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Biomedical subjects

K Inada

Publications and source records attributed to K Inada.

At least 55 records · Page 3Linked to original sources

Increased levels of nitrite/nitrate in the cerebrospinal fluid of patients with subarachnoid hemorrhage.

The role of nitric oxide (NO) in the mechanism of delayed cerebral vasospasm (VS) after subarachnoid hemorrhage (SAH) was investigated by analyzing the stable metabolites of NO, nitrite and nitrate, by the Griess method in the cerebrospinal fluid (CSF) and venous blood of 29 patients with SAH, the CSF of 22 control patients, and venous blood from eight normal subjects. VS was defined as diffuse and severe angiographical vasospasm detected by angiography performed around days 7-9 after the onset. Six of the 29 patients had VS. The nitrite/nitrate levels in the blood of patients with SAH were almost within the range of those in normal subjects, but the levels in the CSF of patients with SAH were significantly higher than those of the control group. Patients with VS after SAH had significantly lower levels in the CSF than patients without VS on days 7-9, when VS is most likely to occur. These observations suggest that NO production in the CSF environment occurs following SAH, but possibly may not provoke VS.

Humans↗

Nuclear matrix protein levels in burn patients with multiple organ dysfunction syndrome.

In this study, we investigated multiple organ dysfunction syndrome (MODS) and nuclear matrix protein (NMP), which is an indicator for apoptosis, in burn patients. The subjects were 17 patients with a total burn surface area (TBSA) of 26% or more. Eight of them had MODS, and nine did not. Seven patients died, and 10 survived. The NMP value in the group with MODS (610 +/- 318 units/ml) was significantly higher than in the group without MODS (82 +/- 31 units/ml). The NMP values of the patients who died (645 +/- 326 units/ml) were significantly higher than in the group who survived (111 +/- 95 units/ml), and they rose significantly as the number of impaired organs increased. Our findings suggested that the NMP level in burn cases associated with MODS was higher when apoptosis developed and larger numbers of organs were impaired.

Adult↗

Helicobacter pylori infection enhances glandular stomach carcinogenesis in Mongolian gerbils treated with chemical carcinogens.

Helicobacter pylori (Hp) is thought to be a stomach carcinogen from epidemiological findings. To determine the effects of infection with the bacteria on experimental carcinogenesis, a study of the glandular stomach of Mongolian gerbils (MGs) was performed. Male MGs were treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by inoculation with Hp or infected with Hp followed by N-methyl-N'-nitro-N-nitrosoguanidine administration. Animals were killed at week 50, and their excised stomachs underwent microbiological and histopathological examinations. In addition, a serological investigation was performed. The incidences of adenocarcinomas were significantly higher in animals treated with 60 or 300 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 10 weeks followed by Hp inoculation or Hp followed by 20 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 30 weeks than in the respective controls. Moreover, tumour-bearing animals had higher titres of anti-Hp antibodies than tumour-free animals. Of interest was the finding that a dose of 100 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine given to infected gerbils eradicated the Hp in about half the animals, with a concomitant reduction in the promoting effect. No tumours were found in animals infected with Hp without N-methyl-N'-nitro-N-nitrosoguanidine or non-treated gerbils. Hp infection enhances glandular stomach carcinogenesis in MGs treated with N-methyl-N'-nitro-N-nitrosoguanidine. Animals with high titres of anti-Hp antibodies are at greatest risk of developing neoplasms.

Adenocarcinoma↗

Influence of methylprednisolone on cytokine balance during cardiac surgery.

OBJECTIVE: To determine the influence of methylprednisolone on the cytokine balance during cardiac surgery. DESIGN: Prospective, randomized, nonblinded study. SETTING: University hospital. PATIENTS: Twenty-one patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery. INTERVENTIONS: According to a randomized sequence, the patients either received methylprednisolone (30 mg/kg) [corrected] before cardiopulmonary bypass and before declamping of the aorta (MPS group, n = 11) or received nothing (control group, n = 10). MEASUREMENTS AND MAIN RESULTS: Serum proinflammatory cytokines (interleukin [IL]-8, IL-6) and anti-inflammatory cytokines (IL-10, IL-1ra) were measured by enzyme-linked immunosorbent assays. Serum IL-6 and IL-8 concentrations in the control group (15.2 +/- 4.1 and 14.1 +/- 1.9 pg/mL, preoperatively) increased to 242 +/- 70.1 and 97.3 +/- 18.3 pg/mL at 60 mins after declamping of the aorta (p < .01, p < .01, respectively). The increases were greater than those from 2.5 +/- 0.6 and 2.5 +/- 0.5 pg/mL to 109.5 +/- 29.0 and 33 +/- 4.1 pg/mL in the MPS group for IL-6 and IL-8, respectively. Serum IL-10 concentrations increased significantly 60 mins after declamping of the aorta compared with its preoperative value in the two groups (the control group, from 1.0 +/- 0 to 537.9 +/- 61.7 pg/mL; the MPS group, from 0.3 +/- 0.2 to 654.9 +/- 24 pg/mL [p < .01, p < .01, respectively]). No difference was found between the two groups. Similarly, serum IL-1ra concentrations in the two groups increased the preoperative value in the control group from 304 +/- 120 to 44,374 +/- 14,631 pg/mL and in the MPS group from 616.5 +/- 109.6 to 35,598 +/- 9,074 pg/mL at 60 mins after declamping of the aorta (p < .01, p < .01, respectively). There was no difference between the two groups. CONCLUSIONS: Methylprednisolone reduces the production of IL-6 and IL-8 but not that of IL-10 and IL-1ra. These results suggest that one of the mechanisms of the cytoprotective effect of methylprednisolone may be to make changes in the proinflammatory and anti-inflammatory cytokine balance.

Aged↗

[Evaluation of procalcitonin levels in patients with systemic inflammatory response syndrome as the diagnosis of infection and the severity of illness].

To understand the presence or absence of bacterial infection in patients with systemic inflammatory response syndrome (SIRS), the level of procalcitonin (PCT), a precursor of calcitonin, was determined. Subjects consisted of 14 SIRS patients without complication by bacterial infection, 14 SIRS patients complicated by sepsis, and 14 SIRS patients complicated by severe sepsis and septic shock. PCT levels in SIRS patients with sepsis (2.9 +/- 2.3 ng/ml) were significantly higher than those in SIRS patients without complication by infection (0.7 +/- 1.1 ng/ml). However, there were no significant differences in the levels of C-reactive protein (CRP), interleukin 6 (I-6) or tumor necrosis factor-alpha (TNF-alpha) between the two groups. PCT levels in SIRS patients with severe sepsis and septic shock (172.2 +/- 276.3 ng/ml) were significantly higher than those in SIRS patients with sepsis. Levels of CRP, IL-6 and TNF-alpha were also significantly higher in the patients with sepsis compared to those in patients with local infection. Significant correlations were observed between the levels of PCT and those of CRP, IL-6 and TNF-alpha in SIRS patients. It was suggested that to measure the levels of procalcitonin in patients with SIRS is useful to diagnose the infection and severity of illness.

Adult↗

Analysis of fusion junctions of circularized chromosomes in Streptomyces griseus.

A filamentous soil bacterium, Streptomyces griseus 2247, carries a 7. 8-Mb linear chromosome. We previously showed by macrorestriction analysis that mutagenic treatments easily caused deletions at both ends of its linear chromosome and changed the chromosome to a circular form. In this study, we confirmed chromosomal circularization by cloning and sequencing the junction fragments from two deletion mutants, 404-23 and N2. The junction sequences were compared with the corresponding right and left deletion end sequences in the parent strain, 2247. No homology and a 6-bp microhomology were found between the two deletion ends of the 404-23 and N2 mutants, respectively, which indicate that the chromosomal circularization was caused by illegitimate recombination without concomitant amplification. The circularized chromosomes were stably maintained in both mutants. Therefore, the chromosomal circularization might have occurred to prevent lethal deletions, which otherwise would progress into the indispensable central regions of the chromosome.

Amino Acid Sequence↗

Effect of magnesium sulfate pretreatment and significance of matrix metalloproteinase-1 and interleukin-6 levels in coronary reperfusion therapy for patients with acute myocardial infarction.

Magnesium (Mg) inhibits the influx of calcium in vascular smooth muscle cells. The purposes of this study were to test the hypothesis that an intravenous administration of magnesium might effect the complement response and to determine the effects of a magnesium pretreatment of patients with acute myocardial infarction (AMI) on the incidence of reperfusion injuries. Thirty-eight AMI patients were treated with coronary reperfusion therapy within 6 hours of onset. They were randomly divided into two groups: group pretreated with intravenous magnesium sulfate (0.27 mmol/kg) (magnesium group, n = 19), and nonpretreated controls (placebo group). The reperfusion injuries observed within 1 hour after the coronary reperfusion included arrhythmias, aggravated chest pain, and ST segment elevation in 12-lead electrocardiograms. Coronary recanalization was performed in 36 patients. The incidence of reperfusion arrhythmia was significantly lower in the magnesium group than in the placebo group (17% vs 78%, p<0.001). At the postreperfusion stage, there was a tendency for the degree of ST segment reelevation in the magnesium group lower than in the placebo group (2.5 +/- 2.3 mm vs 4.7 +/- 3.8 mm, p = 0.07). No marked difference was observed in the incidence of chest pain aggravation between the two groups (67% vs 73%, ns). The peak serum levels of interleukin-6 (IL-6) were significantly lower in the magnesium group than those in the placebo group (38.9 +/- 25.0 vs 92.3 +/- 76.5 pg/mL, p = 0.016). The peak serum levels of matrix metalloproteinase-1 (MMP-1) were lower than those in the placebo group (16.2 +/- 4.8 vs 19.7 +/- 9.0 ng/mL, p = 0.09), but the difference was not significant. A positive correlation was observed between the peak MMP-1 values and the peak IL-6 values (r = 0.57, p = 0.001) in all patients. Increased serum ionized Mg2+ may inhibit arrhythmic recurrence and the production of IL-6 and MMP-1 after reperfusion and prevent the increase of myocardial lesions caused by calcium overload on myocytes. The increased IL-6 production may induce MMP-1, leading to tissue organ injury. Pretreatment with magnesium sulfate may protect the myocardium of AMI patients from reperfusion injuries.

Adult↗

Cascade of acetazolamide-induced vasodilatation.

UNLABELLED: Acetazolamide (AZ) has been found to be effective in inducing vasodilatation. To evaluate the mechanism by which AZ acts, we compared the effects of this agent on vascular PGI2, endothelin (ET-1), and NOx, with those induced by CO2 gas inhalation. METHOD: Blood flow (BF) was measured in the liver, kidneys, stomach wall, and abdominal muscle of anesthetized white rabbits with a laser flow meter at baseline and again after sequential doses of AZ (4 mg/kg) or CO2 inhalation. Cardiac output and serum concentrations of PGI2, ET-1, and NOx were also measured in these animals. RESULTS: AZ increased BF in the liver and kidneys, but had no effect on BF in the stomach wall or abdominal muscle. The level of NOx was decreased following the administration of AZ, while PGI2 and ET-1 levels remained unchanged. In contrast, CO2 inhalation increased PCO2, and decreased pH, significantly. CO2 elevated BF in the liver, kidneys, stomach wall, and abdominal muscle, as well as serum levels of PGI2 and ET-1, while having no effect on NOx levels. The alterations in BF, PGI2, ET-1, and NOx in response to AZ, suggest that the mechanism of AZ-induced vasodilatation may involve a cascade that is triggered by CO2 retention similar to that caused by the inhalation of CO2.

6-Ketoprostaglandin F1 alpha↗

The first report on human cases serologically diagnosed as Japanese encephalitis in Indonesia.

Although Japanese encephalitis (JE) virus was isolated from mosquitos in 1974, human JE cases have never been reported in Indonesia in spite of the prevalence of anti-JE antibodies among human and pig populations as well as abundant JE vector mosquitos. In this report, we describe serological diagnosis of JE cases in Bali. Indonesia. using IgM-capture ELISA both on serum and cerebrospinal fluid (CSF) of the patients. In the first series of our investigation (Series 1), we examined serum specimens from 12 patients with clinical diagnosis of viral encephalitis, meningitis or dengue hemorrhagic fever (DHF), and found 2 possible JE cases. In the next series (Series 2), we examined both serum and CSF from encephalitis patients and gave laboratory diagnosis of JE. One of them was suspected to have concomitant or recent infection with dengue virus, probably type 3. These results strongly indicated that JE has been prevalent in Bali, Indonesia.

Child, Preschool↗

c-Fos induces apoptosis in germinal center B cells.

We examined the role of c-Fos in the differentiation of mature B cells into IgG-producing cells using transgenic mice carrying the c-fos gene under the control of the IFN-alpha/beta-inducible Mx promoter (Mx-c-fos) or the constitutive H-2Kb promoter (H2-c-fos). Splenic B cells from Mx-c-fos mice were cultured with LPS and rIL-4, and IgG1+ B cells were developed in the culture after day 3. When IFN-alpha/beta was added to the culture from day 2, development of IgG1+ B cells was perturbed, and the number of apoptotic cells increased within 24 h, suggesting that c-Fos induces apoptosis in Ig class-switching B cells. To confirm the effect of c-Fos on B cell differentiation in vivo, H2-c-fos mice were immunized with DNP-OVA. The mice produced primary IgM, but not IgG, anti-DNP Ab in serum and failed to generate germinal centers in spleen. The perturbation of germinal center formation in H2-c-fos mice was rescued by mating them with transgenic mice carrying the bcl-2 gene with the Ig promoter. However, primary IgG1 anti-DNP Ab production was still suppressed in doubly transgenic mice, suggesting that Bcl-2 can delay the time of c-Fos-induced apoptosis in Ig class-switching B cells but cannot rescue the death. Since c-Fos is induced in mature B cells reacted with Ags, and clonal deletion of self-reactive B cells in germinal centers is insensitive to Bcl-2, these results suggest that c-Fos plays a causal role in clonal deletion of germinal center B cells.

Animals↗

A new prognostic factor for colorectal carcinoma, thymidylate synthase, and its therapeutic significance.

BACKGROUND: Expression of thymidylate synthase (TS) has been studied as a mechanism of drug resistance and a prognostic factor for various cancers. METHODS: The relation between TS expression in surgically resected specimens and patient survival was examined in 86 patients with colorectal carcinoma (58 of whom received adjuvant chemotherapy and 28 who did not) who had been followed for 10 years. Immunohistochemical demonstration of the protein was achieved using an anti-TS polyclonal antibody. RESULTS: In the 58 patients who received chemotherapy, the overall 10-year survival rate was 77.8% for patients with TS positive tumors and 89.4% for patients with TS negative tumors (difference not significant). However, in the 28 patients who did not receive chemotherapy, these figures were only 42.9% and 85.7%, respectively (P < 0.05). Multivariate analysis also revealed TS expression to be a significant variable for predicting postoperative survival (P < 0.05). CONCLUSIONS: TS expression can be used as an independent prognostic factor for patients with colorectal carcinoma. Patients with TS positive tumors have a poorer prognosis than those with TS negative lesions and therefore should receive special consideration with regard to chemotherapy.

Antibiotics, Antineoplastic↗

Inflammatory cytokines locally elevated in chronic subdural haematoma.

The involvement of inflammation in the development and propagation of chronic subdural haematoma (CSH) was investigated by measuring the levels of inflammatory cytokines (tumour necrosis factor [TNF] alpha, interleukin [IL]-1 beta, IL-6, and IL-8). Peripheral venous blood and subdural fluid were obtained at the time of burr hole surgery from 34 patients with CSH and from 9 with subdural effusion. The levels of the inflammatory cytokines were analysed by enzyme-linked immunosorbent assay. The blood levels of TNF alpha, IL-1 beta, IL-6, and IL-8 in both CSH and subdural effusion groups were almost within the range of normal subjects, and no differences were observed between the two groups. IL-6 and IL-8 in the subdural fluid were much higher than in the blood of both groups, and the levels in CSH patients were significantly higher (10 times) than in subdural effusion patients. Local elevation of inflammatory cytokines in the subdural space of both CSH and subdural effusion without systemic change suggests the presence of local inflammation in the two diseases. The same behavioural patterns of cytokines for these and higher levels of cytokines in the CSH also suggest that inflammatory cytokines may be involved in the continuous development from subdural effusion to CSH and propagation of CSH.

Adult↗

Stenting for airway obstruction in the carinal region.

BACKGROUND: Recent progress on airway stents has provided sufficient airway patency for patients with airway obstruction; however, when the stenosis exists in the carinal zone, establishing an excellent airway condition is still troublesome because of the anatomic structure. METHODS: We treated 15 patients with severe tracheobronchial stenosis involving a carinal bifurcation region, using several types of stenting devices (long T-tube, T-Y tube, wire reinforced Y tracheostomal tube, Freitag Dynamic stent [Karl Storz, Tuttlingen, Germany], and covered metallic stent). All patients had advanced inoperable tumors (lung cancer, n = 6; esophageal cancer, n = 3; thyroid cancer, n = 3; mediastinal tumor, n = 3). RESULTS: All but 2 patients had immediate relief of respiratory symptoms. One patient died of respiratory failure caused by pulmonary lymphatic spread 3 days after Dynamic stent insertion. In 1 patient with severe left main bronchial stenosis due to lung cancer, effective palliation was not achieved by insertion of a covered metallic stent because of its insufficient expansion against the stenosis. Mean survival after successful stenting was 4.3 months (range, 1 to 15 months). There were no complications directly attributable to the stents. CONCLUSIONS: As evidenced by the clinical effectiveness, airway stenting for inoperable tumor is valuable in such patients. Choosing a stent that will fully cover the lesion and allow sufficient tolerance against compression is important to successful stenting. Benefits such as ease of phonation and stent maintenance should also be considered.

Bronchial Diseases↗

Plasma levels of type II phospholipase A2 and nitrite/nitrate in patients with burns.

Type II phospholipase A2 (type II PLA2), nitrite/nitrate (NOx), tumor necrosis factor-alpha (TNF-alpha) and endotoxin were studied in burn patients. Type II PLA2 values and NOx values were both significantly higher in the group that died, the group with shock as a complication and the group with multiple organ dysfunction syndrome (MODS) as a complication, than in the group that survived, the group without shock as a complication and the group without MODS as a complication, respectively. The results suggested that type II PLA2 and nitric oxide (NO) may play a major role in the pathology of burn patients. Significant correlations were found between TNF-alpha and type II PLA2 values and between type II PLA2 and NOx values, suggesting the possibility of involvement in each other's production.

Adult↗

The tracheal tube with a high-volume, low-pressure cuff at various airway inflation pressures.

When the tracheal tube with a high-volume, low-pressure cuff is used, the pressure exerted by the cuff on the tracheal wall is similar to the intracuff pressure, and the pressure is claimed to be lower than the capillary perfusion pressure; however, it is not known if this is the case when a high airway pressure is required. In a randomized, cross-over design, we studied 61 patients (31 men) and measured the intracuff pressures of the tracheal tube at various airway pressures. While the lungs were inflated at five different airway pressures in turn (10, 15, 20, 25 and 30 cm H2O), the cuff of the tracheal tube was inflated with air until it prevented an airleak ('just-seal' pressure). Intracuff pressures [median (range)] at airway pressures of 10, 15, 20, 25 and 30 cm H2O were 8 (0-20), 15 (4-20), 22 (6-32), 26 (11-52) and 31 (16-54) cm H2O, respectively, for men and 6 (0-20), 11 (0-20), 15 (0-24), 21 (0-32) and 25 (1-41) cm H2O, respectively, for women. Therefore, we conclude that the pressure exerted by the cuff of the tracheal tube on the tracheal wall is unlikely to exceed the capillary perfusion pressure (arbitrarily defined as 25 mmHg or 34 cm H2O) when the airway pressure is 25 cm H2O or less, but it may exceed the capillary perfusion pressure when the airway pressure is greater than 25 cm H2O.

Anesthesiology↗

Increased expression of sucrase and intestinal-type alkaline phosphatase in human gastric carcinomas with progression.

The activities of sucrase, total alkaline phosphatase (total ALP) and intestinal-type alkaline phosphatase (I-ALP) were assayed in gastric carcinomas and in their surrounding mucosae from 57 patients with advanced cancers, and the localization of sucrase in 203 carcinomas, including 86 early cancers, was examined immunohistochemically using polyclonal anti-sucrase antibody. All three enzymes were active in the 57 carcinomas as well as in their surrounding mucosae, but the levels were fairly low as compared to those in normal jejunum mucosa. A considerable part of the total ALP activity in tumor specimens was assumed to be due to I-ALP itself. Increased sucrase and I-ALP were found with greater depth of invasion by undifferentiated-type carcinomas. The pattern of immunohistochemical localization of sucrase in the 203 carcinomas also clearly indicated increased expression with greater depth of invasion even in differentiated-type carcinomas.

Adenocarcinoma↗

N-methyl-N-nitrosourea concentration-dependent, rather than total intake-dependent, induction of adenocarcinomas in the glandular stomach of BALB/c mice.

The influence of the level of carcinogen exposure on histopathological types and cellular differentiation of the induced tumors was examined in 100 male BALB/c mice given N-methyl-N-nitrosourea (MNU) in their drinking water at 240 ppm on alternate weeks (total exposure: five weeks) (groups 1), at 120 ppm similarly (total exposure: ten weeks) (group 2), at 60 ppm for 20 weeks continuously (group 3), or at 30 ppm for 40 weeks continuously (group 4). Forty-three differentiated and 17 undifferentiated type adenocarcinomas were induced. Glandular stomach carcinomas and undifferentiated type lesions were more common in mice treated with a high concentration of MNU for a short period than with a low concentration of MNU for a long period, even though total measured intake of MNU was smaller (P < 0.01). All the induced glandular stomach carcinomas, independent of the treatment schedule, consisted entirely of gastric phenotype cells. In conclusion, the induction of glandular stomach cancers and the proportion of undifferentiated type lesion depend not on the total quantity, but rather on the concentration of the carcinogen, while the phenotypic expression of tumor cells in not affected by the differences in the administration protocol.

Adenocarcinoma↗