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Biomedical subjects

Y Dobashi

Publications and source records attributed to Y Dobashi.

At least 37 records · Page 2Linked to original sources

Combined clear and granular cell leiomyoma of soft tissue: evidence of transformation to a histiocytic phenotype.

AIMS: We present an unusual case of leiomyoma with a clear and granular cell pattern in which there was immunohistochemical evidence of transformation to a histiocytic phenotype. METHODS AND RESULTS: A 64-year-old man presented with mild scrotal swelling and pain. A local excision was performed after the clinical diagnosis of epidermal inclusion cyst. In the pathological specimen, another tumour nodule was identified which was composed predominantly of clear cells, with an occasional mixture of granular cells. Immunohistochemical analysis demonstrated positive staining for vimentin, lysozyme, CD68 and HAM56, but complete negativity for desmin, alpha-smooth muscle actin, HHF35, S100 protein, neurone-specific enolase and CD34. Ultrastructural study revealed dilated rough endoplasmic reticulum, glycogen granules, abundant vacuolar structures and also thin microfilaments with subplasmalemmal dense bodies. CONCLUSIONS: Based on these findings, we have interpreted it to be a rare case of leiomyoma with extensive clear cell and granular cell degeneration (combined clear and granular cell leiomyoma). This complete transformation of the immunohistochemical profile into the histiocytic phenotype has not been previously described in the literature.

Actins↗

[Electromyographic activity of neck muscles during the production of inspiratory pressure].

The differential inspiratory EMG activities of the scalene (SCLN), sternocleidomastoid (STERNO), and trapezius (TRAPEZ) muscles were studied in 6 awake and healthy men (mean age, 22 years; and mean weight, 62.4 kg). Pairs of fine wire EMG electrodes were inserted into each of these muscles using a guide needle and high-resolution ultrasonography. With subjects on a mouthpiece, inspiratory effort against an occluded airway was recorded at end expiratory position in the standing position. Mouth pressure and integrated EMG signals were sampled to a computer during the gradual production of maximal static inspiratory pressure (PImax) over 10 s. Maximum EMG activity (EMGmax) was obtained for each muscle during specific respiratory and postural maneuvers. Mouth pressures and integrated EMG activities were expressed as percentages of PImax and EMGmax, respectively. As mouth pressure increased, SCLN, then STERNO, and finally TRAPEZ EMGs were sequentially activated in 5 subjects. In one subject, STERNO preceded SCLN EMG activation. Group mean (+/- SE) mouth pressures at the onset of SCLN, STERNO, and TRAPEZ EMG were 10.3 +/- 5.8% PImax. 30.8 +/- 8.2% PImax, and 79.3 +/- 9.6% PImax, respectively. TRAPEZ mouth pressures differed from SCLN and STERNO values (p < 0.05). At 90% PImax, group mean (+/- SE) SCLN, STERNO, and TRAPEZ EMG activity reached 69.7 +/- 9.0% EMGmax, 51.5 +/- 11.1% EMGmax, and 5.1 +/- 2.4% EMGmax, respectively. TRAPEZ EMG at 90% PImax differed from both SCLN and STERNO values (p < 0.05). These results suggest that SCLN has strong, STERNO intermediate, and TRAPEZ weak, inspiratory activities.

Adult↗

CDK4, a possible critical regulator of apoptosis in rat pheochromocytoma PC12 cells.

The function of cell cycle regulator molecules during apoptosis induced by serum withdrawal was examined in rat pheochromocytoma PC12 cells. When human cDNAs encoding cyclins, cyclin-dependent kinase 2 (CDK2), CDK4, and cell-division cycle 2 (CDC2), were introduced, only CDK4-overexpressing cells were more prone to apoptosis compared with parental cells. In the parental cells, serum withdrawal resulted in the upregulation of CDK4 protein expression 6.6-fold for the first 12 h after serum withdrawal. In contrast, CDK4 protein levels in CDK4-overexpressing cells remained constant for the first 12 h followed by a gradual decline. Expression of cyclin D1 was upregulated in both cell lines. The change in CDK4 kinase activity almost paralleled that of CDK4 protein expression. These results suggest that CDK4 kinase activity is one of the critical regulators in the apoptotic cascade in PC12 cells.

Animals↗

Expression of HuD protein is essential for initial phase of neuronal differentiation in rat pheochromocytoma PC12 cells.

HuD is a neuronal-specific, RNA-binding protein. Here we examined the change in the expression of HuD protein during nerve growth factor-mediated differentiation of PC12 cells. As cells differentiated and extended neurites, expression of HuD gradually increased up to 1.5-fold. When HuD expression was counteracted by antisense oligonucleotide, neurite extension was completely inhibited, yet the morphology of differentiated cells remained unchanged even after that treatment. Furthermore, this morphological change correlated well with the downregulation of cyclin-dependent kinase 2 activity. These results suggest that the HuD is critically involved in the initial phase of neuronal differentiation.

Animals↗

Kinetics of Ca2+ release evoked by photolysis of caged InsP3 in rat submandibular cells.

Quantitative time-resolved measurements of cytosolic Ca2+ release by photolysis of caged InsP3 have been made in single rat submandibular cells using patch clamp whole-cell recording to measure the Ca2+-activated Cl- and K+ currents. Photolytic release of InsP3 from caged InsP3 at 100 Joules caused transient inward (V(H) = 60 mV) and outward (V(H) = 0 mV) currents, which were nearly symmetric in their time course. The inward current was reduced when pipette Cl- concentration was decreased, and the outward current was suppressed by K+ channel blockers, indicating that they were carried by Cl- and K+, respectively. Intracellular pre-loading of the InsP3 receptor antagonist heparin or the Ca2+ chelator EGTA clearly prevented both inward and outward currents, indicating that activation of Ca2+-dependent Cl- and K+ currents underlies the inward and the outward currents. At low flash intensities, InsP3 caused Ca2+ release which normally activated the K+ and Cl- currents in a mono-transient manner. At higher intensities, however, InsP3 induced an additional delayed outward K+ current (I[K,(delay)]). I[K(delay)] was independent of the initial K+ current, independent of extracellular Ca2+, inhibited by TEA, and gradually prolongated by repeated flashes. The photolytic release of Ca2+ from caged Ca2+ did not mimic the I[K(delay)]. It is suggested that Ca2+ releases from the InsP3-sensitive pools in an InsP3 concentration-dependent manner. Low concentrations of InsP3 induce the transient Ca2+-dependent Cl- and K+ currents, which reflects the local Ca2+ release, whereas high concentrations of InsP3 induce a delayed Ca2+-dependent K+ current, which may reflect the Ca2+ wave propagation.

Animals↗

Active cyclin A-CDK2 complex, a possible critical factor for cell proliferation in human primary lung carcinomas.

Expression of cyclins A and E and cyclin-dependent kinase 2 (CDK2) was examined immunohistochemically in 190 cases of human lung carcinoma. Cyclin A and CDK2 were expressed in the majority of squamous cell carcinomas, small cell carcinomas, and large cell carcinomas, but in significantly fewer cases of adenocarcinomas. Cyclin E was expressed in a minority of all subtypes. In particular, well differentiated cells in squamous cell carcinoma stained positively for cyclin E; in contrast, cyclin A was expressed in the nonkeratinized proliferating areas of the tumor nests. Immunoblotting revealed that all these proteins were expressed at higher levels in tumor tissues than in adjacent normal tissues. Immunoprecipitation also revealed higher levels of cyclin A and cyclin E associated with CDK2 in tumor tissues. Furthermore, tumor tissues which exhibited higher cyclin A and CDK2 expression also had higher CDK2 kinase activity. However, cyclin E-associated kinase activity was barely detectable even in tumor samples exhibiting higher cyclin E expression. Consistent with these data, elevated expression of cyclin A correlated to shorter survival periods in contrast to expression of cyclin E, which correlated to longer survival periods. These results suggest that in human lung carcinomas, elevated expression of active cyclin A-CDK2 complexes with associated higher CDK2 kinase activity is critical for promoting cell cycle progression and unrestrained proliferation of tumor cells and can be a predictive marker for patients' prognosis. On the other hand, immunohistochemical detection of cyclin E-CDK2 reflects accumulation of inactive forms of protein complexes, implying differentiation or senescence of the tumor and the better prognosis.

Adenocarcinoma↗

Large cell neuroendocrine carcinoma of the lung: a histologic and immunohistochemical study of 22 cases.

Large cell neuroendocrine carcinoma (LCNEC) of the lung is defined as a poorly differentiated and high-grade neuroendocrine tumor that is morphologically and biologically between atypical carcinoid and small cell lung carcinoma (SCLC). During a survey concerning bcl-2 protein expression in the subtypes of lung cancer, we noticed that two previously diagnosed non-SCLCs met the criteria for LCNEC. Because LCNEC is a newly recognized clinicopathologic entity and because all reported cases have been retrieved from the so-called "neuroendocrine tumor file," we suspected that LCNEC had been underdiagnosed. In the present study, we histologically reviewed 766 surgically resected lung cancers and were able to diagnose 22 (2.87%) LCNECs with the neuroendocrine features subsequently confirmed by immunostaining for multiple neuroendocrine markers. Each case stained positively for at least three general neuroendocrine markers, and 12 (54.5%) also were positive for neuroendocrine hormones. Histologically, most LCNECs showed a marked decrease in or a loss of organoid architecture and could be mistaken for poorly differentiated adenocarcinoma or squamous cell carcinoma. Because our LCNECs are the first to be identified by retrospective review of routinely diagnosed lung cancers, and 18 had been classified as non-SCLC, they may represent cases relatively difficult to diagnose. The present study shows that the most difficult diagnostic factor of LCNEC is the recognition of its light microscopic neuroendocrine features, and LCNEC must be distinguished not only from atypical carcinoid or SCLC, but also from common non-SCLC. Histologically, when an organoid architecture is subtle or absent, the rosettelike structure becomes the best marker for the recognition of neuroendocrine differentiation. Clinically, the prognosis for our LCNECs was significantly worse than that for stage-comparable non-SCLCs (p = 0.046).

Aged↗

Regulation of spontaneous rhythmic contractions in rat pregnant myometrium by corticotrophin-releasing factor.

To elucidate the role of corticotrophin-releasing factor (CRF) in the spontaneous rhythmic contractions of pregnant myometrium, isometric contractions of longitudinal myometrial preparations taken from Sprague-Dawley rats (18-21 days gestation) were measured. CRF (0.03-30 nM) significantly increased the amplitude (117 +/- 4% of control at 30 nM, mean +/- S.E.M.) and significantly decreased the frequency (74 +/- 5%) in a concentration-dependent manner. The area under the tension curve did not increase (89 +/- 8%). Such effects of CRF were not observed in preparations pretreated with the RP diastereomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS, 10 microM), an inhibitor of protein kinase A. In preparations pretreated with indomethacin (1 microM), CRF caused little change in the amplitude but significantly decreased the frequency of the contractions. Intracellular cAMP levels in the preparations, measured by enzyme immunoassay, rose when CRF was applied at 30 nM. These results suggest that the slight positive inotropic action of CRF is due to activation of both cAMP and prostaglandin pathways, whereas the negative chronotropic action is due solely to the cAMP signalling pathway.

Animals↗

[A case report of use of horseshoe kidney as renal transplant from live donor].

This is a report on a surgery performed in February, 1995 describing the donation of a living donor's horseshoe kidney used for renal transplantation. The recipient was a 31 years-old male on hemodialysis since 1994. The donor was the healthy 55 years-old father of the recipient who had an uncomplicated horseshoe kidney. The isthmus was perfused by an accessory artery. Via transperitoneal approach, the horseshoe kidney was mobilized for in situ perfusion. A microwave coagulator was used to divide the isthmus, and the cut surfaces were closed by mattress sutures and fibrin glue. The left kidney was transplanted into the recipient's right iliacfossa. While his post-transplant course was complicated by urinary leakage, the graft remained free of rejection until and beyond the 6 months post transplant period when he was discharged at s-Cr 1.7 mg/dl. The donor's convalescence was uneventful. During the 20 months post-transplant period both the donor and recipient are doing well.

Adult↗

[A study on accuracy of rCBF measurements loaded with acetazolamide based on the microsphere model using iodine-123-IMP SPECT].

We studied the accuracy of the method for measuring regional cerebral blood flow (rCBF) loaded with acetazolamide based on the microsphere model using iodine-123-IMP (IMP) SPECT. Two methods were examined, the super-early microsphere method with continuous withdrawal of arterial blood using the SPECT image obtained 5 min after tracer injection and the early microsphere method with one-point arterial sampling using the SPECT image obtained 30 min postinjection. On five subjects, after acetazolamide administration we measured rCBF by the analysis based on the two-compartment model using the data derived from dynamic SPECT scans and the sequential arterial blood sampling after IMP injection. Values of rCBF obtained by both super-early microsphere method and early microsphere method were significantly correlated with those obtained by the two-compartment model analysis (r = 0.982, 0.930, respectively). We conclude that it is possible to use the method based on the microsphere model in measuring rCBF loaded with acetazolamide. The early microsphere method with one-point sampling should be used clinically because of its simplicity and less-invasiveness.

Acetazolamide↗

Neuron-specific enolase-producing epithelioid leiomyosarcoma with gross vascular invasion and intracardiac involvement.

We present an unusual case of epithelioid leiomyosarcoma in the right shoulder. A 10-cm tumor eroding the right scapula occurred in a 59-year-old man and grew into the subclavian vein with extension to the right atrium. An elevated serum level of neuron-specific enolase was also detected. Clinical presentation suggested small cell carcinoma of the lung (Pancoast tumor) with intravenous extension. Eventually, the patient died of respiratory insufficiency. Autopsy revealed a primary tumor in the right shoulder, numerous tumor emboli in the pulmonary arteries, and associated hemorrhagic infarction. Histopathologic features revealed an epithelioid leiomyosarcoma. Furthermore, immunohistochemical and immunoblotting analyses of the tumor demonstrated positive reactions for neuron-specific enolase. We interpreted this peculiar case to be a neuron-specific enolase-producing epithelioid leiomyosarcoma of the soft tissue associated with gross vascular invasion.

Angiography↗

Cell cycle control with minimal participation of Cdk2 in a murine fibrosarcoma clone cultured in protein-free medium.

The differences in the protein expression of cyclins, cyclin-dependent kinases (cdks), and their inhibitors and cdk kinase activities were examined in serum dependent (SD) and independent (PF) clones of the murine fibrosarcoma cell line, Gc-4. The expression of cyclin A in SD was minimal in contrast to PF. Furthermore, cdk2 kinase activity in PF was remarkably lower than that in SD, yet the G1/S transition in PF appeared normal. PF was also resistant against the selective inhibitor of cdk2, butyrolactone I. These findings suggest that tumor cell proliferation and tumor progression can be promoted by the activation of a molecule(s) downstream of cdk2.

4-Butyrolactone↗

The Wilms tumor protein is persistently associated with the nuclear matrix throughout the cell cycle.

In order to investigate the subnuclear interactions of the WT1 gene product, nuclear fractionation analyses were performed with human osteosarcoma HOS and myelogenous leukemia K562 cells. The WT1 protein was tightly associated with the nucleus and was resistant to high-salt or detergent extraction and DNase I digestion. Both the expression level and stability of WT1 and its resistance to high salt and DNase I treatments remained constant during the cell cycle. In addition, human WT1 ectopically expressed in mouse NIH3T3 cells was also resistant to these treatments. These results suggest that WT1 functions in tight association with the nuclear matrix.

3T3 Cells↗

GLP-I(7-36) amide augments Ba2+ current through L-type Ca2+ channel of rat pancreatic beta-cell in a cAMP-dependent manner.

The whole-cell patch-clamp method was used to examine the effect of glucagon-like peptide I (GLP-I)(7-36) amide on the activation process of L-type Ca2+ channels of rat pancreatic beta-cells. After depolarization, GLP-I (1-100 nmol/l) caused action potentials in cells exposed to a glucose-free solution for 10 min. The percentage of cells producing action potential depended on the concentration of GLP-I. In some cells, GLP-I caused action potentials without the prior depolarization of the membrane. In cells exposed to the glucose-free solution for longer than 30 min, or in cells that were deprived of ATP by a means of the conventional whole-cell configuration, GLP-I (20 nmol/l) did not cause the electrical excitation. Application of GLP-I augmented the maximum Ba2+ current (IBa) through L-type Ca2+ channels and shifted the current voltage curve to the left. Values of changes in the maximum IBa depended on GLP-I concentration. Application of dibutyryl cAMP (dbcAMP, 1 mmol/l) also augmented IBa. In cells pretreated with Rp-cAMP, dbcAMP did not change the magnitude of IBa. Also in cells pretreated with Rp-cAMP, GLP-I failed to augment IBa. These results suggest that in pancreatic beta-cells, GLP-I, by a cAMP-dependent mechanism, increases opening of L-type Ca2+ channels. cAMP-dependent augmentation of Ca2+ entry as well as cAMP production itself by GLP-I plays a crucial role in controlling insulin secretion.

Action Potentials↗

Familial aggregation of soft tissue sarcomas: a report of three cases from a Li-Fraumeni-like family.

Three rare cases of familial aggregation of soft tissue sarcomas (malignant fibrous histiocytoma in a mother and liposarcomas in her two children) are described. The mother developed a late onset of malignant fibrous histiocytoma in her right thigh. Her son and daughter both developed retroperitoneal liposarcomas at the ages of 38 and 33 years, respectively. The mother also developed gastric carcinoma as a second malignancy after a 2-year interval. These clinical features closely resemble those of Li-Fraumeni syndrome, but do not fulfill the exact diagnostic criteria. Genetically, the germline mutation of the p53 gene between exons 4 and 9 was not detected by sequencing DNA obtained from the peripheral blood of the mother. Immunohistochemically, p53 protein was found only in the liposarcoma of the daughter. These results strongly suggest that this familial aggregation of soft tissue sarcomas is very rare, and that it is a unique feature of a familial cancer syndrome that to our knowledge has not been defined or described previously.

Adult↗

[Pulmonary actinomycosis resembling an anterior mediastinal tumor].

A 25-year-old, previously healthy man was referred to us because of fever, left-sided chest pain, and an abnormal mass shadow at the left pulmonary hilum on chest X-ray films. Laboratory tests and fiberoptic bronchoscopy revealed no abnormality. Thoracotomy was done because a mediastinal tumor was suspected. Surgery revealed that the left lingula was atelectatic and that the mass was in the left S4, not in the mediastinum. Pathological examination of tissue from the partially resected lung showed sulfur granules, and a diagnosis of pulmonary actinomycosis was made. At least 80 cases of pulmonary actinomycosis were reported in Japan between 1963 and 1995. Pulmonary actinomycosis is most common among men in the fifth and sixth decades of life, and almost all patients have oral disease. Pulmonary actinomycosis is often difficult to distinguish from lung cancer, because both appear as mass shadows on X-ray films, and almost all cases of pulmonary actinomycosis are diagnosed by thoracotomy.

Actinomycosis↗