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Biomedical subjects

Y Horikawa

Publications and source records attributed to Y Horikawa.

At least 109 records · Page 6Linked to original sources

Growth response of acute myeloblastic leukemia cells to recombinant human thrombopoietin.

Thrombopoietin (TPO) is a newly identified hematopoietic growth factor that stimulates both megakaryopoiesis and thrombopoiesis through its interaction with a specific cell surface receptor encoded by the c-mpl proto-oncogene. In an effort to investigate the effect of TPO on human myeloid leukemia cells, the expression of c-mpl and the proliferative response to recombinant human (rh) TPO were investigated in a series of patients with acute myeloblastic leukemia (AML). Of 50 cases of AML, the c-mpl mRNA was detectable by means of Northern blot analysis in 26 cases, and the in vitro treatment with rhTPO led to proliferation of AML cells in 22 cases. The c-mpl expression and proliferative response to rhTPO was observed in all subtypes of AML and did not correlate with French-American-British classification, whereas all cases of M7-type AML cells expressed c-mpl and proliferated in response to rhTPO. Furthermore, rhTPO-induced proliferation of AML cells was augmented with the addition of interleukin-3 (IL-3), IL-6, stem cell factor, or granulocyte-macrophage colony-stimulating factor. These results suggested that c-mpl may be functional in terms of supporting proliferation of various types of AML cells and that TPO may contribute, at least in part, to abnormal growth of the cells, especially in combination with other hematopoietic growth factors.

Acute Disease↗

The role of cardiac mitochondria in the regulation of intracellular calcium during ischemia and reperfusion: X-ray microanalysis using freeze-dried sections.

The calcium concentration in papillary muscles was measured by X-ray microanalysis in order to clarify the role played by mitochondria in intracellular calcium regulation during ischemia and reperfusion. Rat hearts perfused by the Langendorff method were rapidly frozen prior to and during ischemia, as well as following reperfusion. Sections prepared by cryoultramicrotomy were freeze-dried, carbon-coated, and analyzed in an electron microscope. A new freeze-drying procedure was developed, in which the ultrastructure was well-preserved, with sarcomeres, triads, and mitochondria easily recognized. Calcium accumulation into the mitochondria occurred during 30-min ischemia (29.7 +/- 17.0 mmol/kg dry weight) and increased further after 15-min reperfusion (157.1 +/- 104.5), the calcium concentration decreased after 60-min reperfusion (58.1 +/- 29.0). However, the calcium concentration in the cytosol did not change significantly. It is thought that mitochondrial calcium accumulation is reversible, to a certain degree, and that the mitochondria play a part in intracellular calcium regulation in pathological states.

Animals↗

Mitochondrial DNA mutations in pancreatic biopsy specimens from IDDM patients.

We investigated the contribution of mitochondrial DNA mutations to the pathogenesis of IDDM by analyzing mitochondrial DNA in pancreatic biopsy specimens and peripheral blood cells from 18 patients with newly-diagnosed IDDM. All patients presented with typical abrupt onset of diabetes and ketosis on initial examination. Point mutations at nucleotides 3243, 3271 and 8344 were assayed by polymerase chain reaction and restriction fragment length polymorphism analysis or by mismatch-primer analysis. A common large deletion from nucleotides 8483-13459 was analyzed by a primer shift method. All of these mutations are known to be pathogenic mutations. However, none of the mitochondrial DNA mutations were detected in any of 18 IDDM patients. Several types of mitochondrial DNA mutation have been identified in the peripheral blood cells in some patients with non-insulin-dependent diabetes mellitus as well as in some with IDDM, however, our results suggest that abrupt-onset IDDM does not correlate with any of the known mitochondrial DNA mutations.

Adolescent↗

["Disproportionately large, communicating fourth ventricle" due to membranous obstruction of Magendie's foramen].

A case of disproportionately large, communicating fourth ventricle (DLCFV) with the entire ventricular system dilated symmetrically due to membranous obstruction of Magendie's foramen is reported. A 20-year-old female complained of headache and nausea. Slight papilledema was found in both eyes. CT scan and MRI showed that the entire ventricular system was dilated symmetrically, but we could not locate the cause of this disease, for example, tumor, arachnoid cyst, cerebellar malformation and so on. Although cinemode-MRI showed CSF pulsation as if CSF flowed through Magendie's foramen, we were not convinced that CSF flowed through it. We speculated that something obstructed CSF flow at Magendie's or Luschka's foramen, so surgery was performed by suboccipital craniectomy. As expected, a membranous obstruction was found at Magendie's foramen. After excision of the membrane, all symptoms improved. Postoperative cinemode-MRI clearly demonstrated CSF flow through Magendie's foramen. Ventriculoperitoneal shunting is generally effective for DLCFV, but we do not consider it the optimal treatment. The cause of DLCFV must be confirmed by suboccipital craniectomy if evidence of NPH, mass lesion or cerebellar malformation cannot be found anywhere especially around Magendie's foramen.

Adult↗

Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations.

We have studied brain tissues from three patients with corticobasal degeneration (CBD) histologically, ultrastructurally and immunohistochemically. Ballooned neurons in the cerebral cortex and severe degeneration of the substantia nigra were observed in them all and weakly basophilic neurofibrillary tangles (NFTs) were distributed widely in the basal ganglia and brain stem. Ultrastructural examination demonstrated that the NFTs comprised characteristic 15-nm-wide straight tubules, which showed positive immunohistochemical staining with an antibody against tau, but not ubiquitin. Tau-immunoreactive neuronal cell bodies without NFTs also were found in the cerebral cortex and subcortical nuclei, predominantly in the brain stem, and the greatest number of tau-positive glial inclusions occurred in the cerebral gray and white matter of the pre- and post-central gyri. These inclusions comprised tubular structures with diameters of about 15 nm and were localized in the oligodendroglial cellular cytoplasm and processes. These findings indicate that there is a close cytoskeletal pathological relationship between CBD and progressive supranuclear palsy.

Aged↗

Intracranial aneurysms: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography.

PURPOSE: To assess the accuracy of three-dimensional, Fourier transform, time-of-flight magnetic resonance (MR) angiography in the identification of intracranial aneurysms. MATERIALS AND METHODS: MR angiograms of 126 patients (59 male and 67 female patients, aged 12-77 years) with various intracranial vascular lesions were evaluated. Seventy-eight aneurysms, including 60 less than 5 mm in diameter, in 61 patients were depicted at conventional angiography. Eight projection images, as well as one axial collapsed MR angiogram obtained with a maximum-intensity projection algorithm, were used for evaluation. RESULTS: Sensitivity for the five observers ranged from 58% to 68% (mean, 63%). Higher sensitivity was achieved for anterior communicating and middle cerebral artery aneurysms, while that for internal carotid artery aneurysms was poor. Sensitivities for small and medium aneurysms ranged from 50% to 60% (mean, 56%) and from 77% to 94% (mean, 86%), respectively. CONCLUSION: MR angiography can depict intracranial aneurysms 5 mm or larger with good accuracy but is less useful for the identification of smaller aneurysms.

Algorithms↗

Intracranial vascular stenosis and occlusion: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography.

PURPOSE: To assess the accuracy of three-dimensional, Fourier transform, time-of-flight magnetic resonance (MR) angiography in the detection of intracranial steno-occlusive diseases. MATERIALS AND METHODS: One hundred thirty-one patients (62 male and 69 female patients, aged 6-77 years [mean, 53 years 8 months]) underwent MR and conventional angiography for evaluation of possible intracranial vascular disease. A total of 502 arteries were assessed. Eight projections and a collapsed image postprocessed by means of a maximum-intensity projection algorithm were reviewed by five observers in a blinded manner, with conventional angiography as the standard. RESULTS: A total of 32 steno-occlusive lesions were available for review. Receiver operating characteristic analysis from the pooled data revealed overall sensitivities of 85% and 88% and specificities of 96% and 97% for the internal carotid artery and the middle cerebral artery, respectively. CONCLUSION: MR angiography is useful as the primary diagnostic tool for evaluating suspected intracranial steno-occlusive disease.

Algorithms↗

Familial juvenile parkinsonism: clinical and pathologic study in a family.

We describe a family with juvenile-onset parkinsonism, which improved following sleep. Four of the five siblings in this family developed a similar onset of parkinsonism at an early age, and the parents were first cousins. In one of the siblings, a 67-year-old woman, pathologic changes at autopsy were confined to the substantia nigra pars compacta (SNPC) and locus ceruleus. The SNPC revealed obvious neuronal loss and gliosis in the medial and ventrolateral regions. In the remainder of the SNPC and the locus ceruleus, the population of neurons was reduced and there was low melanin content in most of the neurons but no detectable gliosis or extraneuronal free melanin pigment suggestive of a neurodegenerative process. There were no Lewy bodies. The entire pathologic picture was different from that of Lewy body Parkinson's disease.

Adult↗

Resolution of annular-pupil optical systems.

The resolution of optical systems with annular pupil objectives is discussed, particularly with respect to the imaging properties of soft-x-ray imaging optical systems. Images of two dark bars in a bright field and knife-edge responses, which are calculated with partially coherent transfer functions, were used to estimate the resolution. Resolution for two bright points in a dark field, which is conventionally used in Rayleigh's analysis, is also discussed for comparison. It was found that annular systems with obstruction ratios of more than 0.6 show resolution properties different from those of systems with low-obstruction-ratios. The high-obstruction-ratio systems show lower resolution for the two-dark-bar objects and higher resolution for the two-bright-point objects, whereas the low-obstruction-ratio system show almost the same resolution for both objects.

Light↗

Dynamics of hepatitis B virus core antigen in a transformed yeast cell: analysis with an inducible system.

Transformed yeast cells expressing hepatitis B virus core antigen (HBcAg) were found to accumulate abundant core particles in the same way as human hepatocytes infected with hepatitis B virus (HBV) by the present authors. We, therefore, offer a good model system for studying the dynamics of assembly of HBcAg into core particles. To investigate this problem, we have developed a transformed yeast cell in which expression of HBcAg is highly inducible by deprivation of phosphate in the culture medium. At regular intervals after induction, cells were cryo-fixed and processed for transmission electron microscopy by ultrathin sectioning. After induction, HBcAg activity rapidly increased, becoming several hundred times higher than the initial level after 25 h. The core particles first appeared in the nucleus, then in the cytoplasm, and finally in the vacuole. Core particles passing through nuclear pores from the nucleus to the cytoplasm could be seen. Core particles were either incorporated directly in the vacuole or indirectly by first forming an autophagosome. The core particles were then released into the vacuolar sap, and were digested there. Together with the previous studies, our results suggest that, in human hepatocytes, HBcAg polypeptides are synthesized in the cytoplasm, but are assembled into core particles in the nucleus. The assembled core particles are then transported from the nucleus to the cytoplasm through nuclear pores.

Cell Line, Transformed↗

Intravenous diltiazem versus isosorbide dinitrate for unstable angina: comparison of coronary angiographic morphology in the unstable and stabilized states.

BACKGROUND: The efficacy of intravenous infusion of diltiazem was compared with that of isosorbide dinitrate (ISDN) for the early treatment of unstable angina. METHODS: Sixty-four patients with at least 70% organic stenosis of the culprit artery and prolonged rest angina were enrolled. Coronary angiography was performed on admission. Subsequently, patients were randomly assigned to receive either intravenous diltiazem or ISDN. Coronary angiography was repeated when the angina was under control, and the findings were compared with those on admission. RESULTS: Diltiazem was more effective than ISDN, and symptoms were resolved in 84% of the diltiazem group compared with 47% of the ISDN group (P = 0.0038). Repeat coronary angiography showed that the degree of stenosis remained unchanged in the majority of patients (n = 47, 75.8%). There was no difference between the two groups with regard to the coronary angiographic findings. CONCLUSIONS: Since diltiazem was more effective than ISDN even though the coronary angiographic findings of the two groups were similar, it is possible that some action other than vasodilatation (such as a direct protective effect on the myocardium) may be responsible for the remission of unstable angina.

Aged↗

Noise effects on spike propagation during the refractory period in the FitzHugh-Nagumo model.

Effects of membrane noise on spike propagation on a nerve fiber are studied on the basis of a stochastic version of the FitzHugh-Nagumo model. The noise varies the propagation speeds of spikes and thus changes the interspike intervals of a spike train during propagation. A kinematic description of spike propagation derives expressions for the changes in the interspike intervals. It is shown that the dispersion relation causes the correlation of the interspike intervals characteristic of a spike train propagating in the refractory period.

Electricity↗

Changes in the incidence and duration of electroconvulsions after acute or subchronic treatment with methamphetamine in mice.

The effects of acute or subchronic treatment with methamphetamine on the incidence, intensity, and duration of electroconvulsion were investigated in mice. The convulsion was induced by electrical stimulation (100 Hz, 60 mA, 0.1-s duration) through electrodes located at each ear of mice, then analyzed by the vibration monitoring apparatus. Acute methamphetamine (3 mg/kg) reduced the incidence of the electroconvulsion in mice; however, the duration of each phase of the convulsion was prolonged by acute methamphetamine. Repeated administration of methamphetamine prolonged the duration of clonic phase of the convulsion and enhanced the acute methamphetamine-induced reduction in the incidence of electroconvulsion. These data indicate that the incidence of electroconvulsion is regulated by different mechanisms underlying the duration and intensity of the convulsion.

Animals↗

Simulation study on effects of channel noise on differential conduction at an axon branch.

Effects of membrane channel noise (random opening and closing of ion channels) are studied on spike conduction at a branching point on an axon. Computer simulation is done on the basis of a stochastic version of the Hodgkin-Huxley cable model, into which the channel noise is incorporated. It is shown that the channel noise makes conduction of spikes into daughter branches random; spikes randomly succeed or fail in conduction into daughter branches. The conduction is then randomly differential even though the forms and properties of daughter branches are the same. The randomness is considerable when the radius of an axon is small (approximately 1 microns).

Animals↗

Extramedullary plasmacytoma producing biclonal gammopathy.

A case of extramedullary plasmacytoma presenting with biclonal gammopathy is reported. The patient was an 82-year-old man in whom monoclonal-protein (M-protein) was not noted during his first hospitalization. On his second hospitalization generalized lymph node swelling and biclonal gammopathy (IgG-kappa, IgA-kappa) were observed. Histological findings were compatible with those of extramedullary plasmacytoma. In the terminal stages, the patient became cachexic. The autopsy disclosed dissemination of the plasmacytoma. Only two other cases have been reported in the literature, and a review of these previous reports is included.

Aged↗