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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 235 records · Page 13Linked to original sources

Hyaluronan activates mitogen-activated protein kinase via Ras-signaling pathway.

Hyaluronan (HA) triggers a wide variety of cellular functions, yet its signaling pathway remains largely unclear. We found that HA-treatment of 3Y1 cells activated tyrosine phosphorylation of cellular proteins and mitogen-activated protein (MAP) kinase in a time- and dose-dependent manner, and, subsequently, stimulated cell growth. This HA-activity was resistant to boiling at 100 degrees C but completely abolished by treatment with hyaluronidase, suggesting that HA itself, but not any HA-associated proteins, has the activity. In addition, we found that HA-dependent activation of MAP kinase was strongly suppressed by the expression of dominant negative ras (S17N ras). These results suggest that Ras-MAP kinase pathway is activated by HA and may play an important role in HA-dependent signaling.

Adjuvants, Immunologic↗

[A 96-year-old man with consciousness disturbance, convulsion, and left hemiplegia of acute onset].

We report a 96-year-old Japanese man who developed a sudden onset of left hemiplegia and coma. He was found to have diabetes mellitus, hypertension, and atrial fibrillation since 1996 with occasional episodes of congestive heart failure. He was otherwise apparently well until July 5 of 1997 when he developed a sudden onset of unresponsiveness and convulsion involving his right hand and was admitted to our hospital. On admission, his BP was 210/120 mmHg, heart rate 76/min and irregular, BT 36.5 degrees C, and Cheyne-Stokes respiration. General medical examination was otherwise unremarkable. Neurologic examination revealed semicoma, conjugated deviation to the right, loss of oculocephalic response, left facial paresis of central type, flaccid left hemiplegia, and bilateral Babinski sign. Pertinent laboratory findings are as follows: BUN 47 mg/dl, creatinine 1.46 mg/dl, GPT 69 IU/l, LDH 1,142 IU/l, and CK 385 IU/l. A chest x-ray film revealed cardiac enlargement and EKG showed left ventricular hypertrophy and atrial fibrillation. Cranial CT scan revealed low density areas involving the right anterior cerebral and the right posterior cerebral artery territories. He was treated with an intravenous osmotic agent and short course of intramuscular steroid. He remained unconscious despite these treatment and developed sudden cardiopulmonary arrest three weeks after the admission. The patient was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had suffered from cerebral embolism of cardiac origin. The cause of the death was ascribed to acute subendocardial myocardial infarction. Most of the participants agreed with this conclusion. Postmortem examination revealed an old subendocardial myocardial infarction involving the posterior septal region and posterolateral wall of the left ventricle. Neuropathologic examination revealed hemorrhagic infarctions involving the territories of the right anterior cerebral, right middle cerebral, right posterior cerebral, and left anterior cerebral arteries. The left A1 portion of the anterior cerebral artery was hypoplastic, and the left pericallosal artery appeared to have been receiving blood supply from the right anterior cerebral artery through the anterior communicating artery. The large arteries in the base showed marked arteriosclerosis; particularly, the initial portion of the right posterior artery showed near complete arteriosclerotic occlusions. These characteristic arterial changes appeared to be the reason why this patient suffered from an extensive infarction from what appeared to have been a single episode of cerebral embolism probably initially involving the right internal carotid artery.

Aged↗

[Molecular mechanism of apoptosis].

Apoptosis is a cell death process morphologically distinct from necrosis. Cells undergoing apoptosis shrink, the plasma membrane forms blebs, and the nucleus condenses. The nuclear DNA is degraded into oligonucleosomal fragments. Apoptosis plays regulatory and protective roles by eliminating unnecessary and dangerous cells, respectively. Many factors involved in apoptosis have been identified, their roles and interactions being understood at the molecular level. The bcl-2 family regulates apoptosis, and its members are classified into two groups: anti-apoptotic that inhibits apoptosis and pro-apoptotic that induces or accelerates it. The members form dimers to inactivate each other. Caspases cleave other members of the caspase family to activate their proteolytic activity in a cascade-like fashion, and the final target proteins prosecute apoptosis. In the case of Fas or tumor necrosis factor receptors, apoptotic signals are transmitted to the caspases via protein-protein interactions, whereas in other cases they originate from mitochondria. In the early process of apoptosis, cytochrome c, which usually is involved in the respiratory chain, is released from mitochondria into the cytosol, then bind to Apaf-1, a homologue of CED-4 of nematoda, to process pro-caspase-9. The resulting activated caspase-9 cleaves pro-caspase-3 into an activated form, which is responsible for the later process of apoptosis.

Apoptosis↗

[A 40-year-old woman with progressive dementia and abnormal behavior].

We report a 40-year-old Japanese woman who died after 12 years history of progressive dementia and abnormal behaviors. She was well until 1985 at her age of 28 years old, when she had an onset of behavioral change in which she drank much, neglected house-keeping works, and her life style became sloppy. At age 30, she became unable to understand written sentences, and paced up- and down in and out of her house. She was admitted to other hospital where marked dementia with disorientation and memory loss were noted. Slight increase in CSF protein and decrease in the peripheral nerve conduction velocity were also noted at that time. In the next year, she started to have convulsions. These symptoms had progressively become worse and was admitted to Tokyo Metropolital Matsuzawa Hospital in June of 1991 when she was 34 years of age. Despite marked dementia, she was able to walk normally, no motor paralysis, cerebellar ataxia, nor dyskinesia were noted. Deep tendon reflexes were diminished. MRI revealed T-2 high signal intensity lesions involving the white matter of the cerebrum predominantly in the frontal region. In about one year, she started to show difficulty in gait, and she became bed-ridden in July of 1994. She was discharged to home for a while, but required admission again. She expired on February 5, 1998. Her younger brother had an essentially similar dementing disease and he expired at the age of 35 years. The parents were of first cousins. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had adult form of metachromatic leukodystrophy, because of white matter change in the frontal lobe, decrease in nerve conduction velocity, convulsion, marked dementia, and consanguineous marriage with a similarly affected brother. Most of the audience agreed with this conclusion, but the differential diagnosis from globoid cell leukodystrophy was felt difficult from the clinical findings alone. Post-mortem examination revealed marked atrophy in the frontal lobe. Cerebellum appeared to be smaller than normal. In the coronal sections, marked atrophy of the white matter with brown discoloration was noted. The lateral ventricles were dilated. Klüver-Barrera staining revealed marked demyelination with relative preservation of the U-fibers. PAS-positive materials were deposited in some astrocytes as well as neurons. Metachromatic deposits were noted not only in the cerebrum but also cerebllum after staining with acid cresyl violet. Pathologic diagnosis was consistent with adult type of metachromatic leukodystrophy.

Adult↗

Factors influencing late survival after abdominal aortic aneurysm repair in Japanese patients.

BACKGROUND: To determine the factors influencing the prognosis of patients with abdominal aortic aneurysms (AAA), the clinical characteristics and long-term survival of 366 consecutive patients were examined and compared with those in previous Western studies. METHODS: During the period from January 1979 to December 1995, 376 patients with AAA were admitted to our hospital. Among these, 332 consecutive patients underwent elective reconstruction of infrarenal AAAs. The remaining 44 patients were not surgically treated. With use of the data from the patients who underwent AAA resection, the relationship of various risk factors, such as cardiac dysfunction, hypertension, renal dysfunction, pulmonary dysfunction, and age, to survival rate was investigated by univariate and multivariate analysis. RESULTS: The operative mortality rate was 0.6%. The survival of the patients who underwent the operation at 5 years was 71.0% and at 10 years 51.8%. The survival rate of the patients who were not surgically treated at 5 years was 26.0% and at 10 years 14.9%. There was a significant difference between the 2 groups. A univariate analysis was performed on each possible risk factor affecting survival rates. In relation to the survival rate of 5 and 10 years, there was no statistical significant difference between patients with or without heart disease or hypertension. By contrast, factors influencing long-term survival were associated with renal dysfunction, pulmonary dysfunction, and age at time of surgery. Multivariate analysis of risk factors affecting survival rates demonstrated that renal dysfunction, pulmonary dysfunction, and age at the time of operation were found to be significant, respectively. The main cause of the death for the long-term survival patients with AAA repair was malignancy, whereas that in the patients without repair was rupture. CONCLUSIONS: Risk factors influencing survival after AAA repair were renal dysfunction, pulmonary dysfunction, and advanced age in Japanese patients. In addition, the main cause of death after aneurysmal resection was malignancy. These results were different from outcomes in Western patients. We need to carefully watch out for malignancy during the follow-up period after AAA resection.

Aged↗

Ligation of CD40 induced tumor necrosis factor-alpha in rheumatoid arthritis: a novel mechanism of activation of synoviocytes.

OBJECTIVE: To determine the immunopathological significance of CD40/CD40 ligand (CD40L) interaction in rheumatoid arthritis (RA). METHODS: The expression of CD40 ligand (CD40L) in synovial tissues (ST) from patients with RA was examined by immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) was measured by ELISA. Expression of CD40 on ST cells was quantified by anti-CD40 monoclonal antibodies and 125I labelled anti-mouse IgG. RESULTS: Immunohistochemistry showed CD40L+ T cells in RA ST. Ligation of CD40 on RA ST cells significantly increased the production of TNF-alpha in a dose dependent fashion. Adherent, but not non-adherent, fraction of ST cells responded to ligation of CD40 to produce TNF-alpha. Interferon-gamma (IFN-gamma), interleukin 4 (IL-4), or IL-13 acted synergistically with CD40 ligation to enhance TNF-alpha production by ST cells. IL-10 exerted inhibitory effects on both CD40 ligation induced and CD40 ligation plus IFN-gamma induced TNF-alpha production by ST cells. CONCLUSION: These data indicate activated T cells participate in synovial inflammation of RA via CD40L to stimulate the production of TNF-alpha by ST cells. The effect of CD40 ligation is modulated by the presence of several cytokines, e.g., IFN-gamma, IL-4, IL-10, and IL-13.

Arthritis, Rheumatoid↗

[Intracerebral hemorrhage associated with long-lasting deficiency of factor XIII].

A 5-year-old boy had an intracerebral hematoma evacuated from the left parieto-occipital region at a local hospital. There was a difficulty in hemostasis during the operation. Postoperatively his neurological state gradually deteriorated. CT scans showed a gradual increase in intracerebral hemorrhage at the operated site. He was transferred to our clinic for further treatment. The preoperative blood coagulation profile showed that the activity of factor XIII was only 4%. The hematoma was removed without any trouble under administration of factor XIII. Postoperative course was also uneventful although the plasma level of factor XIII did not go up higher than 26% in spite of its daily administration. Although factor XIII administration was terminated one month after cranioplasty, the patient showed good recovery and the level of factor XIII spontaneously normalized in 6 months. The cause of the extremely low level of factor XIII in this case is not known, but it could be ascribed to massive hemorrhage.

Cerebral Hemorrhage↗

Reductive metabolism In vivo of trans-4-phenyl-3-buten-2-one in rats and dogs.

The reductive metabolism in vivo of a flavoring additive, trans-4-phenyl-3-buten-2-one (PBO; trans-methyl styryl ketone) was investigated in rats and dogs. In both species, the double bond-reduced product, 4-phenyl-2-butanone (PBA), was detected by HPLC as the predominant species in blood after i.v. administration of PBO. PBA detected in rat blood was identified by comparison to the authentic sample. In contrast, the carbonyl-reduced product, trans-4-phenyl-3-buten-2-ol (PBOL) was also detected as a minor metabolite of PBO in both species. The area under the curve of PBOL in rat blood was only 3% of that of PBA. PBO was mutagenic in the Ames test using Salmonella typhimurium TA 100 when S-9 mix was added, but PBA and PBOL were not. It appears that PBO is mainly metabolized to PBA in vivo in rats and dogs as a detoxification pathway.

Animals↗

[A case of Behçet's disease presenting cerebral infarction due to occlusions of the bilateral internal carotid arteries].

This is a case report of a 41-year-old man with Behçet's disease who suffered from cerebral infarction due to complete occlusions of the bilateral internal carotid arteries. His illness began at age 23 with blurred vision of the right eye. The last few years he complained of recurrent painful ulcers on the mucosa or skin of the mouth and the external genitalia. In August 1998, he was admitted to our hospital in an acute confusional state with right hemiplegia. Head CT scans and MRIs revealed acute and subacute ischemic lesions in the left frontal lobe and some other regions of the bilateral hemispheres. Carotid angiography showed complete occlusions of the bilateral internal carotid arteries just rostral to the bifurcations. He did not have any histories of hypertension nor other risks for cerebrovascular diseases. Although direct evidence for the cause of carotid occlusions was not obtained, we speculated that his cervical lesions came from the arterial changes attributable to vasculo-Behçet's disease. Vascular involvements are not infrequent in Behçet's disease, but we believe such occlusive lesions in the bilateral internal carotid arteries as seen in our case are extremely rare. As a construction worker he had undergone a lot of mechanical stress on his neck, which might be a trigger for the carotid lesions.

Adult↗

[A 73-year-old woman with familial Parkinson's disease].

We report a 73-year-old Japanese woman with familial Parkinson's disease. The patient was well until her 67 years of the age, when she noted rest tremor in her right hand. Soon after her gait became short stepped. She visited our clinic on October 6, 1992 when she was 68 years old. She was alert and well oriented without dementia. She showed masked face, small voice, small stepped gait, retropulsion, resting tremor in her right hand, rigidity in the neck, and bradykinesia. She was treated with 400 mg/day of levodopa-carbidopa, which improved her symptoms, however, she developed wearing off phenomenon 3 years after the initiation of levodopa treatment. On August 26, 1998, she developed abdominal pain, diarrhea, and vomiting. She was admitted to another hospital, where abdominal plain x-ray revealed an evidence of intestinal obstruction (ileus). She was treated with nasogastric suction and intravenous fluid. Her condition did not improve and she was transferred to our hospital on August 29, 1998. Her family history revealed no consanguineous marriage. She had two elder brothers and three elder sisters. One of her brothers had been diagnosed as Parkinson's disease. Her husband also suffered from Parkinson's disease, however, her parents apparently did not have Parkinson's disease. On admission, she appeared to be drowsy. Her blood pressure was 102/70 mmHg, body temperature 36.2 degrees C. The lungs were clear and no cardiac murmur was present. Abdomen was flat and bowel sound was audible. No abnormal mass was palpable. Neurologic examination revealed mild consciousness disturbance, masked face, and small voice. No motor paralysis was noted. Muscle tone was hypotonic. No abnormal involuntary movement was noted. Abnormal laboratory findings on admission were as follows; WBC 11,300/microliter, amylase 1,373 IU/l, CK 446 IU/l, BUN 50 mg/dl, creatinine 1.17 mg/dl, CRP 22.7 mg/ dl, Na 134 mEq/l, K 3.1 mEq/l, and Cl 81 mEq/l. A chest x-ray film revealed pneumonic shadows in both lower lung fields. She was treated by nasointestinal suction, intravenous fluids, and chemotherapy for her infection. Her BP started to drop on September 2 and she developed cardiac arrest on the same day. She was discussed in a neurological CPC. The chief discussant arrived at the conclusion that the patient had a form of autosomal dominant familial Parkinson's disease. As parents did not have Parkinson's disease, some of the participants raised the possibility of autosomal recessive inheritance. But the age of onset was too late for autosomal recessive inheritance. Majority thought that the mode of inheritance was autosomal dominant with low penetrance. alpha-Synuclein mutation causes an autosomal dominant familial Parkinson's disease, but this type is very rare in non-Greek populations and the penetrance is high. Chromosome 2-linked autosomal dominant familial Parkinson's disease shows low penetrance. There are many other autosomal dominant forms of familial Parkinson's disease linked to yet unknown chromosome loci. Majority thought that this patient also had a form of Lewy-body positive autosomal dominant familial Parkinson's disease of unknown chromosome locus. Post mortem examination revealed ischemic intestinal lesion with strangulation. This was thought to be the cause of her death. In the central nervous system, the brain appeared to be normal by inspection. In the coronal sections, the substantia nigra and the locus coeruleus showed marked depigmentation. Histologic examination revealed marked neuronal loss and Lewy body formation in the remaining neurons. Pathologic examination was consistent with Parkinson's disease. Mutational analysis for the parkin gene was negative.

Aged↗