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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 433 records · Page 24Linked to original sources

Thrombopoietin enhances proliferation and differentiation of murine yolk sac erythroid progenitors.

Thrombopoietin (TPO), the ligand for the receptor proto-oncogene c-Mpl, has been cloned and shown to be the critical regulator of proliferation and differentiation of megakaryocytic lineage. Initially, TPO was not considered to have the activity on hematopoietic lineages other than megakaryocytes. Recently, however, TPO was reported to enhance the in vitro erythroid colony formation from human bone marrow (BM) CD34+ progenitors or from mouse BM cells in combination with other cytokines. We examined the effects of TPO on the colony formation of hematopoietic progenitors in mouse yolk sac. TPO remarkably enhanced proliferation and differentiation of erythroid-lineage cells in the presence of erythropoietin (Epo). This effect was observed even in the absence of Epo. Compared with adult BM, yolk sac turned out to have relatively abundant erythroid and erythro-megakaryocytic progenitors, which responded to TPO and Epo stimulation. TPO similarly stimulated erythroid colony formation from in vitro differentiation-induced mouse embryonic stem (ES) cells whose hematopoietic differentiation status was similar to that of yolk sac. These findings help to understand the biology of hematopoietic progenitors of the early phase of hematopoiesis. Yolk sac cells or in vitro differentiation-induced ES cells would be good sources to analyze the TPO function on erythropoiesis.

Animals↗

Immunohistochemical localization of D-aspartate in the rat pineal gland.

Specific polyclonal antibody was raised against D-aspartate (D-Asp) which had been conjugated to glutaraldehyde and was purified by affinity chromatography. Immunohistochemical staining of rat pineal gland with the antibody demonstrated the presence of D-Asp in the cytoplasm of pinealocytes, the predominant cell type in this gland. D-Asp immunoreactivity was more evident in the distal region than in the proximal region of the gland. Pinealocytes in the distal region are presumably involved in the synthesis and secretion of the pineal hormone, melatonin, and the results of staining may indicate some yet unknown role of D-Asp in the regulation of melatonin secretion.

Animals↗

Adenocarcinoma of the uterine cervix with predominantly villogladular papillary growth pattern.

We reviewed the clinical and pathological features of seven cases of adenocarcinoma of the uterine cervix with predominantly villogladular papillary growth pattern. The patients, who ranged in age from 33 to 54 (mean, 45) years, underwent radical hysterectomy. In all seven cases, the tumors were papillary exophytic architecture lined by stratified epithelial cells with mild to moderate nuclear atypicality. In one of seven cases, the majority of the tumor showed villogladular papillary component, but the small foci of small cell carcinoma was present in the endocervical end of the tumor. The lymph vascular invasion was demonstrated in two of seven cases, and these two had pelvic lymph node metastases. One of these two patients had recurrence 30 months after the initial treatment and died of disease after 46 months. The follow-up ranged from 9 to 169 (median, 46) months. The presence or absence of lymph vascular invasion and minor components of this tumor such as small cell carcinoma, serous cell carcinoma, and clear cell carcinoma with a poor prognosis may be important histological findings before deciding to manage this tumor by the conservative treatment.

Adenocarcinoma↗

Relationship between pelvic lymph node involvement and other disease sites in patients with ovarian cancer.

In 109 patients with epithelial ovarian cancer, 25 (23%) had pelvic lymph node (PLN) metastasis. Positive rates of PLN metastasis according to the clinical stage based on disease distribution except retroperitoneal lymph node were 2% for stage I, 6% for stage II, 44% for stage III, and 64% for stage IV. The nine disease sites, such as subdiaphragmatic surface, liver and spleen capsule, intestine and mesentery, omentum, pelvic peritoneum, sigmoid colon and rectum, uterus and tubes, peritoneal cytology, and paraaortic lymph node (PAN), were found to have a statistically significant relationship with PLN metastasis by univariate analysis. Multivariate analysis using a logistic regression model selected the omentum and PAN as independent factors with a statistical significance. The incidence of PLN metastasis in epithelial ovarian cancer with the above two parameters can be assumed to be greater than that without the two parameters by 42.6 times. The present data suggested that for the disease with PAN and/or omental metastasis, removal of the PLN may be mandatory from the standpoint of cytoreduction.

Adolescent↗

Early adenocarcinoma of the uterine cervix.

The purpose of this study was to evaluate the prognostic significance of the tumor depth, horizontal spread, and volume in early cervical adenocarcinoma while excluding adenocarcinoma in situ. Thirty cases who had been treated at our institution having cervical adenocarcinoma with a tumor depth of less than 5 mm were clinicopathologically reviewed. The volumes were estimated based on the portion with the largest tumor surface area by multiplying three dimensions: depth, horizontal spread, and a third dimension. The third dimension was calculated by the method of Burghardt to be 1.5 times the largest measured depth or spread. Two of the 30 patients recurred in the vagina at 18 and 163 months after the initial operation; the former patient died of disease 87 months postoperatively. The remaining 28 patients are all doing well without recurrence (range of follow-up from 24 to 232 months; median 79 months). No pelvic or paraaortic lymph node metastases were seen in 25 and 22 cases, respectively. None of the 21 cases with a lesion measuring less than 3 mm in depth had recurrence. On the other hand, 1 of 23 with a tumor volume up to 500 mm3 had recurrence. The estimated 5-year progression-free survival rates for patients with cervical adenocarcinoma with a depth of less than 3 mm and those with a depth of more than 3 mm were 100 and 88.89%, respectively (P = 0.116). The depth of stromal invasion may therefore be a good predictor of lymph node metastasis and recurrence in early cervical adenocarcinoma.

Adenocarcinoma↗

Immunocytochemical study of catecholaminergic neurons in the senescence-accelerated mouse (SAM-P8) brain.

The catecholaminergic neurons of senescence-accelerated mice (SAM-P8) were analyzed by immunohistochemical microphotometry in terms of immunoreactivities to aromatic L-amino acid decarboxylase (AADC), dopamine (DA), or noradrenaline (NA). Accelerated senescence-resistant mice (SAM-R1) were used as control mice. The immunoreactivities to AADC, DA, and NA of the catecholaminergic neurons of the SAM-P8 mice were weaker than those of the SAM-R1 mice in all the brain regions. Immunoelectron microscopy revealed progressive degeneration of dopaminergic neurons and their terminal fibers in the substantia nigra as well as in noradrenergic neurons and their proximal dendrites in the locus coeruleus of the SAM-P8 mice. In contrast, there was no difference between the SAM-P8 and SAM-R1 mice in the distribution of AADC-only positive neurons (designated as D neurons in the rat brain by Jaeger et al.) nor in their immunoreactivities. These results may indicate that DA neurons in the substantia nigra and NA neurons in the locus coeruleus degenarate more rapidly during aging in SAM-P8 mice than in control SAM-R1 mice and that D neurons may function as a part of a compensatory system for the decreases in catecholaminergic neurons during aging.

Aging↗

Preferential activation of different I waves by transcranial magnetic stimulation with a figure-of-eight-shaped coil.

Transcranial magnetic stimulation (TMS) over the human primary motor cortex (MI) evokes motor responses in the contralateral limb muscles. The latencies and amplitudes of those responses depend on the direction of induced current in the brain by the stimuli (Mills et al. 1992, Werhahn et al. 1994). This observation suggests that different neural elements might be activated by the differently directed induced currents. Using a figure-of-eight-shaped coil, which induces current with a certain direction, we analyzed the effect of direction of stimulating current on the latencies of responses to TMS in normal subjects. The latencies were measured from surface electromyographic responses of the first dorsal interosseous muscles and the peaks in the peristimulus time histograms (PSTHs) of single motor units from the same muscles. The coil was placed over the MI, with eight different directions each separated by 45 degrees. Stimulus intensity was adjusted just above the motor threshold while subjects made a weak tonic voluntary contraction, so that we can analyse the most readily elicited descending volley in the pyramidal tracts. In most subjects, TMS with medially and anteriorly directed current in the brain produced responses or a peak that occurred some 1.5 ms later than those to anodal electrical stimulation. In contrast, TMS with laterally and posteriorly directed current produced responses or a peak that occurred about 4.5 ms later. There was a single peak in most of PSTHs under the above stimulation condition, whereas there were occasionally two peaks under the transitional current directions between the above two groups. These results suggest that TMS with medially and anteriorly directed current in the brain readily elicits I1 waves, whereas that with laterally and posteriorly directed current preferentially elicits I3 waves. Functional magnetic resonance imaging studies indicated that this direction was related to the course of the central sulcus. TMS with induced current flowing forward relative to the central sulcus preferentially elicited I1 waves and that flowing backward elicited I3 waves. Our finding of the dependence of preferentially activated I waves on the current direction in the brain suggests that different sets of cortical neurons are responsible for different I waves, and are contrarily oriented. The present method using a figure-of-eight-shaped coil must enable us to study physiological characteristics of each I wave separately and, possibly, analyse different neural elements in MI, since it activates a certain I wave selectively without D waves or other I waves.

Adult↗

Shortening of simple reaction time by peripheral electrical and submotor-threshold magnetic cortical stimulation.

Subthreshold transcranial magnetic stimulation (TMS) over the motor cortex can shorten the simple reaction time in contralateral arm muscles if the cortical shock is given at about the same time as the reaction stimulus. The present experiments were designed to investigate whether this phenomenon is due to a specific facilitatory effect on cortical circuitry. The simple visual reaction time was shortened by 20-50 ms when subthreshold TMS was given over the contralateral motor cortex. Reaction time was reduced to the same level whether the magnetic stimulus was given over the bilateral motor cortices or over other points on the scalp (Cz, Pz). Indeed, similar effects could be seen with conventional electrical stimulation over the neck, or even when the coil was discharged (giving a click sound) near the head. We conclude that much of the effect of TMS on simple reaction time is due to intersensory facilitation, although part of it may be ascribed to a specific effect on the excitability of motor cortex.

Electric Stimulation↗

Solitary plasmacytomas of the occipital bone: a report of two cases.

The radiological appearances of two cases of solitary plasmacytoma in the occipital bone are described. One arose in the lateral part and the other in the squama. They showed characteristic radiological features on CT, MRI and angiography. Bone scintigraphy and gallium scintigraphy were also available. Solitary plasmacytoma of the skull is a rare condition and usually occurs in the calvarium. The skull base is an extremely rare site and only four cases have been reported. The literature of solitary plasmacytoma of the skull is reviewed.

Aged↗

Directional coronary atherectomy for the treatment of acute myocardial infarction.

Directional coronary atherectomy (DCA) was performed after intracoronary thrombolysis in 32 patients with a first acute myocardial infarction. DCA was successful in 31 (97%) of 32 patients. Abrupt closure of the treated segment occurred in one patient but was managed successfully by conventional balloon angioplasty. Repeat angiography was performed in 32 patients before discharge (2.7 +/- 0.7 weeks later) and in 29 patients during the follow-up (4.5 +/- 1.5 months later). No restenosis (stenosis > 50%) occurred before discharge; however restenosis occurred in 12 (41%) of 29 patients during follow-up. The restenosis rate in patients with subintimal resection was significantly higher than in those with intimal resection (78% vs 25%, p < 0.01). These data suggest that DCA in patients with acute myocardial infarction is feasible for persistent early patency of the infarct-related coronary artery, but late restenosis continues to limit success and subintimal resection may increase the restenosis rate during the follow-up.

Aged↗

Clinical implications of cigarette smoking in acute myocardial infarction: acute angiographic findings and long-term prognosis.

This study was undertaken to assess whether reperfusion in smokers could be achieved spontaneously or therapeutically and to assess whether favorable outcome in smokers could be sustained for years after infarction. We studied 260 patients with anterior myocardial infarction who underwent coronary angiography and thrombolysis within 24 hours after the onset of chest pain. There were 158 smokers and 102 nonsmokers. Smoking was associated more with men, younger age, and less multivessel disease. On initial angiography, the distribution of Thrombolysis in Myocardial Infarction grade was similar between smokers and nonsmokers. After thrombolysis, Thrombolysis in Myocardial Infarction grade 3 was more frequent in smokers (32% vs 18%; p = 0.004). In-hospital mortality rates were lower (8% vs 18%; p = 0.022) and long-term cardiac survival was better in smokers (5-year survival: 82% vs 70%; p = 0.022). Our data demonstrated that the infarct artery of smokers responded more efficiently to thrombolysis and favorable outcome in smokers was sustained throughout 5 years.

Aged↗

Spool-like stent for the open sternum after cardiac operations.

Severe edematous heart after a cardiac operation is impossible to treat if there is compression of the heart due to the sternum. In these patients delayed sternal closure may be a useful procedure until the heart decreases in size. We devised a spool-like stent for the open sternum to maintain the optimal cardiac space for the severely edematous heart and to fix the chest wall to allow for management while the sternum is open.

Cardiac Surgical Procedures↗

Myometrial invasion of endometrial carcinoma: assessment with dynamic MR and contrast-enhanced T1-weighted images.

AIM: To evaluate the usefulness of dynamic magnetic resonance (MR) imaging in assessing the depth of myometrial invasion, compared with conventional T2-weighted and contrast-enhanced T1-weighted imaging. PATIENTS AND METHODS: Forty patients with endometrial carcinoma were examined with T2-weighted images, dynamic studies and contrast-enhanced T1-weighted images, preoperatively. We evaluated enhancement patterns of myometrium and tumour, and compared MR findings with histological results concerning the depth of myometrial invasion. RESULTS: In assessing the depth of myometrial invasion, the accuracy of T2-weighted images, dynamic studies and contrast-enhanced T1-weighted images was 58%, 85% and 68%, respectively. The tumour-myometrial contrast of dynamic studies was higher than that of other images. In addition, subendometrial enhancement (SEE) was frequently observed in dynamic studies in post-menopausal women, which was an important landmark in detecting myometrial invasion. CONCLUSION: We consider that dynamic MR imaging has greater advantage in assessing myometrial invasion than T2-weighted or contrast-enhanced T1-weighted imaging.

Adult↗

Coarse-grain parallel computing for very large scale neural simulations in the NEXUS simulation environment.

We describe a neural simulator designed for simulating very large scale models of cortical architectures. This simulator, NEXUS, uses coarse-grain parallel computing by distributing computation and data onto multiple conventional workstations connected via a local area network. Coarse-grain parallel computing offers natural advantages in simulating functionally segregated neural processes. We partition a complete model into modules with locally dense connections--a module may represent a cortical area, column, layer, or functional entity. Asynchronous data communications among workstations are established through the Network File System, which, together with the implicit modularity, decreases communications overhead, and increases overall performance. Coarse-grain parallelism also benefits from the standardization of conventional workstations and LAN, including portability between generations and vendors.

Computer Communication Networks↗

Photochemical grafting of alpha-propylsulphate-poly(ethylene oxide) on polyurethane surfaces and enhanced antithrombogenic potential.

The aim of this study is the grafting of photoreactive alpha-propylsulphate-poly(ethylene oxide) (PEO-SO3), one end of which is capped with an azidophenyl group, on polyurethane (PU) surfaces via a photochemical technique. The anti-Factor Xa activity and the platelet adhesion characteristics of the modified PU surface were evaluated by a chromogenic assay method and by a flow-controlled chamber method, respectively. X-ray photoelectron spectroscopy analysis showed that PEO-SO3 was covalently grafted on the PU surface. The grafted surface showed anti-Factor Xa activity in the presence of antithrombin III, and significantly reduced platelet adhesion characteristics as compared with those of the unmodified PU surface. These results suggest that the grafting of PEO-SO3 improves the antithrombogenicity of PU surfaces.

Antithrombin III↗

Radical radiotherapy for medically inoperable non-small cell lung cancer in clinical stage I: a retrospective analysis of 149 patients.

PURPOSE: In order to obtain the standard treatment results of medically inoperable non-small cell lung cancer (NSCLC) in Stage I in the post-CT scan era, a retrospective analysis of patients who were treated by radical radiotherapy was performed. METHODS AND MATERIALS: 149 cases treated between 1980 and 1989 were accumulated from ten large hospitals in Japan. All patients received a total dose of 55-75 Gy (mean 64.7 Gy) with conventional fractionation. For evaluation of treatment results, complete response (CR) rate, median survival period and long-termed survival rates were used. RESULTS: The median survival of the all cases was 27.2 months and the actuarial 3- and 5-year survival rates were 34.2% and 22.2%, respectively. CR was obtained in 57 cases (38%). The CR rate was strongly correlated with the long-term survival (5-year survival rate in CR group: 35.1% compared with PR + NC group: 14.1% (P < 0.0001)). The size of tumor was also of prognostic importance. In 116 patients who died within 5 years after treatment, 66 patients (57%) died of local tumor regrowth. CONCLUSION: Although the medically inoperable NSCLC patients in Stage I should be offered curative radiation therapy, development of some new steps to increase the CR rate and local control rate is urgently needed.

Aged↗

Magnetic stimulation over the cerebellum in patients with ataxia.

We studied 20 patients with ataxia caused by various disorders using magnetic stimulation over the cerebellum. Results were compared with normal values found for 12 normal volunteers. In normal subjects, a magnetic stimulus over the cerebellum reduced the size of responses evoked by magnetic cortical stimulation when it preceded cortical stimulus by 5, 6 and 7 ms. The grand average of the ratios of the areas of conditioned responses at intervals of 5, 6 and 7 ms to those of control responses was designated the average area ratio (5-7 ms). Suppression of motor cortical excitability was reduced or absent in patients with a lesion in the cerebellum or cerebellothalamocortical pathway, but was normal in patients with a lesion in the afferent pathway to the cerebellum. Normal suppression was observed in Fisher's syndrome. The average area ratio (5-7 ms) correlated well with the severity of ataxia in patients with degenerative late-onset ataxia. These results are consistent with those for electrical stimulation of the cerebellum reported previously. We conclude that magnetic stimulation over the cerebellum produces the same effect as electrical stimulation even in ataxic patients. This less painful method can be used clinically to clarify the pathomechanisms for ataxia. Two other clinical uses of this technique were that it revealed clinically undetectable cerebellar dysfunction in patients whose extrapyramidal signs masked cerebellar signs, and that the slow progression of ataxia could be followed quantitatively in patients with degenerative late-onset ataxia.

Adult↗

AMPA receptors modulate dopamine release in the striatum, as measured by brain microdialysis.

The effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f) quinoxaline (NBQX), a potent and selective antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, on the release of dopamine from the striatum was investigated in freely moving rats using an in vivo microdialysis technique. Perfusion with 1.0 mM AMPA increased the concentration of striatal extracellular dopamine. After systemic administration of NBQX (40 mg/kg, i.p.), dopamine levels in the striatal perfusate decreased. The AMPA-induced increase in dopamine levels was suppressed significantly by the systemic administration of NBQX (40 mg/kg, i.p.). Perfusion with tetrodotoxin (TTX, 5 microM) alone reduced the basal level of dopamine by 80%. Perfusion with 1.0 mM AMPA together with TTX produced a 3.9-fold increase in dopamine efflux from the TTX reduced basal level. However, the maximum dopamine level obtained thereby was close to the basal level of dopamine seen prior to perfusion with TTX. The present results demonstrate that AMPA receptors participate in tonic facilitative modulation of striatal extracellular level of dopamine. In addition, the results support the view that glutamatergic neurons modulate the release of dopamine via subtypes of excitatory amino acid receptors in the central nervous system.

3,4-Dihydroxyphenylacetic Acid↗