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Biomedical subjects

N Matsunaga

Publications and source records attributed to N Matsunaga.

At least 19 recordsLinked to original sources

Advanced glycation end product is implicated in amyloid-related kidney complications.

BACKGROUND: Kidney failure is a common complication in familial amyloidotic polyneuropathy (FAP). It has been suggested that advanced glycation end products (AGEs) play an important role in the development and pathogenesis of FAP. MATERIAL AND METHODS: To evaluate the impact of AGEs on FAP patients' kidney dysfunction, we measured AGE in serum and urine of 28 FAP patients and 18 healthy controls by AGE-specific enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry utilizing antibodies to AGE and the receptor for AGE (RAGE) were used on kidney tissue from 3 FAP patients and 3 diabetic patients to disclose a correlation between amyloid deposits and AGE-RAGE. RESULTS: The glomeruli of FAP patients were heavily deposited with amyloid and the glomerular size was enlarged. The space between Bowman's capsule and glomerulus was totally covered by the enlarged glomerulus. AGE and RAGE were deposited in glomeruli and tubuli and correlated with amyloid deposits. Decreased AGE levels in the liver-transplanted FAP patients' serum compared with that of non-transplanted patients were noted, and AGE concentration in serum tended to be higher in non-transplanted FAP patients compared with normal control subjects. There were no differences in the AGE urine levels in FAP patients compared with controls. No correlation could be found between AGE in urine and serum compared with serum albumin, serum creatinine and creatinine clearance. CONCLUSIONS: The accumulation of AGE, RAGE and amyloid in the kidney of FAP patients suggests that these molecules play an important role in the origin and pathogenesis of renal failure in FAP patients.

Amyloid Neuropathies, Familial↗

Longevity-associated mitochondrial DNA 5178 A/C polymorphism and blood pressure in the Japanese population.

It has been reported that the mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism, also called NADH dehydrogenase subunit 2-237 methionine/leucine (ND2-237 Met/Leu) polymorphism, may be associated with longevity in Japanese individuals, and that the mt5178A genotype may have an antiatherogenic influence. To determine whether mt5178 A/C polymorphism influences blood pressure, we genotyped 412 healthy Japanese individuals and performed a cross-sectional study investigating the relationship between genotype and blood pressure. In women with mt5178A, the mean diastolic blood pressure was higher than in those with mt5178C by 3.2 mmHg (P=0.040). In men, no statistically significant difference in systolic or diastolic blood pressure was observed between mt5178 A/C genotypes. However, a significant correlation between mt5178 A/C genotypes and the effects of habitual drinking on blood pressure was found. After adjustment for several factors, in men carrying mt5178C, both systolic and diastolic blood pressure were significantly higher in daily drinkers than in occasional (P=0.002 and 0.002, respectively) as well as nondrinkers (P<0.001 and 0.001, respectively), whereas in men carrying mt5178A, no significant differences in blood pressure were detected, irrespective of alcohol consumption. These results suggest that mt5178 A/C (=ND2-237 Met/Leu) polymorphism may influence both diastolic blood pressure in Japanese women and the blood-pressure-increasing effect of drinking in Japanese men.

Alcohol Drinking↗

Localization of breast sentinel lymph nodes by MR lymphography with a conventional gadolinium contrast agent. Preliminary observations in dogs and humans.

PURPOSE: To test the capability of an indirect MR lymphography (MRLG) using a conventional extracellular gadolinium (Gd)-based contrast agent for localizing breast sentinel lymph node (SLN). METHODS: A total of 1 and 0.5 ml of undiluted gadopentetate dimeglumine were injected subcutaneously into the two periareolar areas overlying each caudal mammary gland in 10 female dogs. Contiguous 2-mm-thick fast gradient echo MR images were acquired through the upper breast and axilla before and for 60 min after gentle massage at the injection sites, yielding 3D displays. The localized SLN was resected from the living animals, followed by post mortem examinations. MRLG (1 ml contrast agent injected) was also attempted in 5 female volunteers. RESULTS: Even with 0.5-ml contrast agent, the MRLG clearly visualized the connection of SLN and lymphatic vessels directly draining from the injection sites, and the remaining distant nodes, with the maximal enhancement peaks within 10 min after massage. The 3D images provided comprehensive anatomy of these lymphatic pathways in each axilla. Of the 20 SLN and 128 distant nodes visualized on the MRLG, all the SLN (100%) and 107 (83.5%) distant nodes could be resected pre- and post mortem, in good correlation with the locations and sizes on the MR images. MRLG also effectively localized SLN in the volunteers, without significant adverse effects. CONCLUSION: An indirect MRLG using small volumes of conventional Gd-based contrast agent may have potential for accurate identification and surgical biopsy of breast SLN.

Animals↗

Assessment of regional lung ventilation in dog lungs with Gd-DTPA aerosol ventilation MR imaging.

PURPOSE: Gd-DTPA aerosol ventilation MR imaging was obtained using a modified aerosol delivery system with an aerosol reservoir to non-invasively assess regional lung ventilation in dogs. MATERIAL AND METHODS: Seven anesthetized, spontaneously breathing normal dogs inhaled 200 mmol Gd/l Gd-DTPA aerosol produced by an ultrasonic nebulizer, using an open-circuit aerosol delivery system with or without an aerosol reservoir. Fast gradient-echo MR images were sequentially acquired with an interval time of 1 min for 25 min before and after aerosol inhalation. The aerosol study was also performed using the aerosol delivery system with an aerosol reservoir in the same 7 dogs after airway obstruction with a balloon catheter, and in another 7 dogs after pulmonary arterial embolization with enbucrilate. An i.v. Gd-DTPA-enhanced dynamic MR study after i.v. bolus injection of a 0.1 mmol/kg dose of Gd-DTPA was combined to assess regional lung perfusion. Lung enhancement effect was evaluated by time-signal intensity curves and the subtracted ventilation- and perfusion-weighted images. RESULTS: With or without the aerosol reservoir, the normal dog lungs were gradually and gravity-dependently enhanced with time after aerosol inhalation. The use of the aerosol reservoir, however, showed significantly greater lung enhancement without a significant increase in breathing rate and with minimal reduction in PaO2 of less than 5 mm Hg in these animals. The enhancement effect of i.v. injection of Gd-DTPA at pulmonary arterial perfusion phase was significantly greater compared to that of Gd-DTPA aerosol throughout the normal lungs, and the subtracted ventilation-weighted and perfusion-weighted images showed homogeneous but gravity-dependent aerosol deposition and perfusion. These images clearly defined the regionally matched perfusion-ventilation deficits in the lung regions distal to bronchial obstruction in all the airway obstruction dogs, and the regionally mismatched perfusion-ventilation in the embolized regions of all the pulmonary arterial embolization animals. CONCLUSION: Gd-based aerosol can non-invasively image regional lung ventilation in spontaneously breathing animals, using an adequate aerosol delivery system. The combined use of Gd-DTPA perfusion MR imaging may be acceptable for defining regionally impaired lung function associated with acute airway obstruction and pulmonary arterial embolization.

Aerosols↗

Association of the mitochondrial DNA 5178 A/C polymorphism with serum lipid levels in the Japanese population.

As one approach to exploring whether the mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism is associated with atherosclerosis, we genotyped 461 healthy Japanese individuals and studied the relationship of mt5178 A/C genotypes to serum lipid levels. Blood specimens were obtained after at least a 12-h fasting period from the subjects. The mt5178 A/C was genotyped by the polymerase chain reaction/restriction fragment length polymorphism method. The relative frequency of mt5178 A was 41.6% (192/461) and of mt5178 C was 58.4% (269/461). After adjustments for age and body mass index, the high-density lipoprotein cholesterol concentration in males carrying mt5178 A was significantly higher than that in males carrying mt5178 C ( P=0.026). The tryglyceride (TG) concentration in females carrying mt5178 A was significantly lower than that in females carrying mt5178 C ( P=0.012). This difference in the TG level between the two genotypes was more evident in postmenopausal females than in premenopausal females. Mt5178 A seems to have an antiatherogenic effect. This is the first genetic epidemiological report on the association of mt5178 A/C polymorphism with serum lipid levels in the Japanese population.

Adenine↗

Novel magnetism in 3He nanoclusters.

The magnetic susceptibility of 3He nanoclusters embedded in a 4He matrix has been measured from 0.5 to 10 mK at pressures from 2.88 to 3.54 MPa. Even the lowest pressure clusters have a solid fraction in the region of the phase diagram where bulk solid is unstable. At 3.54 MPa, straight theta = -250 microK, equal to that of bulk 3He for v = 21.3 cm3/mole. For 2.88 MPa, straight theta = 140 microK, indicating a ferromagnetic tendency, similar to 2D films at some coverages. At intermediate pressures, chi has a peak near 1.05 mK, but with no discontinuity. Magnetic ordering in nanoclusters appears to be different than the U2D2 phase of bulk 3He.

Journal Article↗

Spider silk has an ice nucleation activity.

Several ice nucleating substances have been identified, which exist in vivo or can be extracted from biological materials. Spider silk, which has a strong ability for water condensation, has also been found to possess an ice nucleation activity. The freezing temperature of water droplets was higher in the presence than in the absence of spider silk. Moreover, by means of environmental scanning electron microscopy, it was observed that the activity is not due to foreign matter attached to the silk but to the silk fibroin itself.

Animals↗

Assessment of leg oedema by dynamic lymphoscintigraphy with intradermal injection of technetium-99m human serum albumin and load produced by standing.

This study was a preliminary evaluation of the utility of dynamic lymphoscintigraphy with technetium-99m human serum albumin (HSA) and a load produced by standing in the assessment of lymphatic dysfunction in patients with leg oedema. The 71 subjects investigated included 53 patients with lymphoedema, six with venous occlusion alone and five with lymphovenous occlusion, as well as seven normal subjects. After intradermal injection of 99mTc-HSA into an interdigital space in each foot, dynamic scintigrams were recorded with the patient supine for 15 min. The subjects then stood in place and images were recorded for an additional 15 min. Relative changes in lymphatic tracer transport before and after standing were analysed on time-activity curves (TACs). This test was compared with a conventional test in a supine position in six patients with lymphoedema, and was repeated in five other patients with lymphoedema. It was found that in the normal limbs, a standing load activated tracer transport to the draining lymphatic vessels, resulting in a rapid stepwise increase in tracer activity, large spiking waves and a decreasing phase following a peak in tracer activity on TACs. In 59 lymphoedematous limbs, including some with a mild form of oedema without morphological abnormalities on scintigrams, this load failed to induce a sufficient activation of tracer transport, and the frequencies of each of the three normally appearing changes described above significantly decreased compared with those in the 14 normal limbs (P < 0.0001, P < 0.01 and P < 0.0001, respectively). In addition, there were significant reductions in the relative increases in maximum activity and clearance times after standing (both P < 0.0001). These abnormalities significantly correlated with the grade of severity of oedema. Six limbs with lymphovenous occlusion showed significant reductions in tracer transport compared to six limbs with venous occlusion. Lymphatic dysfunction was accentuated more by this test than by the conventional test, and repeated tests showed consistent results in the same individuals. It is concluded that under a standardized load, this quick test seems of value in providing a sensitive and objective assessment of lymphatic dysfunction in the lower limbs, and is also advantageous for image interpretation since accelerated tracer transport clearly visualizes compromised lymphatics. This test may also be helpful in distinguishing purely venous oedema from mixed lymphovenous disease.

Adult↗

Relationship between thallium-201 kinetics and proliferative activity assessed by monoclonal antibody MIB-1 in brain tumours.

To clarify the relationship between thallium-201 chloride kinetics and proliferative activity in brain tumours. a single-photon emission tomographic (SPET) study was performed and the results correlated with monoclonal antibody MIB-1 staining of the tumour tissue. 201T1 SPET was performed 10 min (early scan) and 2 h (delayed scan) after intravenous administration of 201TI (111 MBq) in 34 intra-axial tumours including 24 malignant tumours, and in 27 extra-axial tumours including one malignant tumour. Tumour 201T1 kinetic parameters [early and delayed uptake ratios (ER and DR, respectively), retention index (RI), and the ratio of tumour delayed activity to early activity (Td/Te)] were compared with tumour tissue MIB-1 labelling indices (MIB-1 LI) representative of tumour cell proliferative activity. In the intra-axial tumours, ER and DR and MIB-1 LI were significantly higher in the malignant tumours than in the benign tumours. ER and DR were significantly correlated with MIB-1 LI (P<0.01 and P<0.05, respectively), but RI and Td/Te were not. In the extra-axial benign tumours, ER was as high as that in the intra-axial malignant tumours, while MIB-1 LI was equal to that in the intra-axial benign tumours. There were no significant correlations between any 201T1 kinetic parameters and MIB-1 LI. This study indicates that 201T1 ER may be the most reliable parameter for predicting the proliferative activity of intra-axial tumours.

Adolescent↗

Paired inspiratory-expiratory thin-section CT findings in patients with small airway disease.

The objective of this study was to evaluate minimal small airway disease (SAD) as reflected on paired inspiratory-expiratory CT findings. Seventy-two subjects, 34 with SAD, 11 with normal lung function, and 27 with chronic obstructive pulmonary diseases (COPD), underwent thin-section CT during deep inspiration and expiration at upper, middle, and lower lung levels. Evaluation of CT measurement was performed between inspiratory and expiratory CT attenuation of lung parenchyma, in non-dependent and dependent lung at each of the three levels. Visual assessment of mosaic patterns and attenuation differences was also performed using the inspiratory and expiratory images. Patients with SAD were differentiated from those with COPD, by visual assessment and from the CT measurements. Visual assessment failed to differentiate between the SAD and normal groups. However, one measurement, an inspiratory-expiratory attenuation difference in the dependent lower lung, was different between SAD and normal group. Early small airway disease may be indicated by an inspiratory-expiratory attenuation difference in the dependent lower lung using the simple method of a paired inspiratory-expiratory CT.

Adult↗

MR imaging of pancreatic diseases.

This article presents current MR imaging techniques for the pancreas, and review a spectrum of MR imaging features of various pancreatic diseases. These include: 1) congenital anomalies such as anomalous union of pancreatobiliary ducts, divisum, and annular pancreas, 2) inflammatory diseases, including acute or chronic pancreatitis with complications, groove pancreatitis, and autoimmune pancreatitis, tumor-forming pancreatitis, 3) pancreatic neoplasms, including adenocarcinoma, islet cell tumors, and cystic neoplasms (microcystic adenoma, mucinous cystic neoplasms, and intraductal mucin-producing pancreatic tumor). Particular attention is paid to technical advances in MR imaging of the pancreas such as fat-suppression, MR pancreatography (single- or multi-slice HASTE), and thin-section 3D multiphasic contrast-enhanced dynamic sequences. Imaging characteristics that may lead to a specific diagnosis or narrow the differential diagnosis are also discussed.

Acute Disease↗

Effects of the administration of growth hormone-releasing peptide-2 (GHRP-2) orally by gavage and in feed on growth hormone release in swine.

The experiments were conducted to determine the effects of the administration of growth hormone-releasing peptide-2 (GHRP-2, also named KP102), both orally by gavage and in feed, on the release of growth hormone (GH) in swine and to investigate whether attenuation of the GH response occurs after short-term treatment with the peptide in feed. In the first experiment, saline or GHRP-2 at doses of 1, 4.5 and 9 mg/kg body weight (BW) was dissolved in 15 ml saline and administered orally as a bolus by gavage to cross-bred castrated male swine (n = 6). Orally administered GHRP-2 stimulated dose-related increases in peak concentrations of GH, with a return to basal by 120 min. After administering GHRP-2 orally, peak concentrations of GH and areas under the GH response curves (GH AUCs) for 180 min were higher (P < 0.05) than those in saline controls. In Experiment 2, GHRP-2 at doses of 0 (served as control), 1, 4.5 and 9 mg/kg BW was mixed in 150 g of feed and offered to cross-bred castrated male swine (n = 6) at 0900 hr and 1700 hr daily for a 3-d period. Administration of 1 mg/kg BW GHRP-2 to swine in feed failed to stimulate the release of GH, but GHRP-2 at doses of 4.5 and 9 mg/kg BW significantly (P < 0.05) increased plasma concentrations of GH after initial and final treatments at 0900 hr on Days 1 and 3 of treatment, respectively. Peak concentrations of GH and GH AUCs for 180 min after the initial and final treatments in the 4.5 and 9 mg/kg BW GHRP-2-treated swine were higher (P < 0.05) than those in controls. After 3 d of treatment with GHRP-2 in feed at doses of 4.5 and 9 mg/kg BW, GH responses to the peptide were maintained. The results of the present study indicate that the administration of GHRP-2 orally by gavage and in feed stimulates the release of GH in swine, and that the GH-releasing effect of the peptide does not become desensitized after short-term administration in feed.

Administration, Oral↗

The magnitude of variation in temperature within a year has an effect on the seasonal variations of chickenpox incidence in Japan.

We investigated the epidemic pattern of chickenpox incidence among 47 prefectures in Japan. There were two peaks in chickenpox incidence in all prefectures. The first peaks appear at almost the same time in a year, while the second peaks occur at different times with relatively different types of size and shape. The feature of the second peak might characterize the epidemic pattern of chickenpox. We first introduced the second peak index, that is, the ratio of the difference between the incidence at the point of the second peak and the minimum incidence between the first and second peaks to the difference between the incidence at the point of the second peak and the minimum incidence in the year. There was a close correlation between the second peak index and the magnitude of variation in temperature within a year corresponding to the difference between the maximum and the minimum of the monthly mean of the highest daily temperature. This is the first article focusing on the close relationship between the second peak of epidemic pattern of chickenpox incidence and the variation of temperature within a year.

Chickenpox↗

Cyclic oscillations in melanin composition within hairs of baboons.

The wild-type agouti-banding pattern for hair is well characterized in lower mammals such as mice. The switch between eumelanin and pheomelanin in bands in the hair results from the interaction of alpha-melanocyte stimulating hormone and agouti signal protein through the melanocortin 1 receptor on melanocytes. However, such banding patterns have not been described to date in higher mammals. We now report such 'agouti'-banding patterns that occur in several subspecies of baboons, and characterize those hairs using chemical and immunohistochemical methods. Hair and skin samples were obtained from the dorsa of adult male baboons of different subspecies (Papio cynocephalus hamadryas (PCH) and Papio cynocephalus anubis (PCA)). The hairs were excised with scissors into the gray and the white bands of the PCH subspecies and into the black and the yellow bands of the PCA subspecies, and were analyzed for total melanin, eumelanin, and pheomelanin by spectrophotometric and chemical methods. Hairs in the PCA subspecies oscillate between a eumelanic band (with high melanin content) and a pheomelanic band, while hairs in the PCH subspecies oscillate between a eumelanic band (with low melanin content) and a non-pigmented band. Those chemical data are consistent with the histological appearance of the hair bulbs stained by the Fontana-Masson technique. The difference in the melanin content between PCH and PCA subspecies is most likely related to tyrosinase levels, as suggested by the presence of unpigmented muzzle in the PCH subspecies compared with the black muzzle in the PCA subspecies.

Agouti Signaling Protein↗

Production of melanocyte-specific antibodies to human melanosomal proteins: expression patterns in normal human skin and in cutaneous pigmented lesions.

Multiple factors affect skin pigmentation, including those that regulate melanocyte and/or keratinocyte function. Such factors, particularly those that operate at the level of the melanosome, are relatively well characterized in mice, but the expression and function of structural and enzymatic proteins in melanocytes in human skin are not as well known. Some years ago, we generated peptide-specific antibodies to murine melanosomal proteins that proved to be instrumental in elucidating melanocyte development and differentiation in mice, but cross-reactivity of those antibodies with the corresponding human proteins often was weak or absent. In an effort to characterize the roles of melanosomal proteins in human skin pigmentation, and to understand the underlying mechanism(s) of abnormal skin pigmentation, we have now generated polyclonal antibodies against the human melanocyte-specific markers, tyrosinase, tyrosinase-related protein (TYRP1), Dopachrome tautomerase (DCT) and Pmel17 (SILV, also known as GP100). We used these antibodies to determine the distribution and function of melanosomal proteins in normal human skin (adult and newborn) and in various cutaneous pigmented lesions, such as intradermal nevi, lentigo simplex, solar lentigines and malignant melanomas. We also examined cytokeratin expression in these same samples to assess keratinocyte distribution and function. Immunohistochemical staining reveals distinct patterns of melanocyte distribution and function in normal skin and in various types of cutaneous pigmented lesions. Those differences in the expression patterns of melanocyte markers provide important clues to the roles of melanocytes in normal and in disrupted skin pigmentation.

Adult↗

Re-entrainment of the circadian rhythms of plasma melatonin in an 11-h eastward bound flight.

We investigated the re-entrainment of melatonin rhythm in an 11-h eastward-bound flight. Eight male subjects participated in the present study. Blood sampling was carried out once before the flight and twice after the flight. During the daytime the subjects were exposed to natural zeitgeber outdoors on the day except the blood sampling. Seven of eight subjects showed antidromic re-entrainment, and the other subject showed orthodromic re-entrainment. The intensity of natural day light in New York amounted to 20 000 lx. As for the direction of the re-entrainment in New York the antidromic re-entrainment is naturally dominant.

Adaptation, Physiological↗