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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 199 records · Page 11Linked to original sources
PubMed1998

Computed tomographic findings in non-specific interstitial pneumonia/fibrosis.

The entity of non-specific interstitial pneumonia/fibrosis (NIP) has recently been recognized as an addition to the current classification of idiopathic interstitial pneumonia, which includes usual interstitial pneumonia, desquamative interstitial pneumonia, diffuse alveolar damage, and bronchiolitis obliterans organizing pneumonia. We studied the computed tomographic (CT) findings of nine NIP patients who were diagnosed pathologically. The main findings were ground glass opacities (66.7%), airspace consolidation (88.9%) and reticular opacities (89.7%), distributed predominantly in the bilateral and lower lung. In all cases, the clinical and abnormal opacification observed on the chest CT was improved by the administration of corticosteroid. Both the subpleural and patchy distributed opacifications predominantly in the bilateral and lower lung, and the good response to treatment may help to differentiate non-specific interstitial pneumonia from other types of idiopathic interstitial pneumonia.

Adult↗
PubMed1998

Secondary treatment failure without anti-human chorionic gonadotropin antibody in a patient with Kallmann syndrome.

A 29-year-old man with Kallmann syndrome suddenly developed decreased semen volume, azoospermia, and facial hair loss after 11 years of successful human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) treatment. Anti-hCG antibody was not detected in the patient's serum. A high serum level of luteinizing hormone (LH) with nasal LH-releasing hormone analogue administration failed to increase serum testosterone to a sufficient level. Testosterone injection after cessation of hCG and hMG therapy was able to improve semen volume, but not azoospermia. Resumption of hCG and hMG therapy after 6 months cessation partially restored spermatogenesis. The secondary failure of hCG and hMG therapy suggests a decrease of testicular sensitivity to LH as well as hCG.

Adult↗
PubMed1998

Replication error frequencies in primary hepatocellular carcinoma: a comparison of solitary primary versus multiple primary cancers.

AIMS/BACKGROUND: Replication errors (RERs) at microsatellite loci are associated with the development of not only hereditary nonpolyposis colon cancer but also sporadic cancers. To examine the association between RERs and human hepatocarcinogenesis, we looked for microsatellite instability in solitary and multiple primary hepatocellular carcinomas (HCCs). METHODS: DNAs were extracted from 34 solitary primary HCCs and 14 HCCs with multiple primary cancers. Twelve microsatellite alleles were amplified by PCR from the DNAs, and RERs were assessed by their mobility shift. RESULTS: RERs were found in only two cases (6%) of solitary HCC and four cases (29%) of HCC with multiple primary cancers. Two of the four HCCs with multiple primary cancers showed RERs at two and three microsatellite loci, respectively. Of 12 microsatellite loci examined, TP53 and D16S476 sensitively detected RERs in HCCs with multiple primary cancers, at a frequency of 23% and 33%, respectively. CONCLUSIONS: RERs are rarely associated with carcinogenesis in human primary HCC, and RER-related genetic alterations may be associated with a part of HCC with multiple primary cancers. If future studies confirm this association, then the two probes TP53 and D16S476 may be useful for the prediction of development of multiple primary cancers with HCC.

Adolescent↗
PubMed1998

Effects of cytokines and minocycline on subacute lung injuries induced by repeated injection of lipopolysaccharide.

Pathological changes were seen in the lungs of ddY mice one week after repeated intraperitoneal injections of lipopolysaccharide (LPS) of Klebsiella pneumoniae. The infiltration of polymorphonuclear cells (PMN), mainly neutrophils, and lymphocytes into the alveolar septum, the infiltration of PMN into perivascular areas and microthrombi were recognized in this murine model. The blood levels of TNF alpha and IL-1 alpha did not rise at this time, suggesting that the most important cytokine promoting inflammation one week after LPS stimulation was neither TNF alpha nor IL-1 alpha. In the lungs of mice administered minocycline together with LPS, lymphocyte infiltration of alveoli and perivascular areas as well as microthrombi were suppressed. The blood levels of TNF alpha, IL-1 alpha, IL-4 and IL-6 were elevated in these groups, suggesting the suppression of pathological changes to be associated with the anti-inflammatory effect of IL-6 and/or persistent elevation of TNF alpha and/or IL-1 alpha levels. In conclusion, subacute pathological changes in the lung were induced by repeated intraperitoneal injections of LPS to mice. These pathological changes were suppressed by minocycline, suggesting the anti-inflammatory effects of this antibiotic to be the result of stimulating certain cytokines.

Animals↗
PubMed1998

Role of phosphodiesterase 4 isoenzyme in alkaline phosphatase activation by calcitonin in porcine kidney LLC-PK1 cells.

To confirm the intracellular signal transduction in regulation of alkaline phosphatase (ALP) activity by calcitonin in kidney tubular cells, effects of several inhibitors of cyclic nucleotide phosphodiesterase (PDE) isoenzymes and cyclic AMP-dependent protein kinase (PKA) on the action of salmon calcitonin in porcine kidney tubular epithelial cells LLC-PK1 were examined. A confluent culture of LLC-PK1 cells was treated with calcitonin and inhibitors in Dulbecco's modified Eagle's medium supplemented with 0.1% bovine serum albumin, and intracellular cyclic AMP content and ALP activity were measured after incubation for 30 min and 48 hr, respectively. Calcitonin and PDE 4 inhibitors increased cyclic AMP level and ALP activity in the cells, and PDE 4 inhibitors synergistically potentiated the effects of calcitonin. Calcitonin induced ALP activation by treatment for the first 1 hr, as well as continuous treatment for 48 hr, while it never increased the enzyme activity just after 1-hr exposure. Rolipram, an inhibitor of PDE 4 isoenzyme, induced ALP activation by itself and in combination with calcitonin by only a long term treatment (48 hr). The activation of ALP by calcitonin and rolipram each alone and in combination was completely abolished by a PKA inhibitor, H-89. These results confirm that calcitonin induces ALP activation through the cyclic AMP-PKA pathway and that PDE 4 isoenzyme is closely associated with the calcitonin-receptor system and plays a major role in hydrolysis of cyclic AMP produced in the kidney tubular cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

[A proposed method for evaluating short-term exposure condition].

High short-term exposure to toxic chemicals can occur during a workday, even if the daily average exposure is lower than the permissible exposure limit, because the exposure concentration varies from minute to minute. To protect workers from acute health effects due to high short-term exposure, the Japan Society for Occupational Health recommends that the maximum value for 15-min time-weighted average (15-min TWA) exposure during a workday should not exceed 1.5 times the occupational exposure limit for 8-hr TWA, and the American Conference of Governmental Industrial Hygienists issues the threshold limit value-short-term exposure limit (TLV-STEL), that is a 15-min TWA exposure which should not be exceeded at any time during a workday. A workday (8 hr) consists of thirty two 15-min periods. If the thirty-two 15-min TWAs are measured, the short-term exposure situation can be appropriately evaluated by comparing the highest measured value with the standard value (e.g. TLV-STEL), but such continuous monitoring consumes a lot of cost and time. In this paper, we propose a method for evaluating short-term exposure by using three or more measured values. This evaluation method corresponds to two different types of selection of sampling periods. One is a random selection of three or more 15-min periods among the 32 periods. If this selection is adopted, a comparison between the 98.44 percentile of the within-day distribution of 15-min TWAs and the standard value can be made by using one-sided tolerance factors, KI, KII and KIII, and the exposure situation is classified into four exposure classes at 95% and 50% confidence levels. Another is a random selection among high exposure periods. If this selection is adopted, a comparison between the specific percentile of the distribution and the standard value can be made with modified one-sided tolerance factors, and the exposure class is determined similarly. This method can provide a precise evaluation of exposure, so that it is useful in the industrial hygiene field.

Chemical Industry↗
PubMed1998

Effects of excess K+ on carbachol-induced contractions in the guinea-pig tracheal muscle.

1. In smooth muscles isolated from the guinea-pig trachea, the effects of dihydropyridines, nifedipine and nicardipine on contractions produced by carbachol (Cch) were studied in normal (6 mM) and excess K+ concentration (60 mM). The tonic contraction produced by 1 microM Cch was highly dependent on the external Ca2+ concentration ([Ca2+]0) and was not significantly affected by cyclopiazonic acid or thapsigargin, Ca2+ uptake inhibitor. 2. [Ca2+]0-tension curves were steeper in the presence of 1 microM Cch (the Hill coefficient: 2.5) than in the presence of 60 mM K+ (Hill coefficient: 1.6) and their ED50 of Ca2+ was 0.16 and 0.39 mM, respectively. An increase of K+ to 60 mM in the presence of 1 microM Cch shifted the curve to the left roughly in parallel (ED50: 0.12 mM, Hill coefficient: 2.3). 3. [Ca2+]0-tension curve in the presence of 1 microM Cch was shifted to the right in parallel by nifedipine (1 microM). This was markedly potentiated by 60 mM K+ (the increase in ED50 of Ca2+ being 3 times at 6 mM and 15 times at 60 mM K+). No tension was evoked by Ca2+ up to 2.5 mM in 60 mM K+ solution containing 1 microM nifedipine but no Cch. 4. In the absence of nifedipine, Cch-induced contractions were potentiated by 60 mM K+, whereas in the presence of nifedipine, Cch-induced contractions were markedly inhibited by 60 mM K+. These mechanical changes were accompanied by an increase or a decrease in intracellular Ca2+. 5. A hypothesis is presented to explain the results which suggests that the kinetics of Ca2+ influx though a single type of pathway is modulated by membrane potential and receptor activation and that the susceptibility of the pathway to dihydropyridine blockade is closely related to the Ca2+ influx kinetics with receptor activation reducing and membrane depolarization increasing the susceptibility.

Animals↗
PubMed1998

[Risk factors for sudden death during hospitalization].

To determine the risk factors for sudden deaths in hospitalized patients, 209 patients (103 men and 106 women, age 76.7 +/- 12.6 years old, mean +/- S.D.) who died in 1996 were divided into two groups and their records were analyzed. One group, the sudden death group (SD), consisted of 16 patients who had stayed in the hospital for 2 weeks or more before the onset of symptoms that led to death within 24 hours. Those who died more than 24 hours after symptoms began were placed into the non-sudden death group (NSD). Fourteen patients who died within 2 weeks of admission were not analyzed in this study. Comparing the data of the two groups led to the following findings. First, the major causes of death in the SD group were exacerbation of chronic cardiac failure (5 cases), acute cardiac failure (2 cases), exacerbation of chronic respiratory failure (2 cases) and acute respiratory failure (2 cases). Second, patients in the SD group were significantly older than those in the NSD group, and had significantly more prescriptions for digitalis. Third, patients in the SD group had higher levels of hemoglobin and hematocrit, lower levels of BUN and a higher cardiothoracic ratio. Fourth, patients in the SD group had a higher incidence of ST abnormalities and T wave abnormalities in their electrocardiograms. Brugada syndrome or long QT syndrome were not seen in either group. Taken together, these findings suggest that aged patients with cardiac failure and myocardial ischemia may be at higher risk of sudden death.

Aged↗
PubMed1998

Glucosylquestiomycin, a novel antibiotic from Microbispora sp. TP-A0184: fermentation, isolation, structure determination, synthesis and biological activities.

Glucosylquestiomycin, a novel N-glucopyranoside of questiomycin A, was isolated from the culture broth of Microbispora sp. TP-A0184. The absolute configuration of the sugar was determined as D-configuration by chemical synthesis. The new antibiotic showed antibacterial activity against gram-positive and -negative bacteria and yeasts and cytotoxic activity against U937 cells.

Anti-Bacterial Agents↗
PubMed1998

[The effect of hepatic arterial infusion chemotherapy on the prognosis after hepatectomy for hepatocellular carcinoma].

The effect of hepatic arterial infusion chemotherapy on the prognosis after hepatectomy for hepatocellular carcinoma was investigated in patients with risk factors for recurrence. The risk factors for recurrence after hepatectomy were defined to be metastasis in the liver (+), portal tumor embolus (+), and tumor larger than 5 cm in diameter. Out of 87 patients with hepatocellular carcinoma who underwent an operation in the past 7 years in our hospital, 60 survived for more than 1 year and were enrolled in our study. Thirty-eight of them showed one or more risk factors for recurrence, and were considered to be the high-risk group. These 38 patients were divided into two groups: one group of 19 treated by hepatic arterial infusion chemotherapy using mitoxantrone, and the other group of 19 given no treatment. The survival rates and non-recurrence rates were compared between the two groups. The survival rates after 1 and 3 years for the group treated by hepatic arterial infusion chemotherapy were 94.7% and 54.7%, respectively. The survival rates for the non-treated group were 53.9% and 32.8%, respectively (p = 0.012). The non-recurrence rates after 1 year and 3 years were 94.7% and 44.2% for the treated group and 52.6% and 23.6% for the non-treated group (p = 0.005), respectively. The survival rates and non-recurrence rates after 3 years in the treated group were significantly higher (p = 0.012, 0.005), respectively. It was concluded, therefore, that post-operation hepatic arterial infusion chemotherapy improved the prognosis of the high-recurrence probability group.

Antibiotics, Antineoplastic↗
PubMed1998

[Japan Coma Scale as a grading scale of subarachnoid hemorrhage: a way to determine the scale].

BACKGROUND: The grading scale for subarachnoid hemorrhage (SAH) with inter-grade outcome differences is essential for evaluating the effectiveness of newly developed therapeutic modalities. Although Hunt's grade and WFNS scale have been widely used, these grading scales do not meet this requirement. We previously proposed a revised WFNS scale based solely on the Glasgow Coma Scale (GCS) that has intergrade outcome differences of high-level significance. The Japan Coma Scale (JCS) has been long and widely used in Japan. The purpose of this study is to show whether it is possible to determine a reasonable SAH grading scale based on the JCS and to show a way to determine an SAH grading scale. PATIENTS AND METHODS: We retrospectively analyzed 1398 consecutive cases of aneurysmal SAH operated on within Day 7 of the latest onset. The preoperative JCS and GCS were evaluated just before the surgery and the Glasgow Outcome Scale (GOS), analyzed with numerical transformation (1 = dead to 5 = good recovery), was estimated at 6 months after the onset. All 510 possible combinations of scores of JCS were statistically tested under the following 2 assumptions; (1) JCS = 0 and JCS = 100 fall into a single independent grade. (2) No other single JCS score should fall into a single grade. RESULTS: The outcome differences between JCS 0 and 1, and 100 and 200 are significant. The outcome difference between JCS 30 and 100 is relatively higher than any other set of 2 scores of JCS. Only 5 combinations are practical among the candidates to be analyzed. Out of 510 combinations, the following combination shows the highest inter-grade outcome differences; I (JCS = 0, n = 375, mean GOS = 4.78) II (JCS = 1, 2; n = 310; mean GOS = 4.47) III (JCS = 3-30; n = 476; mean GOS = 3.96) IV (JCS = 100; n = 96; mean GOS = 3.10) V (JCS = 200, 300; n = 141; mean GOS = 2.33). In JCS, the mean outcome of JCS = 3 is worse than those of JCS = 10, 20, and 30. The outcome difference between JCS 0 and 1 is only significant in patients over 60 years old. CONCLUSION: Taking all the 510 possible combinations of JCS into consideration, we obtained a reasonable combination containing 5 grades. Although this grading scale showed good inter-grade outcome differences, JCS is not preferable to GCS as a consciousness evaluation system in the acute phase of SAH. We emphasize the importance of this way to determine a grading scale with a combinatorial approach, which can be applicable for re-evaluating the grading scales in the future.

Age Factors↗
PubMed1998

Effects of atrial natriuretic peptide and 8-brom cyclic guanosine monophosphate on human tracheal smooth muscle.

The relaxant effects of intracellular concentration of cyclic guanosine monophosphate (cGMP) on spontaneous tone in human tracheal smooth muscle were investigated in comparison with guinea pig, using isometric tension records. In both human and guinea pig tracheas, application of atrial natriuretic peptide (ANP) and 8-brom cGMP (a membrane permeable analogue of cGMP) caused an inhibition of spontaneous tone in a concentration-dependent fashion. However, ANP was less potent in relaxation of tracheal smooth muscle in human than guinea pigs, and values of % relaxation induced by 1 mmol/l ANP in human and guinea pigs were 37.1 +/- 5.3 and 82.7 +/- 10.5%, respectively (n = 6). In the presence of 30 nmol/l iberiotoxin (IbTX), a potent and selective large conductance Ca(2+)-activated K+ (BKCa) channel inhibitor, relaxant actions of ANP on human tracheal smooth muscle were markedly suppressed, and values of % relaxation by 1 mmol/l ANP decreased to 8.4 +/- 1.2% (n = 6). On the other hand, 8-brom cGMP was roughly equipotent in relaxating tracheal smooth muscle in these two species, different from ANP, and inhibitory effects of 8-brom cGMP on both human and guinea pig tracheal smooth muscle were also markedly suppressed in the presence of 30 nmol/l IbTX, similar to ANP. These results demonstrate that augmentation of BKCa channel activity may play a functionally important role in the cGMP-induced relaxation in human airway smooth muscle. However, ANP may have modest potency as a bronchodilator.

Aged↗
PubMed1998

[Efficacy of granisetron as anti-emetic agent for emesis induced by intra-arterial injection therapy for hepatocellular carcinoma].

The effect of granisetron in preventing nausea and emesis induced by intraarterial chemotherapy was comparatively studied with a historical control group (46 cases) in 50 patients with hepatocellular carcinoma receiving intraarterial anti-tumor drugs such as cisplatin and doxorubicin. Emesis was perfectly controlled in 39 out of 50 patients in the treatment group (78%), in comparison to 33 out of 46 patients (71.7%) in the historical control group. This represented no statistical significance between the two groups. In terms of the severity of nausea, however, the granisetron group demonstrated significant superiority to the control group with 27 out of 50 patients (54%) being free of symptoms compared with 16 out of 46 patients (34.8%) in the control group. A stratified analysis of the data also demonstrated significant superiority of the granisetron group over the historical group in the number of emetic episodes and the severity of nausea in female patients, who are more predisposed to emesis. The above results confirm the usefulness of granisetron as an antiemetic agent used for the prevention of acute nausea and emesis induced by intraarterial chemotherapy.

Adult↗
PubMed1998

Lipid peroxyl radicals from oxidized oils and heme-iron: implication of a high-fat diet in colon carcinogenesis.

A diet high in fat and iron is known as a risk factor in cancer epidemiology. However, the details of the molecular mechanism remains to be elucidated. We examined the possible implication of lipid peroxyl radicals generated from fatty acids and heme-iron in DNA damage, and hence in the possibility of colon cancer. F344 female rats were given N-nitroso-N-methylurea six times during a 2-week period and then fed diets containing different amounts of safflower oil and hemoglobin (rich in iron) for 36 weeks; the occurrence of colon cancer was determined by H&E staining. In this animal model, simultaneous feeding of a fat diet and heme-iron produced a significant increase (P < 0.05) in the incidence of colon cancer compared with a diet without hemoglobin. Electron paramagnetic resonance and chemiluminescence studies revealed that oxidized refined vegetable oils, particularly safflower oil, readily generated lipid peroxyl radicals in the presence of various heme compounds, and the peroxyl radicals did effectively cleave DNA. Unpurified native vegetable oils contain a high amount of peroxyl radical scavengers, whereas conventional refining processes seem to reduce the levels of many valuable anti-peroxyl radical compounds abundant in plant seeds. In conclusion, lipid peroxides and heme components generate peroxyl radical species that exert DNA-cleaving activity. A plausible explanation is that lipid peroxyl radicals thus generated, which originated from routine dietary components such as fat and red meat, may contribute, at least in part, to the high incidence of colon cancer.

Animals↗
PubMed1997

Expression of opioid-binding cell adhesion molecule (OBCAM) and neurotrimin (NTM) in E. coli and their reactivity with monoclonal anti-OBCAM antibody.

Opioid-binding cell adhesion molecule (OBCAM), neurotrimin (NTM) and limbic system-associated membrane protein (LAMP) are homologous and are the members of the IgLON family which is a subfamily within the immunoglobulin superfamily. We cloned the cDNAs for OBCAM and NTM, prepared recombinant proteins, and examined the reactivity of the previously prepared monocolonal anti-OBCAM antibody, OBC53, with the recombinant proteins by immunoblotting. These experiments revealed that OBC53 recognizes OBCAM about 1000 times as efficiently as NTM. Moreover, the NTM and LAMP peptides which have sequences homologous to the OBCAM peptide used for the preparation of OBC53 were 150 times less reactive to OBC53. Thus, the OBC53 antibody is a useful tool for specifically detecting OBCAM in immunochemical experiments.

Amino Acid Sequence↗
PubMed1997

Selective inhibitors of cyclic AMP-specific phosphodiesterase: heterocycle-condensed purines.

To reverse the adverse reactions of alkylxanthines and to develop novel inhibitors of cyclic AMP-specific phosphodiesterase (PDE IV), a series of heterocycle-condensed purines were designed and synthesized. Some of these new compounds had similar or more potent and selective inhibitory activity against PDE IV than known PDE IV inhibitors. The tracheal-relaxant activity of these compounds was closely correlated with their PDE IV-inhibitory activity. Moreover, these purine analogues did not have any positive-chronotropic action or adenosine-antagonistic action on isolated heart preparations, which are the particular adverse reactions of alkylxanthines. Among them, 3,4-dipropyl-4,5,7,8-tetrahydro-3H-imidazo[1,2-i]-purin-5-one (1c), which was the most selective and potent PDE IV inhibitor, did not cause emesis in Suncus murinus at a dosage range of 10-100 mg/kg (po), while an imidazole analogue of 1c (4c) and known PDE IV inhibitors such as rolipram and denbufylline caused emesis even at 10 or 30 mg/kg.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Inhibitory effects of pituitary adenylate cyclase activating polypeptide on histamine-induced respiratory resistance in anesthetized guinea pigs.

Asthma is a chronic inflammatory disorder of the airways in which many cells participate. This inflammation causes recurrent episodes and symptoms that are associated with widespread but variable airflow limitation that is at least partly reversible either spontaneously or with treatment. Therefore, an investigation of useful remedies for the treatment of bronchial asthma is proposed. In this study, we determined whether both forms of pituitary adenylate cyclase activating polypeptide (PACAP 38 and PACAP 27) belonging to the vasoactive intestinal peptide (VIP) family of peptides could inhibit the effects of histamine-induced respiratory resistance (Rr) in anesthetized guinea pigs, when compared with VIP. The order for 50% suppression (ED50) of Rr induced by peptides was VIP > PACAP 27 > PACAP 38. The inhibitory effects induced by PACAP 38 on histamine-induced Rr in guinea pigs were more prolonged than with the other two peptides. Moreover, adding the endopeptidase inhibitor phosphoramidon prolonged the inhibitory effects of PACAPs. These results suggested that the exogenous peptides of the inhibitory nonadrenergic noncholinergic nervous (i-NANC) peptides could become a useful remedy for treatment of bronchial asthma, because these belong to an important intrinsic hormone.

Airway Resistance↗