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Biomedical subjects

K Kumamoto

Publications and source records attributed to K Kumamoto.

At least 19 recordsLinked to original sources

Are there inequities in the assessment of dementia under Japan's LTC insurance system?

BACKGROUND: Just two years after its inception, Japan's Long-term Care (LTC) insurance system is facing considerable criticism about whether or not it has developed a fair and appropriate way of allocating resources to the nation's disabled elderly population, especially those people with dementia. OBJECTIVE: The present study has investigated: (i) the relation of the Government-Certified Disability Index (GCDI) of the LTC insurance system to characteristics of people with dementia and their family caregivers; and (ii) whether the GCDI scores adequately reflect needs of people with DAT (dementia of Alzheimer's type) and VD (vascular-type dementia). METHODS: Subjects were assessed on their visits to outpatient clinics for their Activities of Daily Living (ADL), behavioural disturbances, MMSE, GCDI, service utilization and caregiver burden. Correlation analyses were conducted to examine the relationships among these variables, which were subsequently compared between the DAT and VD patients. RESULTS AND CONCLUSIONS: The GCDI was found to be associated with patients' ADLs and MMSE scores, and not with behavioural disturbances or caregiver burden. Compared to VD patients, people with DAT tended to have more behavioural disturbances but better ADL functioning. As a result, DAT patients were classified as 'less disabled' on their GCDI than VD patients, even though their caregivers felt as much burden as the caregivers of VD patients. These results show that the GCDI probably underestimates the impact of behaviour problems. Suggestions are made for a more balanced assessment of demented patients that is more consistent with their needs.

Activities of Daily Living↗

Immunohistochemical studies on the distribution of nerve fibers in the human prostate with special reference to the anterior fibromuscular stroma.

BACKGROUND: Although the anterior fibromuscular stroma (AFMS) comprises up to one third of the total bulk of the prostate, its physiological function remains unknown. We recently reported the possible contribution of the AFMS to micturition. The aim of this study is to reveal the differences in the distribution of innervation between the AFMS and the other regions of the prostate. METHODS: We performed immunohistochemical stainings using antibodies such as protein gene product (PGP) 9.5, tyrosine hydroxylase(TH), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP). Morphometric analysis was made to examine the density of peripheral nerve fibers containing PGP 9.5, TH, NPY, and VIP by using a computer-assisted imaging system. RESULTS: The number of PGP 9.5-immunoreactive (IR) nerve fibers and the smooth muscle in the AFMS decreased from the base to the apex of the prostate. TH-IR nerve fibers were more abundant in the AFMS than in the transition zone. NPY- and VIP-IR nerve fibers were less numerous in the AFMS than in the peripheral zone. CONCLUSIONS: This study is the first to demonstrate that the AFMS has peculiar neuronal innervation. We observed significantly different innervation in the AFMS compared with the other regions of the prostate.

Aged↗

Increased expression of UDP-galactose transporter messenger RNA in human colon cancer tissues and its implication in synthesis of Thomsen-Friedenreich antigen and sialyl Lewis A/X determinants.

A series of human nucleotide sugar transporters of the Golgi apparatus was recently cloned, including the transporters for UDP-galactose (UDP-Gal), UDP-N-acetylglucosamine (UDP-GlcNAc) and CMP-sialic acid (CMP-SA). We have examined the mRNA expression of these three transporters in human colon cancer tissues by reverse transcription-PCR analysis and compared it with that in nonmalignant colonic mucosa prepared from the same patients. The amount of mRNA for UDP-Gal transporter was significantly increased in colon cancer tissues compared with nonmalignant mucosa tissues (P = 0.035; n = 20). The increase was more prominent in patients with advanced colorectal cancer of Dukes' stages C and D, in which the amount of UDP-Gal transporter mRNA in cancer tissues showed on average about a 3.6-fold increase over the paired nonmalignant mucosa (statistically significant at P = 0.004; n = 14). The mRNA content of the other two transporters showed no significant difference between the paired cancer and normal tissues. When UDP-Gal transporter cDNA was stably transfected to cultured human colon cancer cells, the expression of Thomsen-Friedenreich (TF) antigen and of sialyl Lewis A (NeuAcalpha2-->3Galbeta1-->3[Fucalpha1-->4]GlcNAcbeta1-->R) and sialyl Lewis X (NeuAcalpha2-->3Galbeta1-->4[Fucalpha1-->3]GlcNAcbeta1-->R) determinants was significantly induced on transfectant cells, which resulted in markedly enhanced cell adhesion to vascular E-selectin. These findings suggest that the increase of UDP-Gal transporter mRNA is involved in the enhanced expression of cancer-associated carbohydrate determinants such as TF and sialyl Lewis A/X antigens in colon cancers.

Antigens, Neoplasm↗

Purification of the major allergen of red soft coral (Dendronephthya nipponica).

Red soft coral (RSC; Dendronephthya nipponica, a marine coelenterate) causes spiny lobster fishermen living along the Pacific coast of Miyazaki Prefecture in Japan to develop occupational allergies, such as conjunctivitis, rhinitis, dermatitis and bronchial asthma. The aim of this study was to purify and to characterize RSC allergen, which causes occupational asthma in spiny lobster fishermen. The allergic responsiveness of spiny lobster fishermen to RSC was examined. The examinations included specific IgE production, skin test responses, lymphocyte stimulation tests and specific IgG production. We found that RSC has a strong sensitizing activity in humans at a molecular weight of 10 kD or more, while it has no IgE-producing activity at a molecular weight of less than 10 kD. Neither the nonatopic controls nor the atopic non-coral-allergic controls exhibited any RAST-binding activity to any fraction. For the purification and the identification of this new allergen component, repeated gel filtration of the RSC extract was performed on a Sephacryl S-200 column, followed by gel filtration on a Superose-6 column. The purified major allergen component Den n 1, which is separated on a Mono-Q column, showed intradermal responses, lymphocyte stimulating activity and specific IgG-producing activity in RSC-induced bronchial asthma patients. The 53-kD component was electroblotted on a polyvinylidene difluoride membrane. The N-terminal amino acid sequence of this new allergen component (Den n 1) was determined as Asp-Asp-Ile-Asn-Arg-Tyr-Ala-Phe-Asp-Asn-Lys-Ile-Asn- Asp-Lys-Leu-Phe-Asp-His-Trp-Gln-Ser.

Adult↗

Plasma and BAL fluid concentrations of antimicrobial peptides in patients with Mycobacterium avium-intracellulare infection.

STUDY OBJECTIVES: To investigate the roles of human alpha-defensin (HAD), human beta-defensin (HBD)-1, and HBD-2, novel antimicrobial peptides, in patients with Mycobacterium avium-intracellulare infection (MAI). PATIENTS: The study included 25 patients (10 men) with MAI who visited our hospital between June 1998 and August 1999. MEASUREMENTS AND RESULTS: In patients with pulmonary MAI, we measured HAD and HBD-1, and HBD-2 levels in plasma and in BAL fluid (BALF) by radioimmunoassay. Plasma concentrations of HAD and HBD-2 in those patients were higher than those in control subjects, whereas HBD-1 levels were similar to those in the control subjects. High levels of HAD and HBD-2, but not HBD-1, also were observed in the BALF of MAI patients. There was a positive correlation between HAD and interleukin (IL)-8 concentrations in the BALF of patients with MAI. BALF HBD-2 concentrations also correlated positively with those of plasma HBD-2 and BALF IL-1 beta in MAI patients. Patients with cavity formation on the chest roentgenogram had higher HAD and HBD-2 levels in their BALF than those of patients without cavity formation. Treatment with clarithromycin combined with two or three other antibiotics, including ethambutol, rifampicin, ofloxacin, or ciprofloxacin, for at least 6 months resulted in a significant fall in plasma HBD-2 concentrations in responders, but not in nonresponders. CONCLUSION: Our findings suggest that HAD and HBD-2 may participate in host defense and local remodeling of the respiratory tract in patients with MAI and that plasma HBD-2 levels may be a useful marker of disease activity in patients with pulmonary MAI.

Anti-Bacterial Agents↗

[Beta-defensins in plasma and bronchoalveolar lavage fluid in patients with non-tuberculous mycobacterium infection].

We measured the levels of beta-defensin 1 and 2 (HBD-1, 2), novel antimicrobial peptides in plasma and in bronchoalveolar lavage fluid (BALF) from patients with with non-tuberculous mycobacterium infection (NTM). Plasma HBD-2 levels in NTM patients before treatment were higher than those in the controls, while the HBD-1 levels were similar to the control levels. High levels of HBD-2, but not of HBD-1, in BALF were also observed in NTM patients. In NTM, a positive correlation was found between HBD-2 levels in BALF and plasma, and also between HBD-2 and IL-1 beta levels in BALF. NTM patients with cavities or ectasia on chest radiography had higher HBD-2 levels in BALF than those without. Plasma HBD-2 levels in NTM patients were markedly decreased after successful treatment, while those of patients with an intractable mycobacterium infection maintained the same high plasma HBD-2 levels as those before treatment. These findings suggest that HBD-2 may participate in the host defense and plasma HBD-2 levels may reflect disease activity in pulmonary NTM.

Biomarkers↗

Expression of sialyl 6-sulfo Lewis X is inversely correlated with conventional sialyl Lewis X expression in human colorectal cancer.

Sialyl 6-sulfo Lewis X determinant has been described recently as a major ligand for L-selectin on high endothelial venules of human peripheral lymph nodes. From our investigation of its distribution in human colorectal cancer tissues and cultured colon cancer cells, the sialyl 6-sulfo Lewis X determinant was preferentially expressed in the nonmalignant colonic epithelia rather than cancer cells (P < 0.001; n = 23). This was in contrast to the distribution of conventional sialyl Lewis X, which was preferentially expressed in cancer tissues rather than nonmalignant epithelia (P = 0.007; n = 23), indicating that 6-sulfation predominantly occurs in nonmalignant tissues and is suppressed upon malignant transformation. In confirmation of this, a nonsialylated determinant 6-sulfo Lewis X was also found to be preferentially localized in the nonmalignant epithelia. Significant expression of sialyl 6-sulfo Lewis X was observed in only 2 lines, whereas 8 were positive for conventional sialyl Lewis X, among 13 cultured colon cancer cell lines. Transfection of cells with fucosyltransferase (Fuc-T) VI induced expression of sialyl 6-sulfo Lewis X, whereas transfection of Fuc-T III did not, suggesting that the determinant was synthesized mainly by Fuc-T VI in colonic epithelia. Members of the sialic acid cyclase pathway, the de-N-acetyl sialyl 6-sulfo Lewis X and cyclic sialyl 6-sulfo Lewis X determinants, were also preferentially expressed in the nonmalignant epithelia rather than colonic cancer cells (P < 0.001; n = 23). Stimulation of the sialyl 6-sulfo Lewis X-positive colon cancer cell line with a calcium ionophore ionomycin markedly reduced sialyl 6-sulfo Lewis X and induced cyclic sialyl 6-sulfo Lewis X expression. These results suggested that the metabolic conversion of sialyl 6-sulfo Lewis X into cyclic sialyl 6-sulfo Lewis X by a calcium-dependent enzyme, sialic acid cyclase, as we hypothesized for human leukocytes previously (C. Mitsuoka et al., Proc. Natl. Acad. Sci. USA, 96: 1597-1602, 1999), also occurs in nonmalignant colonic epithelia.

Colorectal Neoplasms↗

Paragonimiasis westermani with multifocal lesions in lungs and skin.

We report a case of Paragonimus westermani infection with a reticulonodular lesion in the right lung, left pleural effusion, and a mobile subcutaneous mass. Analyses of pleural effusion and bronchoalveolar lavage fluid (BALF) showed marked eosinophilia and high levels of eosinophil cationic protein and interleukin (IL)-5. Transbronchial lung biopsy revealed the presence of pneumonia with mild eosinophilic infiltration but remarkable lymphocytic infiltration. In this patient, high IL-5 levels in both BALF and pleural effusion could explain the remarkable eosinophilia.

Aged↗

Nicotine induces uncoupling protein 1 in white adipose tissue of obese mice.

OBJECTIVE: To test the hypothesis that nicotine not only activates uncoupling protein1 (UCP1) in brown adipose tissue (BAT), but also induces UCP1 in white adipose tissue (WAT), which contributes to the mitigation of obesity in obese mice. DESIGN: Weights of the whole body, the gastrocnemius muscle, interscapular BAT and subcutaneous and retroperitoneal WAT, food intake and the mRNA and protein of UCP1 in these tissues were measured and immunohistochemistry using antiserum against UCP1 was also performed in obese yellow KK mice treated with nicotine for 6 months and control mice treated with physiological saline. RESULTS: Obese mice treated with nicotine for 6 months, compared with those injected with saline, weighed significantly less (P < 0.01) and had smaller subcutaneous and retroperitoneal WAT pads (P < 0.01), while obese mice that received nicotine ate less (P < 0.05) than those injected with saline. In mice treated with nicotine, the mRNA and protein of UCP1 was detected not only in BAT, but also in subcutaneous and retroperitoneal WATs. Immunohistochemically, the BAT of obese mice contained large lipid droplets and appeared rather WAT-like, but changed to typical brown adipocytes after nicotine treatment. The fat pads of nicotine-treated mice contained many multilocular cells that were positive for UCP1. CONCLUSION: Nicotine not only activates UCP1 in BAT, but also induces UCP1 in WAT and decreases food intake, which contributes to the mitigation of obesity.

Adipocytes↗

[BCA225].

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Biomarkers, Tumor↗

Specific detection of sialyl Lewis X determinant carried on the mucin GlcNAcbeta1-->6GalNAcalpha core structure as a tumor-associated antigen.

Sialyl Lewis X serves as a ligand for selectins and is proposed to be implicated in hematogenous metastasis of cancers. When a cultured human breast cancer cell line, MCF-7, which does not express sialyl Lewis X, was transfected with human fucosyltransferase VI cDNA, a strong expression of sialyl Lewis X was induced on transfectant cells. The transfectant cells were found to be also reactive to the antibody NCC-ST-439, which was initially raised against human gastric cancer cells and later was shown to recognize a tumor-associated carbohydrate antigen in breast, gastric, and colon cancers. This suggested that the antigen recognized by NCC-ST-439 is closely related to sialyl Lewis X. Subsequent studies indicated that NCC-ST-439 specifically reacts to NeuAcalpha2-->3Galbeta1-->4(Fucalpha1-->3)GlcNAcbet a1-->6GalNAcalpha1 -->R, the sialyl Lewis X on the mucin GlcNAcbeta1-->6 GalNAcalpha structure. The antibody was not reactive to the conventional sialyl Lewis X determinants on straight and/or branched polylactosamine structures including NeuAcalpha2-->3Galbeta1-->4(Fucalpha1-->3)GlcNAcbet a1-->3Galbeta1-->4 Glcbeta1-->R and NeuAcalpha2-->3Galbeta1-->4(Fucalpha1-->3)GlcNAcbet a1-->6Galbeta1-->4 Glcbeta1-->R. This was in clear contrast to most of the known anti-sialyl Lewis X antibodies, which do not discriminate internal structures carrying the sialyl Lewis X determinant. On the other hand, the newly generated monoclonal antibody GSC154-27 had a specificity completely the reverse of the specificity of NCC-ST-439 in that it was strongly reactive to the conventional sialyl Lewis X determinants in straight and branched polylactosamine structures, while far less reactive to the sialyl Lewis X determinant on the mucin GlcNAcbeta1-->6GalNAcalpha core structure. A set of these two antibodies would be useful in discriminating the molecular species of sialyl Lewis X expressed by malignant cells and in studying their functional significance.

Antibodies, Monoclonal↗

[Resection of a pulmonary infarction presenting as a mass shadow on chest X-ray--case report].

Recently the incidence of pulmonary infarction has increased in Japan. The patient was a 67-year-old male who was examined by a local physician for bloody sputum and a cough. A chest X-ray showed a 5-cm mass shadow in the lower left lung area. Bronchofiberscopy and percutaneous needle biopsy were performed, but they did not permit a definite diagnosis, and since the patient had a 13-year history of penile cancer (squamous cell carcinoma), and metastasis or even primary lung cancer could not be completely ruled out, an open chest biopsy was performed. The postoperative histopathological examination allowed a diagnosis of hemorrhagic pulmonary infarction. We report a case of pulmonary infarction resection that was difficult to diagnose preoperatively.

Aged↗

beta 3-Adrenergic agonist induces a functionally active uncoupling protein in fat and slow-twitch muscle fibers.

The mitochondrial uncoupling protein (UCP) has usually been found only in brown adipose tissue. We recently observed that a chronic administration of the beta 3-adrenergic agonist CL-316,243 (CL) induced the ectopic expression of UCP in white fat and skeletal muscle in genetic obese yellow KK mice. The aim of the present study was to examine whether UCP could be induced in nongenetic obese animals produced by neonatal injections of monosodium L-glutamate (MSG). The daily subcutaneous injection of CL (0.1 mg/kg) to MSG-induced obese mice for 2 wk caused significant reductions of body weight (15%) and white fat pad weight (58%). Northern and Western blot analyses showed that CL induced significant expressions of UCP in the white fat and muscle, as well as in brown fat. Immunohistochemical observations revealed that the UCP stains in white fat were localized on multilocular cells and that those in muscle were localized on slow-twitch fibers rich in mitochondria. Immunoelectron microscopy confirmed the mitochondrial localization of UCP in the myocytes. The guanosine 5'-diphosphate (GDP) binding to mitochondria in brown fat doubled after the CL treatment. Moreover, significant GDP binding was detected in the white fat and muscle of the CL-treated mice, at about one-fourth and one-thirteenth the activity of brown fat, respectively, suggesting that ectopically expressed UCP is functionally active. We concluded that the beta 3-adrenergic agonist CL can induce functionally active UCP in white fat and slow-twitch muscle fibers of obese mice.

Adipose Tissue↗

Converting enzyme inhibitor improves forearm reactive hyperemia in essential hypertension.

Endothelial function is known to be impaired in essential hypertensive patients. In this study, we examined whether antihypertensive drugs improve forearm vasodilatory response to reactive hyperemia in 26 patients with essential hypertension (62 +/- 2 years) without diabetes mellitus, hyperlipidemia, coronary heart disease, or cerebrovascular disease. Antihypertensive drugs were never given or were discontinued for at least 4 weeks before the study. Patients were treated with monotherapy of either temocapril (2 or 4 mg, n = 15) or amlodipine (2.5 or 5 mg, n = 11) for 6 months. Forearm blood flow was measured by strain-gauge plethysmography. Vasodilator response to the release of upper arm compression at 300 mm Hg for 5 minutes and to sublingual administration of nitroglycerin (0.3 mg) were assessed. Changes of forearm blood flow response to reactive hyperemia were significantly less in hypertensive patients (99 +/- 18%) than in age-matched normotensive control subjects (150 +/- 22%, P < .01, n = 39). Blood pressure (mm Hg) was similarly decreased by the treatment with temocapril (160 +/- 4/94 +/- 2 to 139 +/- 3/83 +/- 3, P < .001) or amlodipine (165 +/- 5/94 +/- 3 to 141 +/- 4/82 +/- 3, P < .001). Response to nitroglycerin was not changed by either drug. Forearm vasodilatory response to reactive hyperemia was improved by temocapril (102 +/- 20% to 168 +/- 25%, P < .01) but not by amlodipine (97 +/- 16% to 114 +/- 14%, NS). These results indicate that the treatment with the angiotensin-converting enzyme inhibitor temocapril improved forearm vasodilatory response to reactive hyperemia, suggesting its beneficial effect on endothelial function.

Aged↗

Malignant aortic body tumor in a Holstein cow.

A malignant aortic body tumor was observed in a 5-year-old female Holstein cow. The neoplastic mass, of 22 x 17 x 15 cm in size, was located at the base of the left atrium, having irregular lobular structures. The tumor cells had slightly eosinophilic cytoplasm, and a round or oval nucleus. Metastasis was only present in the premediastinal lymph node. The tumor cells exhibited intense immunoreactivity for neuron-specific enolase (NSE) and synaptophysin, and were moderately positive for chromogranin A. Electronmicroscopy revealed membrane-limited granules in the cytoplasm. The cultured cells were spindle in shape, and having projectional cytoplasm. They were intensely positive for NSE, synaptophysin, chromogranin A, and neurofilament (200 kD). Consequently, this case was diagnosed as a malignant aortic body tumor from the neuroecrodermal origin.

Animals↗

High-performance liquid chromatographic analysis of bilirubin and biliverdin from jaundiced broilers.

A sensitive and rapid high-performance liquid chromatographic (HPLC) method was developed and used for the simultaneous determination of bilirubin and biliverdin in pericardial fluid samples collected from broilers at a poultry inspection site. A photodiode array detector distinguishing the bilirubin (UV 450 nm) and biliverdin (365 nm) was used as an analytical detector for HPLC system. An internal-surface reversed-phase silica support column was used, and the mobile phase consisted of acetonitrile: 0.5 M Tris HCl buffer (20:80, pH 7.2). Bilirubin was detected from all of the jaundiced pericardial fluid samples, and a small amount of biliverdin was detected with bilirubin in some samples. These jaundiced broilers had hepatic or bile duct lesions similar to those found in edible animals. From these results, a working definition of jaundiced broilers for poultry inspection sites was suggested: bilirubin is detectable from pericardial fluid and the carcass is in a state of yellow color change.

Animals↗

Anti-obesity and anti-diabetic effects of CL316,243, a highly specific beta 3-adrenoceptor agonist, in Otsuka Long-Evans Tokushima Fatty rats: induction of uncoupling protein and activation of glucose transporter 4 in white fat.

The anti-obesity and anti-diabetic effects of a highly specific beta 3-adrenoceptor agonist, CL316,243 (CL; beta 1: beta 2: beta 3 = 0:1:100,000), were investigated in Otsuka Long-Evans Tokushima Fatty (fatty) and Long-Evans Tokushima Otsuka (control) rats. Daily injection of CL (0.1 mg/kg, s.c.) to these rats (10 weeks old) for 14 weeks caused a significant reduction in body weight (fatty, 27%; control, 15%), associated with a marked decrease in fat pad weight (inguinal: fatty, 60%; control, 36%; retroperitoneal: fatty, 75%; control, 77%) without affecting food intake. The levels of uncoupling protein mRNA and protein levels of uncoupling protein (UCP), as well as guanosine 5'-diphosphate-binding (a reliable index of thermogenesis) in brown adipose tissue, were lower in the fatty than in the control rats. However, after CL treatment, these parameters in brown adipose tissue increased significantly 2- to 3-fold in both groups. Furthermore, uncoupling protein was induced in white adipose tissue as well as in brown adipose tissue. The fatty rats showed hyperglycemia and hyperinsulinemia during the glucose tolerance test, but CL ameliorated these parameters. These findings suggest that decreased thermogenesis in brown adipose tissue may be one of the causes of obesity in the fatty rats and that administration of CL prevents obesity by decreasing white fat mass, by activating brown adipose tissue thermogenesis, and by inducing uncoupling protein in white adipose tissue. Furthermore, CL treatment may inhibit diabetes mellitus by ameliorating obesity and by activating glucose transporter 4 in white adipose tissue and brown adipose tissue.

Adipose Tissue↗