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M Kano

Publications and source records attributed to M Kano.

At least 109 records · Page 6Linked to original sources

[An experimental study of tumor cell infiltration into temporal bones--route into the inner ear from the arachnoid space].

In humans, metastatic tumors which invaded the temporal bones have been studied in regard to the relationship between histopathologic findings and clinical symptoms. On the other hand, there is no experimental study using an animal model for tumor infiltration into the temporal bone. This study was designed to establish such an animal model and examine the temporal bones histopathologically. Rat thymic lymphoma cell (FTL-A2) were inoculated into the cisterna magna of Wistar rats. The animals were decapitated under deep anesthesia with pentobarbital sodium from the 1st to 8th day after inoculation. Their heads were fixed with Heiden-hain SuSa solution, decalcified, dehydrated, embedded in celloidin, and sectioned horizontally at a thickness of 25 microns. These were stained with hematoxylin and eosin, and histologically examined by light microscopy. Inoculated tumor cells showed active viability in the arachnoid space at a rate of 98%. Two major routes of tumor cell infiltration into the inner ear were found: the cochlear aqueduct and the internal auditory canal. At the early stage after the inoculation, tumor cells infiltrated the scala tympani through the cochlear aqueduct. Invading the fiber of the cochlear nerve, tumor cells infiltrated Rosenthal's canal via the tractus spiralis foraminosus, and passed through Rosenthal's canal and the osseous spiral lamina into the scala tymani. However, tumor cells did not infiltrate the organ of Corti through the habenula perporata. Tractus spiralis foraminosus and habenula perforata functioned as a barrier against tumor infiltration. In a few cases, tumor cells infiltrated over the macula cribrosa into the subepithelial space of the utricule and saccule. The macula cribrosa functioned as a barrier.

Acoustic Maculae↗

[Bone mineral density (BMD) of the calcaneus bone in 72 dialysis patients measured by ultrasonic bone absorptiometry].

BACKGROUND: To determine what factors contribute to and change BMD in dialysis patients. METHODS: Bone parameters, namely, osteosono-assessment index (calculated by speed of sound and transmission index) were measured at calcaneus bone by ultrasonic bone absorptiometry with an Aloka Acoustic Osteoscreener (Model AOS-100). Seventy two patients were 62. 8 +/- 10.5 years of age (mean +/- SD) (range 36-81) and 70.8% were males; the patients had received dialytic therapy for 52.7 +/- 41.7 months (range 2-205). The effects of sex, age, height, weight, postmenoposal years, dialysis duration, various blood parameters, oral phosphorus binding agent (CaCO3 dosage) and oral vitamin D3 treatment (D3 dosage) on BMD were assessed statistically. RESULT: BMD in male patients were significantly higher than those in female patients (Mann-Whitney test, p < 0.01). BMD showed significant correlations with age (Spearman's correlation coefficient r = -0.384, p < 0.01), height (r = 0.479, p < 0.00001), postmenoposal years (r = -0.692, p < 0.05), dialysis duration (r = 0.250, p < 0.01), blood Ca level (r = 0.292, p < 0.05) and CaCO3 dosage, postmenoposal years and dialysis duration were the variables that significantly correlated with the BMD (multiple correlation coefficient = 0.646).

Adult↗

Effects of procollagen C-proteinase enhancer protein on the growth of cultured rat fibroblasts revealed by an excisable retroviral vector.

An excisable retroviral vector, TSN-lox, was developed by exploiting Cre-loxP homologous recombination. An integrated TSN-lox provirus could be excised, leaving a solo long terminal repeat at the integration site; inverse PCR, taking advantage of the solo long terminal repeat, was used to characterize cellular flanking sequences. A TSN-lox-transduced Rat2 cell clone, lox-7, was found to harbor the provirus in an intron of the procollagen C-proteinase enhancer protein (PCPE) gene, whose expression was lowered compared with that of the parental Rat2. When the vector provirus in lox-7 cells was excised, PCPE expression was elevated. The level of PCPE expression seemed to affect cell growth properties such as morphology, contact inhibition, and anchorage-independent growth. These results suggested that the excisable retroviral vector may be useful for studying the molecular basis for proviral insertion mutagenesis, and that PCPE may play a significant role in controlling cell growth and differentiation.

Animals↗

Impaired parallel fiber-->Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor delta2 subunit.

The glutamate receptor delta2 subunit (GluRdelta2) is specifically expressed in cerebellar Purkinje cells (PCs) from early developmental stages and is selectively localized at dendritic spines forming synapses with parallel fibers (PFs). Targeted disruption of the GluRdelta2 gene leads to a significant reduction of PF-->PC synapses. To address its role in the synaptogenesis, the morphology and electrophysiology of PF-->PC synapses were comparatively examined in developing GluRdelta2 mutant and wild-type cerebella. PCs in GluRdelta2 mutant mice were normally produced, migrated, and formed spines, as did those in wild-type mice. At the end of the first postnatal week, 74-78% of PC spines in both mice formed immature synapses, which were characterized by small synaptic contact, few synaptic vesicles, and incomplete surrounding by astroglial processes, eliciting little electrophysiological response. During the second and third postnatal weeks when spines and terminals are actively generated, the percentage of PC spines forming synapses attained 98-99% in wild type but remained as low as 55-60% in mutants, and the rest were unattached to any nerve terminals. As a result, the number of PF synapses per single-mutant PCs was reduced to nearly a half-level of wild-type PCs. Parallelly, PF stimulation less effectively elicited EPSCs in mutant PCs than in wild-type PCs during and after the second postnatal week. These results suggest that the GluRdelta2 is involved in the stabilization and strengthening of synaptic connectivity between PFs and PCs, leading to the association of all PC spines with PF terminals to form functionally mature synapses.

Animals↗

Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Galphaq.

Mice lacking the alpha-subunit of the heterotrimeric guanine nucleotide binding protein Gq (Galphaq) are viable but suffer from ataxia with typical signs of motor discoordination. The anatomy of the cerebellum is not overtly disturbed, and excitatory synaptic transmission from parallel fibers to cerebellar Purkinje cells (PCs) and from climbing fibers (CFs) to PCs is functional. However, about 40% of adult Galphaq mutant PCs remain multiply innervated by CFs because of a defect in regression of supernumerary CFs in the third postnatal week. Evidence is provided suggesting that Galphaq is part of a signaling pathway that is involved in the elimination of multiple CF innervation during this period.

Age Factors↗

Arterial embolization as preoperative treatment for pulmonary aspergillosis with hemoptysis.

Pulmonary aspergillosis associated with old tuberculosis is generally resistant to treatment. Thus, if patients are treated only with conservative therapy, their condition continues to deteriorate due to repetitive hemoptysis, and may even become critical. Surgical treatment is required for these patients; however, it is extremely difficult to resect the lesion due to severe adhesions to the chest wall and vascular proliferation surrounding the lesion. We performed preoperative arterial embolization, achieving good results in three patients with hemoptysis caused by pulmonary aspergillosis. The feeding arteries were embolized using microcoils and/or gelatin sponges, and a lobectomy was safely carried out in all patients. We concluded that preoperative arterial embolization is a safe and effective technique to prevent massive hemorrhage occurring at the time of surgery.

Aged↗

Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluR1.

Most of the cerebellar Purkinje cells (PCs) of an adult animal are innervated individually by a single climbing fiber (CF) that forms strong excitatory synapses with the PCs. This one-to-one relationship between a PC and a CF is a consequence of a developmentally regulated regression of the innervation of PCs by CFs. We found that, in mice deficient in the type 1 metabotropic glutamate receptor (mGluR1), the regression of supernumerary CFs ceases by the end of the second postnatal week, which is about one week earlier than in normal mice. Consequently, about one third of PCs in the mGluR1 mutant mice are innervated by multiple CFs in adulthood. We conclude that the regression of CFs normally occurs in two developmental phases and that mGluR1 plays a crucial role in the second phase.

Aging↗

Increased biliary group II phospholipase A2 and altered gallbladder bile in patients with multiple cholesterol stones.

BACKGROUND & AIMS: Multiple cholesterol stones are associated with more biliary complications and show more rapid cholesterol nucleation than solitary stones. Group II phospholipase A2 (PLA2-II) may play a critical role in the process of mucosal inflammation, which in turn may produce pronucleating agents. PLA2-II concentrations in gallbladders and gallbladder bile from patients with different types of gallstone disease were assayed to correlate PLA2-II with alterations in biliary composition. METHODS: PLA2-II protein concentrations were assayed immunoradiometrically using monoclonal antibodies against human splenic PLA2-II. RESULTS: Immunoreactive PLA2-II levels in gallbladder bile were significantly higher in patients with multiple cholesterol stones (68.2 +/- 6.3 ng/dL, mean +/- SEM; n = 24) than in those with solitary stones (24.9 +/- 2.8; n = 20; P < 0.01), those with multiple pigment stones (24.2 +/- 3.7; n = 18; P < 0.01), or control subjects (13.4 +/- 1.7; n = 19; P < 0.01). Increased biliary immunoreactive PLA2-II levels in multiple cholesterol stones were associated with a concomitant increase in the lysophosphatidylcholine to phosphatidylcholine ratio; free arachidonate, protein, and hexosamine concentrations; and gallbladder bile viscosity. The gallbladders showed an increased PLA2-II protein mass and steady-state messenger RNA levels, which was associated with increased prostaglandin E2 levels. CONCLUSIONS: Increased biliary PLA2-II may be of pathogenetic importance in multiple cholesterol stones, probably through potentiating gallbladder mucosal inflammation with associated biliary alterations favoring cholesterol crystal formation.

Adult↗

Simultaneous determination of plasma mevalonate and 7alpha-hydroxy-4-cholesten-3-one levels in hyperlipoproteinemia: convenient indices for estimating hepatic defects of cholesterol and bile acid syntheses and biliary cholesterol supersaturation.

The high prevalence of cholesterol gallstone disease in hypertriglyceridemic patients may be associated with frequent metabolic defects in cholesterol and bile acid syntheses and in the concomitant formation of bile supersaturated with cholesterol. This study had the two aims: 1) to assess whether the defects as well as the degree of biliary cholesterol supersaturation in patients with hyperlipoproteinemia (HLP) can be estimated by the simultaneous determination of plasma mevalonate (MVL) and 7alpha-hydroxy-4-cholesten-3-one (C4); and 2) to assess the possible application of an estimated cholesterol saturation index ([CSI]E) as a means of evaluating the clinical effects of simvastatin on biliary lipid composition. Biliary cholesterol supersaturation was observed in patients with both IIa and IV HLP types. Consistent with the high activity and steady-state messenger RNA level of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase, plasma MVL was significantly higher in 86 patients with HLP (38 type IIa, 44.1 +/- 2.4 nmol/L and 48 type IV, 56.7 +/- 2.3; P < .01) than in 41 normolipidemic subjects (34.2 +/- 1.5), closely correlating with the molar percentage of cholesterol in bile (r = .61, P = .0001; n = 86). On the other hand, consistent with the high activity and messenger RNA level of cholesterol 7alpha-hydroxylase, plasma C4 was significantly higher in patients with HLP (type IIa, 28.8 +/- 2.3 nmol/L and type IV, 38.3 +/- 2.7; P < .01) than in normolipidemic subjects (17.4 +/- 1.5). Plasma C4 was closely correlated with plasma MVL (r = .40, P = .0001; n = 86), but was inversely correlated with the molar percentage of bile acids in bile (r = .49, P = .0001; n = 86). Assuming that cholesterol supersaturation in patients with HLP may be governed by both an enhanced cholesterol secretion (closely reflected by plasma MVL) and a decreased secretion of bile acids (closely reflected by plasma C4), the multivariate linear regression-analyses revealed that an index defined as estimated CSI ([CSI]E) (%) in patients with HLP was given by the following equation using plasma MVL and C4 (nmol/L): [CSI]E = 1[MVL] + 0.7[C4] + 44.4. Biliary cholesterol supersaturation in patients treated with simvastatin improved in a manner parallel to the time course of decreases in plasma MVL and C4. The [CSI]E before and at the end of treatment were correlated with biliary CSI. These results indicate that defects of hepatic cholesterogenesis, and bile acid synthesis, and the degree of biliary cholesterol supersaturation in patients with HLP can be estimated exactly by the simultaneous determination of plasma MVL and C4; furthermore [CSI]E may be adopted for clinical use as a convenient index of biliary CSI.

Adult↗

Expression of Fas in renal cell carcinoma.

We have investigated whether the Fas-mediated cell death pathway is functional in renal cell carcinoma. The expression of Fas in surgical specimens and cell lines of renal cell carcinoma was examined. Fas expression was positive in six out of 18 tumors measured by flow cytometry and was prominent in advanced tumors. Three out of the six Fas-positive tumors had already metastasized at the time of surgery. A significant correlation was found between the tumor volume and the percentage of Fas-positive cells in a tumor (r = 0.70, P = 0.0007). Fas-positive tumors were larger than Fas-negative tumors [mean tumor volume (ml) +/- SD, Fas(+), 265.6 +/- 136.8; Fas(-), 65.8 +/- 80.9, P = 0.0012]. All human renal carcinoma cell lines tested (ACHN, Caki-1, SMKT-R-2, SMKT-R-3 and SMKT-R-4) expressed Fas abundantly, as Fas-positive cells accounted for > 50% in all cell lines by flow cytometry. Treatment with anti-Fas antibody caused apoptosis in Fas-positive renal cell carcinoma cell lines. However, the effectiveness of apoptosis induction in individual cell lines was not correlated with the level of Fas expressed. These data suggest that Fas targeting may be a therapeutic option for treatment of advanced renal cell carcinoma which is refractory to either chemotherapy or irradiation.

Apoptosis↗

Altered distribution and expression of protein tyrosine phosphatases in normal human skin as compared to squamous cell carcinomas.

Amounts and subcellular localizations of 4 protein tyrosine phosphatases (PTPs) were compared in cultured normal human keratinocytes, an immortalized keratinocyte cell line, and 2 squamous cell carcinoma (SCC) lines. Cellular localizations for PTPs were determined in biopsies of normal human skin and SCCs. Compared to normal keratinocytes, SCC cell lines had higher levels of PTP-1B and T-cell PTP and comparable levels of PTP-1C or PTP-1D. The subcellular localization of each PTP was similar in the 3 types of keratinocytes with PTP-1B localizing to the endoplasmic reticulum, T-cell PTP exclusively found in the nucleus, PTP-1C localized to the plasma membrane, cytosol and nucleus, and PTP-1D present in both cytosol and nucleus. Compared to normal skin, immunoreactive PTP-1B was markedly increased in the invasive margins of SCCs while T-cell PTP was generally increased in tumors. PTP-1C immunostaining varied between cells with no obvious difference between normal and neoplastic tissues. The intensity and distribution of immunoreactive PTP-1D varied greatly between cells within tumors. These differences in amounts and in cellular and subcellular localization of these PTPs, especially those differences in invasive margins of SCCs, may reflect the diverse roles these PTPs play in the proliferation and invasive potential of neoplastic keratinocytes.

Blotting, Western↗

[Usefulness of transcranial magnetic stimulation in the objective assessment of therapy for adrenoleukodystrophy].

Adrenoleukodystrophy (ALD) is a hitherto untreatable, X-linked recessive disorder of the central nervous system characterized by the systemic accumulation of very-long-chain fatty acids. Although various treatments have been proposed, objective evidence of their efficacy is insufficient. This is partly due to the absence of an appropriate method for evaluating the functions of the central nervous system (CNS). In this study, we took up the central motor conduction time (CMCT) as an index of the CNS functions, and measured it in two patients with ALD under steroid pulse therapy to know if this parameter is useful in assessing the effects of therapy. The right and the left motor cortex was stimulated separately with a MAGSTIM 200 magnetic stimulator, using a round coil of 9cm mean diameter to stimulate the hand area or a double cone coil to stimulate the leg area. CMCT, the time an impulse takes to travel from the motor cortex to the anterior horn cells in the corresponding region, was measured by a combination of transcranial magnetic stimulation (TMS) and F wave technique. Before treatment, CMCT to the cervical cord was prolonged slightly in both patients; CMCT to the lumbar cord was prolonged slightly in one and moderately in the other. After repeated steroid pulse therapy, a definite improvement, although partial and transient, was observed in either case. TMS thus seems to be useful not only for detecting functional derangement of the pyramidal tract but for evaluating the efficacy of therapy for this disease.

Adrenoleukodystrophy↗

Ca(2+)-induced rebound potentiation of gamma-aminobutyric acid-mediated currents requires activation of Ca2+/calmodulin-dependent kinase II.

In cerebellar Purkinje neurons, gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission undergoes a long-lasting "rebound potentiation" after the activation of excitatory climbing fiber inputs. Rebound potentiation is triggered by the climbing-fiber-induced transient elevation of intracellular Ca2+ concentration and is expressed as a long-lasting increase of postsynaptic GABAA receptor sensitivity. Herein we show that inhibitors of the Ca2+/calmodulin-dependent protein kinase II (CaM-KII) signal transduction pathway effectively block the induction of rebound potentiation. These inhibitors have no effect on the once established rebound potentiation, on voltage-gated Ca2+ channel currents, or on the basal inhibitory transmission itself. Furthermore, a protein phosphatase inhibitor and the intracellularly applied CaM-KII markedly enhanced GABA-mediated currents in Purkinje neurons. Our results demonstrate that CaM-KII activation and the following phosphorylation are key steps for rebound potentiation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Fractional calcium current through neuronal AMPA-receptor channels with a low calcium permeability.

The Ca(2+)-permeation properties of AMPA-receptor (AMPA-R) channels in Purkinje neurons in rat cerebellar slices were studied using a combination of whole-cell patch-clamp recordings, Fura-2 fluorometry, and single-cell reverse-transcription (RT)-PCR. Several lines of evidence indicate that Purkinje neurons, at both early and late stages of postnatal development, express exclusively AMPA-R channels with a low Ca2+ permeability. First, no Ca2+ signal was detected during application of either AMPA or kainate to Purkinje neurons loaded with the Ca2+ indicator Fura-2 AM. In contrast, kainate application induced large Ca2+ transients in Bergmann glia cells. Second, in ion substitution experiments, when Ca2+ is the only extracellular permeant cation, the reversal potential corresponds to that expected for AMPA-R channels with a low permeability for Ca2+. Third, using a fluorometric flux-measurement approach (Schneggenburger et al., 1993a), we found that the Ca2+ fraction of the total cation current through AMPA-R channels is approximately 0.6%. This value is approximately sixfold lower than that found for recombinant AMPA-R lacking the AMPA-R subunit GluR2. Furthermore, single-cell RT-PCR experiments revealed the presence of the AMPA-R subunits GluR1, GluR2, and GluR3 in Purkinje neurons in cerebellar slices at developmental stages corresponding to those studied electrophysiologically. The expression of GluR2 in all cells tested (n = 14) is consistent with the subunit composition predicted from studies of recombinant AMPA-R channels with a low permeability for Ca2+ (Burnashev et al., 1992b). In conclusion, this study establishes that cerebellar Purkinje neurons at all postnatal developmental stages possess AMPA-R channels with a low permeability for Ca2+.

Animals↗

Prognostic value of monolayer culture patterning in primary cell culture of oesophageal cancer.

The growth of primary cell cultures of oesophageal cancer was compared with the clinical outcome of patients from whom the cancers were taken. Ninety-three patients underwent curative resection, with no operative deaths, and were divided into three groups according to the monolayer culture pattern of the primary cell culture: culture from 43 patients (46 per cent) grew no malignant cells (group 1), 21 (23 per cent) produced monolayer epithelial growth (group 2) and the rest (from 29 patients) established cell lines (group 3). The 5-year survival rate of patients in group 2 (29 per cent) and group 3 (23 per cent) was significantly lower (P < 0.005) than that of those in group 1 (51 per cent). Monolayer epithelial growth potential is a significant prognostic factor in patients with oesophageal cancer.

Adult↗

Life-threatening cardiac involvement throughout life in a case of Costello syndrome.

Costello syndrome is characterized by poor postnatal growth, mental retardation, curly hair, coarse face, loose skin of the hands and feet, and nasal papillomata. Patients with Costello syndrome have a high incidence of cardiac involvement, such as arrhythmias, hypertrophic cardiomyopathy, or congenital anomalies. The importance of cardiac involvement in Costello syndrome has not been strongly emphasized thus far, although arrhythmia and hypertrophic cardiomyopathy are both serious forms of cardiac involvement. We report the case of a Japanese girl with Costello syndrome, who experienced life-threatening cardiac involvement throughout her life.

Anus Neoplasms↗