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Biomedical subjects

Y Namba

Publications and source records attributed to Y Namba.

At least 19 recordsLinked to original sources
PubMed2000

Clinico-radiological study of total knee arthroplasty after high tibial osteotomy.

The results of total knee arthroplasty (TKA) after high tibial osteotomy (HTO) and problems encountered during the operation were investigated in 23 patients (28 knees). HTO was performed by Coventry's method in 18 knees and by Maquet's method in 10 knees. The mean interval from HTO to TKA was 86 months (range, 3 to 288 months) and the mean follow-up period after TKA was 25 months (range, 6 to 116 months). Radiological evaluation showed that the proximal part of the tibia was shifted and tilted lateroinferiorly after HTO. Thus, a tendency to patella infera was observed. Lateral shift of the proximal part of the tibia was more marked with Maquet's method than with Coventry's method (P < 0.01). Posterior inclination of the tibial articular surface before TKA was smaller in the patients who gained a range of motion of 90 degrees or more after TKA than in those with less than 90 degrees (P < 0.05). In patients with 70 points or more on the three-university score after TKA, there was no change in the joint line level between before and after TKA, while the joint line was significantly lower after TKA in those with less than 70 points (P < 0.01). When TKA is done after HTO, various technical problems may influence the outcome, such as correction of the soft tissue imbalance, in addition to difficulties with patellar eversion and exposure of the proximal part of the tibia. The clinical results of TKA after HTO tend to be slightly inferior to those of primary TKA, probably because of such technical problems.

Aged↗
PubMed2000

Effects of fructose and glucose on plasma leptin, insulin, and insulin resistance in lean and VMH-lesioned obese rats.

To determine the influence of dietary fructose and glucose on circulating leptin levels in lean and obese rats, plasma leptin concentrations were measured in ventromedial hypothalamic (VMH)-lesioned obese and sham-operated lean rats fed either normal chow or fructose- or glucose-enriched diets (60% by calories) for 2 wk. Insulin resistance was evaluated by the steady-state plasma glucose method and intravenous glucose tolerance test. In lean rats, glucose-enriched diet significantly increased plasma leptin with enlarged parametrial fat pad, whereas neither leptin nor fat-pad weight was altered by fructose. Two weeks after the lesions, the rats fed normal chow had marked greater body weight gain, enlarged fat pads, and higher insulin and leptin compared with sham-operated rats. Despite a marked adiposity and hyperinsulinemia, insulin resistance was not increased in VMH-lesioned rats. Fructose brought about substantial insulin resistance and hyperinsulinemia in both lean and obese rats, whereas glucose led to rather enhanced insulin sensitivity. Leptin, body weight, and fat pad were not significantly altered by either fructose or glucose in the obese rats. These results suggest that dietary glucose stimulates leptin production by increasing adipose tissue or stimulating glucose metabolism in lean rats. Hyperleptinemia in VMH-lesioned rats is associated with both increased adiposity and hyperinsulinemia but not with insulin resistance. Dietary fructose does not alter leptin levels, although this sugar brings about hyperinsulinemia and insulin resistance, suggesting that hyperinsulinemia compensated for insulin resistance does not stimulate leptin production.

Animals↗
PubMed2000

Magnetic resonance lymphography of profundus lymph nodes with liposomal gadolinium-diethylenetriamine pentaacetic acid.

Lymphography, especially imaging of profundus lymph nodes, is a useful tool for diagnosis of cancer metastases in lymph nodes. However, positive enhancement agents for magnetic resonance lymphography (MRL) have not been available, since the positive imaging agents so far introduced are low-molecular-weight materials that are not trapped in lymph nodes. For the purpose of improved positive enhanced MRL, we employed liposomes as carriers of a positive enhancer, gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). Magnetic resonance (MR) imaging was performed after subcutaneous injection of Gd-liposomes into the hind feet of rabbits which had reactive enlarged retroperitoneal lymph nodes. As a result, not only popliteal but also profundus retroperitoneal lymph nodes were positively enhanced by Gd-liposomes, especially after 20 min massage of the injected sites. Gd-Liposomes containing dipalmitoylphosphatidylglycerol were more effective than Gd-liposomes containing palmityl-D-glucuronide, a type of long-circulating liposomes, suggesting that liposomal accumulation in lymph node is, at least partly, mediated by the trapping of liposomes by macrophages. These data show that liposomes modified with Gd-DTPA are effective for positive enhancement of both regional and profundus lymph nodes in MR lymphography.

Animals↗
PubMed1999

Involvement of sympathetic activation and brown adipose tissue in calcitonin gene-related peptide-induced heat production in the rat.

We previously reported that microinjection of calcitonin gene-related peptide (CGRP; 1.6-8.0 pmol, 0.2-1.0 microliter) into the ventromedial hypothalamus (VMH) increased oxygen consumption (VO(2)), heart rate (HR), colonic temperature (T(co)), and temperature of interscapular brown adipose tissue (T(IBAT)). In the present study, we investigated whether the autonomic nervous system is involved in the CGRP-induced heat production in urethane-anesthetized rats. Intraperitoneal administration of the ganglion blocker hexamethonium (20 mg/kg) or the beta-adrenergic antagonist propranolol (5 mg/kg) suppressed the CGRP-induced increases in VO(2), HR, T(co), and T(IBAT). Pretreatment with the alpha-adrenergic antagonist phentolamine (5 mg/kg) partly attenuated the heat production response but did not affect the tachycardiac response. Bilateral sectioning of the nerves supplying the IBAT attenuated the CGRP-induced increase in T(IBAT) but not significantly that in VO(2) or T(co). In rats with adrenal demedullation, the effects of CGRP were similar to those in intact rats. These results suggest that the CGRP-induced heat production is mediated by the sympathetic nervous system and, at least in part, by the BAT through the alpha- and beta-adrenoceptors.

Adipose Tissue, Brown↗
PubMed1999

Neuronal localization of a novel mosaic apolipoprotein E receptor, LR11, in rat and human brain.

A new type of mosaic protein was recently discovered as a new member of the low density lipoprotein receptor (LDLR) family, designated as LR11. The predominant expression of LR11 transcripts in brain tissue and the presence of elements found in neural adhesion molecules suggested a function(s) in the central nervous system (CNS). In order to gain insight about this complex receptor in the CNS, we raised a rabbit polyclonal antibody and examined immunohistochemically rat and human brain tissue. A strong LR11 immunoreactivity was found to be localized mainly in neurons throughout the brain in both species. A detailed mapping in the rat brain showed a distribution of LR11 immunoreactivity in a widespread population of neurons, though the intensity varied between different locations. The most prominent immunoreactivity was observed in neurons of the hippocampus, some nuclei of brain stem and Purkinje cells, whereas neurons of the thalamus and the hypothalamus showed weak staining. Uniquely, the single LR11 immunoreactive cytoplasmic puncta were observed in the proximity of apical dendrites, most conspicuously in the pyramidal neurons of hippocampus. In the human brain, one to four immunoreactive puncta were seen within individual neurons. The neuronal localization of LR11 and its unique association of cytoplasmic structure, presumably botrysome, may suggest the roles of LR11 in both the lipoprotein metabolism and intracellular trafficking in certain neuronal population of the CNS.

Adult↗
PubMed1999

Bleomycin hydrolase immunoreactivity in senile plaque in the brains of patients with Alzheimer's disease.

Bleomycin hydrolase (BH), a cysteine protease belonging to the papain superfamily, is one of the candidate beta secretases. We performed immunohistochemical studies of Alzheimer's disease (AD) brains using an antibody to BH. Polyclonal antibody to BH immunostained neocortical neurons. The immunoreactivity was also found in senile plaques in AD. These results may suggest a role of BH in amyloid formation.

Alzheimer Disease↗
PubMed1999

CGRP microinjection into the ventromedial or dorsomedial hypothalamic nucleus activates heat production.

Unilateral microinjection of calcitonin gene-related peptide (CGRP, 1.6 pmol; 0.2 microl) into the ventromedial hypothalamus (VMH) and dorsomedial hypothalamus (DMH) immediately increased oxygen consumption (VO2), heart rate (HR), colonic temperature (Tco), and temperature of interscapular brown adipose tissue (TIBAT) in urethane-anesthetized rats, whereas vehicle saline injection into the VMH and CGRP injection into other hypothalamic regions such as the preoptic area, lateral hypothalamic area, paraventricular nucleus, and bed nucleus of the stria terminalis had no effect. The effects of CGRP injection into the VMH were dose-dependent over the range of 0.016-1.6 pmol. CGRP administration to the lateral ventricle (LV) required 16-320 pmol to elicit similar degrees of responses that were observed after the injection into the VMH. The increase in TIBAT was always higher than that in Tco after CGRP injection. Injection of [Cys(ACM)2,7]hCGRPalpha, a selective CGRP2 receptor agonist, did not induce any thermogenic effects. Human CGRP8-37, a proposed CGRP1 receptor antagonist, by itself induced heat production responses with no signs of inhibition of CGRP-induced responses. Thus, the receptor subtype of the thermogenic effect of CGRP could not be determined by the available pharmacological tools. The present results show that centrally administrated CGRP induces heat production in the BAT specifically through the VMH or DMH.

Adipose Tissue, Brown↗
PubMed1999

Radioimmunotherapy of human glioma xenografts in nude mice by indium-111 labelled internalising monoclonal antibody.

The potential of 111Indium (111In)-labelled internalising anti-integrin alpha 3 antibody GA17 in the radioimmunotherapy of human glioblastoma xenografts in nude mice was investigated. A radioisotope retention assay showed a rapid release of radioiodine from the glioblastoma cells after the binding of 125I-GA17, whilst 111In-GA17 was retained in the cells for a longer time period. The glioblastoma xenografts showed a high and prolonged uptake of 111In-GA17, and tumour uptake of 125I-GA17 was lower and decreased with time. In the mice which received two injections of 18.5 MBq of 111In-GA17, the growth of the subcutaneous tumour was significantly suppressed compared with the untreated group and mice injected with an 111In-labelled control antibody. These results indicate that GA17 was internalized into the glioblastoma cells and that 111In was retained within the cancer cells. The injection of a high-dose of 111In-GA17 can suppress the growth of tumour xenografts in nude mice.

Animals↗
PubMed1999

Application of surface-coated liposomes for oral delivery of peptide: effects of coating the liposome's surface on the GI transit of insulin.

We prepared two kinds of surface-coated liposomes and investigated their potencies as oral dosage forms for peptide drugs by focusing on their effects on the gastrointestinal (GI) transit of drugs. The surface of the liposomes was coated with poly(ethylene glycol) 2000 (PEG-Lip) or the sugar chain of mucin (Mucin-Lip). As a model peptide drug, insulin was encapsulated in these liposomes. Coating the surface with poly(ethylene glycol) was found to reduce the transit rate of liposomes in the small intestine after oral administration to rats in vivo. Mucin-Lip was retained in the stomach longer than PEG-Lip or uncoated liposomes. The effect of surface coating on the intestinal transit of liposomes was determined by means of in situ single pass perfusion in the rat small intestine. Statistical moment analysis was applied to the outflow pattern of both liposomes and encapsulated insulin. The mean transit time (MTT) and deviation of transit time (DTT) in the intestinal tract were calculated. The MTT of PEG-Lip was much longer than those of uncoated liposomes and Mucin-Lip and was significantly shortened after removal of the intestinal mucous layer. These results indicated that PEG-Lip interacts strongly with the intestinal mucous layer, leading to its slow transit in the intestine. In contrast, coating the liposome's surface with mucin did not affect either the MTT or DTT of liposomes in the intestine. This result is in accordance with the in vivo observation that Mucin-Lip was highly retained in the stomach, but not in any region of the small intestine in vivo. Both the MTT and DTT values of insulin encapsulated in PEG-Lip and Mucin-Lip were almost the same as those of liposomes themselves, suggesting that surface-coated liposomes retained insulin in the intestinal tract. However, MTT and DTT of insulin were significantly shorter than those of uncoated liposomes because these liposomes degraded and released significant amounts of insulin during single pass perfusion. The ability of surface-coated liposomes, especially of PEG-Lip, to interact with the mucus layer and slow the transit rate in the GI tract is considered desirable for oral delivery of peptide drugs. Modification of the liposomal surface with appropriate materials, therefore, should be an effective method by which to achieve the oral delivery of peptide drugs.

Animals↗
PubMed1999

Specific cutaneous lesions of the scalp in myelodysplastic syndrome with deletion of 20q.

We reported a specific skin lesion on the scalp in a patient with myelodysplastic syndrome (MDS), treated as refractory anemia with excess of blasts (RAEB). Histologically, a specimen from a nodule of the scalp consisted of a diffuse infiltration of atypical cells in the dermis and subcutaneous tissue. The patient died of acute leukemia 3 months later. Chromosomal examination of bone marrow cells revealed deletion of 20q and 21 trisomy. The specific cutaneous lesions in this patient were associated with acute transformation. The deletion of 20q and specific cutaneous lesions are regarded as signs of poor prognosis.

Biopsy, Needle↗
PubMed1999

Plasma leptin levels and triglyceride secretion rates in VMH-lesioned obese rats: a role of adiposity.

To explore the role of adiposity on hypertriglyceridemia associated with obesity, we examined the relation between triglyceride secretion rate (TGSR) and plasma leptin, insulin, or insulin resistance in ventromedial hypothalamus (VMH)-lesioned rats in the dynamic and static phases (2 and 14 wk after lesions, respectively). VMH-lesioned rats gained body weight (BW) at fivefold higher rates in the dynamic phase compared with sham-operated control (sham) rats, and BW gain reached a plateau in the static phase. Parametrial fat pad mass was increased 2.5-fold in VMH-lesioned rats compared with sham rats in both phases. Leptin levels were sixfold higher in VMH-lesioned rats of the dynamic phase and even higher in the static phase. Insulin levels were twofold higher in VMH-lesioned rats than in sham rats in both phases. In the dynamic phase, VMH-lesioned rats had 2-fold higher plasma triglyceride (TG) levels and 2.6-fold higher TGSRs, whereas steady-state plasma glucose (SSPG) values, an indicator of insulin resistance, were lower. SSPG values became significantly higher in VMH-lesioned rats in the static phase, but TGSR was not further accelerated. TGSR was significantly associated with leptin, independent of insulin. Leptin was highly correlated with BW, fat mass, and nonesterified fatty acids (NEFA). These results suggest that adiposity itself plays a critical role in TGSR probably through increased NEFA flux from enlarged adipose tissues. Insulin resistance is not associated with the overproduction of TG in this animal model for obesity.

Adipose Tissue↗
PubMed1999

Rapid increase in circulating leptin in ventromedial hypothalamus-lesioned rats: role of hyperinsulinemia and implication for upregulation mechanism.

The mechanisms of marked increase in plasma leptin soon after ventromedial hypothalamus (VMH) lesions were investigated. Although rats did not gain body weight or parametrial fat-pad mass 24 h after the operation, the acute VMH-lesioned rats exhibited substantial five- and fourfold increases in plasma leptin levels compared with sham-operated control rats in fed (22.6 +/- 3.2 vs. 5.8 +/- 1.2 ng/ml) and fasted (8.8 +/- 2.0 vs. 2.3 +/- 0.3 ng/ml) states, respectively. Plasma insulin concentration was doubled in VMH-lesioned rats compared with sham-operated controls in both fed and fasting states. Northern blot analysis revealed that mRNA of ob gene was not increased in parametrial fat pad of animals 24 h after the creation of VMH lesions. However, leptin content in the fat pad was significantly increased in VMH-lesioned rats compared with sham-operated controls (32.2 +/- 4.7 vs. 17.4 +/- 2.3 ng/g wet tissue). The leptin content in parametrial fat pad was highly correlated with plasma leptin concentrations (r = 0.898, P < 0.001). To define the effect of hyperinsulinemia on their hyperleptinemia, a small dose of streptozotocin (STZ) (25 mg/kg body wt) was intravenously administered into rats 5 days before the creation of VMH lesions. Plasma insulin levels were not increased after VMH lesions in STZ-pretreated rats. Plasma leptin levels were halved in the absence of hyperinsulinemia, but still remained twofold higher than those in their sham-operated counterparts (9.9 +/- 1.3 vs. 4.8 +/- 0.7 ng/ml). These results indicate that the destruction of VMH rapidly promotes leptin production before obesity develops through an enhanced translational process in which hyperinsulinemia occurring after VMH lesioning plays an important role. The present study also suggests that there are other mechanisms that rapidly upregulate leptin production in adipocytes in VMH-lesioned rats in which the target organ of this hormone has been destroyed.

Animals↗
PubMed1999

[A case of subclinical IgA nephropathy and cyclosporin associated arteriolopathy diagnosed by non-episode biopsy of graft kidney after renal transplantation].

We report a case of subclinical immunoglobulin A (IgA) nephropathy and cyclosporin associated arteriolopathy following renal transplantation. A 39-year-old male with chronic glomerulonephritis received kidney transplantation from a two- human leukocyte antigen (HLA) mismatched cadaveric donor. The initial immunosuppressive therapy was triple-drug therapy with cyclosporin, prednisolone and mizoribine. Four months after transplantation, he had an acute rejection episode, and the renal function was recovered by steroid pulse and 15-deoxyspergualin therapy. Eight years after transplantation, we conducted a non-episode biopsy of the renal allograft to examine subclinical lesions. The histopathological findings showed cyclosporin associate arteriolopathy (CAA) and IgA nephropathy. There was no sign of acute or chronic rejection. At the present time, the renal function of the allograft is good. In conclusion, the non-episode biopsy of renal allograft is useful for examination of subclinical lesions.

Biopsy↗
PubMed1998

Increased uncoupling protein-2 and -3 gene expressions in skeletal muscle of STZ-induced diabetic rats.

Streptozotocin (STZ)-induced diabetic animals are vulnerable to cold stress. Uncoupling proteins (UCPs) play an important role in regulating thermogenesis. We investigated the gene expressions of UCPs in brown adipose tissue (BAT), white adipose tissue (WAT), liver and gastrocnemius muscle of STZ-diabetic rats using Northern blot. UCP-1, -2 and -3 mRNA expressions in BAT were all remarkably lower in STZ-diabetic rats than those in control rats. Both UCP-2 and -3 gene expressions in gastrocnemius muscle were substantially elevated in STZ-diabetic rats and insulin treatment restored UCP gene expressions to normal levels. These results suggest that in STZ-diabetic rats, the overexpression of UCP-2 and UCP-3 in skeletal muscle provides a defense against hypothermogenesis caused by decreased UCPs in BAT.

Adipose Tissue, Brown↗
PubMed1998

Temperature- and capsaicin-sensitive nerve fibers in brown adipose tissue attenuate thermogenesis in the rat.

We examined the function of putative sensory fibers that are contained in intercostal nerves and innervate interscapular brown adipose tissue (IBAT) in urethane-anesthetized rats. Warming the IBAT to 40-44 degrees C with two small heaters placed bilaterally on the skin above it attenuated the subsequent noradrenaline-induced thermogenesis (NIT) of the IBAT. In this range of warming, higher IBAT temperatures resulted in more attenuation. Denervation of IBAT blocked the effect of thermal stimulation on the NIT. Thus, activation of nerve fibers in IBAT that are sensitive to warmth or to the nociceptive effects of heat probably attenuated the NIT. Since the putative sensory fibers in the IBAT contain calcitonin gene-related peptide (CGRP) and substance P, which are thought to act in peripheral tissues, we tested the effects of injection of these neuropeptides into the IBAT. Administration of 5.2 nmol CGRP but not substance P or vehicle saline mimicked the effect of thermal stimulation of IBAT. As the neuropeptide-containing primary sensory neurons are characterized by their sensitivity to capsaicin, we also tested its effects (1 mg/kg, s.c.) and found that it also attenuated the NIT. Denervation of the IBAT or pretreatment with capsazepine, a capsaicin receptor antagonist, blocked the effect of capsaicin. We propose that temperature- and capsaicin-sensitive nerve fibers release CGRP to attenuate the NIT of brown adipocytes.

Adipose Tissue, Brown↗