel with DNA cleavage in the CA1 region. In contrast, disappearance of the immunoreaction for microtubule-associated protein 2 was much faster than genomic DNA cleavage after unilateral hemispheric ischemia and reperfusion. The microtubule-associated protein 2 immunoreactivity was completely lost before development of changes in nuclear morphology or DNA cleavage after complete ischemia. The present study demonstrated the differences between necrosis and delayed neuronal death, but the nuclear morphology in the latter was not exactly the same as seen in apoptosis. Some elements of both necrotic and apoptotic machineries may work following transient ischemia, and the degree of ischemic insult may determine the character of cell death process.

Animals↗

SGT1 encodes an essential component of the yeast kinetochore assembly pathway and a novel subunit of the SCF ubiquitin ligase complex.

We have identified SGT1 as a dosage suppressor of skp1-4, a mutation causing defects in yeast kinetochore function. Sgt1p physically associates with Skp1p in vivo and in vitro. SGT1 is an essential gene, and different sgt1 conditional mutants arrest with either a G1 or G2 DNA content. Genetic and phenotypic analyses of sgt1-3 (G2 allele) mutants support an essential role in kinetochore function. Sgt1p is required for assembling the yeast kinetochore complex, CBF3, via activation of Ctf13p. Sgt1p also associates with SCF (Skp1p/Cdc53p/F box protein) ubiquitin ligase. sgt1-5 (G1 allele) mutants are defective in Sic1p turnover in vivo and Cln1p ubiquitination in vitro. Human SGT1 rescues an sgt1 null mutation, suggesting that the function of SGT1 is conserved in evolution.

Amino Acid Sequence↗

Molecular cloning of a novel member of the HSP110 family of genes, ischemia-responsive protein 94 kDa (irp94), expressed in rat brain after transient forebrain ischemia.

To identify genes induced by transient forebrain ischemia, we used the mRNA differential display technique in the four-vessel occlusion model in rats. Some genes were identified as candidates that encode ischemia-responsive protein, and one of them was cloned as ischemia-responsive protein 94 kDa (irp94) from the rat hippocampal cDNA library. Sequence analysis suggested that rat irp94 was a transcriptional variant or a homologue of mouse apg-2 and human heat shock protein (hsp) 70RY and a member of the HSP110 family, because IRP94 was >90% identical to APG-2 and HSP70RY and approximately 60% identical to the other members of the HSP110 family. Although irp94 mRNA was constitutively expressed in the normal hippocampus, it was clearly enhanced 4-24 h after ischemia for 10 (1.9-fold increase) and 15 min (3.4-fold increase). These changes mainly occurred in neuronal cells, as judged by the localization of irp94 mRNA using in situ hybridization histochemistry. On the other hand, hyperthermic stress did not enhance irp94 mRNA expression, suggesting that irp94 expression was enhanced under ischemic stress and not related to the heat shock signaling mechanism. Our study suggested that irp94, a novel member of the HSP110 family, might play an important role in the environment altering neuronal functions, especially after transient forebrain ischemia.

Animals↗

Physiological characteristics of well-trained synchronized swimmers in relation to performance scores.

The purpose of this study was to examine the relationships between the physiological characteristics of synchronized swimmers and their performance scores. The subjects were 16 trained female synchronized swimmers with a mean age of 17.2 +/- 1.7 years (mean +/- SD). The examined variables were body dimensions (height, width, body mass, circumference of the body and segment length), body composition, isokinetic muscle strength of the elbow and knee during extension and flexion, abdominal muscle endurance, anaerobic power (leg extension power and peak blood lactate concentration), aerobic power (maximum oxygen uptake [VO2max], swimming velocity at the onset of blood lactate accumulation [OBLA-V]), and flexibility (standing trunk flexion, prone trunk extension and distance between the open legs). The performance scores had significant correlations (p < 0.05) with isokinetic muscle strength of the elbow extension and flexion, and the knee extension, abdominal muscle endurance, leg extension power, VO2max x wt(-1), OBLA-V and distance between the open legs. However, no significant correlations were found between the performance scores and anthropometric variables. This study showed that the performance scores of synchronized swimmers correlated significantly with the functional aspects, and that muscle strength, muscle endurance and aerobic capacity seem to be particularly important determinants.

Adolescent↗

Neutron generator (HIRRAC) and dosimetry study.

Dosimetry studies have been made for neutrons from a neutron generator at Hiroshima University (HIRRAC) which is designed for radiobiological research. Neutrons in an energy range from 0.07 to 2.7 MeV are available for biological irradiations. The produced neutron energies were measured and evaluated by a 3He-gas proportional counter. Energy spread was made certain to be small enough for radiobiological studies. Dose evaluations were performed by two different methods, namely use of tissue equivalent paired ionization chambers and activation of method with indium foils. Moreover, energy deposition spectra in small targets of tissue equivalent materials, so-called lineal energy spectrum, were also measured and are discussed. Specifications for biological irradiation are presented in terms of monoenergetic beam conditions, dose rates and deposited energy spectra.

Dose-Response Relationship, Radiation↗

Human lymphocytes express hGH-N gene transcripts of 22kDa, 20kDa and minor forms of GH, but not hGH-V gene.

Expression of human growth hormone (hGH) in lymphocytes was examined by reverse transcription polymerase chain reaction (RT-PCR) in five normal subjects. Transcripts of hGH-N gene, but not hGH-V gene, were detected. Sequence analysis revealed four kinds of transcripts: 22kDa GH, 20kDa GH and two other forms of variant GH. The 20kDa GH transcript was generated by alternative splicing within exon 3, resulting in a 45bp deletion. One of the variant GH transcripts was also generated by alternative splicing within exon 3, but at a different site, resulting in a 73bp deletion. Because of a frameshift, this variant GH transcript may encode a 6.6kDa protein (truncated GH) that structurally differs from that of 22kDa GH after residue 31. In the other variant GH mRNA, exons 3 and 4 were completely skipped. The proportions of expression of 22kDa GH, 20kDa GH and the truncated GH were 60.9+/-13.6 (+/-S.D.)%, 32.7+/-14.1% and 6.4+/-1.1% (n=5), respectively, by comparative RT-PCR. We conclude that human lymphocytes, like the pituitary gland, express hGH-N gene transcripts of mainly 22kDa GH, but also 20kDa GH and minor variant forms of GH.

Adult↗