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Biomedical subjects

Y Nakano

Publications and source records attributed to Y Nakano.

At least 235 records · Page 13Linked to original sources

Identification of pathologic parathyroid glands in patients with primary hyperparathyroidism.

Localization of the parathyroid glands is not necessarily easy before surgery and can also be troublesome during surgery. This study focuses on the identification of pathologic parathyroid glands. The records of 32 patients who underwent parathyroidectomy at our institution in the past 14 years for primary hyperparathyroidism were reviewed. Twenty-three patients had a single lesion while 9 had multiple-gland involvement. Localization studies identified 17 of 23 patients with a single lesion. All patients with multiple lesions were diagnosed with an enlargement of the parathyroids, but not all glands were identified in each patient preoperatively. At surgery, 8 of 32 patients were explored unilaterally. Solitary enlarged glands were resected, and a subtotal parathyroidectomy was performed for multiple-gland involvement. The intraoperative serum intact parathyroid hormone (PTH) level dropped after resection of the largest gland. The serum PTH level correlated with the gland size (r = 0.861, intact PTH assay). Eight of 9 patients with multiple-gland involvement had an elevated serum PTH (>2000 pg/ml in midportion and >200 pg/ml in intact PTH assays, respectively). No patient developed persistent or recurrent hyperparathyroidism. The serum PTH level was normalized by a resection of relatively enlarged glands in our cases. It is usual to explore all glands during surgery, and in cases with a high serum PTH level, multiple-gland involvement should also be considered.

Adult↗

DD genotype of the angiotensin I-converting enzyme gene is a risk factor for early onset of essential hypertension in Japanese patients.

Although angiotensin-converting enzyme (ACE) plays an important role in blood pressure regulation, no relationship between the insertion/deletion (I/D) polymorphism of the ACE gene and essential hypertension has been observed. However, as the pathogenesis and genetic background of essential hypertension are heterogeneous, we investigated whether the ACE gene is a marker of subgroups of patients with essential hypertension. A group of 178 patients with essential hypertension (90 men/88 women; 53 +/- 13 years of age, mean age +/- SD ) and 101 normotensive control subjects (54 men/47 women; 51 +/- 14 years of age, mean age +/- SD ) were included in the study. The allele frequencies of the two groups were similar. There were no differences in age, blood pressure, retinopathy grade, presence of proteinuria, or resting plasma renin activity (PRA) among the hypertensive patients with the II, ID, and DD genotypes. However, the age of onset of hypertension of patients with the DD genotype was lower (p < 20.05) and their left ventricular mass index was higher (p < 2 0.05) than those in patients with the non-DD genotype. These data suggest that the I/D polymorphism of the ACE gene is associated with an early onset of hypertension and left ventricular hypertrophy in Japanese patients with essential hypertension.

Adult↗

From behavior to development: genes for sexual behavior define the neuronal sexual switch in Drosophila.

The isolation and analysis of Drosophila mutants with altered sexual orientation lead to the identification of novel branches in the sex-determination cascade which govern the sexually dimorphic development of the nervous system. One such example is the fruitless (fru) gene, the mutation of which induces male-to-male courtship and malformation of a male-specific muscle, the muscle of Lawrence (MOL). Since the MOL is formed in wild-type flies when the innervating nerve is male, regardless of the sex of the MOL itself, the primary site of Fru function is likely to be the motoneurons controlling the MOL. The fru gene produces multiple transcripts including sex-specific ones. A female-specific mRNA from the fru locus has a putative Transformer (Tra) binding site in its 5' untranslated region, suggesting that fru is a direct target of Tra. The fru transcripts encode a set of proteins similar to the BTB (Bric à brac, Tramtrack and Broad-complex)-Zn finger family of transcription factors. Mutations in the dissatisfaction (dsf) gene result in male-to-male courtship and reduced sexual receptivity of females. The dsf mutations also give rise to poor curling of the abdomen in males during copulation and failure of egg-laying by females. The latter phenotypes are ascribable to aberrant innervation of the relevant muscles. A genetic analysis reveals that expression of the dsf phenotypes depends on Tra but not on Doublesex (Dsx) or Fru, suggesting that dsf represents another target of Tra. Taken together, these findings suggest that the sex-determination protein Tra has at least three different targets, dsx, fru and dsf, each of which represents the first gene in a branch of the sex-determination hierarchy functioning in a mutually-exclusive set of neuronal cells in the Drosophila central nervous system.

Animals↗

Short-term treatment of recombinant murine interleukin-4 rapidly inhibits bone formation in normal and ovariectomized mice.

Estrogen deficiency contributes to an increase in bone resorption and bone formation characterized by a high rate of bone turnover. Interleukin-4 (IL-4) is a rapid and potent inhibitor of bone resorption. We examined the short term in vivo effects of recombinant murine IL-4 (rmIL-4) on bone remodeling in normal and ovariectomized mice. Eight-week-old mice were randomized into the following five groups: (1) sham-operated mice (sham); (2) sham-operated mice infused with rmIL-4; (3) ovariectomized mice (ovx); (4) ovx infused with rmIL-4; and (5) ovx replaced by 10 or 20 microg of 17beta-estradiol (E2) for 14 or 28 days after ovariectomy, respectively. rmIL-4 at a dose of 5 microg/day was infused into ovx and sham for 3 days prior to sacrifice. Analyses were performed 14 and 28 days after operation. An increase in serum alkaline phosphatase and urinary deoxypyridinoline levels induced by ovariectomy was inhibited by the 3-day infusion of rmIL-4. In ovx, serum and urinary IL-6 levels were also increased significantly 14 days after ovariectomy, which were restored by E2 but not by rmIL-4. Histomorphometrical analysis of trabecular bone revealed that the 3-day infusion of rmIL-4 inhibited the high rate of bone turnover induced by ovariectomy, such as an increase in the osteoclastic surface (Oc.S/BS), number of osteoclasts per mm bone surface (N.Oc/BS), mineralized surface per mm bone surface (MS/BS), and bone mineral apposition rate (MAR). A significant decrease in the bone volume (BV/TV) observed in ovx was not modulated by a 3-day infusion of rmIL-4 prior to sacrifice. In sham, rmIL-4 also caused a significant decrease in the Oc.S/BS, N.Oc/BS, MS/BS, and MAR, but the BV/TV was not modulated by rmIL-4. We conclude that short term infusion of rmIL-4 in vivo rapidly inhibits not only bone resorption but also its formation in both sham-operated and ovariectomized growing mice, resulting in a low rate of bone turnover without modulating bone volume.

Alkaline Phosphatase↗

Antigen-presenting cell function of epidermal cells activated by hapten application.

Exposure to haptens initiates a series of immune and inflammatory reactions that cause migration of epidermal Langerhans cells (LC) to draining lymph nodes, antigen processing, and presentation to T cells. In the present study, the antigen-presenting cell (APC) function of epidermal cells (EC) following hapten application was determined using a cell transfer system. This function of EC in inducing contact sensitivity (CS) in the recipient mice appeared as early as 6 h after hapten painting, and reached its maximum at 24 h. The amount of hapten on EC did not correlate with the function, i.e. the amount retained on the cells was greatest immediately after hapten painting and decreased over time. Several experiments were performed to identify the cell type responsible for the APC function. Through immunomagnetic bead separation, the APC function was detected in Ia- EC, as well as in unfractionated EC from hapten-painted mice. A purified population of Ia+ cells (LC) induced CS with much less efficiency than unseparated cells. Depletion of LC by anti-Ia monoclonal antibody (mAb) and complement-mediated lysis did not impair the APC function, whereas it was reduced by the depletion of Thy-1+ cells by anti-Thy-1 mAb and complement-mediated lysis. Moreover, adherent cells that were harvested from a 48-h culture of EC obtained from hapten-painted skin, and were free of contaminating LC and gamma omega T cells, had a strong capacity to induce CS. These findings indicate that keratinocytes (KC) acquire APC function as well as LC, with hapten application. Phenotypically increased expression of intercellular adhesion molecule-1 (ICAM-1) and Thy-1 on EC was observed following hapten application, whereas expression of Ia and B7/BB1 was unaltered. The APC function of EC from hapten-painted skin was dependent on ICAM-1 and Thy-1 expression, as the mAbs for these molecules reduced the capacity to induce CS. These results suggest that hapten application induces not only LC but also KC to mature functionally and become potent APCs, and that these KC exert the APC function complementarily at local sites following the migration of LC with potent APC function to the draining lymph node.

Animals↗

Delusions and hallucinations in patients with borderline personality disorder.

To clarify the nature of delusional and hallucinatory symptoms in borderline personality disorder (BPD), the authors investigated five patients with BPD who developed those symptoms, and discussed their duration, recurrence, types of variants and relation to the situation. The duration of these symptoms tended to vary widely, although six of 11 episodes lasted more than 7 days. Episodes tended to recur in all patients two or three times. Each episode could be classified into three types of delusions and hallucinations, such as delusions without hallucinations, complicated delusion and hallucination, and hallucinations without delusion. Delusions without hallucination occurred a total of four times in two patients and had a tendency to occur when the patient confronted personal adversities. They projected their feelings directly toward the person concerned. A complicated delusion and hallucination was observed three times in two patients. This type of symptom also tended to occur at the time of interpersonal problems but the patient's attitude was more passive. Hallucination without delusion occurred a total of four times in three patients. This symptom tended to occur when the patient avoided an interpersonal relationship. In this case the patients isolated themselves from others and withdrew.

Adolescent↗

OPC-15161 suppresses the proliferation of Tenon's capsule fibroblasts and the production of type I collagen and fibronectin stimulated by TGF-beta1 in vitro.

PURPOSE: We investigated the effects of OPC-15161 on the growth of cultured human Tenon's capsule fibroblasts (TCFs), as well as on the production of type I procollagen, fibronectin, and laminin. These effects were examined in the presence or absence of TGF-beta1. METHODS: Cell proliferation was assayed by counting cell number and assay of DNA synthesis. Cytotoxicity was determined by the MTT method. Matrix components were assayed by enzyme immunoassay of material in the medium and in the cell lysate with or without OPC-15161. Total protein content was determined. Cellular ultrastructure was also evaluated. RESULTS: Treatment with OPC-15161 (up to 100.0 microg ml(-1)) significantly reduced the proliferation and DNA synthesis of TCFs. No significant decrease in MTT values was observed in confluent TCF cultures with OPC-15161 (up to 100.0 microg ml(-1)). TGF-beta1 enhanced the TCF production of procollagen I and fibronectin. OPC-15161 significantly decreased the procollagen I content in both the medium, in the cell lysate of TGF-beta1-stimulated cells, and fibronectin content in the lysate. OPC-15161 did not affect the laminin or total protein content, either with or without TGF-beta1. No ultrastructural evidence of cytotoxicity was observed. CONCLUSIONS: OPC-15161 inhibited the proliferation of TCFs, and reduced their production of procollagen I and fibronectin in the presence of TGF-beta1 without evidence of cytotoxicity. OPC-15161 may be useful in inhibiting the excessive fibrosis produced in the wound in response to filtering surgery.

Adult↗

Growth factors in infant germinal matrix: relationship to extracellular matrix and cell adhesion molecules.

We examined the expression of selected growth factors, growth factor receptors, elements of extracellular matrix and cell adhesion molecules in the germinal matrix layer (GML) utilizing immunohistochemistry and reverse transcriptase polymerase chain reaction. At autopsy brain samples from 10 neonatal infants were used. Epidermal growth factor receptor (EGFR) was significantly expressed in the matrix cells. While transforming growth factor alpha and heparin-binding epidermal growth factor-like growth factor were found in the matrix cells or vascular wall as ligands, epidermal growth factor was not expressed. EGFR and its ligands are thought to be important factors for the maintenance of the matrix cells and cell-to-cell interactions. Insulin like growth factor I, its receptor Ibeta and tenascin were found in the stroma of the GML and periventricular region. Vascular endothelial growth factor and receptor Flk-1, laminin A and B2, fibronectin, collagen type IV and integrins such as beta3, alpha5beta1 and alphaVbeta3 were found mainly in or around the vascular wall indicating their important roles for vascularization. Transforming growth factor beta2 and its receptor II were expressed in the matrix cells and/or vascular wall suggesting a role in proliferation and/or regression of the vasculature. CD44 and Thy-1 were also expressed in the matrix cells.

Autopsy↗

A case of glycogen storage disease type Ia with multiple hepatic adenomas and G727T mutation in the glucose-6-phosphatase gene, and a comparison with other mutations previously reported.

We report a case of 23-yr-old man with glycogen storage disease (GSD) type Ia complicated by multiple hepatic adenomas. Analysis of the G-6-Pase gene using peripheral blood sample showed this patient to be homozygous for a G-to-T transversion at nucleotide 727 in exon 5. This mutation is prevalent among Japanese patients, suggesting that specific genotypes may correlate with different clinical courses or outcomes.

Adenoma↗

Identification of a genetic locus essential for serotype b-specific antigen synthesis in Actinobacillus actinomycetemcomitans.

A large gene cluster associated with the biosynthesis of the serotype-specific polysaccharide antigen (SPA) of Actinobacillus actinomycetemcomitans Y4 (serotype b) was cloned and characterized. Western blot analysis showed that Escherichia coli DH5alpha, containing a plasmid carrying this cluster, produced a polysaccharide which reacted with a monoclonal antibody directed against the SPA of A. actinomycetemcomitans Y4. High-performance liquid chromatography analysis indicated that the polysaccharide produced by an E. coli transformant, as well as A. actinomycetemcomitans Y4 SPA, was composed of rhamnose and fucose. Furthermore, using various derivatives of the plasmid, we demonstrated that the cloned 13-kb BssHII-BspHI fragment was indispensable for SPA synthesis in E. coli DH5alpha. The 24,909-bp nucleotide sequence, which included this fragment and its flanking regions, was determined. In the sequenced area, 24 open reading frames (ORFs) with the same orientation were found. Most of these were located sequentially within a short distance of each other. Many of the deduced amino acid sequences were similar to the gene products of the polysaccharide synthetic genes of other bacteria. The average G+C content (37.7%) of all 24 ORFs in the sequenced area was lower than that (45.6%) of the whole chromosome of A. actinomycetemcomitans Y4. It is noteworthy the average G+C content of the nine ORFs in the 8.5-kb central region of the 13-kb BssHII-BspHI fragment indispensable for SPA synthesis in E. coli was found to be especially low (27.0%).

Acetylglucosamine↗

Genes involved in cell wall localization and side chain formation of rhamnose-glucose polysaccharide in Streptococcus mutans.

We identified in Streptococcus mutans six new genes (rgpA through rgpF), whose disruption results in a loss of serotype-specific antigenicity, specified by the glucose side chains of rhamnose-glucose polysaccharide from the cell wall. Rhamnose and glucose content of the cell wall decreased drastically in all these disruption mutants, except that in the rgpE mutant only the glucose content decreased. RgpC and RgpD are homologous to ATP-binding cassette transporter components and may be involved in polysaccharide export, whereas RgpE may be a transferase of side chain glucose.

Amino Acid Sequence↗

Posterior lobe of the pituitary gland: correlation between signal intensity on T1-weighted MR images and vasopressin concentration.

PURPOSE: To correlate the signal intensity on magnetic resonance (MR) images in the posterior lobe of the pituitary gland with the vasopressin content. MATERIALS AND METHODS: Fourteen rabbits were studied: 12 water-deprived rabbits (two each at 48, 74, 96, 120, 144, or 168 hours of deprivation) and two control rabbits. Sagittal T1-weighted MR images were obtained before and after water deprivation. The signal intensity ratio of the posterior lobe to the pons was correlated with the vasopressin content in the posterior lobe, which was measured by means of radioimmunoassay. RESULTS: Before water deprivation, high signal intensity in the posterior lobe was demonstrated clearly in all rabbits. The signal intensity ratio and vasopressin content in the posterior lobe gradually decreased with water deprivation. The signal intensity ratio correlated strongly with the vasopressin content in the posterior lobe (Pearson correlation coefficient, .809; P < .001). CONCLUSION: The signal intensity ratio on T1-weighted MR images may be used as an indicator for the quantitative evaluation of the vasopressin content in the posterior lobe. The results strongly suggest that the origin of the high signal intensity in the posterior lobe on T1-weighted MR images is the vasopressin-neurophysin II-copeptin complex.

Animals↗

Increased cytosolic free Mg2+ and Ca2+ in platelets of patients with vasospastic angina.

This study was designed to test the hypothesis that the cellular metabolism of Ca2+ and Mg2+, which is important in platelet function, is abnormal in the platelets of patients with vasospastic angina. Cytosolic free Mg2+ concentration ([Mg2+]i) and Ca2+ handling were determined in the platelets of 24 patients with vasospastic angina and 24 control subjects by use of mag-fura 2 and fura 2. Platelet aggregation was also examined. Basal [Mg2+]i and cytosolic free Ca2+ concentration ([Ca2+]i) in platelets were significantly higher in patients with vasospastic angina than in control subjects. The amplitude of the [Ca2+]i transient induced by thrombin (0.03-1.0 U/ml) was significantly increased in the presence, but not in the absence, of extracellular Ca2+ in patients with vasospastic angina, as compared with controls. Therefore, the influx of Ca2+ across the plasma membrane may be accelerated in vasospastic angina. Thrombin (0.1-1.0 U/ml)-induced maximum aggregation response was significantly greater in patients with vasospastic angina than in controls. Results suggest that increased [Mg2+]i and altered Ca2+ handling by platelets may be associated with coronary vasospasm.

Adenosine Diphosphate↗

Induction of protection against tetanus toxin in mice by tetanus toxoid-liposome conjugate.

Tetanus toxoid (Ttd) was coupled to liposomes via glutaraldehyde. Intraperitoneal injection in BALB/c mice with Ttd-liposomes induced a substantial amount of anti-Ttd IgG antibody production and an extremely low level of anti-Ttd IgE antibody production. Mice immunized with Ttd-liposomes were successfully protected against a subsequent challenge with a lethal dose of tetanus toxin (Ttx). On the other hand, aluminum hydroxide-adsorbed Ttd (Ttd-alum) and plain Ttd solution induced the production of both IgG and IgE antibodies against Ttd. Moreover, secondary immunization with Ttd-liposomes in mice, in which anti-Ttd IgE antibody production was induced by Ttd-alum led to enhanced anti-Ttd IgG and a limited anti-Ttd IgE antibody production. When Ttd-liposome preparation was lyophilized, the efficacy of Ttd-liposomes was maintained for 6 months at 37 C, suggesting that this vaccine preparation would be stable without refrigeration. These results demonstrate the potential ability of Ttd-liposome conjugates to produce a tetanus vaccine which provides protection against (Ttx) while inducing the least amount of anti-Ttd IgE antibodies.

Animals↗

Induction of protection against oral infection with cytotoxin-producing Escherichia coli O157:H7 in mice by shiga-like toxin-liposome conjugate.

We have previously reported that purified Shiga-like toxins (SLT), SLT-I and SLT-II coupled with liposomes induced a substantial amount of anti-SLT-I and anti-SLT-II IgG antibody production, respectively, in mice. The levels of anti-SLT antibody in the sera of SLT-liposome-immune mice correlated well with the protection against subsequent challenge with SLT. In this study, mice were immunized intraperitoneally with the mixture of SLT-I-liposome and SLT-II-liposome and protection against oral infection with cytotoxin-producing Escherichia coli O157:H7 was evaluated. All of the mice that received immunization with the mixture of SLT-I-liposome and SLT-II-liposome were protected against subsequent intravenous challenge with 10 LD50 of either SLT-I or SLT-II. Eight weeks after primary immunization, mice were inoculated intragastrically with 10(9) CFU of E. coli O157:H7 strain 96-60. All SLT-liposome-immune mice tested survived without any apparent symptom while control mice died within 5 days. In addition, as shown by other antigen-liposome conjugates, SLT-liposome induced undetectable anti-SLT IgE antibody production while they induced substantial amounts of anti-SLT IgG antibodies. These results suggest that SLT-liposome conjugate may serve as a candidate vaccine that induces protection against cytotoxin-producing E. coli infection.

Animals↗

Effect of 17beta-estradiol on inhibition of platelet aggregation in vitro is mediated by an increase in NO synthesis.

The low prevalence of coronary heart disease in premenopausal women and its increase after menopause are well established. Although estrogen is thought to play a role in protecting the vasculature, the mechanism has not been fully clarified. The contribution of platelets to atherosclerotic cardiovascular diseases is well recognized. The present study focused on the still-controversial effect of estrogen on platelet function. We investigated the in vitro effects of estrogen on human platelets, including their aggregation, Ca2+ metabolism, the synthesis of cyclic nucleotides, and NO (nitrite/nitrate) synthesis after stimulation with thrombin or ADP. Pretreatment of platelets with 17beta-estradiol reduced the platelet aggregation induced by thrombin or ADP, whereas 17alpha-estradiol had no effect. 17Beta-estradiol accelerated the recovery of [Ca2+]i after the agonist-induced peak and reduced the area under the curve of accumulated platelet [Ca2+]i but did not alter the baseline [Ca2+]i, Ca2+ influx induced by thrombin or ADP, the release of Ca2+ from internal stores, or the size of internal Ca2+ stores. Pretreatment of platelets with 17beta-estradiol had no effect on the intracellular concentration of cAMP but increased that of cGMP in agonist-stimulated platelets. Additionally, 17beta-estradiol increased the platelet concentration of nitrite/nitrate in a dose-dependent manner. These effects of 17beta-estradiol on platelet aggregation, Ca2+ metabolism, and NO synthesis were abolished by exposure to N(G)-monomethyl-L-arginine, an NO synthesis inhibitor. These results suggest that 17beta-estradiol plays an important role in inhibiting platelet aggregation by promoting Ca2+ extrusion or reuptake activity that is dependent on the production of cGMP by increasing NO synthesis.

Adult↗

Angiotensin-converting enzyme inhibition, but not calcium antagonism, improves a response of the renal vasculature to L-arginine in patients with essential hypertension.

Endothelial function has been shown to be impaired in patients with essential hypertension. The purpose of the present study was to determine whether antihypertensive drug therapy improves impaired endothelium-dependent renal vasorelaxation in essential hypertensive patients without atherosclerosis. We evaluated the effects of intravenous infusion of L-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 27 patients with mild to moderate essential hypertension who were randomly assigned to treatment with either the angiotensin-converting enzyme inhibitor imidapril or the calcium antagonist amlodipine for 12 weeks in a double-blind fashion. After the 12 weeks, the decrease in blood pressure was similar in the imidapril (n=14) and amlodipine (n=13) groups. The increase in renal plasma flow was also similar in both groups. L-Arginine-induced renovascular relaxation was increased by imidapril (renal plasma flow, 9.6+/-5.1% to 14.4+/-7.4%; renal vascular resistance, -10.4+/-8.1% to -16.7+/-9.2%, P<0.05, respectively) but not by amlodipine. Urinary excretion of nitrite/nitrate in response to L-arginine was significantly increased by imidapril (90+/-29% to 134+/-63%, P<0.05) but remained unchanged by amlodipine. These findings suggest that angiotensin-converting enzyme inhibition improves the impaired endothelium-dependent renovascular relaxation in patients with essential hypertension due to the increase in nitric oxide production and that the reduction in blood pressure with a calcium antagonist does not play a major role in the potentiation of L-arginine/nitric oxide-mediated effects.

Adult↗