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Biomedical subjects

K Kitagawa

Publications and source records attributed to K Kitagawa.

At least 19 recordsLinked to original sources
PubMed2000

Twenty-three Cases of Primary Cornea Guttata.

Purpose: An evaluation of 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 one eye of a 79-year-old man who was speculated to be at an early stage of Fuch's 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 Fuch's dystrophy.

Journal Article↗
PubMed2000

Regional difference of neuronal vulnerability in the murine hippocampus after transient forebrain ischemia.

We have investigated the regional difference of neuronal vulnerability within the hippocampus in the C57BL/6 strain mice after forebrain ischemia. Both common carotid arteries of fifty mice were occluded for 12 min and the mouse brain was examined with cresyl violet staining. The CA4 sector was found to be the most vulnerable within the hippocampus. The CA2 and the medial CA1 sector was the 2nd and 3rd most vulnerable regions. However, The lateral part of the CA1 sector, CA3 sector and the dentate gyrus were resistant to ischemic insult.

Animals↗
PubMed2000

Aldehyde dehydrogenase (ALDH) 2 associates with oxidation of methoxyacetaldehyde; in vitro analysis with liver subcellular fraction derived from human and Aldh2 gene targeting mouse.

A principal pathway of 2-methoxyethanol (ME) metabolism is to the toxic oxidative product, methoxyacetaldehyde (MALD). To assess the role of aldehyde dehydrogenase (ALDH) in MALD metabolism, in vitro MALD oxidation was examined with liver subcellular fractions from Japanese subjects who carried three different ALDH2 genotypes and Aldh2 knockout mice, which were generated in this study. The activity was distributed in mitochondrial fractions of ALDH2*1/*1 and wild type (Aldh2+/+) mice but not ALDH2*1/*2, *2/*2 subjects or Aldh2 homozygous mutant (Aldh2-/-) mice. These data suggest that ALDH2 is a key enzyme for MALD oxidation and ME susceptibility may be influenced by the ALDH2 genotype.

Acetaldehyde↗
PubMed2000

Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans.

Expansion of polyglutamine repeats in several unrelated proteins causes neurodegenerative diseases with distinct but related pathologies. To provide a model system for investigating common pathogenic features, we have examined the behavior of polyglutamine expansions expressed in Caenorhabditis elegans. The expression of polyglutamine repeats as green fluorescent protein (GFP)-fusion proteins in body wall muscle cells causes discrete cytoplasmic aggregates that appear early in embryogenesis and correlates with a delay in larval to adult development. The heat shock response is activated idiosyncratically in individual cells in a polyglutamine length-dependent fashion. The toxic effect of polyglutamine expression and the formation of aggregates can be reversed by coexpression of the yeast chaperone Hsp104. The altered homeostasis associated with polyglutamine aggregates causes both the sequestration of an otherwise soluble protein with shorter arrays of glutamine repeats and the relocalization of a nuclear glutamine-rich protein. These observations of induced aggregation and relocalization have implications for disorders involving protein aggregation.

Animals↗
PubMed2000

Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication.

The ubiquitin-proteasome pathway plays an important role in control of the abundance of cell cycle regulators. Mice lacking Skp2, an F-box protein and substrate recognition component of an Skp1-Cullin-F-box protein (SCF) ubiquitin ligase, were generated. Although Skp2(-/-) animals are viable, cells in the mutant mice contain markedly enlarged nuclei with polyploidy and multiple centrosomes, and show a reduced growth rate and increased apoptosis. Skp2(-/-) cells also exhibit increased accumulation of both cyclin E and p27(Kip1). The elimination of cyclin E during S and G(2) phases is impaired in Skp2(-/-) cells, resulting in loss of cyclin E periodicity. Biochemical studies showed that Skp2 interacts specifically with cyclin E and thereby promotes its ubiquitylation and degradation both in vivo and in vitro. These results suggest that specific degradation of cyclin E and p27(Kip1) is mediated by the SCF(Skp2) ubiquitin ligase complex, and that Skp2 may control chromosome replication and centrosome duplication by determining the abundance of cell cycle regulators.

Animals↗
PubMed2000

Inherited polymorphism in the N-acetyltransferase 1 (NAT1) and 2 (NAT2) genes and susceptibility to gastric and colorectal adenocarcinoma.

The polymorphic arylamine N-acetyltransferases (NAT1 and NAT2) have been implicated in increased susceptibility to certain malignancies. We analyzed genetic polymorphisms in both the NAT1 and NAT2 genes among 140 gastric adenocarcinoma patients, 103 colorectal adenocarcinoma patients and 122 healthy controls from Japan. The frequency of the specific genotype NAT1*10 allele, which contains a variant polyadenylation signal, was higher among all gastric adenocarcinoma cases, but this increase did not reach statistical significance. After grouping according to tumor differentiation of gastric adenocarcinoma patients, NAT1 polymorphism was a risk factor among the well-differentiated type of tumors (OR = 3.03, 95% CI 1. 08-8.46). Stratifying by smoking status, we found that the OR for heavy smokers with the NAT1*10 allele was 2.97 (95% CI 1.23-7.14). When the combined risk of NAT1*10 allele from smoking and tumor differentiation was calculated, we found that the risk of the NAT1*10 allele with heavy smoking was increased among the well - differentiated type of gastric adenocarcinoma (OR = 4.24, 95% CI 0. 87-20.6). The NAT1*10 genotype was not a significant risk factor in colorectal adenocarcinoma. No statistically significant differences were observed in the frequency of NAT2 rapid acetylation genotype in gastric (91.4%) or colorectal (95.2%) adenocarcinoma patients when compared with the control population (94.3%). Our results suggest the NAT1*10 allele may be an important genetic determinant of the well-differentiated type of gastric adenocarcinoma, which may be induced by smoking.

Acetyltransferases↗
PubMed2000

Extended neuronal protection induced after sublethal ischemia adjacent to the area with delayed neuronal death.

In the present study, we investigated whether neurons adjacent to an ischemic lesion acquire tolerance against subsequent ischemia or not. We initially used unilateral hemispheric ischemia for 3 min in gerbils to produce an ischemic lesion confined to the unilateral CA1 sector, and the presence of tolerance was examined in the adjacent CA3 sector through transient global ischemia by occlusion of both common carotid arteries. Attenuation of neuronal damage was clearly observed in neurons in the CA3 sector adjacent to the ischemic lesion in the CA1 sector. The phenomenon lasted for up to two weeks after the initial hemispheric ischemia, but was no longer present two months later. Reactive astrocytes as identified by the presence of glial fibrillary acidic protein were visible in the CA3 hippocampus four days and two weeks after hemispheric ischemia, but they were scarce two months later. Expression of heat shock protein 72 in the CA3 neurons was observed four days after hemispheric ischemia, but the reaction returned to the control level two weeks later. In conclusion, the present study showed that tolerance in the neurons adjacent to an ischemic lesion could be sustained at least for two weeks, and raised the possibility that reactive astrocytes might contribute to the extended tolerance in neurons.

Animals↗
PubMed2000

Stabilization of a tyrosine O-sulfate residue by a cationic functional group: formation of a conjugate acid-base pair.

Sulfated tyrosine [Tyr(SO3H)]-containing peptides showed characteristic peak patterns in their liquid secondary-ion mass spectrometry (LSIMS) spectra. Protonated molecules were desulfated more easily than their deprotonated counterparts. Therefore, the stabilities of the Tyr(SO3H) residues were well-reflected by peak patterns in their positive-ion spectra. These intrinsic peak patterns were investigated by comparing the behavior of each Tyr(SO3H) residue in acidic solution. As the peptide chain was lengthened and the number of cationic functional groups increased, the peak representing the [MH]+ of a Tyr(SO3H)-containing peptide became more prominent than that representing the desulfated [MH-SO3]+. These alterations in peptide structure also increased the stability of the Tyr(SO3H) residue in acidic solution. Based on the desulfation mechanism of an aryl monosulfate, we predicted that intramolecular cationic functional groups would stabilize Tyr(SO3H) residues by forming conjugate acid-base pairs (or salt bridges) both in the gaseous phase and in acidic solution. In accordance with this theory, Arg residues would take primary responsibility for this self-stabilization within Tyr(SO3H)-containing peptides. Moreover, a long peptide backbone was expected to have a weak protective effect against desulfation of the [MH]+ in the gaseous phase. Tyr(SO3H) residues were also stabilized by adding an external basic peptide containing multiple Arg residues. Formation of such intermolecular acid-base pairs was demonstrated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) which detected conjugated peptide ions. The energetically favorable formation of conjugate acid-base pairs prompted by Tyr(SO3H) residues might be a driving force for protein folding and protein-protein interaction.

Amino Acid Sequence↗
PubMed2000

Relationship among oxygenation, myoelectric activity, and lactic acid accumulation in vastus lateralis muscle during exercise with constant work rate.

The purpose of this study was to determine whether oxygenation in localized working muscle depended on the muscle activity and on the lactic acidosis level. Seven healthy male subjects underwent the five 6-min cycling exercises with work rates of 50 watts (25.0 +/- 5.0% VO2max), 100 watts (36.6 +/- 6.2% VO2max), 150 watts (50.6 +/- 7.7% VO2max), 200 watts (67.8 + 6.9% VO2max), and 250 watts (82.9 +/- 7.5% VO2max) while gas exchange parameters and blood lactate concentration (BL) were measured. We also measured oxygenated hemoglobin and myoglobin concentration (oxy-Hb/Mb) with continuous-wave near infrared spectroscopy (NIR) and surface myoelectric activity with surface electrodes (EMG). The NIR probe and electrodes were positioned on the vastus lateralis muscle of the right leg. The relative change in oxy-Hb/Mb was estimated by regarding oxy-Hb/Mb in the resting condition as 100% and that obtained during thigh occlusion as 0%. The mean values of oxy-Hb/Mb and integrated EMG (iEMG) were determined from 5'30" to 6'00" at each work rate. The percentage of oxy-Hb/Mb was sustained at the first two work rates corresponding to 25.0 +/- 5.0 and 36.6 +/- 6.2% VO2max and decreased slightly at 150 watts corresponding to 50.6 +/- 7.7% VO2max, which was followed by a linear decrease at 200 and 250 watts corresponding to 67.8 +/- 6.9 and 82.9 +/- 7.5% VO2max. The iEMG, however, was increased slowly at 25.0 +/- 5.0 to 50.6 +/- 7.7% VO2max, and a rapid increment of the iEMG occurred at 67.8 +/- 6.9 and 82.9 +/- 7.5% VO2max. BL was sustained at 25.0 +/- 5.0 to 50.6 +/- 7.7% VO2max and increased linearly at 67.8 +/- 6.9 and 82.9 +/- 7.5% VO2max. There was a significant negative correlation for each subject between the percentage of oxy-Hb/Mb and iEMG (r = -0.947 to -0.993), between the percentage of oxy-Hb/Mb and BL (r = -0.890 to -0.982), and between the percentage of oxy-Hb/Mb and VO2 (r = -0.929 to -0.994) These results indicated that oxygenated hemoglobin/myoglobin concentration measured with NIR reflected the muscle activity and the lactic acidosis.

Acidosis, Lactic↗
PubMed2000

Physiological loads in the team technical and free routines of synchronized swimmers.

PURPOSE: The purpose of the present study was to examine the physiological loads on synchronized swimmers during team technical and free routines by measuring their blood lactate concentrations and percentage of peak blood lactate concentration. METHODS: Four trained college female synchronized swimmers participated as the subjects. The blood lactate concentration was measured in the first and middle periods and after the team technical and free routines. Peak blood lactate concentration was measured after maximum exertion in 100-m freestyle swimming. RESULTS: Average values and SD of blood lactate concentration and the percentage of peak blood lactate concentration after the team technical and free routines were 4.7 +/- 1.1 mmol x L(-1), 46.2 +/- 11.0% and 4.3 +/- 1.1 mmol x L(-1), 42.8 +/- 11.5%, respectively. The blood lactate concentration and percentage of peak blood lactate concentration after the team technical routine were significantly higher than those in the first period, and the blood lactate concentration after the team free routine was significantly higher than in the middle period. CONCLUSIONS: The blood lactate concentration of synchronized swimmers during the team technical and free routines in the present study tended to increase with the performance time. Thus, the predominant sources of energy may be phosphocreatine stores and aerobic metabolism during these routines, although glycolysis may also play an important role in relation to the energy requirements in the final period.

Adolescent↗
PubMed2000

Contribution of microglia/macrophages to expansion of infarction and response of oligodendrocytes after focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: The purpose of this study was (1) to examine the contribution of microglia and macrophages with their interleukin-1beta production and (2) to assess the vulnerability and response of oligodendrocytes in cerebral infarction. METHODS: Male Wistar rats were subjected to permanent occlusion of the left middle cerebral artery. Expansion of ischemic infarction and response of oligodendrocytes were investigated together with accumulation of inflammatory cells, production of interleukin-1beta, and disruption of the blood-brain barrier. Apoptotic cell death was inferred from fragmented DNA and the expression of proapoptotic Bax protein. RESULTS: During expansion of infarction, amoeboid microglia and extravasation of serum albumin were observed not only in the infarcted area but also in the adjacent surviving area, whereas macrophages accumulated along the boundary and granulocytes migrated into the center of the infarction. Both amoeboid microglia and macrophages produced interleukin-1beta, an inflammatory cytokine, during an early ischemic period. Furthermore, macrophages within the infarcted tissue expressed Bax protein and subsequently showed fragmented nuclear DNA. Oligodendrocytes were detected in the infarcted area even after 24 hours following middle cerebral artery occlusion, but they subsequently developed fragmented DNA. A week after onset of ischemia, oligodendrocytes were found to be accumulated in the intact area bordered with the infarct together with reactive astrocytes. CONCLUSIONS: Our results suggest the importance of amoeboid microglia, macrophages, and their interleukin-1beta production in gradual expansion of cerebral infarction. Resident oligodendrocytes may be resistant to ischemic insults, and oligodendrocytes accumulated at the border of the infarction may participate in tissue repair after cerebral infarction.

Animals↗
PubMed2000

Synthesis of [1]benzopyrano[2,3,4-kl]acridin-3-ol and its analogues as pentacyclic compounds.

A new heterocyclic compound, [1]benzopyrano[2,3,4-kl]acridin-3-ol was synthesized by cyclization of xanthone derivatives. The key compound, 1-(3'-methoxyanilino)-xanthone, was prepared from 1-aminoxanthone. [1]benzopyrano[2,3,4-kl]acridin-3-ol analogues, [1]benzothiopyrano[2,3,4-kl]acridin-3-ol, pyrido[3',2':5,6]pyrano[2,3,4-kl]acridin-3-ol and pyrido[3',2':5,6]thiopyrano[2,3,4-kl]acridin-3-ol were synthesized by the same method.

Acridines↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

[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↗
PubMed2000

[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↗