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Biomedical subjects

H Obata

Publications and source records attributed to H Obata.

At least 19 recordsLinked to original sources

Changes of plasma des-gamma-carboxy prothrombin levels in patients with hepatocellular carcinoma in response to vitamin K.

The effect of menaquinone-4 (MK-4, vitamin K2) was studied on des-gamma-carboxy prothrombin (DCP or PIVKA-II) levels in three subjects with vitamin K deficiency and five patients with hepatocellular carcinoma (HCC) with positive DCP. The half-life of DCP in HCC patients after intravenous MK-4 administration (50 mg daily for 14 days) was determined to be 60 hours, identical to that found in vitamin K-deficient subjects who received MK-4. When a single dose of MK-4 (10 mg) was given intravenously to three patients with HCC and elevated DCP, the levels decreased with a reduction rate identical to that in vitamin K-deficient subjects for the first 1 to 3 days, followed by an increase reaching the previous level in 7 to 10 days. Changes in plasma coagulant activity were compared between subjects with vitamin K deficiency and those with HCC before and after a single dose of MK-4 (10 mg). The activity increased in DCP-positive patients with HCC as in vitamin K-deficient subjects who received the same single dose of MK-4. The increase was greater in HCC patients with higher DCP levels. These results suggest that the level of plasma DCP in patients with HCC responded to vitamin K with the same sensitivity as that in vitamin K-deficient subjects. When patients with HCC underwent effective tumor therapy (resection or arterial embolization), the reduction rate (slope of DCP decline) was found to be identical to that in vitamin K-deficient subjects given with MK-4. In patients with less effective therapy, the reduction rate was smaller, or there was an increase in DCP. These observations strongly suggest that sequential measurements of the DCP reduction rate after treatment for HCC are useful for assessing therapeutic effects.

Aged

Elevated serum interleukin-6 levels in patients with acute hepatitis.

To study the mechanisms of hepatocyte injury, we examined serum interleukin-6 (IL-6) level in acute hepatitis patients. Based on their clinical features, these patients were divided into three groups, acute hepatitis (AH), severe acute hepatitis, and fulminant hepatic failure (FHF). The present study demonstrated that, in association with their clinical status, their serum IL-6 levels were gradually increased (16.5 +/- 14.5 pg/ml in AH, 26.3 +/- 19.0 pg/ml in severe AH, and 470.2 +/- 261.4 pg/ml in FHF; control level, 5.2 +/- 0.6 pg/ml). Furthermore, we found that a significant correlation between serum IL-6 level and prothrombin time existed in these patients and that the elevated serum IL-6 returned to a normal range after recovery from their hepatocyte injury. Thus, our study demonstrates that the serum IL-6 level is a possible marker for identifying the clinical status in acute hepatitis and that this cytokine may have some roles in hepatocyte injury.

Acute Disease

Successful arterial embolization of arteriovenous fistula in the portal circulation.

We successfully performed arterial embolization of an arteriovenous fistula between the left gastric artery and vein. The increased blood flow in the portal vein via the left gastric vein and the arteriovenous fistula induced severe portal hypertension. After obliteration of the left gastric artery, the arteriovenous fistula was not opacified on angiography and the portal hypertension improved.

Arteriovenous Fistula

Extensive varices of ileocecum. Report of a case.

A man was admitted to our hospital because of intestinal reddish bleeding. Colonic varices were found at the cecum by colonoscopy. Angiography of the superior mesenteric artery showed that blood vessels were scant from the end of the ileum to the ascending colon. An operative view revealed the varices, but there was no trace of the ileocecal vein. This case, presenting a deficit of the ileocecal vein, indicated that the blood flow could not return via the ileocecal vein, and therefore there was an outflow through the varices to the surrounding intestine or abdominal veins. Such a case is probably unrepresented in the literature because it was caused by the total deficiency of the ileocecal vein and it was in the right colon.

Angiography

Significance of serum sialic acid in patients with Crohn's disease.

Serum sialic acid was measured to evaluate the activity of Crohn's disease. The sialic acid levels of patients with Crohn's disease in remission (CRP 0.0 mg/dl) were significantly higher than those of healthy subjects and postoperative patients with Crohn's disease. In patients in remission, serum sialic acid was significantly correlated with hemoglobin, hematocrit, platelet, and rapid turnover protein. Correlations with platelet, retinol-binding protein, and prealbumin were especially strong. From these findings, it was concluded that serum sialic acid level provides a useful index of the activity of Crohn's disease.

Adult

Hepatitis B virus-DNA transfected myeloma cell-specific cytotoxic T cells in chronic hepatitis B patients.

To study the mechanisms of hepatitis B virus (HBV)-induced chronic hepatitis (B-CH), we took chronic hepatitis B patients' peripheral blood lymphocytes (PBL) and examined their cytotoxic activities against human myeloma cells (ARH77) transfected by HBV-DNA. Two different transfected cells, one expressing HBV envelope antigens (S6) and the other expressing HBV core antigens (C4), were prepared and used as targets in the in vitro cytotoxic test. We found that PBL of B-CH patients had specific cytotoxic activity against these target cells (S6, 22.0 +/- 4.8%; C4, 21.6 +/- 4.8%), whereas no remarkable cytotoxic activity was observed in non-B chronic hepatitis patients as well as asymptomatic chronic HBV carriers. These specific cytotoxic activities were inhibited with anti-CD3 antibody, hence these killer cells belonged to T cells (cytotoxic T cells; CTL). The requirement of HLA class 1 antigens to exert these CTL activities was demonstrated by the absence of CTL activity with PBL obtained from HLA-nonidentical B-CH patients and by the inhibition of their activities with anti-HLA class 1 antibody. Thus, our results indicate that, at least two different CTL, one recognizing envelop antigen and the other recognizing core antigen, exist in chronic hepatitis B patients.

Adolescent

A sensitive method for the detection of enterotoxigenic Escherichia coli by the polymerase chain reaction using multiple primer pairs.

In this study, a polymerase chain reaction (PCR) method has been developed for the detection of enterotoxigenic Escherichia coli (ETEC). Three different sets of oligonucleotide primers synthesized were used to amplify the enterotoxin genes of heat-labile (LTh) and heat-stable (STIa and STIb) enterotoxins of ETEC. These primers amplified a 627, 240, or 169 base pair (bp) DNA fragment from LTh, STIa and STIb gene, respectively, of the reference ETEC strains. The addition of RNase A (10 micrograms/ml) to the PCR reaction solution diminished nonspecific amplification of DNA fragments other than the enterotoxin genes. Five types of ETEC strains corresponding to the LTh, STIa, STIb, LTh-STIa, or LTh-STIb genotypes were distinguished by a single procedure of PCR using the mixture of the three sets of primers. PCR, hybridization, and conventional methods were subjected to one hundred stool specimens from diarrheal patients. It was found that PCR was the most sensitive method among them. These results suggested that PCR with triple primer pairs would be useful for the laboratory diagnosis of ETEC in the stool specimens.

Bacterial Toxins

Guinea pig model of immunologic asthma induced by inhalation of trimellitic anhydride.

We established a model of asthma induced by trimellitic anhydride (TMA) in guinea pigs and assessed the role of sensitization in the development of their bronchial hyperresponsiveness, and relationship between bronchial responsiveness and bronchial inflammation. Fourteen guinea pigs (sensitized group) were administered 1 mg/0.5 ml of trimellity 36-bovine serum albumin intramuscularly and 0.5 ml of complete Freund adjuvant on Day 1 as the priming dose. Booster doses were repeated on Day 15. By Day 28, all of the sensitized animals showed a high passive hemagglutination titer against trimellityl 14-ovalbumin. On Day 29, they were challenged by an inhalation of TMA (150 mg/m3) for 30 min, and respiratory resistance (Rrs) was monitored by the oscillation method. In all sensitized animals, Rrs increased immediately upon challenge and returned to baseline within 6 h. The bronchial reactivity to acetylcholine (Ach), measured 6 h after TMA challenge in the sensitized animals, increased significantly (p < 0.01) compared with that measured 24 h before challenge; that measured 24 h later was not different from that before challenge. There was also a significant difference (p < 0.01) in the number of eosinophils in the lamina propria and the epithelium 6 and 24 h after the challenge inhalation in the sensitized group. The increased airway responsiveness to Ach in the sensitized animals was correlated with an increase in the number of eosinophils in the lamina propria and the epithelium. These observations suggest that humoral antibody and eosinophils are involved in the pathogenesis of TMA-induced asthma.

Acetylcholine

Functional and metabolic responses to ischemia in the isolated perfused hypothyroid rat heart.

It has been demonstrated that the V3 cardiac myosin isozyme has a higher efficiency and consumes less oxygen in doing mechanical work than the V1 myosin isozyme. The purpose of the present study is to investigate the functional and metabolic responses to ischemia following reperfusion of the hypothyroid heart, in which ventricular myosin isozyme is shifted from V1 predominance to V3 predominance. The heart was perfused by the working heart method for 15 min, and then global ischemia was induced for 10, 20 and 30 min with pacing at a rate of 320/min until cardiac cessation. The ischemic heart was reperfused for 30 min. The extent of recovery of pressure-rate product after reperfusion, following 20 min of ischemia in the hypothyroid heart, was higher than that in the control heart (p less than 0.01). The level of adenosine triphosphate (ATP) declined more slowly in the hypothyroid heart than in the control heart. The level of ATP and energy charge potential in the hypothyroid heart reperfused after 20 min of ischemia were higher than those in the reperfused control heart (p less than 0.01, p less than 0.05, respectively), though they did not differ from each other in preischemia. There were no significant differences in the levels of tissue lactate between the 2 hearts during ischemia and reperfusion. The recovery rate of the coronary flow of the 2 hearts did not differ from each other significantly. These data suggest that there is probability of the V3 predominant heart recovering from ischemic damage to the metabolism and cardiac function better than the V1 predominant heart because the transformation of myocardium, due to an increase in V3 into a slower but more efficiently working muscle results in conservation of tissue ATP during ischemia.

Adenosine Triphosphate

[A case of small cell carcinoma of the lung with carcinomatous lymphangiosis-like shadow].

A 60-year-old man was admitted to our hospital on January 29, 1991 with dry cough, shortness of breath on exertion, appetite loss and abnormal shadows on chest X-ray. Chest X-ray on admission showed marked vascular shadows in both lung fields accompanied by left interlobar effusion. Chest CT showed thickening of vessels and bronchial walls with prominent interlobular septa in the subpleural regions. These findings suggested that the lesions were located in the peribronchial and perivascular interstitium and interlobular septa. Biopsy specimens of bronchial epithelium, lung tissue and right supraclavicular lymph nodes revealed small cell carcinoma (intermediate cell type). Because of the absence of lesions in other organs, the initial diagnosis was carcinomatous lymphangiosis of small cell carcinoma of the lung. However, the mild symptoms, normal arterial blood gas and good response to chemotherapy suggested the possibility of extensive small cell carcinoma of longitudinal spread type. Although small cell carcinoma of the lung is not a rare disease, this case suggests two possibilities. 1) Carcinomatous lymphangiosis of small cell carcinoma may have different symptoms, clinical course and prognosis from that of non-small cell carcinoma. 2) Carcinomatous lymphangiosis of small cell carcinoma may not be a clinical entity and in fact may simply represent extensive small cell carcinoma of longitudinal spread type.

Carcinoma, Small Cell

[A case of sarcoidosis with primary acute pulmonary cavitation].

A 23-year-old man was admitted to our hospital on June 24, 1991, because of worsening chest X-ray findings of sarcoidosis. In August 1990, he was referred to our outpatient office, because of BHL and nodular lesions on chest X-ray film performed at his company 4 months earlier. At that time, serum ACE was elevated to 34.0 IU/l, and Ga scintigraphy showed abnormal uptake in bilateral lacrimal and salivary glands, mediastinal and hilar lymph nodes, and in the lung fields. TBLB specimen showed noncaseating epithelioid granuloma with giant cells and negative stains for acid-fast bacilli. Although it was planned to follow this patient without medication, he did not return to our outpatient department. In June 1991, because of worsening of lesions in the lung at annual checkup at his company, he was referred and admitted for steroid therapy. Chest X-ray film on admission showed BHL, multiple nodular lesions in both lung fields, and bullous change in the left upper lobe. Chest CT on admission showed three cavitating lesions within preexisting nodules. PPD skin test was negative, and sputum smears and cultures were repeatedly negative for pyogenic bacteria and acid-fast bacilli. Therapy was initiated with prednisolone 30 mg daily. Four months later, there was marked resolution of BHL and nodular lesions, and the cavitating lesions were no longer visible on chest X-ray film. From the clinical and radiological observations, it is concluded that the cavitating lesions in the present case were primary acute pulmonary cavitation in sarcoidosis, distinct from infection, bullae, or cystic bronchiectasis which are seen in the chronic and fibrotic stages of sarcoidosis.

Adult

[Corneal endothelial cell damage in penetrating keratoplasty].

Fifty-eight corneal grafts were investigated by specular microscopy to determine the corneal endothelial damage in penetrating keratoplasty. The center of the donor corneal endothelium was examined before and after 2 weeks, 1, 3, 6 and 12 months after surgery. The cell density decreased periodically during the observation period, and the endothelial cell loss in all the cases averaged 10. 4% at 2 weeks after the operation, 16.0% at 1 month, 33.0% at 3 months, 39.4% at 6 months, and 48. 2% at 12 months. However, the cell loss in the keratoconus subgroup averaged -1.9%, 1.2%, 9.9%, 30. 6%, and 33.4% corresponding to the above period. The least cell loss among the diagnostic subgroups was in the keratoconus, followed by corneal leukoma. The cell loss in bullous keratopathy was higher than in keratoconus and corneal leukoma case. It was concluded that the cell loss in penetrating keratoplasty during the first postoperative year depends on the primary disease.

Adolescent

Association of hepatitis B viral precore mutations with fulminant hepatitis B in Japan.

We studied the precore DNA sequences of hepatitis B viral genomes in five patients with fulminant hepatitis B and in five with acute self-limited hepatitis B from Japan. Using the polymerase chain reaction, three to four independent HBV DNA clones from each patient were obtained and analyzed. We demonstrated that patients with fulminant hepatitis B carried HBV genomes with a G to A mutation at nucleotide positions 1898 (five of five patients; 18 of 18 clones, 100%) and 1901 (five of five patients; 12 of 18 clones, 66%) in the precore region. The first mutation results in an in-phase stop codon (TAG) in the precore open reading frame and the absence of HBeAg production. In contrast, a G to A mutation was found in 6 of 16 clones (37%) in position 1898 and in 0 of 16 clones (0%) in position 1901 from patients with acute self-limited hepatitis. We concluded that both of the precore mutations are commonly associated with fulminant hepatitis B and may contribute to the pathogenesis of fulminant hepatitis. A hypothetical model for the biological significance of these two mutations is proposed.

Adult

Effects of regression of left ventricular hypertrophy following atenolol or bunazosin therapy on ischemic cardiac function and myocardial metabolism in spontaneously hypertensive rats.

The effects of regression of left ventricular hypertrophy following atenolol and bunazosin therapy on ischemic cardiac function and myocardial metabolism in spontaneously hypertensive rats (SHR) were studied. Atenolol (50 mg/kg/day) and bunazosin (5 mg/kg/day) were administered to SHR from 19 to 26 weeks of age, whereas tap water was given to control SHR and normotensive Wistar-Kyoto rats (WKY). Both atenolol and bunazosin significantly decreased arterial blood pressure and significantly decelerated the increase in left ventricular weight in SHR. At the end of the long-term treatment, hearts were removed and perfused by the working heart technique for 15 min, and then global ischemia was induced for either 10 or 30 min. The ischemic heart was reperfused for 30 min. The pressure-rate product and the extent of recovery of the coronary flow after reperfusion following 30 min of ischemia in the bunazosin-treated SHR were significantly higher than those in the control SHR and the atenolol-treated SHR. The levels of adenosine triphosphate (ATP), creatine phosphate (CrP), and energy charge potential in the SHR heart reperfused after 30 min of ischemia were significantly lower than those in the reperfused WKY. Both atenolol and bunazosin improved the restoration of ATP and CrP in SHR after reperfusion following 30 min of ischemia. In conclusion, antihypertensive therapy with either atenolol or bunazosin was effective in preventing cardiac hypertrophy and ischemic damage caused by different mechanisms. Factors resulting from stimulation of the cardiac alpha 1 adrenoceptor may play an important role in the development of hypertensive cardiac hypertrophy, just as factors resulting from stimulation of the beta 1-adrenoceptor do.

Adenosine Diphosphate