Familial Angelman syndrome caused by imprinted submicroscopic deletion encompassing GABAA receptor beta 3-subunit gene.
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Biomedical subjects
Publications and source records attributed to T Sugimoto.
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To elucidate the role of sympathovagal interaction in diurnal variation of QT interval, 24-hour ambulatory electrocardiographic recordings from 56 subjects (23 control subjects, 18 patients with atherosclerotic coronary artery disease, and 15 patients with diabetes mellitus) were studied. The QT interval at a heart rate of 60 beats/min (QT60) was determined for each of the day and night periods by regression analysis. Sympathetic and parasympathetic activities were assessed by spectral analysis of heart rate variability and represented by the low- and high-frequency components, respectively. The proportion of high-frequency component to the sum of low- and high-frequency components was used as an index of sympathovagal balance. The relative increase in QT60 at night (delta QT60 [%]) was larger in control subjects (4.2 +/- 2.1%) than in patients with coronary artery disease (2.2 +/- 1.8%; p less than 0.01) and diabetes mellitus (-1.5 +/- 4.0%; p less than 0.001). When the data from the 3 subject groups were pooled and analyzed, delta QT60 was correlated with the change in the sympathovagal balance (r = 0.554; p less than 0.001). Low-frequency component in the day alone was also related with delta QT60 (r = 0.554; p less than 0.001), but the ratio or difference of the high-frequency component value between day and night was not. These results indicate that although change in sympathovagal balance was responsible for the diurnal variation in QT interval, the enhanced sympathetic activity in the day was a major determinant of this phenomenon.
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Using anti-murine interleukin-2 receptor beta chain (IL-2R beta) monoclonal antibody (mAb), we have examined the expression of IL-2R beta on murine thymocyte subpopulations. We found that it was constitutively expressed on 1%-4% of thymocytes in an almost mutually exclusive fashion with IL-2R alpha. The expression of IL-2R beta is developmentally regulated. While it is expressed mainly on T cell receptor gamma delta+ (TcR gamma delta+) cells during fetal age, the major subpopulation expressing IL-2R beta in adult mouse shifts to CD4-CD8-TcR alpha beta+ thymocytes. A considerable portion of CD4-CD8- TcR alpha beta+ cells in other organs, including spleen, bone marrow and liver, was also found to express IL-2R beta. In fetal thymus organ culture, the above thymocyte subset was induced to expand in response to exogeneous IL-2, and the expansion was inhibited by addition of anti-IL-2R beta mAb, suggesting that IL-2R beta is functional in this subpopulation. However, in vivo blockade of the IL-2/IL-2R pathway with the mAb did not exert any effects on the appearance of CD4-CD8- TcR alpha beta+ cells both in the thymus and the periphery. This indicates that the development of CD4-CD8- TcR alpha beta+ cells is not solely controlled by IL-2 but also by other complex elements.
This study investigates the role of hepatic asialo GM1-positive cells in inhibiting hepatic metastasis of colon carcinoma (colon adenocarcinoma 38) in mice after administration of a biological response modifier, streptococcal derivative (OK432). Administration of OK432 increased the number of asialo GM1-positive cells in the liver, enhanced natural killer activity of hepatic mononuclear cells and reduced the number of hepatic metastases of colon carcinoma inoculated into the superior mesenteric vein. Administration of antiserum against asialo GM1 reduced the number of hepatic asialo GM1-positive cells, abolished natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases. In addition, administration of antiserum against asialo GM1 even after OK432 treatment also decreased the number of asialo GM1-positive cells, reduced natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases of colon carcinoma. However, administration of gadolinium chloride, which suppresses phagocytic function of Kupffer cells, did not influence the natural killer activity of hepatic mononuclear cells or the number of hepatic metastases. In vivo tumor-neutralization assay revealed that tumor growth was inhibited by the hepatic mononuclear asialo GM1-positive cells, but not by T lymphocytes or Kupffer cells after OK432 administration. These results suggest that an increased number of hepatic asialo GM1-positive cells after administration of OK432 plays an important role in protecting against metastasis of colon carcinoma in the liver.
Throughout the world the diagnosis and management of osteoporosis currently involves the measurement of bone mineral content. There are, however, no studies comparing bone mineral content among Asian people. This cross-sectional study was designed to quantify spine and femur bone mineral density (BMD) in Japanese and compare BMD among Asian people (Japanese, Koreans, and Taiwanese) using the same model dual-photon system (Norland Model 2600). Following a peak BMD in the third and fourth decades, the Japanese BMD values of the lumbar spine and femoral neck showed a clear decrease (annual loss of 0.99 and 0.74%, respectively) with age in females. On the other hand, Japanese BMD values were stable in males until the fifth decade. There was some decrease in BMD with age after the fifth decade, which was much less obvious than that in females. An age-dependent loss of BMD was clearly observed in Japanese and Korean but not in Taiwanese females. Korean males seemed to have a clearer age-dependent loss of BMD compared to Japanese males. Our findings indicate that differences may exist in the BMD of Asian people and that in addition to the quantitative determination of individual BMD, dual-photon absorptiometry may be useful for the comparison of BMD among different ethnic and cultural groups.
The present study was performed to investigate the regulation of cytosolic pH (pHi) and DNA synthesis by parathyroid hormone(PTH) and PTH-related peptide (PTHrP) in osteoblasts, using osteoblastic osteosarcoma cells, UMR-106 which possessed PTH-responsive dual signal transduction systems (cAMP-dependent protein kinase (PKA) and calcium/protein kinase C [Ca/PKC]) and amiloride-inhibitable Na+/H+ exchange system. Both human (h)PTH-(1-34) and hPTHrP-(1-34) caused a progressive decrease in pHi and the inhibition of [3H]thymidine incorporation (TdR) to the same degree in a dose-dependent manner with a minimal effective dose of 10(-10) M. Dibutyryl cAMP (10(-4) M and Sp-cAMPS (10(-4) M), a direct stimulator of PKA also caused a progressive decrease in pHi, and calcium ionophores (A23187 and ionomycin, 10(-6) M) caused a transient decrease in pHi. Pretreatment with amiloride (0.3 mM) mostly blocked dbcAMP- and Sp-cAMPS-induced decrease in pHi but did not affect calcium ionophore-induced decrease in pHi. In the presence of amiloride, PTH and PTHrP caused a transient decrease in pHi, which was similar to the pattern of calcium ionophore-induced change in pHi. Amiloride did not affect the inhibition of TdR by PTH or PTHrP as well as that by cAMP analogues or calcium ionophores. The present study indicated that PTH and PTHrP caused cytosolic acidification through PKA-inhibited Na+/H+ exchange and increased cytosolic calcium-induced pathway and that the regulation of DNA synthesis by PTH and PTHrP was not via Na+/H+ exchange system.
A full-length cDNA encoding a subunit of phosphoenolpyruvate carboxylase (PEPC) was isolated from a developing seed expression library of the C3 plant Glycine max. The corresponding mRNA is present at similar levels in leaf, stem, root and developing seed. Two potential start codons exist, and the activity of protein initiated from the first such codon could be subject to regulation by protein kinase. Sequence comparison shows a similar upstream start codon in the case of the Ppc2 gene from Mesembryanthemum crystallinum, previously assumed to lack the sequences necessary for phosphorylation. The soybean encoded protein tends to resemble other 'C3-type' PEPC proteins more closely than those implicated in C4 or crassulacean acid metabolism.
The active sliding of cardiac myosin on actin cables was studied using an in vitro movement assay. Cardiac myosin prepared from either adult rabbit or rat hearts was mixed with small latex beads to coat them. Actin cables were obtained from the internodal cells of green algae, Characeae. When the myosin-coated beads suspended in physiological buffer were introduced into the internodal cells, the myosin started to interact with the actin causing the beads to move. The sliding movement of the beads was observed under microscopy and the sliding velocity measured. The observed movement was smooth and the velocity was constant over a long distance. The movement was physiological in nature: a) it was ATP-dependent, but above a certain level of ATP, the velocity was constant; b) the velocity was maximum at pH 7.0, and decreased in both acidic and alkaline conditions. The average sliding velocity of cardiac myosin obtained from rabbit ventricles (0.31 +/- 0.11 micron/s) was slower than that from rat ventricles (1.04 +/- 0.26 micron/s) reflecting the lower ATPase activity of rabbit cardiac myosin. This assay system is considered to be a useful tool linking biochemistry and physiology at the molecular level.
Hypothalamic hormones as well as anterior pituitary hormones were detected in the peripheral plasma after the diagnosis of brain death. It is possible that residual hypothalamic tissue was functioning after satisfying the usual criteria of total brain death. To examine this possibility, endocrinological and morphological alterations of the hypothalamic-pituitary system was evaluated in 28 brain dead patients. Intrinsic ADH was depleted in the plasma shortly after the diagnosis of brain death. Anterior pituitary hormones were initially detected in all patients, but gradually disappeared. The direct TRH (thyrotropin releasing hormone) stimulation to the anterior lobe was responded to well. Morphological studies showed a partial necrosis of the anterior lobe and the preservation of the posterior lobe for as long as a week. These data prove that the pituitary is partially preserved after brain death. LH-RH (luteinizing hormone releasing hormone) was detected in the peripheral plasma of all patients and GRF (growth hormone releasing factor) was detected in half of the patients for as long as 15 days, but autopsy revealed the fact that the brain tissue including the hypothalamus became extensively necrotic after the sixth day of brain death. In order to solve this controversy it is proposed that these hormones originate from extracranial tissues such as pancreas. The detection of hypothalamic hormones after the diagnosis of brain death therefore is not contradictory to the concept of total brain death.
We examined the effects of four kinds of intravascular contrast agents (amidtrizoic acid, iohexol, iopamidol, and ioxaglic acid) on [Ca2+]i transients (indo-1 fluorescence) and cell contraction (video motion analyzer), using cultured chick embryo ventricular myocytes. Exposure of ventricular myocytes to amidtrizoic acid (a conventional contrast agent) reduced the [Ca2+]i transients and the sensitivity of the contractile elements to [Ca2+]i. Ioxaglic acid (a low osmotic contrast agent) also reduced the [Ca2+]i transients, but did not significantly change the sensitivity of the contractile elements to [Ca2+]i. Neither iohexol nor iopamidol (nonionic contrast agents) reduced the [Ca2+]i transients, but both significantly decreased the sensitivity of the contractile elements to [Ca2+]i. A marked negative inotropic effect of amidtrizoic acid was caused by both calcium binding and hypertonicity. The less marked depression of contractility produced by ioxaglic acid is possibly the result of calcium binding, but is not caused by hypertonicity. The negative inotropism produced by nonionic contrast agents (iohexol and iopamidol) was due to hypertonicity, but not due to alterations in the [Ca2+]i transients. Exposure of ventricular myocytes to nonionic contrast agents (iohexol and iopamidol) slowed decay in the [Ca2+]i transients with increased end-diastolic [Ca2+]i. After washing out the nonionic contrast agents, these parameters returned to control levels. On the other hand, exposure to amidtrizoic acid decreased end-diastolic [Ca2+]i without changing decay time in the [Ca2+]i transients. After washing out amidtrizoic acid, there was a prolongation of half decay time in [Ca2+]i transients with a significant increase in end-diastolic [Ca2+]i and cell position. Diastolic dysfunction just after washout of amidtrizoic acid was possibly caused by an increase in [Na+]i due to sodium influx during exposure to the contrast agent.
To determine the role of anatomic architecture in atrial flutter, electrophysiologic findings were correlated with anatomic features in a modified model of atrial flutter with ligation of the crista terminalis. Crista ligation in the middle right atrium prolonged intraatrial conduction time in a rate-dependent manner in 12 dogs, particularly in the low right atrium. With burst atrial pacing, unidirectional block occurred either in the low right atrium or in the interatrial septal region near the superior vena cava, leading to initiation of atrial flutter. Atrial activation mapping revealed a slow conduction area in the low right atrium where conduction had been delayed by crista ligation. On the intact tissues between the venae cavae, double potentials were recorded, a finding indicative of functional block in the center of the reentrant circuit. The interdeflection time of double potentials changed with the activation sequence of atrial flutter. This change could be explained by assuming that the functional center of the reentrant circuit leaned on the right atrial free wall side. Anatomic study demonstrated that areas of slow conduction, unidirectional block, and functional block in the center of the reentrant circuit were closely related to the location of the intact crista terminalis. In conclusion, the intact portion of the crista terminalis played an important role in the genesis of atrial flutter after blockage of longitudinal conduction through the crista.
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The Nalm-16 cell line was originally described as being of the null acute lymphoblastic leukaemia (ALL) phenotype. Using phenotypic and genotypic markers, we have demonstrated the line carries markers associated with cells of the B lineage. In addition, Nalm-16 binds a series of monoclonal antibodies characterized as predominantly recognising neuroectodermal tissues. Amongst these antibodies, UJ13A, 5.1.H11 and ERIC-1 have been shown to recognise the neural cell adhesion molecule (NCAM). Expression of the NCAM molecule is highly complex, with several isoforms of the protein resulting from the differential splicing of the NCAM mRNA transcript. Western-blot analysis of Nalm-16 cell extracts indicates that cells express the heavily polysialylated form of the molecule found on many embryonic tumours. Neuraminidase digestion indicates that the 140 kD isoform is predominantly expressed on Nalm-16, although the 120 kD isoform is present to a lesser degree. These findings have been confirmed using Northern-blot analysis.
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Islet amyloid polypeptide (IAPP) is a major constituent of pancreatic amyloid deposits in many patients with non-insulin-dependent diabetes mellitus (NIDDM). We analyzed the IAPP gene in a Japanese diabetic with marked islet amyloid deposition. Pancreatic specimens were obtained from an 87-year-old NIDDM patient who had had diabetes for 37 years. All islets (100/100) in his pancreas had IAPP-positive amyloid deposition, and 70% of the area of the islet was replaced by amyloid. We amplified the coding regions as well as the upstream region of the IAPP gene by polymerase chain reaction (PCR). The products of PCR were sequenced, and the sequences of the coding regions were identical to the Caucasian ones. However, the nucleotides of two positions of 5'-upstream and one position of intron 2 were different from the Caucasian data: the upstream region of the IAPP gene in the patient had cytosine substituted for thymine at -259, and had two alleles including cytosine and adenine at -229, respectively. The nucleotide of position 539, that is guanine, was deleted. A possible difference in the IAPP promoting region between the Japanese and Caucasian population was suggested.
By using immunohistochemistry combined with lesioning and retrograde neuronal labeling techniques, cholinergic neurons and corticotropin-releasing factor-immunoreactive neurons were examined for their distribution, coincidence and cerebellar projections in feline vestibular nuclear complex and adjacent brainstem structures. Cholinergic neurons as revealed here with choline acetyltransferase immunoreactivity were found massively in the abducens and hypoglossal nuclei, dorsal motor nucleus of the vagus nerve and nucleus of Roller; less numerously in the medial vestibular, prepositus hypoglossi and solitary nuclei and the caudal two-thirds of descending vestibular nucleus; and only occasionally in the intercalated and supravestibular nuclei and cell groups f, x and z. Corticotropin-releasing factor-immunoreactive neurons were found clustered in the prepositus hypoglossi nucleus and also in cell groups f and x and the rostral two-thirds of descending vestibular nucleus, less numerously in the medial vestibular, intercalated and solitary nuclei and nucleus of Roller, and only occasionally in the caudal one-third of descending vestibular nucleus, the dorsal motor nucleus of the vagus nerve, supravestibular nucleus and cell group z. The lateral and superior vestibular nuclei did not contain either type of neuron. The two types of immunopositive neurons observed in most of the brainstem nuclei differed in cell size, distribution-pattern and rostrocaudal level of occurrence. While there were many regions which exhibited both types of immunopositive neurons, perikarya colocalizing the cholinergic and peptide markers were not detected in the brainstem. Following unilateral, partial lesioning of the vestibular nuclear complex, corticotropin-releasing factor-immunoreactive mossy fiber terminals (rosettes) disappeared from the ipsilateral flocculus. However, such lesions did not produce clear-cut changes of cholinergic terminals in the vermis. Following retrograde neuronal labeling combined with immunohistochemistry, the two types of immunopositive neurons observed in most of the brainstem sites were found to project to the vermal lobules I-III, IX and X. On comparison of these immunopositive projection neurons with non-immunoreactive, retrogradely labeled neurons, the cholinergic neurons and the peptide-immunoreactive neurons were found to constitute a major part of the total vestibulocerebellar neuronal population. The results indicate chemical heterogeneity in vestibular nuclear complex and cerebellar afferents.