Search PubMed⌕ Search

Biomedical subjects

S Tsunoda

Publications and source records attributed to S Tsunoda.

At least 127 records · Page 7Linked to original sources
PubMed1995

Molecular design of hybrid tumour necrosis factor alpha with polyethylene glycol increases its anti-tumour potency.

This study was conducted to increase the anti-tumour potency and reduce the toxic side-effects of tumour necrosis factor alpha (TNF-alpha). Natural human TNF-alpha was chemically conjugated with monomethoxy polyethylene glycol (PEG) using succinimidyl coupling of lysine amino groups of TNF-alpha. The number-average molecular weight of PEG-modified TNF-alpha (PEG-TNF-alpha) increased with an increase in the reaction time and the initial molar ratio of PEG relative to TNF-alpha. The resulting modified TNF-alpha was separated into fractions of various molecular weights. The specific activity of separated PEG-TNF-alpha s relative to that of native TNF-alpha gradually decreased with an increase in the degree of PEG modification, but the plasma half-life was drastically increased with the increase in molecular weight of modified TNF-alpha. PEG-TNF-alpha s, in which 29% and 56% of lysine residues were coupled to PEG, had anti-tumour activity approximately 4 and 100 times greater than unmodified TNF-alpha in the murine Meth-A fibrosarcoma model. Extensive PEG modification did not increase its in vivo activity. A high dose of unmodified TNF-alpha induced toxic side-effects, but these were not observed with the modified TNF-alpha s. Optimal PEG modification of TNF-alpha markedly increased its bioavailability and may facilitate its potential anti-tumour therapeutic use.

Animals↗
PubMed1995

G10BP, an E1A-inducible negative regulator of Sp1, represses transcription of the rat fibronectin gene.

Downregulation of the fibronectin (FN) gene in a rat 3Y1 derivative cell line, XhoC, transformed by the adenovirus E1A and E1B genes seems to be caused by the induction of a negative regulator, G10BP, which binds to three G-rich sequences in the promoter (T. Nakamura, T. Nakajima, S. Tsunoda, S. Nakada, K. Oda, H. Tsurui, and A. Wada, J. Virol. 66:6436-6450, 1992). These are the G10 stretch and two GC boxes consisting of the G10 stretch with one internal C residue insertion. The recognition sequences of G10BP and Sp1 (GGGCGG) overlap in these GC boxes. To analyze the mechanism of the downregulation, G10BP was purified by DNA affinity chromatography, and its molecular mass was estimated to be about 30 kDa. The promoter was modified by substituting the sequence GGGG with ATCC or CTTA in these G-rich sequences, leaving the Sp1 motif intact, and by replacing the Sp1 motif by the T stretch. Transcription of FN promoter-chloramphenicol acetyltransferase fusion genes carrying the base substitution in one or more of these G-rich sequences both in vivo and in vitro revealed that the base substitution in any G-rich sequence results in reduction of promoter activity, although the downstream GC box (GCd) plays a primary role. The addition of G10BP severely inhibited the activities of the FN promoters carrying the wild-type GCd in vitro, while the promoters carrying the mutant GCd were unaffected. The binding affinity of G10BP and Sp1 to each of the G-rich sequences, analyzed by gel shift assays, indicated that G10BP binds strongly to the GCd, moderately to the G10 stretch, and weakly to GCu, while Sp1 binds strongly to GCu, moderately to GCd, and weakly to the G10 stretch. Sp1 binding to GCd and the G10 stretch was inhibited by G10BP, while binding to GCu was unaffected. These results indicate that FN gene transcription is inhibited in XhoC cells primarily by exclusion of Sp1 binding to GCd by G10BP and that G10BP is a new class of Sp1 negative regulator.

Adenovirus E1A Proteins↗
PubMed1995

Immunohistochemical study of glutathione S-transferase-pi in meningiomas.

Immunostaining for glutathione S-transferase-pi was investigated in various subtypes of meningioma for the purpose of biological characterization. Specimens included five normal meninges and 25 meningiomas (10 meningothelial type, 6 fibrous type, 5 transitional type, 3 microcystic type, and 1 secretory type). In the meningothelial type, most cells showed strongly positive staining. In the fibrous type, all cells were negative. In the transitional type, only the meningothelial components were positive. In the microcystic type, meningothelial cell clusters and arachnoid trabecular cells were positive. In the secretory type, the meningothelial components and the pseudopsammoma-body-producing cells were positive. These results suggest that the meningothelial type and the fibrous type have a different basis of development and biological features. The results also suggest that arachnoid trabecular cells and meningothelial cells share the same origin, and that the arachnoid trabecular cells serve as supportive cells and as cells which detoxify harmful substances in the subarachnoid space. The pseudopsammoma-body-producing cells in the secretory type represent the outcome of epithelial differentiation of meningothelial cells with their biological character being preserved.

Culture Techniques↗
PubMed1995

The major delayed rectifier in both Drosophila neurons and muscle is encoded by Shab.

The delayed rectifier K+ current in Drosophila is similar to the classical delayed rectifier, originally described by Hodgkin and Huxley. Drosophila provides unique tools of mutant analysis to unambiguously determine the genetic identity of this native K+ current. We identified the Shab gene as the exclusive gene underlying delayed rectifier currents in both muscle and neurons. In muscles, a genetic mutation of Shab removes virtually all the whole cell delayed rectifier current (IK), while leaving unaltered the transient A-current encoded by the Shaker gene. In neurons, the Shab mutation also removes the bulk of IK, but leaves unaltered the transient A-current encoded by the Shal gene. Although most of the delayed rectifier current is the product of the Shab gene, the Shaw gene contributes a small "leak" current to most neurons and muscle cells. Thus, in contrast to the A-currents which are encoded by different genes in muscle and neuronal cell bodies (Shaker and Shal, respectively), the predominant IK in both muscle and neurons is encoded by the same gene (Shab). With the genetic identity of IK confirmed, all of the major K+ currents in embryonic Drosophila neurons and muscle are now known.

Animals↗
PubMed1995

Clinicopathological study on pineocytoma.

Six cases of pineocytoma, which had developed in the parenchyma of the adult pineal body, were examined immunohistochemically and under an electron microscope, after the malignancy of each case had been determined using our classification. One case was rated as grade 1 showing a lobular structure and resembling the normal pineal body. Two cases were rated as grade 2 without a lobular structure but with pineocytomatous rosettes (P-rosettes). Two cases were rated as grade 3 without P-rosettes but with few mitotic figures. One case was rated as grade 4 with marked cellular pleomorphism, numerous mitotic figures and necrotic foci. When examined immunohistochemically, neuron-specific enolase was positive but glial fibrillary acidic protein was negative in all cases. Under an electron microscope, all cases showed abortive synapses, and clear or dense core vesicles. These findings allow us to make two conclusions. First, pineocytoma is always a tumor of neuronal lineage, regardless of their grade of malignancy. Second, the grade 4 pineocytoma should be distinguished from the type of tumor classically called "pineoblastoma." That is, the former seems to be a biologically dedifferentiated tumor, while the latter seems to be biologically undifferentiated tumor.

Adult↗
PubMed1995

Genetic analysis of Drosophila neurons: Shal, Shaw, and Shab encode most embryonic potassium currents.

In this study, we perform the first genetic analysis of K+ currents in Drosophila embryonic neurons revealing the identity of the currents present. Unlike muscles, where the presence of Shaker is obvious, Shaker currents are not detectable in these neurons. In contrast, we show that Shal is as important in these neuronal cell bodies as Shaker is in muscles. Only three single-channel currents were found, all of which are genetically separable. Shal encodes a 4 pS transient channel. Whole-cell Shal currents have a wide variety of inactivation rates which, in contrast to a mechanism such as heteromultimer formation, is due to single Shal channels assuming different gating modes. Shaw encodes a 42 pS noninactivating channel distinctive for its extremely low voltage sensitivity; Shaw channels have a total equivalent gating charge of 0.90 e- charges, in sharp contrast to 7 e- reported for Shaker channels. An 11 pS slowly inactivating channel also present in these neurons may be encoded by the Shab gene. Thus, of four voltage-dependent K+ channel genes now cloned in Drosophila, all except Shaker appear to be expressed in the cell bodies of these neurons. It is only in Drosophila that a study such as this one can be done. Because Drosophila contains only a single member of each of the four subfamilies of K+ channel genes (unlike mammals), we can eliminate an entire subfamily with a mutation to a single gene. Here, we have examined the effect of eliminating each of three subfamilies. Such a task is presently impossible to accomplish in any mammalian system.

Animals↗
PubMed1995

TGF-beta upregulates interleukin 6 production by rat glomerular epithelial cells in vitro.

BACKGROUND: Glomerular epithelial cells (GECs) play an important role in maintaining normal glomerular permselectivity in vivo. Recent in-vitro studies have suggested that GECs are able to secrete substances which may modulate glomerular injury. Interleukin 6 (IL-6) has been shown to be a potent mediator of glomerular injury. It is also known that IL-6 could be produced by various cells. METHODS: IL-6 production by rat GECs in culture was examined in this study. IL-6 bioactivity in conditioned medium collected from cultured GECs (GEC-CM) was measured using IL-6 dependent murine hybridoma cell line, namely B9 cells. IL-6 gene expression by GECs was analysed by reverse transcriptase polymerase chain reaction (RT-PCR). Effects of recombinant IL-6 on the proliferation of GECs and type IV collagen secretion by GECs were evaluated to examine the possible role of GECs derived IL-6. RESULTS: GEC-CM stimulated B9 cells growth in a dose dependent fashion. The mitogenic activity was inhibitable by anti-murine IL-6 antibody. De-novo synthesis of IL-6 was suggested by the demonstration of IL-6 mRNA by GECs using the RT-PCR. Secretion of IL-6 by GECs was increased by transforming growth factor beta but not by IL-1 beta. Recombinant murine IL-6 stimulated GECs growth and their type IV collagen secretion. CONCLUSIONS: These results indicate that rat GECs could produce IL-6 which may modulate glomerular inflammation and that IL-6 may function as an autocrine factor for GECs.

Animals↗
PubMed1995

[Muscle sympathetic nerve activity in patients with spinocerebellar degeneration without orthostatic hypotension].

Muscle sympathetic nerve activity (MSNA) was compared in 6 patients (age; 45-76 years old, 3 males and 3 females) with spinocerebellar degeneration (SCD) without orthostatic hypotension (OH) and in 10 (age; 38-78 years old, 3 males and 7 females) with other neurologic disorders (controls). MSNA was elicited from the peroneal nerve at the resting recumbent position by using a microneurographic method. MSNA, heart rate (HR) from the electrocardiogram and mean blood pressure (MBP) measured by Finapres were recorded simultaneously at rest and during the head-up tilting at 45 degrees. Although there were no significant differences in MBP and HR between both groups, burst rate (bursts per minute) and burst incidence (bursts per 100 heart beats) of MSNA in SCD patients were significantly decreased as compared with controls (p < 0.01). During the head-up tilting, responses in MBP and MSNA showed a tendency to decrease in SCD patients. We concluded that the sympathetic noradrenergic system might be potentially impaired in SCD patients without OH.

Aged↗
PubMed1994

Electron microscopic evidence of a viral nature for osteoclast inclusions in Paget's disease of bone.

Circumstantial evidence from electron microscopic and immunological studies support the view that Paget's disease of bone represents a slow virus infection. However, there is only limited information available regarding its electron microscopic, enzyme and immunocytochemical characteristics. Two cases were studied using electron microscopy with particular emphasis on the inclusions in osteoclasts. Detailed ultrastructural and cytochemical studies including immuno-electron microscopy were performed. Some osteoclasts demonstrated specific virus-like structures composed of aggregations of microtubules in the nucleus and cytoplasm. The structures were easily digested by trypsin or protease, and were sensitive to RNase, which provided substantial evidence of a proteinaceous nature and inclusion of ribonucleic acid. Immunocytochemical examination identified binding of anti-respiratory syncytial virus and anti-measles virus antibodies in the tissue obtained from one of the two cases examined. The presence of viral antigens in structures in the cytoplasm of Pagetic osteoclasts supports the theory of paramyxovirus involvement in this disease.

Antigens, Viral↗
PubMed1994

Management of dissecting aneurysms of the posterior circulation.

We analysed the clinical presentation, treatment and outcome of our own 36 cases of posterior circulation dissecting aneurysms (DA) and discussed the surgical indications and procedures regarding posterior fossa DA. Twenty one cases were male, 15 cases were female. Their mean age was 54 +/- 14 years. Clinical manifestations were subarachnoid haemorrhage (SAH) in 14 cases (39%) and ischaemic attacks in 22 cases (61%). Three of 14 SAH cases had rebleeding in the acute stage. Angiographic findings were aneurysmal dilatation in 16 cases, retention of contrast medium in 12 cases, string sign in 9 cases, double lumen in 4 cases, pearl and string sign in 3 cases, and occlusion of parent artery in 2 cases. Surgical treatment was performed on nineteen cases (53%). The operation was carried out in the acute stage on the SAH group; in the subacute or chronic stage on the ischaemic group. The surgical procedure was the proximal ligation, trapping and removal of DA with or without revascularization of the parent artery. 84% of the surgically managed patients and 71% of the nonsurgical cases had a favourable outcome (good recovery or moderate disability). Poor prognosis was revealed from the rebleeding and primary neurological stage. We recommend surgical treatment in the acute stage on the SAH group. On the ischaemic group surgical treatment in the subacute or chronic stage is recommended, if the DA has the risk of rupture or progression of the dissection.

Adolescent↗
PubMed1994

Bilateral organized chronic subdural haematomas: high field magnetic resonance images and histological considerations.

The authors describe a 66-year-old man with progressive gait disturbance caused by bilateral organized chronic subdural haematomas. The characteristics of these lesions on magnetic resonance (MR) images have not yet been clarified. The organized haematoma in our patient exhibited slight hypo-intensity on T 1-weighted MR images and marked hypo-intensity on T 2-weighted MR images obtained at 1.5T. Preoperative MR imaging may give us useful information about surgical strategy in the case of chronic subdural haematoma with an unusual appearance on computed tomographic (CT) scans.

Aged↗
PubMed1994

Muscle spasm induced sympathetic reflex bursts on microneurography in a case with pontine demyelination.

Microneurography was performed in a 39-year-old woman with demyelination of the pontine white matter associated with muscle spasms in the lower extremities. Single bursts on the microneurogram were observed immediately after cessation of the spasm with no systemic changes in the blood pressure or heart rate. Voluntary tonic flexion of the lower extremities induced similar bursts with small amplitudes. These reflex bursts possessed a characteristic of muscle sympathetic nerve activity, because the latency between the peak of each burst and the prior R-wave on the electrocardiograph was constant. The occurrence of these bursts suggests that a segmental compensatory mechanism in the spinal cord may stabilize the muscle blood flow influenced by muscle contraction.

Adult↗
PubMed1994

Inhibition by Guan-mu-tong (Caulis aristolochiae manshuriensis) of the growth of spontaneous mammary tumors in SHN virgin mice.

Multiparous SHN mice with spontaneous mammary tumors (5-10 mm in size) were given water extract of Guan-mu-tong (Gmt; Caulis aristolochiae manshuriensis) (0.5%) ad libitum as drinking water for 10 days. This treatment retarded significantly the growth of mammary tumors compared with the controls. By contrast, normal mammary gland growth, histology of adrenals and ovaries, and body weight were affected little by the Gmt treatment. Gmt appears to be the first agent inhibiting the growth of spontaneous mouse mammary tumors of palpable size by per os treatment.

Animals↗
PubMed1994

Intravenous administration of polyethylene glycol-modified tumor necrosis factor-alpha completely regressed solid tumor in Meth-A murine sarcoma model.

Complete regression of solid tumors was achieved by plural intravenous (i.v.) administrations of polyethylene glycol (PEG)-modified tumor necrosis factor-alpha (TNF-alpha), prepared by covalently modifying natural human TNF-alpha with N-succinimidyl succinate PEG. The anti-tumor efficacy of PEG-modified TNF-alpha (MPEG-TNF-alpha), in which 56% of the TNF-alpha-lysine residues were coupled with PEG, was compared with that of native TNF-alpha in the Meth-A murine fibrosarcoma model. MPEG-TNF-alpha and native TNF-alpha were given as i.v. injections twice a week for 2 weeks. The anti-tumor activity of MPEG-TNF-alpha was dose-dependent and was far superior to that of native TNF-alpha. Complete regression was observed in 3 of the 8 mice administered native TNF-alpha at the dose of 10,000 JRU (Japan reference unit), but 4 of the 5 remaining mice died during the therapeutic period. At 5,000 JRU of native TNF-alpha, no case of complete regression was observed. By contrast, complete regression was obtained in all 10 mice given 200 JRU of MPEG-TNF-alpha. No side-effects were observed at the dose of 500 JRU of MPEG-TNF-alpha, which was 2.5 times the minimal dose (200 JRU) of MPEG-TNF-alpha required for complete regression in all treated mice. MPEG-TNF-alpha appears to have potential as a candidate anti-tumor therapeutic agent.

Animals↗
PubMed1994

[Studies on analysis of gastric mucosal blood flow by electronic endoscopic image. Especially on atrophic gastritis].

The electronic endoscopic image of gastric mucosa was converted by image processing unit SP-1000 (A/D changed) into the one, which was treated with the color conversion method to measure the gastric mucosal hemoglobin index (Hb-index: HI). At the same time, biopsy specimens of gastric mucosa were removed from such 4 different sites as antrum lesser curvature, lower body lesser curvature, lower body anterior wall and upper body posterior wall. On pathohistological examination, the author observed the inflammatory cell infiltration, mucin production, the number and diameter of blood vessels, the degree of atrophic changes in gastric mucosa. HI values were compared with histological findings and with the degree of endoscopic appearance of blood vessel in the lower body lesser curvature. The following results were obtained. HI values were lower in the group with higher inflammatory cell infiltration and less mucin production, while the values were higher in the group with more numerous vessels and larger size ones in diameter. In the group with higher degrees of the pathohistological atrophic change and the endoscopic appearance of blood vessel, HI showed lower values.

Adult↗
PubMed1994

Medulloblastoma associated with cysts and calcifications--case report.

An 11-year-old boy presented with medulloblastoma occurring in the cerebellar vermis. Computed tomography and magnetic resonance imaging revealed numerous cysts and calcifications in the tumor. The tumor was subtotally removed and cellular synchronization radiation therapy given. He was discharged without neurological deficits. Histological examination showed the cysts represented necrotic foci. Macrophages, which appeared around the necrotic foci, were important in the development of the calcifications via proliferation of collagen fibers.

Brain↗
PubMed1994

Pleomorphic adenoma of the lacrimal gland manifesting as exophthalmos in adolescence--case report.

A 16-year-old girl presented with a pleomorphic adenoma of the lacrimal gland manifesting as left painless exophthalmos which had persisted for 3 years. Computed tomography revealed a tumor about 15 mm in diameter in the superolateral site of the left orbit. The tumor was removed completely by combined orbitofrontal craniotomy through a transcranial approach. Histological examination demonstrated the growth of tumor cells as glandular cavities or sheets, with myxoid and partly chondroid connective tissue stroma. Pleomorphic adenoma of the lacrimal gland is unusual in adolescents.

Adenoma, Pleomorphic↗