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Biomedical subjects

S Koyama

Publications and source records attributed to S Koyama.

At least 163 records · Page 9Linked to original sources

Effect of protamine on cation-selective permeability in hamster medullary thick ascending limb of Henle's loop.

To estimate the contribution of the paracellular shunt pathway to cation-selective permeability in the hamster medullary thick ascending limb of Henle's loop, we observed the effect of protamine, a selective blocker of paracellular conductance, on salt-diffusion voltage (dVT) in the isolated nephron segment perfused in vitro. When 300 microg/ml protamine was added to the lumen, the lumen-positive dVT generated upon reduction of the lumen NaCl concentration was decreased from 5.1 +/- 0.9 to 0.8 +/- 0.8 mV and the calculated Na+/Cl- permeability ratio was decreased from 1.40 +/- 0.14 to 0.86 +/- 0.08. Although the effect of protamine persisted after removal of the agent from the lumen, addition of 30 U/ml heparin, which neutralizes protamine, returned the dVT toward the control level. This effect was almost the same when the orientation of the imposed NaCl gradient was reversed. Protamine exhibited a similar effect on dVT in the presence of ouabain added to the bath. Protamine was without effect from the bath. Protamine did not affect the basel VT perfused with the control solution. Increased VT by decreasing perfusion pressure was inhibited by adding protamine from the lumen. These observations suggest that the paracellular pathway contributes to the cation selectivity of the medullary thick ascending limb. The cation selectivity of the paracellular shunt pathway may mainly account for the changes in VT which are either dependent on the luminal flow rate or transmural NaCl concentration gradient, while it may not contribute to the basal level of VT.

Animals↗

Elevated serum CA19-9 level and regional lymphadenopathy in a young man with allergic bronchopulmonary aspergillosis.

A 21-year-old man with bronchial asthma who suffered from productive cough; his chest X-rays and computed tomographic (CT) scans revealed central atelectasis and pulmonary infiltrates with paratracheal and hilar lymphadenopathy. The serum CA19-9 level was elevated. He was suspected to have malignant neoplasms on admission, but he was diagnosed with allergic bronchopulmonary aspergillosis (ABPA) by Rosenberg's criteria. After steroid therapy, his symptoms and radiographic findings improved and the serum CA19-9 level decreased. ABPA should be considered in the differential diagnosis of asthmatic patients with or without lymphadenopathy and an elevated serum CA19-9 level.

Adult↗

[Facial nerve anomalies of children with congenital anomalies].

It is well known that congenital anomalies are often associated with malformation of the inner, middle and external ear. In temporal bone studies, it has been found that abnormality of the facial nerve often occurs in patients with congenital aberrations. The temporal bone collections of the Teikyo University School of Medicine include 32 human temporal bones obtained from 19 infants ranging in age from one day to 7 months, who had chromosomal aberration and severe visceral anomalies. We histologically studied routinely processed sections of these temporal bones under a light microscope. Facial anomaly was observed in 20 of the 32 ears (63%). An abnormal course was observed in 18 ears (56%); 5 ears showed hypoplastic development, 4 showed displacement of geniculate ganglion cells into the internal auditory meatus, and 3 ears showed bifurcation. Abnormal course of the facial nerve was found in a significant number of ears with aural and mandibulal abnormalities (76%). However patients with multiple inner ear anomalies showed an abnormal course and hypoplasia of the facial nerve. There was no correlation between the incidence of facial abnormalities and inner ear anomalies.

Abnormalities, Multiple↗

[Bickerstaff's brainstem encephalitis with one-and-a-half syndrome].

We presented a case of Bickerstaff's brainstem encephalitis. A 50-year-old woman developed semicoma, external ophthalmoplegia, hyporeflexia, extensor plantar responses. A high titer of anti-GQ1b IgG antibody was detected in her acute phase serum. Auditory brainstem response suggested the presence of brainstem lesion. Although MRI and CSF showed no abnormality, one-and-a-half syndrome was observed during the clinical course, suggesting involvement of the pontine tegmentum. She received steroid pulse-therapy and symptoms disappeared completely. Our case suggested that anti-GQ1b IgG antibody might relate to the pathogenesis of intramedullary as well as extramedullary lesions.

Biomarkers↗

[A comparison of the incidence of postoperative nausea and vomiting after propofol-fentanyl anesthesia and that after nitrous oxide-isoflurane anesthesia].

We compared the incidence of postoperative nausea and vomiting after total intravenous propofol-fentanyl anesthesia (TIVA group) and that after thiamylal-nitrous oxide-isoflurane anesthesia (GOI group) in 60 ASA physical I and II patients for elective abdominal simple total hysterectomy. When the patients returned to the ward, the incidence of nausea was lower in TIVA group than in GOI group (P < 0.05), but no difference was found in the incidence of vomiting between the two groups. There were no differences in the incidence of nausea and vomiting 6 hours after the operation and on the next morning between the two groups. Postoperative pain scores were similar between the two groups, while total postoperative evaluation scores (nausea, vomiting, pain, fever, and sleep disturbance) were lower in TIVA group (P < 0.05). We conclude that TIVA with propofol-fentanyl reduced the incidence of nausea and improved total evaluation scores in the immediate postoperative period.

Adult↗

Visual evoked magnetic responses to central and peripheral stimulation: simultaneous VEP recordings.

Visual evoked magnetic field (VEF) and visual evoked potentials (VEP) in response to pattern reversal left half-field central (0-2 degrees, 0-5 degrees) and to left half-field peripheral stimulation (2-15 degrees, 5-15 degrees) were simultaneously recorded in 10 normal subjects. The aim was to localize the origin of the largest wave around 100 ms. By comparing the magnetic evoked 100m wave and electric evoked P100 wave, we found that the response to the small central field (0-2 degrees) stimulation was clearly evident in the VEP and not in the VEF, while the response to the peripheral field (2-15 degrees, 5-15 degrees) stimulation was clearly present in both the VEP and VEF. Our findings show that in contrast to the already recognized predominantly macular origin of VEP activity, VEF activity has a peripheral rather than macular prevalence. Our VEF findings are related to the retinotopic organization of the visual cortex; the 100m dipole to the central field (0-5 degrees) was localized more (1.04 +/- 0.84 cm) posterior than was the 100m dipole to peripheral stimulation (5-15 degrees). The localization of 100m dipoles superimposed on magnetic resonance images (MRI) to central stimuli showed interindividual variations that were in agreement with the known variability of the central field representation in the striate cortex: on the convexity of the occipital pole, in the outer surface of the occipital lobe, and around the calcarine fissure of the right hemisphere. In contrast, following peripheral stimulation, the 100m dipole was located along the medial surface of the hemisphere or in the calcarine fissure. Our results suggest that the main origin of the largest wave around l00ms in response to pattern reversal stimuli is in the striate cortex.

Adult↗

[A case of hepatocellular carcinoma with reduction of primary tumor and disappearance of multiple lung metastasis].

A 56-year-old male had suffered from hepatocellular carcinoma treated by operation, PHoT and TAE since 1994. In December 1995, he had multiple metastases of lung in addition to recurrence of primary hepatic lesions. We discontinued treatment of TAE and decided to administer UFT (400 mg/day) orally as an outpatient. After seven months, the primary hepatic lesions were decreased in size, and metastatic lesions of lung were completely eliminated with reduction of AFP level. Generally, hepatocellular carcinoma with metastasis is refractory to treatment. However, this result suggests that UFT is one of the effective treatments for such advanced cases as having lung metastasis.

Administration, Oral↗

Cochlear neuronal loss are determined by use of a neurofilament protein antibody in cases of bilateral profound deafness.

The temporal bones of two patients with profound bilateral deafness from infancy were studied immunohistochemically, using a neurofilament protein antibody to detect the cochlear neuronal elements. One patient exhibited Mondini dysplasia of the inner ear, with the organ of Corti almost completely deteriorated. The other patient is the first reported case involving complete aplasia of the organ of Corti in all turns. In both cases, the immunohistochemical staining clearly revealed a severe reduction in the number of afferent neurons, such as dendrites, spiral ganglion cells and cochlear axons. The number of efferent spiral bundles in the osseous spiral lamina and intraganglionic portion also decreased in parallel with the reduction in the number of cochlear afferent neurons. Our results are inconsistent with previously reported cases of presbycusis and acquired deafness induced by the measles virus, in which efferent neurons were preserved while afferent neurons degenerated. The loss of both the efferent and afferent neurons might be characteristics of congenital deafness.

Aged↗

[Small cell lung cancer associated with subacute sensori-motor neuropathy in a patient whose symptoms subsided during chemotherapy].

A 71-year-old man was referred to us with diplopia, left peripheral facial nerve dysfunction, ataxic gait and dysesthesia of the extremities. Neurological examination revealed mild reduction of sensation to pinprick and light touch in the left dominant lower leg. His standing position was wide based, and he showed Romberg's sign. The patient also presented signs of left peripheral facial, bilateral abducent, and left oculomotor nerve dysfunction. Serum levels of CEA, CA 19-9, and proGRP were high. 67Gallium scintigraphy showed an accumulation of radioactivity at the hilum of the right lung, and the findings of bronchofiberscopy were compatible with the diagnosis of small cell lung cancer. Because the symptoms gradually worsened to the point that the patient could not move by himself, chemotherapy and radiotherapy were initiated 3 months after the onset of symptoms. While under chemotherapy, symptoms of neuropathy subsided and the patient was able to walk with the aid of a walking stick. Although all symptoms were indicative of carcinomatous neuropathy, no antineuronal antibodies were detected in the patient's serum by immunohistochemical techniques. However, because the lung cancer deteriorated gradually despite therapy, the patient died of respiratory failure. At autopsy, tumor metastases were found in the pericardium, left lung, both adrenal glands, right hilum lymph nodes, and mediasternal lymph nodes. No microscopic signs of metastases were found in the frontal, parietal, temporal, or occipital lobes, or in the basal ganglia, thalamus, midbrain, pons, cerebellar vermis and hemispheres, or upper medulla. Histopathologically, there was no degeneration of neuronal cell bodies in cerebellar or cervical dorsal root ganglia; however, almost total loss of myelinated fibers or variegated demyelination of myelinated fibers was observed in the anterior, lateral and posterior funiculus at both cervical segments of the spinal cord. The number of myelinated fibers was smaller in the 5th and 6th cervical left ventral roots. The reason why the patient's symptoms subsided during chemotherapy was probably a suppression of antineuronal antigen by chemotherapy and the repair of myelinated fibers.

Aged↗

Colocalization of Ras and Ral on the membrane is required for Ras-dependent Ral activation through Ral GDP dissociation stimulator.

Ral GDP dissociation stimulator (RalGDS), a putative effector protein of Ras, stimulated the GDP/GTP exchange reaction of the post-tanslationally lipid-modified but not the unmodified form of Ral in response to epidermal growth factor in COS cells. The RalGDS action on Ral was enhanced by an active form of Ras but not a Ras mutant which was not post-translationally modified in the cells. The RalGDS activity was inhibited by acidic membrane phospholipids such as phosphatidylinositol and phosphatidylserine but not by phosphatidylcholine or phosphatidylethanolamine in vitro. The post-translationally modified form but not unmodified form of Ras, Ral, and Rap were incorporated in liposomes consisting of these phospholipids. When Ral was incorporated alone in the liposomes, RalGDS did not stimulate the dissociation of GDP from Ral. When Ral was incorporated with the GTP-bound form of Ras in the liposomes, RalGDS stimulated the dissociation of GDP from Ral, while the GDP-bound form of Ras did not affect the RalGDS action. The Ras-dependent Ral activation through RalGDS required the Ras-binding domain of RalGDS. Rap, which shared the same effector loop as Ras, also stimulated the dissociation of GDP from Ral through RalGDS in the liposomes, although Rap did not enhance the RalGDS action in COS cells. Taken together with our previous observations that Ras recruits RalGDS to the membrane, these results indicate that the post-translational modifications of Ras and Ral are important for Ras-dependent Ral activation through RalGDS and that colocalization of Ras and Ral on the membrane is necessary for Ral activation in intact cells.

Animals↗

The post-translational modifications of Ral and Rac1 are important for the action of Ral-binding protein 1, a putative effector protein of Ral.

Ral-binding protein 1 (RalBP1) is a putative effector protein of Ral and possesses the GTPase-activating activity for Rac1 and CDC42. We examined the roles of the post-translational modifications of Ral and Rac1 for the action of RalBP1. In COS cells, Ral(G23V), a constitutively active form, was mainly detected in the membrane fraction while most of Ral(G23V/C203S), a Ral mutant which is not post-translationally modified, was found in the cytosol fraction. When RalBP1 was expressed alone in COS cells, it was found in the cytosol but not in the membrane fraction. When RalBP1 was coexpressed with Ral(G23V), a part of RalBP1 was found in the membrane fraction. However, when RalBP1 was coexpressed with Ral(G23V/C203S), all of RalBP1 was recovered in the cytosol fraction. Although Ral bound to RalBP1 at a molar ratio of 1:1, the interaction of Ral with RalBP1 did not affect the GTPase-activating activity of RalBP1 for Rac1. Furthermore, RalBP1 was more active on the post-translationally modified form of Rac1 and CDC42 than the unmodified form. These results suggest that the post-translational modification of Ral is important for the subcellular localization of RalBP1 and that the interaction of Ral with RalBP1 is not essential for the activity of RalBP1 but plays a role in recruiting RalBP1 to the membrane where its substrates, Rac1 and CDC42, reside.

Animals↗

Pain-related somatosensory evoked magnetic fields following lower limb stimulation.

Somatosensory evoked magnetic fields (SEFs) following painful electrical stimulation of the sural nerve were examined in 6 normal subjects. Equivalent current dipoles (ECDs) of the deflections shorter than 100 ms in latency were located in the foot area of the primary sensory cortex (SI) in the contralateral hemisphere following both weak and painful stimulations. Two main deflections, N150m-P150m and N250m-P250m, were independently identified only following painful stimulation. ECDs of the N150m-P150m were considered to be located in bilateral second sensory cortices (SII). ECDs of the N250m-P250m were identified in multiple areas including bilateral cingulate cortices and SII. These findings were consistent with the pain-related SEFs following upper limb stimulation. Therefore, we considered that bilateral SII and the cingulate cortices were activated by the painful stimulation and that pain-specific brain activities in those areas did not depend on the stimulation site.

Adult↗

Human cortical area responding to stimuli in apparent motion.

Apparent motion is the perception of the realistic smooth motion of an object which flashes first at one place then at another. To investigate human cortical responses to stimuli in apparent motion, we used a multichannel biomagnetometer to record the magnetic fields evoked by these stimuli in four normal subjects. The results showed the presence of a localized cortical area exclusively sensitive to apparent motion stimuli that is identical to that for smooth motion. In three subjects this area corresponded to the human homologue of MT/V5. Moreover, the same region in the extrastriate cortex was involved in the short range (0.1 degree) apparent motion process as well as the long range (1.0 degree) process.

Adult↗

Augmented human-tumor-cytolytic activity of peripheral blood lymphocytes and cells from a mixed lymphocyte/tumor culture activated by interleukin-12 plus interleukin-2, and the phenotypic characterization of the cells in patients with advanced carcinoma.

In this study, we evaluated the ability of combination regimens of interleukin-12 (IL-12) and interleukin-2 (IL-2) to induce effective killer cells against human tumors in vitro, in peripheral blood lymphocytes (PBL) from 15 cancer patients and mixed lymphocyte/tumor culture (MLTC) cells from 16 cancer patients, and carried out a phenotypic analysis of the cells responsible for the lysis of the human tumors. The freshly prepared PBL were cultivated with IL-2 alone or IL-12/IL-2 for 10 days [lymphokine-activated killer (LAK) cell generation system]. The MLTC cells (PBL cultured with mitomycin-C-treated allogeneic G-415 tumor cells for 3 days) were further cultivated with IL-2 or IL-12/IL-2 for 7 days [cytotoxic T lymphocytes (CTL) generation system]. The cytolytic activities of the lymphoid cells cultivated with IL-12/IL-2 were significantly augmented in both the LAK and CTL generation systems, as compared with those of cells treated with IL-2 alone. In the LAK generation system, the cytolytic activities of the cells cultivated with IL-12/IL-2 were significantly decreased by the method of negative selection of CD11b- or CD56+ cells using immunomagnetic beads. The CD8(+)-depleted cells showed a slight decrease of activity. The killer cell activities of the CD4(+)-depleted cells remained unchanged. In the CTL generation system, the activity was markedly reduced by the elimination of the CD8+ or CD11b+ or CD56+ cells. The combined data suggested that IL-12/IL-2-induced killer effector cells in the LAK generation system were mainly of the natural killer (NK) type, comprising CD8-CD11b+, CD8- CD16b+, CD3-CD56+, and partly possible CD8+ CD11b- T cells. CD8+ CD11b- T cells mixed with cells of the NK type, comprising CD8-CD11b+, CD8- CD16b+ and CD3-CD56+ cells, were the population of killer effector cells induced by IL-12/IL-2 in the CTL generation system.

Aged↗

Transforming growth factor-alpha (TGF alpha)-producing gastric carcinoma with acanthosis nigricans: an endocrine effect of TGF alpha in the pathogenesis of cutaneous paraneoplastic syndrome and epithelial hyperplasia of the esophagus.

A case of well-differentiated adenocarcinoma (Borrmann type 3) of the stomach in a 76-year-old man associated with the typical skin manifestations of acanthosis nigricans and with multiple protruding lesions showing epithelial hyperplasia of the esophagus is reported. The advanced tumor was located in the cardiac region of the stomach, and measured approximately 8 cm in diameter, with partial invasion to the esophagus. The associated cutaneous lesions were characterized by hyperpigmentation and by protruding verrucous papules on the torso, head, face, neck, upper extremities, perineum, and inguinal region. Histologically, the protruding skin lesions showed keratinocytes proliferation throughout the epidermis, resulting in diffuse hyperkeratosis, papillomatosis, and acanthosis of the skin. Immunohistological analysis showed coexpression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) receptors in the tumor from the stomach. It is reasonable to conclude from this evidence that gastric carcinoma cells secrete TGF alpha in an autocrine for auto-stimulation. EGF receptor expression was also noted on the papillomatous hyperplasia of the cutaneous lesion. Serum level of TGF alpha, determined by an enzyme-linked immunosorbent assay, was high (144 pg/ml; normal, 22.0 +/- 16 pg/ml (Mean +/- SD)). Serum TGF alpha abruptly decreased to 49 pg/ml on day 7 after the total gastrectomy, and then gradually increased to 77 pg/ml within 28 days. Amelioration of the cutaneous lesions and the protruding lesions in the esophagus was observed after surgical resection of the gastric carcinoma. This suggests that the TGF alpha stimulates the proliferation of keratinocytes involved with EGF receptor. Large amounts of circulating TGF alpha in the blood over a long period released by the primary tumor seem to act as an endocrine-like mechanism causing epidermal and esophageal epithelial cells to proliferate. There is a possible link in the pathogenesis of the acanthosis nigricans as a cutaneous paraneoplastic syndrome, and epithelial hyperplasia of the esophagus.

Acanthosis Nigricans↗