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Biomedical subjects

M Naito

Publications and source records attributed to M Naito.

At least 73 records · Page 4Linked to original sources
PubMed2001

Role of heme oxygenase-1 and Kupffer cells in the production of bilirubin in the rat liver.

Heme oxygenase (HO)-1, the heme-degrading enzyme in macrophages, plays a key role in bilirubin metabolism. HO-1 is expressed in various tissue macrophages, especially Kupffer cells. This study aimed to examine the roles of macrophages and HO-1 in the modulation of heme catabolism in rat livers. Rats treated with or without liposome-encapsulated dichloromethylene diphosphonate, a macrophage-depleting reagent, were administered with heat-denatured red blood cells (h-RBC), and the time course of the biliary output of bilirubin and the expressions of HO-1 mRNA and protein were monitored. Immunohistochemistry in the control rat liver revealed that Kupffer cells constitute a major cellular component expressing HO-1, while hepatocytes exhibited little expression. The levels of HO-1 expression in Kupffer cells were elevated immediately after injection of h-RBC. In Kupffer cell-depleted livers, however, HO-1-expressing cells were not detected even after h-RBC administration. HO-1 mRNA levels were elevated at 2 h after administration of h-RBC in control rat livers, while they were very low in Kupffer cell-depleted rat livers. The control and Kupffer cell-depleted groups exhibited distinct time courses of biliary bilirubin excretion. In the untreated control rats, total bilirubin excretion increased about two-fold at 5 h after h-RBC administration. In contrast, the Kupffer cell-depleting treatment decreased the level of bilirubin production; administration of h-RBC to Kupffer cell-depleted rats did not accelerate the generation of bilirubin. These results suggest that Kupffer cells serve both as a sensor for scenesent RBC clearance and an effector that upregulates heme-degrading capacity and bilirubin production.

Animals↗
PubMed2001

[A survey on how medical student consider end-if-life care in the elderly].

We examined the way medical students think about end-of-life care in the elderly by a questionnaire survey. The major variables of the evaluation instrument included the students' idea of the special nature of end-of-life care for the elderly, the necessity for disclosure of the name of disease, consideration for patient's age on disclosure, advance directives concerning their life-sustaining treatment, and communication concerning preferences for end-of-life care. The final items on the instrument asked for student comments about end-of-life care in the elderly. We analyzed this qualitative data using the process of immersion/crystallization. We received 95 responses, and of these 65 (68%) provided written commentaries that were analyzed using qualitative techniques. Fifty-nine (62%) students pointed out the special nature of end-of-life care in the elderly and most of them (96%) needed the disclosure of the name of disease. Fifty-two (55%) students agreed with advance directives for end-of-life care and 88 (93%) students pointed out the importance of communication with regard to patients' preferences. Medical students' concerns about end-of-life care in the elderly related to three major domains: 1) patient-physician relationship; 2) the procedures of end-of-life care; and 3) emotional and intuitive comments. These results suggest that in the education of geriatric medicine the patient-physician's relationship about end-of-life care is important and we may need to introduce systematic lectures and practical training.

Aged↗
PubMed2001

[Questionnaire survey comparing first-year medical students and non-medical students with regard to their level of interest and knowledge of care and terminal care for the elderly].

To study the level of interest and knowledge about care and terminal care for the elderly of medical students in Nagoya University, we made a questionnaire for first-year medical students (about 90 students per year) each April from 1998 to 2000. To assess the differences, we also gave the same questionnaire to 75 first-year non-medical students in 1999. Only about 10% of students had experienced providing care for member(s) of their family, but about one third stated that other family member(s) such as their mother, cared for older family member(s). The introduction of long-term care insurance was known by 22%, 43.5% and 96.6% of medical students in 1998, 1999 and 2000, respectively. Moreover, 19.8%, 13.0% and 52.3% of medical students knew about the care managers, respectively. About 80% of students hoped to be informed about their disease if they had terminal-stage cancer. However, about half of students could not decide whether to tell a family member who had terminal-stage cancer. Medical students had significantly more interest in the care system (68.5% in 1999) and terminal care (72.8% in 1999) for the elderly than non-medical students (41.3% and 40.0% in 1999, respectively). There were no significant differences between medical and non-medical students with regard to experiences of care, knowledge of long-term care insurance system and the attitudes to informing about terminal-stage cancer. However, more medical students had an interest in the elderly care system and terminal care than non-medical students.

Adult↗
PubMed2001

[Factors contributing to dying at home in elderly patients who received home care service].

This study examine whether around-the-clock medical support is a contributing factor to dying at home, and also tried to identify other such factors. Visiting nursing records of 81 elderly patients who died at home or in hospital after receiving home care at two facilities, one with and one without 24-hour medical support respectively were examined retrospectively. The subjects were divided into two groups: those who died at home and those who died in a hospital or nursing home. The two groups were compared in terms of clinical and sociodemographic characteristics and preferences for dying at home, expressed by patients, families and medical staff. Those who died at home showed a significantly higher rate of total dependence (84.6% vs. 48.1%) at month before death. Dying at home was significantly more preferred by all patients, families and medical staff. The major reason for hospitalization was rapid deterioration of the patients' condition. The facility with around-the-clock medical service had a higher rate of dying at home (42% vs. 27%, p = 0.18). Also, patients, families, and medical staff associated with their facility showed a higher preference for dying at home. We concluded from the above that the contributing factors for dying at home are: 1) total dependence level of ADL at one month before the death, and 2) preference for dying at home expressed by the patient, family and medical staff. This study suggests 24-hour medical support should be a requirement for in-home terminal care. Supporting advice from the staff to the family seems to be another contributing factor.

Aged↗
PubMed2001

Pathological fracture through a C-6 aneurysmal bone cyst. Case report.

The authors describe the case of an 18-year-old man who presented with complaints of weakness and paresis in his arms following an injury. Radiological examination demonstrated an aneurysmal bone cyst of C-6. The patient underwent a two-stage operation. Satisfactory results were obtained after complete resection of the lesion, laminoplasty, and anterior fusion without placement of instrumentation. The authors consider a two-stage operation supplemented by fusion without instrumentation to be the best treatment for young patients with aneurysmal bone cysts occurring at C-6.

Adolescent↗
PubMed2001

Comparison of direct methods and HPLC for the measurement of HDL- and LDL-cholesterol with ultracentrifugation.

Although ultracentrifugation is the gold standard for lipoprotein analysis, inexpensive and easy direct methods for HDL- and LDL-cholesterol (C) have recently been developed. In this study, we compared representative methods of lipoprotein analysis, namely, ultracentrifugation, direct assay methods, and HPLC, to measure LDL- and HDL-C. A good correlation was observed between HDL-C by ultracentrifugation and HDL-C by direct methods or HPLC. A good correlation was also observed between LDL-C (d1.006-1.063) by ultracentrifugation and LDL-C by direct methods or HPLC. Although the correlation between LDL-C (d1.019-1.063) by ultracentrifugation and LDL-C by direct methods was also good, the correlation coefficient was significantly decreased, suggesting that 'LDL-C' by direct methods correlates better with LDL-C (d1.006-1.063) than LDL-C (d1.019-1.063) by ultracentrifugation. Although the correlation between IDL-C (d1.006-1.019) by ultracentrifugation and the difference in LDL-C by direct methods and LDL-C (d1.019-1.063) by ultracentrifugation was investigated, no significant correlation was observed. The IDL-C contained in LDL-C (d1.006-1.063) varied from 2-28%. In homozygous CETP-deficient and LCAT-deficient subjects, the dissociation was marked. It is crucial to understand that 'LDL-C' in the Guidelines for the Diagnosis and Treatment of Hyperlipidemias in Adults by the Japanese Atherosclerosis Society should be considered to be LDL-C (d1.006-1.063) and that 'LDL-C' by direct assay methods means LDL-C (d1.006-1.063) by ultracentrifugation.

Aged↗
PubMed2001

Supernumerary ring chromosome in a Bednar tumor (pigmented dermatofibrosarcoma protuberans) is composed of interspersed sequences from chromosomes 17 and 22: a fluorescence in situ hybridization and comparative genomic hybridization analysis.

Cytogenetic analysis of Bednar tumor (pigmented dermatofibrosarcoma protuberans) has not been reported previously. Here, we report the identification of a supernumerary ring chromosome in a Bednar tumor by chromosome painting with fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Chromosome painting with FISH demonstrated that the supernumerary ring chromosome was composed of discontinuous, interwoven sequences from chromosomes 17 and 22. Amplification of chromosomes 17 and 22 sequences was confirmed by CGH. These results indicate that Bednar tumor and dermatofibrosarcoma protuberans are characterized by the same chromosomal features. To our knowledge, this is the first report that the ring chromosome in Bednar tumor is composed of amplified material from chromosomes 17 and 22.

Chromosome Banding↗
PubMed2001

Localization of primordial germ cells or their precursors in stage X blastoderm of chickens and their ability to differentiate into functional gametes in opposite-sex recipient gonads.

This study was performed to determine the distribution of primordial germ cells and their precursors in stage X blastoderm of chickens. The blastoderm (Barred Plymouth Rock chickens) isolated from the yolk was separated into three portions: the central disc, the marginal zone and the area opaca. The dissociated blastodermal cells derived from the central disc, marginal zone and area opaca were transferred into a recipient blastoderm (White Leghorn chicken) from which a cell cluster was removed from the centre of the central disc. The manipulated embryos were cultured in host eggshells until hatching. The chicks were raised until sexual maturity and test mated with Barred Plymouth Rock chickens to assess the donor cell contribution to the recipient germline. Germline chimaeric chickens were produced efficiently (46.7%, 7/15) when the blastodermal cells derived from the central disc were transferred into recipient embryos of the same sex, whereas no germline chimaeric chickens were produced when the blastodermal cells derived from the marginal zone or area opaca were transferred into recipient embryos of the same sex (0/12). Germline chimaeric chickens were also produced by transfer of blastodermal cells derived from the central disc (6.7%, 1/15), marginal zone (10.0%, 1/10) or area opaca (11.1%, 1/9) into recipient embryos of the opposite sex. It is concluded that primordial germ cells are induced during or shortly after stage X and that the cells derived from the central disc have the highest potential to give rise to germ cells. Cells derived from the marginal zone and area opaca can also give rise to germ cells, although the frequency is low.

Animals↗
PubMed2001

[Hemophagocytic syndrome with hemophagocytes in the peripheral blood].

A 79-year-old man developed a high fever, facial erythema, anemia and thrombocytopenia during conservative therapy for ischemic colitis. Peripheral hemophagocytes (PHP) were identified in smear specimens of peripheral blood, and hemophagocytes also showed proliferation in the bone marrow. After treatment with steroid and antibiotics under a diagnosis of bacteria-associated hemophagocytic syndrome, the patient recovered rapidly. Although the prognosis of hemophagocytic syndrome (HPS) depends on the underlying disease, any delay in diagnosis can sometimes result in a poor outcome in cases of infection-associated hemophagocytic syndrome. In the present case, early diagnosis of bacteria-associated hemophagocytic syndrome was made by detection of PHP. The appearance of PHP in virus-associated hemophagocytic syndrome (VAHS) and after administration of macrophage colony stimulating factor has been described. However, the significance and cytological characteristics of PHP have been unknown. In this report, we propose that PHP can be a useful indicator for early diagnosis of HPS, and we report 7 additional cases in which the PHP was detected retrospectively. The cytological characteristics and biological significance of PHP are discussed.

Aged↗
PubMed2001

Treatment of developmental dysplasia of the hip with the Pavlik harness: factors for predicting unsuccessful reduction.

To evaluate the risk factors for unsuccessful reduction, we reviewed 100 hips with developmental dysplasia of the hip treated with the Pavlik harness. We divided them into a successful reduction group (reduced without avascular necrosis) and an unsuccessful reduction group (reduced followed by avascular necrosis or unreduced). We compared Yamamuro's distance A, the acetabular angle and age at initial application of the Pavlik harness between the two groups. Our data suggest that a Yamamuro's distance A of 7 mm or smaller, an acetabular angle of 36 degrees or greater, and an age at initial application of 4 months or older are risk factors.

Acetabulum↗
PubMed2000

Inhibition of P-glycoprotein by orange juice components, polymethoxyflavones in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells.

We investigated the effects of the ethyl acetate extract of grapefruit juice (GFJ), that of orange juice (OJ) and their components on the uptake of [(3)H]vincristine into adriamycin-resistant human myelogenous leukemia cells. Its uptake was increased by the extracts of GFJ and OJ up to 7- and 3-fold, respectively, as well as verapamil and cyclosporin A. OJ components, i.e. 3,3',4',5,6,7,8-heptamethoxyflavone, nobiletin and tangeretin, also increased the uptake of [(3)H]vincristine in a concentration-dependent manner. Although GFJ components, dihydroxybergamottin and bergamottin, significantly increased the uptake, their potencies were considerably weaker than those of OJ components. These data suggest that OJ components inhibit P-gp-mediated efflux of [(3)H]vincristine, resulting in the intracellular accumulation of chemotherapeutic drugs. These components may become candidates of multi-drug resistance reversing agents in cancer chemotherapy.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors.

Interaction between endothelial cells and mural cells (pericytes and vascular smooth muscle) is essential for vascular development and maintenance. Endothelial cells arise from Flk1-expressing (Flk1+) mesoderm cells, whereas mural cells are believed to derive from mesoderm, neural crest or epicardial cells and migrate to form the vessel wall. Difficulty in preparing pure populations of these lineages has hampered dissection of the mechanisms underlying vascular formation. Here we show that Flk1+ cells derived from embryonic stem cells can differentiate into both endothelial and mural cells and can reproduce the vascular organization process. Vascular endothelial growth factor promotes endothelial cell differentiation, whereas mural cells are induced by platelet-derived growth factor-BB. Vascular cells derived from Flk1+ cells can organize into vessel-like structures consisting of endothelial tubes supported by mural cells in three-dimensional culture. Injection of Flk1+ cells into chick embryos showed that they can incorporate as endothelial and mural cells and contribute to the developing vasculature in vivo. Our findings indicate that Flk1+ cells can act as 'vascular progenitor cells' to form mature vessels and thus offer potential for tissue engineering of the vascular system.

Animals↗
PubMed2000

The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier.

L-DOPA is transported across the blood-brain barrier (BBB) by an amino acid transporter, system L. Recently, it has been demonstrated that system L consists of two subunits, 4F2hc and either LAT1 or LAT2. 4F2hc/LAT1 and 4F2hc/LAT2 show different transport characteristics, while their distribution in the brain has not been determined. To clarify whether 4F2hc/LAT1 participates in L-DOPA transport across the BBB, we first examined the expression of 4F2hc/LAT1 in the mouse brain capillary endothelial cell line, MBEC4, as an in vitro BBB model. Northern hybridization and immunoblotting revealed that both 4F2hc and LAT1 are expressed and form a heterodimer in MBEC4 cells. To confirm whether 4F2hc/LAT1 acts as system L to transport L-DOPA, we characterized L-DOPA uptake into the cells. The uptake process was time-dependent, temperature-sensitive, and Na(+)-independent. Neutral amino acids with bulky side chains and a bicyclic amino acid, 2-aminobicyclo-[2, 2,1]-heptane-2-carboxylic acid (BCH), inhibited L-DOPA uptake into MBEC4 cells to a great extent, while an acidic amino acid, basic amino acids, and glycine had no effect. Other neutral amino acids, such as alanine, asparagine, glutamine, serine, and threonine inhibited L-DOPA uptake by 40-70% at most. These characteristics are more compatible with those of 4F2hc/LAT1, rather than those of 4F2hc/LAT2. Finally, immunohistochemistry with anti-LAT1 antibody demonstrated that LAT1 is predominantly expressed in the microvessels of the central nervous system. This is the first report showing that the 4F2hc/LAT1 complex participates in L-DOPA transport across the BBB.

Amino Acid Transport Systems↗
PubMed2000

Immunochemical detection of protein dityrosine in atherosclerotic lesion of apo-E-deficient mice using a novel monoclonal antibody.

Dityrosine is one of the specific biomarkers for proteinoxidation. We prepared an antibody specific for proteindityrosine using a dimer of 3-p-(hydroxyphenyl)propionic acid (di-HP) as a hapten. Three clones (A8, G6, and 1C3) were obtained, and the antibody from the A8 clone reacted with the di-HP-conjugated protein but not with a dityrosine conjugate. The others (G6 and 1C3 clones) recognized both the di-HP and dityrosine conjugates. The antibodies reacted with peptidyl dityrosine, derived from Thr-Tyr-Ser, rather than the free dityrosine. The reactivity of the latter two antibodies with lens proteins oxidized by incubation with H(2)O(2)/Cu was in good accordance with the formation of the dityrosine-like fluorescence. Using the obtained monoclonal antibody, the immunopositive staining of atherosclerotic lesions in Apo E-deficient mice was confirmed by an immunohistochemical technique.

Animals↗
PubMed2000

Constitutive regulation of cardiac fatty acid metabolism through peroxisome proliferator-activated receptor alpha associated with age-dependent cardiac toxicity.

The peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear receptor superfamily and mediates the biological effects of peroxisome proliferators. To determine the physiological role of PPARalpha in cardiac fatty acid metabolism, we examined the regulation of expression of cardiac fatty acid-metabolizing proteins using PPARalpha-null mice. The capacity for constitutive myocardial beta-oxidation of the medium and long chain fatty acids, octanoic acid and palmitic acid, was markedly reduced in the PPARalpha-null mice as compared with the wild-type mice, indicating that mitochondrial fatty acid catabolism is impaired in the absence of PPARalpha. In contrast, constitutive beta-oxidation of the very long chain fatty acid, lignoceric acid, did not differ between the mice, suggesting that the constitutive expression of enzymes involved in peroxisomal beta-oxidation is independent of PPARalpha(.) Indeed, PPARalpha-null mice had normal levels of the peroxisomal beta-oxidation enzymes except the D-type bifunctional protein. At least seven mitochondrial fatty acid-metabolizing enzymes were expressed at much lower levels in the PPARalpha-null mice, whereas other fatty acid-metabolizing enzymes were present at similar or slightly lower levels in the PPARalpha-null, as compared with wild-type mice. Additionally, lower constitutive mRNA expression levels of fatty acid transporters were found in the PPARalpha-null mice, suggesting a role for PPARalpha in fatty acid transport and catabolism. Indeed, in fatty acid metabolism experiments in vivo, myocardial uptake of iodophenyl 9-methylpentadecanoic acid and its conversion to 3-methylnonanoic acid were reduced in the PPARalpha-null mice. Interestingly, a decreased ATP concentration after exposure to stress, abnormal cristae of the mitochondria, abnormal caveolae, and fibrosis were observed only in the myocardium of the PPARalpha-null mice. These cardiac abnormalities appeared to proceed in an age-dependent manner. Taken together, the results presented here indicate that PPARalpha controls constitutive fatty acid oxidation, thus establishing a role for the receptor in cardiac fatty acid homeostasis. Furthermore, altered expression of fatty acid-metabolizing proteins seems to lead to myocardial damage and fibrosis, as inflammation and abnormal cell growth control can cause these conditions.

Aging↗
PubMed2000

Glyoxalase I is involved in resistance of human leukemia cells to antitumor agent-induced apoptosis.

Abnormality in the machinery of apoptosis is associated with a resistant phenotype of the tumor cell to chemotherapy. To determine the molecular basis of resistance to antitumor agent-induced apoptosis, we performed a complementary DNA (cDNA) subtractive hybridization with messenger RNA (mRNA) from human monocytic leukemia U937 and its variant UK711, which is resistant to apoptosis induced by antitumor agents. We found that glyoxalase I (GLO1), an enzyme that detoxifies methylglyoxal, is selectively overexpressed in the apoptosis-resistant UK711 cells. The GLO1 enzyme activity was significantly elevated in UK711 and UK110 cells, another drug-resistant mutant, as well as in K562/ADM, adriamycin-resistant leukemia cells, compared with their parental cells. When overexpressed in human Jurkat cells, GLO1 inhibited etoposide- and adriamycin-induced caspase activation and apoptosis, indicating the involvement of GLO1 in apoptosis suppression caused by these drugs. Moreover, cotreatment with S-p-bromobenzylglutathione cyclopentyl diester (BBGC), a cell-permeable inhibitor of GLO1, enhanced etoposide-induced apoptosis in resistant UK711 cells but not in parental U937 cells. Taken together, these results indicate that GLO1 is a resistant factor to antitumor agent-induced apoptosis in human leukemia cells and that the GLO1 inhibitor could be a drug resistance-reversing agent.

Antineoplastic Agents↗