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Biomedical subjects

H Suwa

Publications and source records attributed to H Suwa.

At least 55 records · Page 3Linked to original sources

Utriculoocular reflex arc of the cat.

1. Intracellular recordings of synaptic potentials in extraocular motoneurons were studied to determine the connectivities between the utricular nerve and the extraocular motoneurons in cats. 2. Stimulating electrodes were placed within the left utricular nerve, while other branches of the vestibular nerve were removed. Subsequently, the N1 field potentials evoked by utricular nerve stimulation were recorded in the vestibular nuclei. The potential typically grew until reaching a plateau (submaximal stimulation). Stimulus spread to the other nerve branches appeared as an additional increase in N1 amplitude after the plateau discontinued (supramaximal stimulation). 3. Intracellular recordings were made from 200 identified motoneurons in the bilateral III, IV, and VI cranial nuclei. 4. Stimulation of the utricular nerve at submaximal intensity evoked a longer latency depolarizing and hyperpolarizing potentials in contra- and ipsilateral medial rectus motoneurons, respectively. Complex potentials with longer latencies also were recorded in ipsilateral inferior oblique and contralateral trochlear motoneurons after stimulation of the utricular nerve at a submaximal intensity. Monosynaptic and disynaptic connections between the utricular nerve and ipsilateral abducens motoneurons and interneurons were recorded as described previously. 5. The results of the present study confirm our initial findings that a disynaptic pathway from the utricular nerve to contralateral trochlear motoneurons is absent or very poorly developed, whereas polysynaptic circuits from the utricular nerve to inferior oblique and trochlear motoneurons may play a role in eye rotation during head tilt.

Animals↗

Solitary metastasis of lung cancer to the cerebellopontine angle--case report.

A 44-year-old male presented with a solitary cerebellopontine angle (CPA) metastasis from lung cancer. His initial symptoms were vertigo and hearing loss beginning 5 months after the diagnosis of the primary cancer. Two months later, right facial paresis developed. His neurological deterioration was rapid. Magnetic resonance (MR) imaging with enhancement disclosed the CPA tumor. The tumor was partially removed through the retroauricular retromastoid approach. Histological examination of the specimen revealed adenocarcinoma. The characteristic rapidly progressive symptoms and MR imaging with enhancement are the most sensitive and essential examinations for this lesion.

Adenocarcinoma↗

[Effect of estradiol on 5 alpha-reductase activity in osteoblast-like cell (UMR106-01)].

Bone is known to be a target organ of not only estrogens, but also androgens. The mechanism by which these steroids exert their action on bone cells is still poorly understood. In the present study, the effect of 17 beta-estradiol (E2) on 5 alpha-reductase activity, converting testosterone (T) to a more potent biological androgen, dihydrotestosterone (DHT), was assessed in an osteoblast-like cell line of rat origin (UMR106-01). Cells were incubated under standardized conditions with varying concentrations of E2 (10(-12)-10(-6) M) for 48 hours. Incubation medium was replaced when the cells were preconfluent and thereafter at 24 hour intervals. Then the cells were harvested. Each cell homogenate was incubated with [4-14C]-T. DHT was detected as a single metabolite on silicagel thin layer chromatography. 5 alpha-reductase activity was determined by measuring the amount of labeled DHT from T. The radiochemical purity of DHT recovered after incubation was confirmed by recrystallization to constant specific activity. Under the conditions used, no estrogen was detected. Production of insulin-like growth factor-I and alkaline phosphatase in UMR106-01 was increased when E2 was added into the culture medium, however, 5 alpha-reductase activity was significantly decreased by the addition of 10(-12) M to 10(-6) M of E2. Maximum inhibition was noticed at 10(-10) M. Our results demonstrate that UMR106-01 cells have a capacity to transform T into the biologically more potent androgen, DHT. The result, that the enzyme activity was influenced by E2, suggests the regulatory mechanism of both sex steroids on the steroid metabolism in osteoblasts.

Animals↗

Immunohistochemical staining for type IV collagen and laminin in the stroma of human pancreatic cancer.

Fourteen human pancreatic cancer, six normal pancreatic, and four alcoholic chronic pancreatitis tissue samples were examined by immunohistochemistry with antitype IV collagen and antilaminin monoclonal antibodies (MAb). The basement membranes of acinar, ductal, and endothelial cells from all of the normal pancreatic and alcoholic chronic pancreatitis tissue samples were continuously immunostained, but the stroma was negatively immunostained by both antibodies. On the other hand, all 14 pancreatic cancer tissues showed irregular immunostaining on the basement membranes surrounding cancer cells, and positive fibrillar immunostaining for type IV collagen in the stroma of the carcinomatous parenchyma. Six of the 14 pancreatic cancer tissue samples also showed positive immunostaining for laminin in the stroma. The stromal type IV collagen with or without laminin in human pancreatic cancer tissues may have originated from basement membranes degraded through cancer invasion and proliferation.

Adult↗

Dysregulated expression of the IL-2 receptor beta-chain abrogates development of NK cells and Thy-1+ dendritic epidermal cells in transgenic mice.

The IL-2 receptor beta-chain (IL-2R beta), a specificity-determining subunit in the IL-2R complex with a restricted tissue distribution pattern, is essential for signal transduction. Our previous studies demonstrate that the continuous treatment of mice with anti-IL-2R beta resulted in the complete disappearance of NK cells and Thy-1+ dendritic epidermal cells (Thy-1+ dEC), suggesting that signals through IL-2R beta are critically involved in development of these lymphocyte subsets. However, these lymphocyte subsets are reported to be apparently unaffected in the IL-2-deficient mice. To further examine the biological roles of the IL-2R beta, transgenic mice carrying the IL-2R beta transgene were generated. In these mice, high levels of the cell surface expression of the IL-2R beta were observed in essentially all hematopoietic lineage cells, and CD4+ T cells as well as CD8+ T cells showed vigorous cell proliferation upon IL-2 stimulation. Surprisingly, NK cells marked with a high expression of NK1.1 in the spleen and Thy-1+ dEC in the skin were completely absent in transgenic mice. However, the development of other lymphocyte subsets including conventional alpha beta TCR+ cells, gamma delta TCR+ cells and B cells remained apparently intact. From these observations together with previous data on IL-2-deficient mice, we speculate that factors, other than IL-2 that utilizes the IL-2R beta as its functional receptor subunit, may have a vital role in the development of NK cells and Thy-1+ dEC. Implications for possible in vivo functions of over-expressed IL-2R beta are discussed.

Animals↗

Quantitative analysis of collagen and collagen subtypes I, III, and V in human pancreatic cancer, tumor-associated chronic pancreatitis, and alcoholic chronic pancreatitis.

The collagen content in human pancreatic cancer tissue, tissue of tumor-associated chronic pancreatitis (TACP), and normal pancreatic tissue was determined in 14 patients with pancreatic cancer by measuring the amount of 4-hydroxyproline. Four patients with alcoholic chronic pancreatitis (AlCP) were also analyzed. The mean collagen content in both pancreatic cancer tissue and TACP tissue was approximately threefold higher than in normal pancreatic tissue. Cyanogen bromide peptides of type I, III, and V collagens from invasive ductal carcinomatous tissue of the pancreas and from TACP tissue of eight patients were analyzed sequentially using high-performance liquid chromatography with ion-exchange and gel-permeation columns. No difference in the proportion of type I, III, and V collagens was detected between pancreatic cancer tissue and TACP tissue. The mean collagen content in AlCP tissue was significantly lower than that in TACP tissue, but no difference in the proportion of type I, III, and V collagens was detected between these two tissues. These results indicate a similar quantity and distribution pattern of fibrillar collagen in human pancreatic cancer and TACP.

Alcoholism↗

Low incidence of point mutations in H-, K- and N-ras oncogenes and p53 tumor suppressor gene in renal cell carcinoma and peritoneal mesothelioma of Wistar rats induced by ferric nitrilotriacetate.

An iron chelate, ferric nitrilotriacetate (Fe-NTA, induces renal proximal tubular damage, a consequence of iron-catalyzed free radical reactions, that finally leads to a high incidence of renal cell carcinoma (RCC) in rodents. Previous studies have identified, within 24 h after administration of Fe-NTA, lipid peroxidation products, aldehyde-modified proteins and a variety of modified DNA bases such as 8-hydroxyguanine that may be mutagenic in vivo. In the present study, pathological features of the RCCs were studied, and, in an effort to correlate them with carcinogen-specific molecular events in Fe-NTA-induced carcinogenesis, the H-, K- and N-ras oncogenes and the p53 tumor suppressor gene were investigated for the presence of mutations. Fe-NTA-induced RCCs showed similarity to human RCCs in that they are often invasive, metastatic and fatal. None (0 of 12) of the tumors had mutation in codons 12, 13 and 61 of the H-, K- and N-ras genes by direct sequencing. Only one (1 of 12) tumor with high grade histology revealed a CGC-to-CTC (Arg to Leu) transversion in codon 246 of the p53 gene by the use of single strand conformation polymorphism (SSCP) analysis and direct sequencing. High expression of mutant p53 protein was confirmed by Western blotting and immunohistochemistry. Study of three peritoneal mesotheliomas induced by Fe-NTA revealed no mutation in ras and p53 genes. These results suggest that the ras and p53 genes are not the major targets of mutation in Fe-NTA-induced carcinogenesis of kidney and mesothelium. Instead, p53 mutation may work for potentiation of malignant character in Fe-NTA-induced renal carcinogenesis.

Animals↗

Expression of multidrug resistance gene and localization of P-glycoprotein in human primary ovarian cancer.

Resistance to chemotherapy is the major obstacle to controlling malignant tumors. To characterize multidrug resistance phenotype in human primary ovarian cancer without chemotherapy, expressions of the mdr1 gene in 52 cases of ovarian cancer (44 common epithelial, 5 nonepithelial, and 3 metastatic cancers) were analyzed by polymerase chain reaction of RNA after reverse transcription. Furthermore, localization of P-glycoprotein, which is encoded by the mdr1 gene, was studied immunohistochemically. Although overall expression of the mdr1 gene was relatively low, its expression level was the highest in well-differentiated cancer tissues. Serous and mucinous adenocarcinomas showed higher levels of expression compared with clear cell and endometrioid carcinomas. P-glycoprotein was positive on luminal surfaces of lining cells of ovarian cancer and on those of inclusion cysts from which epithelial ovarian cancer is considered to develop. Thus, some ovarian cancer cases before chemotherapy are intrinsically multidrug resistant, which can be determined by mdr1 gene expression, and this phenotype should be taken into account for effective chemotherapy of ovarian epithelial carcinomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The significance of the cervical soft disc herniation in the ossification of the posterior longitudinal ligament.

The significance and role of cervical soft disc hernia in ossification of the posterior longitudinal ligament were investigated based on 54 surgical cases. The types of ossification of the posterior longitudinal ligament were divided into three sub-types: segmental, continuous, and mixed types. In the current series, there were 29 segmental type, 12 continuous type, and 13 mixed type. In the 29 segmental type, 23 patients had accompanying cervical disc hernias (79%). In the 12 continuous type, only 2 patients (17%), and in the 13 mixed type, 5 patients (33%), had accompanying disc hernias. According to the current study, an essential difference exists between the segmental type and the continuous or mixed types. In addition, the current result seems to indicate that, at least in the segmental type, disc herniation is not the promoting or initiating factor of ossification of the posterior longitudinal ligament, but that, in these cases, the fragility of the posterior longitudinal ligament may increase the chance of a disc hernia.

Adult↗

Immunohistochemical study of heparan sulfate proteoglycan in adenocarcinomas of the pancreas.

The prognosis for carcinoma of the pancreas is extremely poor. One of the characteristics of this tumor is its invasion of the surrounding tissues. Reduction of glycoprotein is considered to be conducive to invasion of the basement membrane by carcinoma cells. Heparan sulfate proteoglycan (HSPG), a kind of glycoprotein, is an important component of basement membrane. In this study, the relation between HSPG and carcinoma of the pancreas was examined by using the immunohistochemical method, and the survival rate of pancreatic adenocarcinoma was evaluated. We found that some carcinomas contained little or no HSPG. The poorer the differentiation of an adenocarcinoma of the pancreas, the lower was its content of HSPG. The level of HSPG was significantly different in carcinomatous and in noncarcinomatous cells. There was a close correlation among the content of HSPG, the degree of differentiation of carcinomas of the pancreas, and the survival time. HSPG seems to be useful in prognosis of adenocarcinoma of the pancreas.

Adenocarcinoma↗

K-ras and p53 alterations in genomic DNA and transcripts of human pancreatic adenocarcinoma cell lines.

We analyzed 15 human pancreatic adenocarcinoma cell lines for alterations of the K-ras and the p53 genes and their transcripts. In 11 cell lines (73.3%), point mutations of the K-ras gene were found at codon 12 in exon 1. In 9 cell lines one allele was mutated and the other was wild type, and both the alleles were expressed into mRNA. In one cell line both alleles of codon 12 were mutated to TGT and GTT, respectively, but only TGT was transcribed into mRNA. Alterations in mRNA of the p53 gene were detected in 10 cell lines (66.7%). Analysis of the genomic sequence of the p53 gene revealed that the alterations consisted of 6 cases of base pair substitutions and 1 case of 1-bp deletion in evolutionarily conserved exons 5 to 8, 2 cases of splicing mutations in exon 4, and 1 case of novel deletion from exons 2 to 9. In 14 cell lines (93.3%), alterations were identified in the K-ras or p53 gene. Of these, 4 cell lines harbored K-ras mutations without p53 alteration, whereas 3 cell lines exhibited p53 alterations without K-ras mutation. Thus, it is suggested that activation of the K-ras gene and inactivation of the p53 gene are strongly and cooperatively associated with pancreatic carcinogenesis.

Adenocarcinoma↗

Selective long-term elimination of natural killer cells in vivo by an anti-interleukin 2 receptor beta chain monoclonal antibody in mice.

The interleukin 2 receptor beta chain (IL-2R beta) is preferentially expressed in natural killer (NK) cells, but is not detected in a majority of resting T and B cells. We recently established a novel monoclonal antibody (mAb) to murine IL-2R beta and examined in vivo the effect of the mAb in mice. We found that intraperitoneal injection of the anti-IL-2R beta mAb into adult mice resulted in a selective in vivo elimination of splenic NK function in various mouse strains. The reduction of NK cell function is associated with complete disappearance of NK1.1+ cells in C57BL/6 mice. Other lymphocyte subsets in the thymus and spleen were uncompromised. T cell function was not affected by the mAb treatment as judged by allogeneic cytotoxic T cell induction. The single injection of anti-IL-2R beta mAb caused a long-term elimination of splenic NK cells, lasting for at least 5 wk. We also found that NK and/or NK precursor cells become susceptible to the mAb treatment only after birth, suggesting that functional maturation of NK cells in terms of IL-2R beta expression is a later event in the course of NK cell development. The use of the anti-IL-2R beta mAb will be useful in defining the physiological role of NK cells in host defense as well as dissecting their developmental pathway in vivo.

Animals↗

The role of the interleukin-2 (IL-2)/IL-2 receptor pathway in MRL/lpr lymphadenopathy: the expanded CD4-8- T cell subset completely lacks functional IL-2 receptors.

Autoimmune MRL/MP-lpr/lpr (MRL/lpr) mice spontaneously develop a systemic lupus erythematosus-like disease accompanied by a profound lymphadenopathy that consists of CD4-8-B220+ alpha beta T cells. By the use of cross-linking experiments with radiolabeled interleukin-2 (IL-2), these abnormal T cells have been reported to constitutively express the IL-2 receptor beta chain (IL-2R beta), a signal transducing component of IL-2R, in the absence of the alpha chain (IL-2R alpha). To critically reevaluate the role of the IL-2/IL-2R pathway in the pathogenesis of lymphadenopathy we examined expression of the IL-2R alpha and IL-2R beta in MRL/lpr mice by 125I-IL-2 binding analysis and also by flow cytometric analysis using monoclonal antibodies against each component of the receptor. We found that, contrary to the previous report, the CD4-8-B220+ alpha beta T cells in lymph node (LN) of MRL/lpr mice were negative for both IL-2R alpha and IL-2R beta expression. The lpr liver CD4-8-B220+ alpha beta T cells that had been implicated in the genesis of these abnormal LN T cells were also negative for IL-2R beta expression. Therefore, our results indicate that the IL-2/IL-2R system plays little role, if any, in the expansion of abnormal CD4-8-B220+ alpha beta T cells in MRL/lpr mice.

Animals↗

Nuclear DNA content as a prognostic predictor in carcinoma of the pancreas.

Eighty-six patients with carcinoma of the pancreas were studied retrospectively. Paraffin-embedded specimens and flow cytometry were used to evaluate the accuracy of the measurement of nuclear DNA as a predictor of the postoperative prognosis. From the series of 86 patients, 72 with a diagnosis of tubular adenocarcinoma (Japanese classification) were selected, and their DNA ploidy pattern and clinical and pathological features were correlated; 52.3% of the 86 patients and 52.8% of the 72 tubular adenocarcinoma patients showed DNA aneuploidy. Histological examinations of the tubular adenocarcinomas showed 42.9% DNA aneuploidy in well differentiated, 56.8% in moderately differentiated, and 71.4% in poorly differentiated types. The DNA ploidy showed a statistically significant positive correlation with the T category. The presence or absence of retroperitoneal invasion was thought to be the most important prognostic factor. Cumulative survival rates showed that the prognosis for patients with retroperitoneal invasion and DNA aneuploidy was significantly worse than for those with DNA diploidy or those without retroperitoneal invasion.

Adenocarcinoma↗

Effect of synthetic protease inhibitor on histologic changes and free radical activity in hamsters with pancreatic cancer.

To investigate the effects of synthetic trypsin inhibitors on pancreatic cancer, camostat (FOY-305) was administered orally to hamsters with experimental pancreatic cancer induced by diisopropanol nitrosamine (DIPN). The effect of free radicals on carcinogenesis was examined by measuring the tissue levels of the scavengers superoxide dismutase (SOD) and glutathione peroxidase (GSX-Px), and pancreatic tissues were examined histologically. Cancers developed in all hamsters that survived 24 weeks in the DIPN group and the FOY group, but 80% of the cancers in the DIPN group were tubular adenocarcinomas, and 91% of those in the FOY group papillary adenocarcinomas. The SOD activity in the DIPN group was significantly lower in the cancerous area and the borderline region than in the non-cancerous region and normal tissue. SOD activity in the cancerous and borderline regions was higher in the FOY groups than in the DIPN group. GSH-Px levels in the borderline and non-cancerous regions were significantly higher in the FOY group than in the DIPN group. These results suggest that the synthetic protease inhibitor slows the progress of pancreatic cancer by its free radical scavenging activity.

Adenocarcinoma↗

Thoracic mobile neurinoma. Case report.

The authors report a rare case of intraspinal thoracic mobile neurinoma in a 51-year-old man. The clinical symptoms, especially thoracoabdominal discomfort, changed remarkably according to the patient's posture. Magnetic resonance images demonstrated that the level of the caudal end of the tumor varied between T4-5 and T9-10 with changes in the patient's position. Intraoperative myelography was useful in identifying the tumor location and choosing the level of the laminectomy.

Humans↗

[Long-term follow up of trigeminal neuralgic patients treated by retrogasserian rhizotomy or by microvascular decompression].

The authors studied the long-term follow up of trigeminal neuralgic patients treated by retrogasserian rhizotomy with anhydrous glycerol injection (GI) or by microvascular decompression (MVD) and compared the satisfaction rates between them. Since 1983, 67 patients had been treated either by GI or MVD. The authors analyzed the results of the treatment by the method of questionnaire. Fifty-two patients of these 67 answered the questions, on which the present analysis was based. GI group consisted of 27 patients and MVD group 29 patients. The average follow-up period was 30.9 months in GI group (maximum follow-up: 84 months) and 50.9 months in MVD group (maximum follow-up: 95 months), respectively. The technique of GI used was Härtel's method with cisternography of Meckel's cave. The operations of MVD were performed by J.H. and A.K.. One patient out of 29 failed to be treated by MVD and two recurred within one year. On the other hand, 2 patients out of 27 failed to be treated by GI and 11 recurred. The recurrence was seen earlier in patients who had undergone GI, while one patient recurred the neuralgia at 76 months later. The recurrence rate in patients treated by MVD is 7.0% at 95 months, while that by GI is 49.0% at 84 months based on Kaplan-Meier survival analysis. The pathogenesis of trigeminal neuralgia is speculated to be an emphatic conduction caused by segmental demyelination and artificial synapse formation at the junction of central and peripheral myelin. The factors of this demyelination may be multiple sclerosis, basilar impression, aneurysm, arteriovenous malformation, atheroscleroses and natural aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Dumbbell cervical neurinomas with subcutaneous extension: report of two cases].

Two cases of dumbbell cervical neurinomas with massive subcutaneous extension were reported. The first case was A 30-year-old woman who was admitted to our hospital because she had been aware of a left lateral cervical subcutaneous mass and was suffering from shoulder dullness. On admission, neurological examination revealed hypesthesia to touch and pain in the segmental area of C4, and hyperreflexia in the left biceps and patellar tendon reflexes. Plain X-ray showed enlargement of the left C3/4 intervertebral foramen. CT scan, post-myelogram CT and MRI demonstrated a dumbbell shaped tumor at the level of C3-4. Angiogram showed an anterior shift of the left vertebral artery (VA) and tumor stain. Temporary occlusion of the left VA by a balloon catheter was performed leaving no neurological deficits. The second case was a 36-year-old woman who had been aware of a left lateral cervical subcutaneous mass. She complained of shoulder pain and finger clumsiness. On admission, neurological examination revealed weakness of the left deltoid muscle, hypesthesia in the segmental area of C3-4 and exaggeration of all deep tendon reflexes in the left-side extremities. Plain X-ray showed enlargement of the C2/3, C3/4 and C4/5 intervertebral foramina. CT scan, post myelogram CT and MRI demonstrated a dumbbell shaped tumor at the level of C2-5. Angiogram showed an anteromedial shift of the left VA and tumor stain. Temporary occlusion test of the left VA by a balloon catheter was performed with negative results. In each case two-stage operations were undertaken with excellent results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗