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Biomedical subjects

H Tsukada

Publications and source records attributed to H Tsukada.

At least 163 records · Page 9Linked to original sources
PubMed1994

Haemophilus parainfluenzae antigen and antibody in renal biopsy samples and serum of patients with IgA nephropathy.

IgA nephropathy may be associated with colonisation with Haemophilus parainfluenzae. In patients with glomerular diseases, we examined renal-biopsy specimens for presence of bacterial antigen by immunofluorescence microscopy with rabbit antiserum against H parainfluenzae, and by enzyme-linked immunosorbent assay looked for IgA antibody against H parainfluenzae in patient sera. The rabbit antiserum recognised by immunoblotting four components of H parainfluenzae outer membranes (OMHP) of molecular weights 19.5, 30, 33, and 40.5 kDa. All 44 patients with IgA nephropathy and 2 of 39 patients with other glomerular diseases showed mesangial deposition of OMHP antigens (p < 0.001). Patients with IgA nephropathy had significantly more IgA antibody against H parainfluenzae than did patients with other glomerular diseases. IgA antibody in the sera of patients with IgA nephropathy recognised by immunoblotting the same four components of OMHP as recognised by rabbit antiserum. Glomerular deposition of OMHP antigens and the presence of IgA antibody against OMHP in patients with IgA nephropathy suggest that H parainfluenzae has a role in the aetiology of this disease.

Adult↗
PubMed1994

Disseminated Mycobacterium avium-intracellulare infection in a patient with myelodysplastic syndrome (refractory anemia).

A 31-year-old woman presented with fever and arthralgia. Despite treatment with antimicrobials and corticosteroids, her symptoms persisted. A diagnosis of myelodysplastic syndrome (MDS)-refractory anemia (RA) was made by pancytopenia, dysplasia, and trisomy 8. Cultures of bone marrow, blood, and gastric juice showed Mycobacterium avium-intracellulare (MAI). She was treated with antimycobacterial drugs and recombinant human G-CSF/M-CSF and showed an initial response, but spike fever recurred and pancytopenia progressed. Hepatosplenomegaly and marked retroperitoneal lymphadenopathy were revealed, indicating further dissemination of MAI. Treatment with recombinant human GM-CSF and very-low-dose cytosine arabinoside, was started but was not effective. This case showed significant reduction in peripheral blood T-lymphocytes, especially the CD4+ population, and low immunoglobulin levels. Immunodeficiency state associated with long-term steroid therapy and MDS seemed to contribute to the development of the disseminated infection with MAI.

AIDS-Related Opportunistic Infections↗
PubMed1994

Pleural dissemination in non-small cell lung cancer: results of radiological evaluation and surgical treatment.

The aims of this study are to evaluate the diagnostic ability of chest computed tomography (CT) in the early detection of pleural disease and to analyze the results of surgical treatment for lung cancer with pleural dissemination. Twenty-three non-small cell lung cancer patients with pleural dissemination, but without distant metastasis, underwent pleuropulmonary resection during the past 15 years. Chest CT scans were obtained preoperatively in 21 of those patients. In eight patients without pleural effusion, small pleural nodules, about 3-5 mm in size, were found in their chest CT. However, during surgery, small nodules were more frequently observed on the parietal pleura than on the visceral pleura in five of them. Therefore, early detection of the dissemination by chest CT seemed limited to only those of the visceral pleura. In the survival curve after resection, there was no difference among the patients with n2 disease, but there was a significant difference between the patients without n2 disease and those with it (P < 0.05). The presence of n2 disease appeared to be a poor prognostic sign in this form of advanced lung cancer.

Adult↗
PubMed1994

Effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin on in vivo L-[beta-11C]dopa turnover in the rat striatum with infusion of L-tyrosine.

L-[11C]DOPA, combined with positron emission tomography (PET), has made possible the assessment of dopamine turnover in vivo. Before the evaluation of PET study with L-[11C]DOPA in the primate, the effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) and/or L-tyrosine infusion on L-[11C]DOPA turnover was analyzed in the rat striatal tissue and in the striatal extracellular fluid using microdialysis. L-[11C]DOPA was rapidly taken up into the brain after intravenous injection and converted to [11C]dopamine, [11C]DOPAC and [11C]HVA in the striatal tissue. Small amount of 3-O-methyl-[11C]DOPA, a product of DOPA by 3-O-methylation in peripheral tissues, was also detected in the striatal tissue. The striatum/cerebellum ratio of total radioactivity uptake was linear against time up to 40 min after L-[11C]DOPA injection. The uptake ratio, increased by 6R-BH4 administration, was further increased by L-tyrosine infusion. The in vivo microdialysis technique was further applied to determine L-[11C]DOPA and its metabolites in striatal extracellular fluid (ECF). The peripheral administration of 6R-BH4 (50 mg/kg) induced elevation of [11C]DOPA concentration in ECF in the early phase after injection, following higher radioactivity in [11C]dopamine and [11C]HVA fractions than those in control animals at late phase. The 6R-BH4-induced elevation of [11C]DOPA uptake and the radioactivity of its metabolites was further enhanced by the continuous infusion of L-tyrosine at a dose of 1.0 mumol/min/kg. L-Tyrosine infusion alone did not induce the elevation of radioactivity. The results suggest that [11C]DOPA might be a useful probe to evaluate the effect of 6R-BH4 and/or L-tyrosine loading in the primate.

Animals↗
PubMed1994

Dose and route dependency of metabolism and toxicity of chloroform in ethanol-treated rats.

The effects of a single dose of ethanol on the metabolism and toxicity of chloroform administered to rats per os (p.o.), intraperitoneally (i.p.), or by inhalation (inh) at different doses were investigated. Rats that had been given either ethanol (2 g/kg) or vehicle (water) alone at 4 p.m. on the previous day were challenged with chloroform at 10 a.m. p.o. (0.01, 0.2, or 0.4 g/kg), i.p. (0, 0.1, 0.2, or 0.4 g/kg), or inh (for 6 h each at 0, 50, 100, or 500 ppm). The ethanol treatment, which had no influence on the intake of food and water, increased chloroform metabolism in vitro about 1.5-fold with no significant influence on liver glutathione content. The treatment had a dose-dependent effect on the metabolism and toxicity of chloroform, and the effect differed depending on the route of administration. Compared at the same dose level, the area under the curve (AUC) of blood chloroform concentration was invariably smaller following p.o. than i.p. administration. In accordance with this, chloroform administered p.o. caused more deleterious hepatic damage than the same amount of chloroform administered i.p. Although ethanol treatment had no significant influence on the AUC at any dose by any route of administration, the toxicity of p.o.-administered chloroform was significantly higher in ethanol-treated rats than in control rats at a dose as low as 0.1 g/kg, whereas no significant difference was observed in toxicity between both groups of rats at such a low dose administered i.p.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

[A study of postmortem infectious lesions of bacteremia and fungemia patients--relationship between fungemia and deep mycoses].

Postmortem infectious lesions were analyzed in 63 patients with bacteremia and fungemia. Bacterial infection was found in 36 patients, deep mycoses in 27 and cytomegalovirus infection in 7. Among deep mycoses patients, yeast was noticed in 17, Aspergillus in 13 and Mucor in one. Infectious lesions were not observed in 10 cases. Fifteen cases of 23 leukopenic patients were complicated with deep mycoses. Deep mycoses was noticed in 43% of bacteremia and fungemia patients, but not in candicemia patients. Fungemia due to Candida was related to blood access, however, not to deep mycoses. On the other hand, disseminated mycoses was found in 4 of 5 cases with Trichosporon beigelii fungemia. T. beigelii infection is noticeably life-threatening to the immunocompromised host.

Adolescent↗
PubMed1994

Diameters of juxtacapillary venules determined by oil-drop method in rat lung.

We report a new method for precise quantification of lung microvascular diameter. Isolated blood-perfused rat lungs (500-g Sprague-Dawley rats) at constant inflation pressure [alveolar pressure (PA)] and stopped blood flow were viewed by microscopy and video. Subpleural venules of the second and third postcapillary generations were microinjected with oil colored with Sudan Black. Vascular pressure (Pvas) was varied in steps, and at each step the horizontal diameter (DH) and the length of the oil-filled segment were determined by microcaliper measurements of the replayed video image. At PA = 5 cmH2O, a decrease in Pvas from 25 to 0 cmH2O decreased DH in the second-generation venules from 55 +/- 2 (SE) to 41 +/- 1 microns (n = 13) and in the third-generation venules from 96 +/- 6 to 73 +/- 6 microns (n = 6). The constant-volume oil-filled segment conformed to the cylinder formula in that decreases in DH correlated linearly with 1/ square root of length, thereby indicating that at all Pvas values venular geometry was constant and probably circular in cross section. The decrease in Pvas to -5 cmH2O did not further decrease DH. At Pvas = 10-25 cmH2O, an increase in PA to 15 cmH2O did not significantly increase DH, although the increase in PA did diminish the slope (compliance) of the DH-Pvas relationship in second- but not third-generation venules. We conclude that 1) lung expansion decreases compliance of juxtacapillary venules, 2) venules retain circular cross sections at Pvas between -5 and 25 cmH2O, and 3) venules are patent at subzero Pvas.

Animals↗
PubMed1994

Antihypertensive effect of interleukin-2 in salt-sensitive Dahl rats.

We investigated the effects of interleukin-2, which stimulates the proliferation and maturation of thymus-derived lymphocytes, on hypertension and organ injuries in genetically hypertensive rats. Interleukin-2 (5 x 10(4) U/kg body wt) was subcutaneously injected into Dahl salt-sensitive rats fed a 4% NaCl diet and spontaneously hypertensive rats once a week for 10 weeks. The effects on blood pressure, cardiovascular hypertrophy, and renal function were evaluated. Interleukin-2 treatment lowered blood pressure in Dahl salt-sensitive rats (162 versus 187 mm Hg, P < .005). This antihypertensive effect was associated with an increase in glomerular filtration rate (589 versus 428 mL/d per 100 g body weight, P < .005) and reduction in cardiac weight (268 versus 305 mg/100 g body weight, P < .05). Interleukin-2 also alleviated the marked glomerular sclerosis in Dahl salt-sensitive rats (glomerular injury score, 151 versus 220; P < .001). In contrast, interleukin-2 did not affect the development of hypertension or organ injuries in spontaneously hypertensive rats. Histologically, glomerular and arterial lesions of the kidney were much less marked in spontaneously hypertensive rats than in Dahl salt-sensitive rats. These data indicate that interleukin-2 ameliorates the development of hypertension and cardiac and renal injuries in Dahl salt-sensitive rats.

Animals↗
PubMed1994

Phase I and pharmacologic study of irinotecan and etoposide with recombinant human granulocyte colony-stimulating factor support for advanced lung cancer.

PURPOSE: We conducted a phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) support because of the overlapping neutrophil toxicity of both drugs. The aim was to determine the maximum-tolerated dose of CPT-11 combined with a fixed dose of etoposide in patients with advanced lung cancer, as well as the dose-limiting toxicities of this combination. PATIENTS AND METHODS: Twenty-five patients with stage III or IV lung cancer, 15 (60%) with prior chemotherapy, were treated at 4-week intervals using CPT-11 (90-minute intravenous infusion on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3). In addition, rhG-CSF (2 micrograms/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration. The starting dose of CPT-11 was 60 mg/m2, and it was escalated in 10-mg/m2 increments until the maximum-tolerated dose was reached. RESULTS: The maximum-tolerated dose of CPT-11 was 90 mg/m2, since two of the three patients developed grade 3 to 4 leukopenia or grade 3 to 4 diarrhea during the first cycle of treatment at this dose level. Diarrhea and leukopenia were the dose-limiting toxicities, while thrombocytopenia was only a moderate problem. Elimination of CPT-11 was biphasic, with a mean +/- SD beta half-life of 18.17 +/- 9.09 hours. The mean terminal half-life of 7-ethyl-10-hydroxycamptothecin (SN-38; the major metabolite of CPT-11) was 43.40 +/- 37.84 hours. There was one complete response (5%) and eight partial responses (38%) among 21 assessable patients, for an overall response rate of 43%. The response rates for small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) were 58% (seven of 12 patients) and 22% (two of nine patients), respectively. CONCLUSION: The combination of CPT-11 and etoposide with rhG-CSF support seems to be active against lung cancer, especially SCLC, with acceptable toxicity. The recommended dose for phase II studies in previously untreated patients is 80 mg/m2 of CPT-11 (days 1, 8, and 15) and 80 mg/m2 of etoposide (days 1 to 3) plus 2 micrograms/kg of rhG-CSF (days 4 to 21, except when CPT-11 is given). In addition, 70 mg/m2 of CPT-11 appears to be the appropriate dose for previously treated patients receiving this regimen.

Adult↗
PubMed1994

Benefits and demerits of antihypertensive therapy by high-dose calcium channel blocker in severely hypertensive rats.

This study examined the protective effects of a calcium channel blocker, nisoldipine (NSL), against organ damage secondary to severe hypertension. Severe hypertension was induced in male 7-week-old spontaneously hypertensive rats (n = 21) by heminephrectomy and substitution of 1% NaCl solution for drinking water. They were fed a chow containing 0%, 0.03% (low dose) or 0.1% (high dose) NSL for 12 weeks. The systolic blood pressures after 12 weeks were 228 mmHg in the control group, 201 in the low dose NSL group and 188 in the high dose NSL group. Body weight gain was blunted in the high dose NSL group (at 12 weeks: control 289g; low dose NSL 286; high dose NSL 263, p < 0.04). Although a further reduction in cardiac weight was seen in the high dose NSL rate (low NSL -5.2%, p < 0.05; high NSL -9%, p < 0.01), reductions in aortic thickness did not differ between the 2 doses (low NSL -18%, p < 0.001; high NSL -17%, p < 0.001). Moreover, dose-dependent effects of NSL treatment were absent for such endpoints as plasma creatinine (low NSL -15%, p < 0.04; high NSL -17%, p < 0.05), glomerular filtration rate (low NSL +21%, p < 0.05; high NSL +20%, p < 0.03) and urinary protein excretion (low NSL -22%, p < 0.05; high NSL -29%, p < 0.02). Thus, a high dose calcium channel blocker hampered growth and did not further improve vascular wall thickening or renal injury in severely hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Renoprotective effect of nisoldipine in rats with severe hypertension.

OBJECTIVE: To compare the protective effect against cardiac and renal damage of a beta-blocker, an angiotensin converting enzyme inhibitor and a calcium antagonist in severely hypertensive rats. METHODS: Six-week-old male spontaneously hypertensive rats (n = 24) were given 100 mg/kg deoxycorticosterone and a 4% NaCl diet. They were then treated orally with vehicle, atenolol (70 mg/kg), enalapril (5 mg/kg) or nisoldipine (7 mg/kg) for 8 weeks. RESULTS: Control (vehicle-treated) rats developed marked hypertension after 8 weeks. The antihypertensive effect of the three drugs was similar, as were the reductions achieved in cardiac weight and aortic thickness. However, histological examination revealed that nisoldipine was significantly more effective than the other drugs in reducing renal arteriolar lesions and renal glomerular sclerosis. Only nisoldipine significantly improved plasma creatinine and the glomerular filtration rate. CONCLUSION: These findings suggest that calcium antagonists have a renoprotective effect in severely hypertensive rats, which may derive from the inhibition of arteriolar damage and glomerular sclerosis.

Animals↗
PubMed1994

[Clinical analysis of MRSA pneumonia. Niigata Research Group of MRSA.ABK].

Aged or immuno-compromised patients were mostly affected, by pneumonia caused by infection of MRSA, and more than half of the cases were superinfected with glucose-nonfermentative Gram-negative rods including Pseudomonas aeruginosa. These patients were treated with a monotherapy of arbekacin (ABK) by intravenous drip administration or with a combination of ABK and imipenem/cilastatin, ceftazidime or antifungals. The clinical efficiencies were 55.6% in 11 monotherapy cases and 83.3% in combined therapy. MRSA was eradicated in 31.9% of the patients. These results are comparable with, or superior to the vancomycin therapy in the treatment of MRSA pneumonia. When MRSA is isolated from sputum of pneumonia patients, the discrimination between colonization and infection is important, but the diagnosis is very difficult in many clinical cases before the initiation of chemotherapy. The number of bacteria and the grade of inflammation should be carefully scored before starting a chemotherapy.

Aged↗
PubMed1994

[Clinical evaluation of endoscopic variceal ligation (EVL)].

From August 1992 through February 1993, we treated 21 patients with endoscopic variceal ligation (EVL). Two patients had a history of the esophageal variceal bleeding, but 19 patients did not have bleeding episodes. To evaluate preventive effect of bleeding, we selected the patients who had grade F2 or red color sign positive varices. We repeated EVL until varices improved into grade F0 or F1 and red color sign negative. The therapeutic goal was sometimes changed according to patient's general condition. No additional therapy was performed to eradicate varices, such as endoscopic injection sclerotherapy. As a result of our therapy, eradication rate was 73.7% and period of hospitalization were 25 +/- 11 days. No major complications were found during and after EVL. EVL affected neither liver function test nor size of gastric varices. Recurrent varices with red color sign were found in 4 patients, but easily controlled by retreatment with EVL. EVL seems to be convenient and effective therapy in our short-term study, and useful for preventive therapy of the esophageal variceal bleeding.

Aged↗
PubMed1993

Positron emission tomographic studies on aromatic L-amino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain.

The regional brain kinetics following 5-hydroxy-L-(beta-11 C)tryptophan and L-(beta-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or D-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 +/- 0.0007 (S. D) and 0.0121 +/- 0.0010 min-1 for 5-hydroxy-L-(beta-11 C)tryptophan and L-(beta-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-(beta-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4 mg/kg of unlabelled compound. A decreased utilization rate of L-(beta-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.

5-Hydroxytryptophan↗
PubMed1993

Genetic predisposition to hypertension facilitates blood pressure elevation in hemodialysis patients treated with erythropoietin.

PURPOSE: This study investigated the hypothesis that a genetic predisposition to hypertension is involved in the etiology of the elevation in blood pressure induced by human recombinant erythropoietin (rHuEPO). PATIENTS AND METHODS: Blood pressure changes after 10 weeks of treatment with rHuEPO were compared between 26 patients with a positive family history of hypertension and 27 with a negative family history. RESULTS: Mean blood pressure was significantly increased in patients with a positive family history of hypertension (+8.8 mm Hg, p < 0.001). In contrast, the change was not significant in those whose family history was negative (+1.8 mm Hg, not significant). The mean blood pressure of 14 of 26 patients with a positive family history of hypertension increased by more than 10%, whereas such an increase occurred in only 2 of 27 patients with a negative family history (p < 0.001). The two groups were similar in terms of the total dose of rHuEPO given, the degree to which their anemia improved, and their basal blood pressures. CONCLUSION: It appears that hemodialysis patients with a positive family history of hypertension are susceptible to developing hypertension during treatment with rHuEPO.

Antihypertensive Agents↗
PubMed1993

Direct vasopressor effects of erythropoietin in genetically hypertensive rats.

The purpose of this study is to compare the direct vasopressor effects of erythropoietin between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The aortic rings from SHR or WKY were suspended in tissue baths coupled with tension-recording devices. High concentrations of recombinant human erythropoietin (more than 20 U/ml) induced vasoconstriction in the aortic ring of genetically hypertensive SHR. Furthermore, only in SHR, 10 U/ml erythropoietin enhanced contraction induced by 10(-7) M norepinephrine (+145% vs +121%, p < 0.04) and reduced relaxation by 10(-7) M acetylcholine (-69% vs -96%, p < 0.05). On the other hand, erythropoietin did not influence the contractility of aortic ring in normotensive WKY. These results suggest that erythropoietin exhibits its direct vasopressor effect preferentially in the blood vessels of genetically hypertensive animals.

Acetylcholine↗
PubMed1993

[An infection model which was induced in a carboxymethyl cellulose (CMC) pouch on the back of the rat].

The air-pouch model of inflammation in rats is excellent in that it allows quantitative evaluation of inflammation, and it is used for analysis of inflammatory mediators and as an evaluation system for anti-inflammatory drugs. We investigated the possibility of using this system as an experimental infection system. As a result, inflammation was found to be caused by injection of a constant amount of Staphylococcus aureus solution (10(4)-10(8)). The amount of infiltration and the number of infiltrating cells varied with quantity of bacteria. The infiltrating cells consisted mainly of neutrophils. In this experimental model of infectious disease, the severity of inflammation could be quantitatively evaluated as a function of time in terms of bacterial proliferation and the body's response to bacterial proliferation based on the amount of fluid in the air pouch and the number of infiltrating cells, suggesting that the model is useful. In this experimental system, there were no differences between the number of live bacteria, the number of infiltrating cells or the amount of infiltration when S. aureus Smith strain and clinically-isolated methicillin-resistant S. aureus (MRSA) were used, suggesting that there is no difference between the inflammation-induced activity of MRSA and MSSA.

Animals↗