Biomedical subjects
Publications and source records attributed to Y Nakashima.
Neurogenic tumors of the liver are very rare, irrespective of associated neurofibromatosis. We report here a well-documented case of benign schwannoma in a 56-year-old woman without neurofibromatosis, including imaging and pathological examinations.
Cloning and sequence analysis of cDNA showed that the brain type of ryanodine receptor (RYR) is expressed in human Jurkat T-lymphocyte cells. Fura-2 measurements revealed that the RYR in T-cells functions as a ryanodine-sensitive, caffeine-insensitive Ca2+ release channel. Furthermore, ryanodine stimulated proliferation and altered the growth pattern of cultured human T-cells when added together with FK506.
1. The gating properties of the hyperpolarization-activated cation current (I(f) or Ih) were investigated in single pacemaker cells dissociated from the rabbit sino-atrial node. 2. The whole-cell I(f) was recorded in the presence of different external cations. The inward I(f) was increased when external Na+ was replaced with K+, and was decreased in Li+ or Rb+ solution. In Tris+ and Cs+ solutions, the inward I(f) was negligible. The outward tail current recorded upon depolarization was largest in Li+ solution and smaller in a sequence of Na+, Tris+ and K+ solutions. In Rb+ and Cs+ solutions, only a small tail current was recorded. 3. The outward tail current had a 'shoulder' in Na+ solution, which was much delayed by replacing Na+ with Li+. In K+ solution, the decay of the tail current was much faster, and no obvious shoulder was recorded. The tail current was slowest in Li(+)-rich and 0 mM K+ solution, and was progressively accelerated by adding K+ over the range from 0 to 3 mM. The tail current at 30 mM [K+]o showed only a small shoulder. A common binding site to modulate the I(f) deactivation was suggested for monovalent cations. 4. The shoulder of the I(f) tail became more evident as I(f) was activated to a larger extent either by prolonging the duration or by increasing the amplitude of the preceding hyperpolarization in both Na+ and Li+ solutions. 5. The I(f) was first activated by hyperpolarizing the membrane to -110 mV, and then deactivated by depolarization. The inward tail current at -50 mV showed a single exponential decay. At more positive potentials, the shoulder of the outward tail currents became more evident and the rate of the final decay was increased. 6. The time course of I(f) activation was well fitted with the sum of two exponential functions. Time constants of both components were not affected by the external cation (Na+, K+ or Li+) replacement. Likewise, the quasi-steady state activation was conserved when external Na+ was replaced with Li+. 7. Two closed and three open states were assumed in a sequential state model of the I(f) channel. The cation effects were well simulated by assuming that the deactivation rate was selectively modulated. The flow of I(f) during the spontaneous action potential was calculated. The activation of I(f) started on repolarization to the maximum diastolic potential and reached a maximum in the middle of the diastolic period. Its peak amplitude was 14% of the net inward current during the diastolic period.
Patients with coronary artery disease reportedly have an impaired left ventricular filling. To evaluate the effects of coronary collaterals on diastolic function in patients with effort-induced angina, resting radionuclide ventriculography was performed in 14 patients with severe isolated (> or = 90% diameter) stenosis of the left anterior descending coronary artery and in seven normal subjects. Contrast ventriculography showed normal wall motion in all patients. Functional indices obtained by radionuclide ventriculography were compared between those patients with collateral vessels, Rentrop classification grades 1 (n = 7) and 3 (n = 1), and those patients without (n = 6) collateral vessels. Global peak filling rate was significantly (P < 0.01) reduced in the patients with collaterals. The septal, apical and lateral peak filling rates were also reduced in patients with collateral vessels, with the reduction in lateral peak filling rate being statistically significant (P < 0.05). The indices of systolic function and the temporal diastolic asynchronous index were similar, irrespective of the presence of collaterals. The exercise tolerance as evaluated by the rate-pressure product at peak treadmill exercise stress testing in 12 patients was significantly (P < 0.01) lower in those with collateral vessels. Angiographically visible collaterals could be a marker for more severe coronary stenosis in patients with effort-induced angina, and an indicator of the severity of deterioration in left ventricular diastolic function.
Mucopolysaccharidosis IV A (MPS IV A) is the result of a genetic deficiency in a lysosomal hydrolase, N-acetylgalactosamine-6-sulfatase (GALNS). To investigate MPS IV A patients at the level of the genome, we analyzed the structure of the human GALNS-encoding gene. From the genomic library of a normal subject in lambda EMBL3, we isolated five overlapping clones covering the coding region of the GALNS cDNA and determined the structural organization. The gene is about 50 kb long and contains 14 exons. The 5'-flanking region lacks a canonical TATA box and CCAAT sequences, but is G+C-rich (70.5%), with four GC boxes, characteristic of a housekeeping gene promoter. The transcription initiation site was determined by primer extension analysis, using RNA from human liver and HeLa cells. Transcription was found to initiate at a few sites, the major ones being 58 and 22 bp upstream of the translation initiation codon. The 5'-flanking region had promoter activity by transient expression, determined using a CAT assay. In addition, this region retained promoter activity, even in reverse orientation. The region -98 to -1 upstream of the ATG codon was defined by deletion analysis to be a minimal promoter. One GC box in this region is likely to be a binding site of a regulatory element.
Some physiological functions of the heart are modulated through cardiac beta-adrenoceptors. In acute myocardial infarction, ventricular arrhythmias occur frequently and class I antiarrhythmic drugs such as lidocaine are often administered continuously over long period. The aim of this study was to investigate the effects of long-term treatment with lidocaine on cardiac beta-adrenoceptors. Ventricular cardiocytes from 2-day-old Wistar rat were cultured in the presence or absence of lidocaine, and beta-adrenoceptors of the membrane fraction of the cells were measured with a binding assay using [125I]-iodocyanopindolol ([125I]CYP) as a radioligand. When the cells were cultured in the presence of lidocaine at clinical or toxic concentrations, the binding of [125I]CYP to the cells increased in a concentration (10(-5) mol/l-10(-3) mol/l)--and time (12-72 h)--dependent manner. The effect was due to an increase in maximum binding and was not due to a change in the dissociation constant for the ligand. The stimulation of adenylyl cyclase activity in the cell membrane by 1 mumol/l isoproterenol increased in lidocaine-treated cells. The increased number of receptors returned to the control level when the cells were cultured without lidocaine for a further 24 h. These results indicate that lidocaine up-regulates cardiac beta-adrenoceptors at both clinical or toxic doses during the period of treatment. Other antiarrhythmic drugs such as disopyramide (Ia), mexiletine (Ib) and flecainide (Ic) also increased the number of beta-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunohistochemical examination showed no significant expression of platelet-derived growth factor-A (PDGF-A), PDGF-B, PDGF receptors, or of c-myc in the thoracic and abdominal aortas of normal roosters. In cholesterol-fed roosters, intense immunohistochemical reaction for PDGF-B, PDGF receptor, and c-myc was seen in the lipid-rich thickened intimal lesions of the thoracic and abdominal aortas while no significant immunoreaction for PDGF-A was demonstrated in the same lesions. In accordance with immunohistochemical findings, in situ hybridization demonstrated a significant level of expression of PDGF-B, PDGF-A receptor, PDGF-B receptor, and c-myc genes in proliferating intimal cells of the thoracic and abdominal aortas. These results suggest that coordinate actions of PDGF-B and c-myc play an important role in proliferation of intimal cells in the developing atherosclerotic lesions in chickens.
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The usefulness of transesophageal echocardiography (TEE) for guiding the placement of a pulmonary artery (PA) catheter was evaluated in 31 patients (TEE group); 31 patients who were treated before TEE guidance was used (control group). In the control group, use of the PA catheter was abandoned in two patients; because of an unstable condition and marked arrhythmias, respectively. The key findings for TEE guidance were: (1) pulsatile to-and-fro movement of the balloon, i.e., "shuttle movement" and (2) loss of shuttle movement at wedging of the balloon, i.e., "anchoring sign." When the PA catheter did not enter the right vertricle (RV), the balloon was found to be in the inferior vena cava or the right atrium (RA) without shuttle movement. Coiling of the catheter was suggested in the latter situation. Coiling also occurred in the RV, often associated with frequent arrhythmias. These findings indicate that the catheter should be withdrawn once. TEE allowed for readjustment of the catheter tip position by enabling the balloon to be wedged twice. An excessively deep placement of the catheter tip was seen in 5 of the controls, but in none of the TEE group. Biplane TEE was found to be advantageous for guiding PA catheter placement and for visualizing the RV inflow and outflow tract in a single view, with the shuttle movement of the balloon in its long axis. TEE acts as an "eye" in the operating room, as does fluoroscopy, enabling smooth placement of the PA catheter.
We describe a 12-year-old patient with focal fatty liver change (FFLC). The lesion was incidentally detected by ultrasonography which showed a circumscribed hyperechoic lesion measuring approximately 6 x 4 cm. The lesion was also examined by CT and MRI. Histologically, the lesion corresponded to a focal area of lipid-laden hepatocytes. FFLC has been delineated as a disease entity in adults. As shown by this report, it may also occur in children. There was no associated clinical morbidity and the lesion was incidentally detected by modern imaging techniques. The aetiology and pathogenesis are unknown. The significance of focal fatty lesions is their differentiation from other focal lesions such as hepatic cell carcinomas, metastatic tumours, abscess and benign tumours including lipoma, haemangioma and angiomyolipoma.
The mechanism of vasodepressor reaction induced by head-up tilt test in patients with vasodepressor syncope is not clearly understood. We hypothesized that an abnormal alteration of beta-adrenergic transmission could be involved in these patients. We measured plasma catecholamine concentration during tilt and density of beta-adrenoceptors and tested the effects of beta-adrenergic blockers in the prevention of the vasodepressor reaction in patients with vasodepressor syncope. Ten patients had reproducibly induced vasodepressor syncope (mean 3.1 +/- 0.3 episodes in each patient) with head-up tilt (80 degrees) for 10 minutes with isoproterenol infusion (1 to 3 micrograms/min). Syncope occurred at 6.3 +/- 1.7 minutes during tilt with isoproterenol infusion. The plasma norepinephrine concentration before administration of beta-blocker was significantly elevated during tilt compared to the supine position (0.347 +/- 0.079 ng/ml in supine position with isoproterenol vs 0.468 +/- 0.082 ng/ml at 3 minutes of tilt, p < 0.001, and vs 0.503 +/- 0.106 ng/ml at the onset of vasodepressor reaction, p < 0.005; n = 8). Plasma norepinephrine after administration of the selective beta 1-adrenergic blocker metoprolol (40 mg/day) was similarly elevated (0.282 +/- 0.071 ng/ml in supine position with isoproterenol vs 0.390 +/- 0.078 ng/ml at 3 minutes of tilt, p < 0.05, n = 6; and vs 0.547 +/- 0.152 ng/ml at the onset of vasodepressor reaction, p < 0.001, n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)
We have investigated the bone-implant interface shear strength of hydroxyapatite (HA)-coated Ti-6Al-4V (HA-coating A) (roughness average, Ra = 3.4 +/- 0.5 microns) and HA-coated Ti-6Al-4V with a rougher surface (HA-coating B) (Ra = 8.4 +/- 1.8 microns). There was no significant difference between HA-coating A and HA-coating B implants with respect to the bone-implant interface shear strength as determined in push-out tests using the transcortical model in adult dogs. The bone-implant interface shear strength of bead-coated porous Ti-6Al-4V was significantly greater than that of both HA-coating A and HA-coating B implants. The failure site, as determined by scanning electron microscopy, was the coating-substrate interface, not the coating-bone interface. This indicates a need to protect the HA coating from the direct shear forces. HA coating enhances early bone growth into the porous surface of the implant. Long-term fixation should depend on bone anchoring to this porous surface. Hydroxyapatite coatings must be developed which do not obstruct the pores of the surface of the implant.
In this study, positron emission tomography (PET) was used to evaluate cortical control of saccades. Regional cerebral blood flow (rCBF) patterns demonstrated by 15O water PET during saccadic task performance were tested in 13 normal volunteers and 20 ICD-9 schizo phrenics (10 unmedicated and 10 medicated). The following 3 saccadic tasks, which were controlled for sensory input and oculomotor output, were applied: (1) reflexive saccade = visually guided saccade, (2) volitional saccade = visually guided saccade with distracting stimuli, and (3) memory guided saccade. Schizophrenics lacked the frontal eye field (FEF) activation during every saccadic task. The left dorsolateral prefrontal cortex (DLPFC) was activated during volitional saccade only in normal controls. The rCBF of posterior parietal cortex increased in parallel with that in the DLPFC. These findings suggest functional hypofrontality in schizophrenia and the left DLPFC-PPC's crucial role in saccade against distracting stimuli and its dysfunction in the disease.
The distribution of lipopolysaccharide (LPS) and sequential thrombus formation in the liver was investigated by immunohistochemical and cytochemical techniques in endotoxemic rats, using horseshoe crab factor C, a specific ligand for biologically active LPS, a monoclonal antibody against it, and rabbit anti-rat fibrinogen IgG. One hour after the intravenous administration of LPS (5 mg/kg), LPS was localized in the secondary lysosomes of Kupffer cells and in the vesicles of endothelial cells, mainly at the peripheries of the hepatic lobules. Small necrotic foci of hepatic tissue were scattered close to the LPS-containing Kupffer cells, and were frequently associated with infiltration of neutrophils and deposition of fibrin. Three hours after the administration of LPS, the immunohistochemical reaction of LPS became stronger and was mostly confined to Kupffer cells. Strands of polymerized fibrin were frequently observed on both the surface of the LPS-containing Kupffer cells and on endothelial cells. These findings suggest that the activation of the coagulation cascade in plasma is first initiated, even though only transiently, by hepatic necrosis which is probably caused by LPS-activated leukocytes, and then by the procoagulant activity expressed on the surface of both Kupffer cells and endothelial cells. Fibrinogen-related antigens were also immuno-ultrastructurally detected in the lysosomes of Kupffer cells three hours after the injection of LPS, which suggested that the Kupffer cells phagocytozed and degraded fibrin. Therefore Kupffer cells in endotoxemia may closely participate in both the sinusoidal thrombogenesis and degradation of fibrin.
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A young female patient developed acute myocardial infarction during physical exercise. Coronary arteriography in the acute phase demonstrated a coronary fistula originating from the left coronary main trunk and communicating with the right atrium. Several branches of the left coronary artery were obstructed by thrombotic material originating from the fistula, causing an acute myocardial infarction.
A restriction map of the genomic DNA of Lactobacillus casei phage PL-1 was constructed using the restriction endonucleases BamHI, EcoRI, HindIII, KpnI, NruI and XhoI. The PL-1 genome was 42.2 kb in size and had complementary cohesive ends forming a ring-like monomer. The cohesive ends, analysed with exonuclease III and S1 nuclease, were 3'-terminated single strands protruding from both ends. The nucleotide sequence of the cohesive ends, determined by the dideoxynucleotide method, comprised four A + T and 10 G + C pairs: 5' GAGGCCGACCGTTC 3'/3' CTCCGGCTGGCAAG 5'. Thus, the cohesive ends of PL-1 DNA were higher in G + C content than those of other known bacteriophage DNAs.
A high dose intravenous immunoglobulin (IVIG) therapy is used in the treatment of a wide range of autoimmune disorders. However, the mechanisms of the action of IVIGs remain poorly understood. To analyse the mechanisms of effects of IVIGs on immunoglobulin (Ig) production of B cells, the effects of IVIGs on B lymphoblastoid cell lines transformed by Epstein-Barr virus (LCLs) were investigated. The productions of IgG or IgM of LCLs were dose-dependently suppressed by polyethylene glycol (PEG)-treated IVIG or pH 4-treated IVIG though the productions were not or only slightly suppressed by pepsin-treated IVIG. The suppression by IVIGs was blocked by anti-human IgG Fc or anti-Fc gamma RII. C mu gene expression and mu s C terminal gene expression of LCLs were suppressed by PEG-treated IVIG, whereas neither C mu gene expression nor mu s C terminal gene expression of LCLs were suppressed by pepsin-treated IVIG. Although the increase in intracellular calcium concentration in LCLs was not suppressed by pepsin-treated IVIG, the increase was suppressed by PEG-treated IVIG. This suppressing effect of PEG-treated IVIG on intracellular calcium concentration of LCLs was blocked by anti-human IgG Fc or anti- Fc gamma RII. Our results suggest that IVIGs suppressed the Ca(2+)-dependent signal transduction through Fc gamma R on B-cell membrane, consequently, the transcription of C mu mRNA, especially secreted mu mRNA was suppressed in the B cells.