Biomedical subjects
Publications and source records attributed to N Hoshi.
NGK2 (mKv3.1a) K+ channel cDNA was introduced into mouse B82 fibroblast cells to express in a mammalian system. The NGK2 current in the stably transformed fibroblast cells exhibited a high threshold for activation and slow decay with two components. The data suggest that the NGK2 channel may contribute to slowly inactivating K+ currents observed in excitable and inexcitable cells.
Nineteen granular cell tumors (GCT) of adults, two congenital granular cell epulides and five epulides fibrosae were immunohistochemically examined to detect the expression of 75 kDa nerve growth factor receptor (NGFR), trk gene product, phosphotyrosine (PT), protein gene product 9.5 (PGP9.5) and S-100 protein. The NGFR-immunoreactivity (IR) and trk gene product-IR were expressed on almost all granular cells of GCT. PT-IR was also demonstrated on granular cells of all GCT examined, although the frequency of positive cells was low. Congenital granular cell epulides and epulides fibrosae were negative for NGFR-IR, trk gene product-IR and PT-IR. S-100 protein was localized in granular cells of adult GCT but not in the granular cells of congenital epulis. On the other hand, PGP9.5 was detected in granular cells of both conditions and in fibroblastic cells of epulis fibrosa. The present results further indicate that GCT is of peripheral nerve Schwann cell origin, while the congenital granular cell epulides are not of neural origin. NGFR and trk gene product expressed on GCT seems to be functional in terms of phosphorylation of the tyrosine residue in the receptor or downstream protein in signal transduction.
Five cases of primary sclerosing scrotal lipogranuloma were examined histologically and immunohistochemically. Every case lacked a history of injection or trauma, and revealed common histological features: a typical granuloma composed of epithelioid cells and multinucleated giant cells, and inflammatory infiltrates of eosinophils, lymphocytes and macrophage/monocytes in the interstitium. Immunohistochemistry disclosed the epithelioid cells and multinucleated giant cells of the granuloma to be monocytes in nature, as both types of cells were positive for lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and KP-1. In the interstitium, KP-1 positive monocytes, L-26 positive B lymphocytes, UCHL-1 positive T lymphocytes and S-100 protein positive Langerhans-like cells were frequently found. S-100 protein positive cells could not be detected in the granuloma. Primary sclerosing lipogranuloma of the scrotum, therefore, is a peculiar inflammation characterized by granulomas consisting of monocytes and marked tissue eosinophilia of unknown etiology.
The distribution of human intestinal 15 kDa protein (I-15P), a new fatty acid-binding protein (FABP), was observed in normal tissues using immunohistochemical techniques. The antiserum against human I-15P intensely reacted with the villous epithelium of the terminal ileum but not with the enterocytes of the crypts. Although the surface epithelium of the stomach and villous epithelium of the duodenum showed weak reactivities, the epithelial cells of the jejunum, proximal ileum, colon and rectum, and also glandular epithelia with intestinal metaplasia of the stomach were not immunostained. The other human tissues examined were negative for anti-human I-15P antibody. Human I-15P thus represents a distinctive, confined tissue distribution different from the other FABPs and is expected to serve as a useful cellular marker of terminal ileal enterocytes.
A case of a 68-year-old male with prostatic carcinoma which was partially well differentiated but largely poorly differentiated is presented in this report. The poorly differentiated area of the adenocarcinoma seemed to arise from the well-differentiated portion. The former was populated with Grimelius argyrophilic cells, and occasionally contained round, eosinophilic intracytoplasmic inclusions which appeared to be composed of a secretory substance. Immunocytochemistry revealed that endocrine cells were present in the normal portion of the gland as well as in the well-differentiated adenocarcinoma, but were more numerous in the poorly differentiated portion. The latter portion was positive for chromogranin A, endocrine granule constituents, neuroendocrine markers, serotonin, Leu 7, ACTH and neuron specific enolase. In addition, cells of poorly differentiated portion were reactive with CEA, prostatic acid phosphatase and human prostate specific antigen. Ultrastructural features observed in the poorly differentiated adenocarcinoma included five kinds of round neurosecretory granules. This was a rare case of prostatic adenocarcinoma in which the evolution from well differentiated to poorly differentiated tissue containing neuroendocrine constituents could be clearly observed.
A case of glomangiosarcoma (GS) arising on the lateral side of the left upper arm is reported here. GS is very rare compared with benign glomus tumor (GT) and there has been some controversy regarding whether it is a true malignant tumor. Histologically, the tumor consisted of two different components. In the periphery of the tumor, a solid sheet-like growth of small cuboidal cells identical to benign GT was seen. However, in the central portion, the tumor was composed of short spindle cells with hyperchromatic atypical nuclei arranged in weak fascicles, mimicking leiomyosarcoma. Mitotic figures were not uncommon in the latter area. Immunohistochemistry revealed that both cuboidal and spindle-shaped tumor cells were positive for vimentin and muscle actin as were cells of other benign GTs used for controls. In addition, only spindle-shaped cells expressed protein produced by the suppressive oncogene p53 in the nuclei, a phenomenon not seen in the five benign GTs or in cuboidal cells of GS. These results suggest that GS may exhibit more aggressive behavior than benign GT.
Diffuse and neuritic plaques are sites of accumulation of beta-amyloid peptides (A beta) in the brains of Alzheimer's disease (AD) patients. Although amyloid fibrils are formed from A beta, the contribution of other plaque-associated proteins and peptides to the pathogenesis of AD amyloidosis is unknown. To pursue this issue, we sought to identify proteins and peptides that were consistently associated with neuritic plaques in six different cortical areas of AD and control brains. We accomplished this by using quantitative, single and double label immunohistochemistry and a panel of antibodies to proteins or peptides that are known to be associated with neuritic plaques in the AD hippocampus. Our data showed that the molecular composition of neuritic plaques in association, limbic, sensory, and motor cortex was similar regardless of the type of cortex in which they were found or the apolipoprotein E genotype of the patient. Further, proteins and peptides associated with neuritic plaques in the cortical areas of the AD brain studied here were similar to those found in neuritic plaques of the AD hippocampus. Specifically, in addition to A beta 1-40 and A beta 1-42, these plaques contained immunoreactivity for other domains in A beta precursor proteins, neurofilament and tau proteins, as well as phosphotyrosine residues. We conclude that the recurrent association of a distinct group of neuronal and other proteins and peptides with neuritic plaques suggests that these plaque-associated components play a mechanistic role in the pathogenesis of amyloidosis in AD.
One hundred and three benign, and 10 malignant peripheral nerve tumours were examined immunohistochemically for expression of 75 kDa nerve growth factor receptor (NGFR). In benign tumours NGFR was demonstrated at 61% in neurinoma, 71% in neurofibroma, 93% in neurofibromatosis and 90% in traumatic neuroma. Malignant neurogenic tumours were 100% positive for NGFR. Phosphotyrosine-immunoreactivity was detected in 76% of NGFR-positive tumours but the frequency of immunostained tumour cells was low. These results suggest that both benign and malignant peripheral nerve tumours express 75 kDa NGFR. The receptor seems to serve as growth signal transduction of the tumour cells in terms of phosphorylation of the tyrosine residue of the receptor or the target protein of the NGFR protein tyrosine kinase.
In a previous study the authors reported that external mechanical vibration applied to the left ventricular (LV) epicardium induces contractility-dependent depression in LV pressure, stroke volume and stroke work. It was suggested that this depression may be caused by the direct effect of external vibration on contractile protein. In another paper in this issue, it is proved that LV function with various myocardial contractilities and the actual process of deterioration in heart failure are well simulated in the model proposed by Beyar and Sideman, after some modifications have been made. In the study reported here it is assumed that an external mechanical vibration induces sudden reduction in myocardial active stress in the model of Beyar and Sideman; in this way the contractility-dependent effect of external vibration on LV function has been simulated. The results of this simulation support the suggestion that external mechanical vibration directly affects contractile protein and reduces LV function, and it is further suggested that the reduction of LV function induced by external vibration reflects the reserve or tolerance capacity of LV to a sudden reduction of myocardial contractility.
We examined Advani and Lee's equation (ALeq) and a dimension analysis-derived equation (DAeq), both of which treat vibration of the elastic spherical shell and are able to estimate elasticity of the shell noninvasively when the sizes and eigen-frequency are provided. We confirmed that ALeq was numerically identical to DAeq and that both equations gave the precise elasticity of the silicone shell. Then we estimated left ventricular (LV) myocardial elasticity noninvasively at the moment of the first heart sound emission (1HS) in 25 healthy subjects and 14 hypertrophic cardiomyopathy (HCM) patients, based on the LV eigen-frequency detected by an intraesophageal miniature vibration sensor. HCM patients had a higher mean value of LV myocardial elasticity at 1HS than healthy subjects [102.3 +/- 33.4 vs. 70.7 +/- 24.4 kPa, P < 0.01 (Pa = N/m2 = 10 dyn/cm2)]. We thereby demonstrated the possibility of a noninvasive estimate of myocardial elasticity.
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Muscarinic acetylcholine receptor (mAChR) subtype (m1-m4)-specific cDNAs were transfected into NL308 neuroblastoma-fibroblast hybrid cells and clones expressing each of the individual mAChR subtypes m1, m2, m3 and m4 obtained. Acetylcholine increased phosphoinositide (PI) turnover in m1- and m3-transformed cells, but did not produce detectable changes in m2- and m4-transformed cells. In cells expressing m1 and m3 subtypes, ACh produced an initial outward K+ current, followed by a cationic current. In cells expressing m2 and m4 receptors, only the initial K+ current was detected. The outward currents were associated with a rise in intracellular Ca2+ as measured with Fura-2 or Indo-1, and were inhibited by chelating intracellular Ca2+ with external BAPTA-AM, or by external charybdotoxin or Ba2+: hence they were attributed to the activation of a Ca(2+)-dependent K+ current. However, the outward current produced in m2- and m4-transformed cells was blocked by pretreatment with 5 ng ml-1 Pertussis toxin (PTX), whereas that in m1- and m3-transformed cells was not. These results suggest that m2- and m4-receptors in transformed NL308 cells coupled to PTX-sensitive G-protein which is capable of mobilizing intracellular Ca2+ and activate IK(Ca), whereas m1 and m3 receptors activate a similar process through a different, PTX-insensitive G-protein.
Two rare cases of intestinal epithelioid angiosarcoma arising in the sigmoid colon and small intestine are reported. The small intestinal tumours were located in the duodenum and upper jejunum. All tumours showed reddish-black protuberant masses with comparatively clear margins. Histology reveals solid and epithelioid growth of large polygonal cells, mimicking undifferentiated carcinoma. Vascular differentiation such as lamina containing red cells and intracytoplasmic vacuolization is noticed. Intense immunoreactivity to Ulex europaeus agglutinin I and JC70 (CD31), and sporadic positive reaction to factor VIII related antigen were detected in one case but not in the other. However, both tumours have cells which show intense endothelin-1 immunoreactivity. Positive immunostaining occurred with low molecular weight keratins suggesting epithelial differentiation and suggested epithelioid angiosarcoma as a diagnosis, a specific entity within angiosarcoma. Because of their histological features, epithelioid angiosarcomas may be confused with undifferentiated carcinomas. Endothelin-1-like immunoreactivity seems to be a good marker for this type of angiosarcoma, even when the tumour cells lack usual marker substances for endothelial cells.
The authors measured the transfer function (TF) of the left ventricle (LV) in an isolated canine preparation. Here TF indicates the ratio of induced vibration in LV to input vibration when an external mechanical oscillation is applied. TF had a single peak the frequency of which changed from 40 Hz to 80 Hz when LV pressure (LVP) increased from 6 mm Hg to 96 mm Hg. A mathematical model was formulated to estimate the viscoelasticity of the spherical shell. This model was constructed of the material points, elastic components which connected all the material points, and viscous components placed in series with elastic components. Theoretical TF can be computed if the viscoelastic values are given. The value of viscoelasticity at which the theoretical TF best fitted the experimental TF was considered to be the viscoelasticity of the model. The validity of this approach was verified using a silicone spherical shell. The estimated myocardial elasticity was 40 kPa when LVP was 6 mm Hg, 160-170 kPa when LVP was 96 mm Hg and was approximately proportional to LVP, whereas viscosity showed small change. The inclination of elasticity was consistent with previous reports. These results proved that myocardial elasticity can be estimated by analysing the transfer function of the left ventricle.
Ion selectivity of divalent cations on Ba2+ inward current oscillations was examined by voltage-clamp recording in v-Ki-ras-transformed NIH/3T3 (DT) fibroblasts where repetitive transient increases in cytoplasmic Ca2+ concentration were evoked by bradykinin. Application of bradykinin onto DT cells in 50 mM Ba2+ solution initiated Ba2+ inward current oscillations. The inward currents were inhibited in equimolar Sr2+ or Ca2+ solutions. Ba2+ current oscillations were dependent upon extracellular Ba2+ concentration. The results suggest that inward current oscillations are highly selective to Ba2+.
An oscillatory influx of divalent cations was measured as Ba2+ inward currents (Ba2+ current oscillations) by voltage-clamp recording in v-Ki-ras-transformed NIH/3T3 (DT) fibroblasts after activation with bradykinin or serum. Application of forskolin or dibutyryl cyclic AMP onto DT cells initiated Ba2+ current oscillations. Increasing intracellular cyclic AMP reduced the amplitude but increased the frequency of the Ba2+ current oscillations. Activation of protein kinase C by phorbol esters terminated Ba2+ current oscillations. No inhibition of Ba2+ current oscillations by phorbol esters was observed in down-regulated cells that had been pretreated with phorbol esters for 24 hrs. The results suggest that Ba2+ current oscillations are regulated by intracellular second messengers.
To examine the effect of mechanical vibration on ventricular relaxation and diastolic chamber stiffness under global ischemia, we studied eight coronary perfused, isolated, isovolumic canine left ventricles (LV). To produce varying degrees of impaired relaxation, graded coronary flow reduction and paced tachycardia were imposed. A mechanical 50-Hz, 2-mm-amplitude vibration was applied during diastole and was turned off during systole. Without diastolic vibration, the relaxation time constant of LV pressure (tau) increased with the severity of ischemia. The chamber stiffness index (K) from the diastolic pressure-volume relationship showed a slight increase during ischemia; tau decreased with diastolic vibration. The change in tau with vibration increased with ischemia and was dependent on vibration amplitude but not heart rate. The ratio of tau to the diastolic interval (DI, the time from peak negative rate of LV pressure change to end diastole) always decreased with vibration and was linearly correlated with K (r = 0.93; P less than 0.01). K decreased with vibration when tau/DI was greater than 0.3. We conclude that diastolic vibration improves impaired relaxation and chamber stiffness under myocardial ischemia.