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Biomedical subjects

K Gotoh

Publications and source records attributed to K Gotoh.

At least 73 records · Page 4Linked to original sources

Altered nitric oxide synthase immunoreactivity in the brain of stroke-prone spontaneously hypertensive rats.

To obtain information about the role of nitric oxide (NO) in the development of hypertensive cerebral lesions, we used immunohistochemical methods to study the distribution and level of nitric oxide synthase (NOS) in the brain of stroke-prone spontaneously hypertensive rats (SHRSPs). The early changes in the brain of SHRSPs were petechiae, edema and massive glial accumulation around fibrin deposits, which contained necrotized microvessels, whereas advanced cerebral lesions comprised massive bleeding, cavity formation and diffuse degeneration of the white matter. In the normotensive control rats, immunoreactivity for NOS was demonstrated in scattered neuronal cells, as has been reported previously, but there was no reactivity in glial cells. In the present study in SHRSPs, however, considerable NOS immunoreactivity was observed in most reactive astrocytes and in a proportion of the microglial cells and macrophages in the vicinity of the cortical lesions and in the subcortical white matter both ipsi- and contralateral to the cortical lesion. The nerve cells in the edematous region also showed weak immunoreactivity for NOS. The distribution of increased NOS in SHRSP brains corresponded well with the sites of extravasated plasma fluid as demonstrated by anti-fibrinogen antibody. Based on these findings, we postulate that edema and the simultaneously generated free radicals or some extravasated plasma components may induce expression of NOS in the reactive cells and nerve cells, and that the NO thus generated may be involved in the development of hypertensive cerebral lesions.

Animals↗

Degradation of T-kininogen by cathepsin D and matrix metalloproteinases.

Cathepsin D, matrix metalloproteinase (MMP)-2, MMP-3 (stromelysin), and MMP-9 were isolated from rat granulomatous tissues. HT1080 human fibrosarcoma cells and rheumatoid synovial cell CM. At acidic conditions, cathepsin D cleaved T-kininogen into small peptides and released Met-T-kinin-Leu (kinin precursor), but failed to release kinin. MMP-3 cleaved T-kininogen into a 57 kDa fragment as measured by SDS-PAGE and Western blot analysis using anti-T-kininogen antiserum. On the other hand, no degradation of T-kininogen occurred during incubation with MMP-2 or MMP-9100/1) at pH 7.5 for 7 h.

Cathepsin D↗

Detection of contamination of vaccines with the reticuloendotheliosis virus by reverse transcriptase polymerase chain reaction (RT-PCR).

The reverse transcriptase polymerase chain reaction (RT-PCR) was applied to detect contamination of Marek's disease (MD) vaccine with reticuloendotheliosis virus (REV). The env primers were used for the 1st RT-PCR to amplify the DNA fragments of REV-A and -T. The rel and env primers were used for nested-PCR to confirm the sites deleted from REV-T and REV-A. Specific amplification products were detected in the 1st RT-PCR with these primers. By nested PCR with the env and the rel primer pairs, the products originating from REV-A and -T were identified. This system, using the env primer pairs, showed a specific amplification with several REV strains (REV-T, DE, CE, KI and 0202), but no amplified product was detected with MDV, NDV, IBV or ILTV. The 1st RT-PCR detected the virus in a concentration of 10(3) in 50% fluorescent antibody infectious dose per ml (FAID50/ml) and the nested PCR detected 10(1) FAID50/ml virus. The sensitivity of the RT-PCR system was found to be higher than that of the FA assay. This system provides a rapid, sensitive and specific method for detection of contamination of MD vaccines with REV-RNA, and it may be applied for quality control of live vaccines.

Animals↗

Mixed germ-cell tumor of the brain. Pathologic study of six autopsy cases.

Intracranial mixed germ-cell tumors are rare. We describe the findings from six autopsies of patients with these tumors. The patients were all young at presentation (mean age, 16 years), and five of the six were male. Headache, vomiting, polyuria and diplopia were common symptoms. Radiographic evaluation demonstrated a mass on the midline of the brain. The patients were treated mainly with radiation, but survival (mean, 3.7 years) was not as long as predicted. At autopsy, the tumors occupied most of the ventricular spaces, and ranged from being well-circumscribed to invasive. All tumors contained both germinoma components and nongerminomatous germ-cell tumor components. Because the distribution of these components was not homogenous, at least two sections were necessary for the diagnosis. Immunoreactivity for placental alkaline phosphatase was found in all tumors. Immunostaining for human chorional gonadotropin, alpha-fetoprotein and carcinoembryonic antigen was usually associated with abnormally high serum levels of these tumors markers in life. A number of the cells in both kinds of tumor components expressed proliferating cell nuclear antigen, probably reflecting the intense malignant potential.

Adolescent↗

Treatment of gastric fundal varices by balloon-occluded retrograde transvenous obliteration.

Although less common than oesophageal varices in portal hypertension, gastric fundal varices carry a higher mortality rate when they rupture. They are less amenable to sclerotherapy. We have developed a minimally invasive balloon-occluded retrograde transverse obliteration (B-RTO) procedure to treat gastric fundal varices. B-RTO involves inserting a balloon catheter into an outflow shunt (gastric-renal or gastric-vena caval inferior) via the femoral or internal jugular vein. Blood flow is then blocked by inflating the balloon, and 5% ethanolamine oleate iopamidol is injected in a retrograde manner. The embolized gastric varix subsequently disappears. B-RTO was performed in 32 patients with gastric varices. Follow-up endoscopies were performed at intervals of 2-4 months for an average observation period of 14 months. Eradication of the varices has been confirmed in 31 of 32 patients. No recurrence occurred in any patients in the follow-up period. There were no significant changes in liver function after the procedure. We conclude that B-RTO is a safe and effective procedure for the treatment of gastric fundal varices.

Adult↗

Single application extracorporeal shock wave lithotripsy is the first choice for patients with pancreatic duct stones.

OBJECTIVES: We performed extracorporeal shock wave lithotripsy (ESWL) as the treatment of first choice on 32 chronic pancreatitis patients with main pancreatic duct (MPD) stones prospectively to establish more convenient and safer treatment. METHODS: All patients were treated in a prone position, and shock waves were discharged from the ventral side. ESWL was performed once or twice a week, and no other treatments before ESWL had been applied. RESULTS: Disintegration of all MPD stones to 3 mm or less in diameter could be achieved in all treated patients. Complete clearance of the stones was obtained in 24 patients (75%) without the necessity of endoscopic extraction of fragments. Reduction of MPD diameters after ESWL was statistically significant (p < 0.01). Epigastric and/or back pain complaints before ESWL were completely alleviated in 79% (periods of follow-up: 16-63 months, mean 44), and the pancreatic exocrine function also improved in 61%. No severe complications occurred in any of the patients. CONCLUSIONS: ESWL, which is comparatively easy to perform, is a safe and efficient approach that changes endoscopy's status as an indispensable pretreatment. Therefore, ESWL can be recommended as the first choice treatment for patients with chronic pancreatitis accompanied by MPD stones that should be tried before consideration of either surgical or endoscopic procedures.

Adult↗

[Left cardiac output curve and pulmonary venous return curve in patients with various heart diseases].

This study assessed the cardiac function of humans by drawing simultaneous left cardiac output and pulmonary venous return curves using radionuclide angiocardiography and right heart catheterization which allows recording of the pressure-flow relationship. Thirty-one subjects with various cardiac diseases were divided into two groups [18 patients with New York Heart Association (NYHA) functional class I and 13 patients with NYHA classes II or III]. Mean pulmonary filling pressure (Pmp) was calculated from the formula of Guyton, using pulmonary arterial compliance which was measured by Reuben's method and pulmonary venous compliance measured as reported previously. On the pressure-flow plane, the down slope of the pulmonary venous return curve was drawn by joining the points of (Pmp, 0) and (mean pulmonary capillary wedge pressure, cardiac output). To construct the cardiac output curve, two levels of lower body negative pressure were used to regulate the venous return to the heart. Pmp and the resistance to pulmonary venous return in NYHA II or III patients were significantly higher than those in NYHA I patients (Pmp: 16.3 +/- 1.5 vs 9.0 +/- 0.5 mmHg, p < 0.01; resistance to pulmonary venous return: 0.75 +/- 0.09 vs 0.43 +/- 0.04 mmHg/l/min, p < 0.01, respectively). The slope of pulmonary venous return curve in NYHA II or III patients was smaller than that in NYHA I patients and the pulmonary venous return curve in NYHA II or III patients shifted rightward. The slope of cardiac output curve in NYHA II or III patients was significantly smaller than that in NYHA I patients. This curve in NYHA II or III patients shifted downward and rightward. These results indicate that simultaneous cardiac output and pulmonary venous return curves may be a useful method for assessing the cardiac function in patients with various heart diseases.

Adult↗

-A successful case of hypertrophic cranial pachymeningitis treated by optic nerve decompression.

A successful direct operation in a case of hypertrophic cranial pachymeningitis (HCP) is described. A 51-year-old male was admitted with right visual disturbance. CT scanning revealed a mass lesion in the right middle cranial fossa extending into the right orbita. From MRI it was ascertained that this mass lesion consisted of thickening of the skull base dura. The effect of steroids was transient and his visual disturbance was rapidly increasing. A direct operation was performed consisting of partial dissection of the thickening dura and decompression of the right optic nerve. Histological diagnosis showed HCP. After surgery his symptoms dramatically improved. The etiology, natural course and treatment of HCP are well reported in the literature. in the present case the etiology was not clear, but there was a possible relationship with intraorbital pseudotumor or multifocal fibrosclerosis. The reported occasional transitory effect of steroids on HCP and a poor prognosis for visual acuity are common traits in these patients. The authors thus feel that a direct operation should be immediately carried out when the effect of steroids on visual disturbances associated with HCP is judged transient.

Humans↗

[Rapidly progressing BOOP in a patient with positive anti-Jo-1 antibody: response to corticosteroid pulse and immunosuppressant therapy].

A 61-year-old woman was admitted to our hospital with a two week history of knee-joint pain, dry coughing and dyspnea on exertion. A chest roentgenogram revealed bilateral patchy and infiltrative shadows. Laboratory examination revealed high CK and aldolase levels. Although myositic symptoms were absent, the respiratory symptoms rapidly worsened and respiratory failure developed. An open-lung biopsy and a muscle biopsy were done. The open-lung biopsy specimen showed bronchiolitis obliterans organizing pneumonia (BOOP), but the muscle biopsy specimen revealed non-specific findings. After 4 weeks of intravenous intermittent high-dose corticosteroid therapy, 50mg of cyclophosphamide was given daily, along with 20mg of prednisolone on alternate days. There were marked clinical, physiological and roentgenographic improvements. A test for anti-Jo-1 antibody was positive, which suggested that this patients had pulmonary manifestations of polymyositis/dermatomyositis. Although BOOP can have an indolent course and a good prognosis, it may rapidly worsen and respiratory failure may develop, in which case it should be treated aggressively with a combination of intravenous high-dose corticosteroids and immunosuppressants.

Antibodies, Antinuclear↗

[Sarcoidosis in a patient with autoimmune hemolytic anemia].

A 65-year-old woman was admitted to our hospital because of severe anemia. A skin biopsy was done in January 1994 and sarcoidosis was diagnosed. Diffuse reticular shadows were seen in both lung fields on a chest X-ray film and mediastinal lymph node swelling was seen on a chest CT scan. She was followed as an outpatient and was not treated. She suddenly experienced vertigo and general fatigue in March 1995. Laboratory findings on admission were as follows: Hb 6.2 g/dl, MCV 115.9 fl, Ret 198%, LDH 732 IU/L, I-Bil 1.9 mg/dl, and Coombs' test was positive. Autoimmune hemolytic anemia was diagnosed, and she was treated with prednisolone (1 mg/kg). As of the time of this writing, she has no relapse of hemolytic anemia though prednisolone was discontinued 6 months ago.

Anemia, Hemolytic, Autoimmune↗

[Effect of long-term treatment with an inhaled corticosteroid on bronchial hyper-responsiveness and clinical asthma in asthmatic subjects].

We studied retrospectively the effect of long-term treatment with an inhaled corticosteroid on bronchial hyperresponsiveness (BHR) and clinical asthma in moderate-severe asthmatic subjects. Fifty-eight patients who had used beclomethasone dipropionate (BDP) over one year, were enrolled in this study. BHR was measured before and after treatment with BDP by the methods recommended by Japanese Society of Allergology. Moreover we examined the clinical factors and the frequency of acute exacerbations. The results as follows: 1) The mean age was 48.8 years and the mean asthma history was 9.2 years. The mean dose and mean time of BDP administration was 801 micrograms/day and 28.1 months, respectively. 2) Patients during BDP treatment over one year showed about 6-fold mean improvements in BHR, but there were many patients who showed no improvements in BHR. 3) We retrospectively divided all the patients into two groups. Namely, the improved group (n = 25) showed more than 4 fold improvement in BHR and unchanged group (n = 33), less than 4-fold. But there were no significant differences in clinical characteristics and %FEV1 during treatment with BDP. 4) The unchanged group had more near fatal episodes in the past than the improved group. 5) There was significant decrease in acute exacerbation during treatment with BDP, but the unchanged group had more acute exacerbations than the improved group during treatment with BDP. These results indicates that there are many patients who had no improvement on BHR with long term BDP treatment and they have more acute exacerbations due to various stimuli. In conclusion, asthma is recognized chronic inflammatory disease and inhaled corticosteroid therapy has been recommended as the first line therapy. We must further study the clinical problems and underlying mechanisms concerning about treatment with an inhaled corticosteroid.

Anti-Asthmatic Agents↗

Complete nucleotide sequences and the characteristics of two hepatitis B virus mutants causing serologically negative acute or chronic hepatitis B.

Hepatitis B virus (HBV) DNA was amplified by the polymerase chain reaction from the sera of a patient with acute hepatitis and a patient with chronic hepatitis. Both patients were negative for serum hepatitis B surface antigen and hepatitis B core antibodies and had been previously diagnosed as non-A, non-B, non-C, non-D, non-E hepatitis. The nucleotide sequence revealed an 8-nucleotide deletion in the X-gene coding region creating a C-terminally truncated X protein, and probable mutation of the enhancer II/core promoter element. In addition, DR2 showed a T-to-C mutation at the extreme 5'-terminus. These mutations within the X-gene coding region must suppress replication and expression of HBV DNA, and this seems to be responsible for absence of serological markers despite the presence of HBV infection.

Acute Disease↗

Nucleotide sequence of hepatitis B virus isolated from subjects without serum anti-hepatitis B core antibody.

The nucleotide sequences of the precore/core and X open reading frames (ORFs) of hepatitis B virus (HBV) were studied in four subjects who were serologically negative for anti-hepatitis B core antibody. These subjects were positive for serum hepatitis B surface antigen and were considered to be asymptomatic HBV carriers. Sequencing of the precore/core ORF revealed precore wild type and 3 to 8 nucleotide substitutions (replacing 0 to 2 amino acids) in the core region compared with the sequence of subtype adr. These substitutions were not considered to have changed the epitope of the core antigen, resulting in the absence of anti-HBc as determined by a conventional diagnostic kit. The X ORF showed 1 to 5 nucleotide substitutions (replacing 1 to 3 amino acids) and the structure of the X protein and the core promoter/enhancer II complex appeared to be conserved. These findings strongly suggest that the absence of serum anti-HBc is not due to mutation of the HBV DNA but to an aberrant immune reaction of the host to HBV.

Adult↗

Probable implication of mutations of the X open reading frame in the onset of fulminant hepatitis B.

A pathogenic role of precore-defective mutation in the onset of fulminant hepatitis B has been suggested. However, precore-defective mutants do not always cause fulminant hepatitis B and are not always isolated from affected patients. These findings strongly suggest the presence of some additional important mutations outside the precore region in fulminant hepatitis. In the present investigation an attempt was made to sequence the X open reading frame of hepatitis B virus DNA isolated from seven patients with fulminant hepatitis B and five patients with acute hepatitis B. The latter were used as controls. Since the X open reading frame encodes the X protein and contains the core promoter/enhancer II complex, some critical mutations may enhance or disrupt the replication and expression of hepatitis B virus DNA leading to fulminant hepatitis. A C-to-T substitution was found at nucleotide (nt) 1655, an A-to-T substitution at nt 1764 and a G-to-A substitution at nt 1766 in 4, 5 and 5 patients, respectively, out of the seven with fulminant hepatitis. These substitutions were not recognized in the patients with acute hepatitis. These mutations might change the function of the X protein and core promoter/enhancer II complex. It is suggested, therefore, that these mutations, as well as the precore-defective mutation, may play an important role in the pathogenesis of fulminant hepatitis.

Acute Disease↗

Comparison of the entire nucleotide and deduced amino acid sequences of the attenuated hog cholera vaccine strain GPE- and the wild-type parental strain ALD.

We have determined the complete nucleotide sequences of a live attenuated hog cholera virus (HCV) and its progenitor strain. The viral RNA of each strain consisted of 12,298 nucleotides including untranslated regions of 373 and 228 bases at the 5' and 3' end, respectively. There was a single large open reading frame spanning 11,697 nucleotides which could encode a large protein of 3,899 amino acids with a calculated molecular weight of 438-kDa. We have found 225 nucleotide difference between the two strains, of which six were located in the untranslated region. Four-sixths of these differences resulted in amino acid substitutions.

Amino Acid Sequence↗