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Biomedical subjects

S Kohno

Publications and source records attributed to S Kohno.

At least 307 records · Page 17Linked to original sources
PubMed1999

Phase I study of irinotecan combined with carboplatin in previously untreated solid cancers.

Irinotecan (CPT-11) and carboplatin have broad anti-tumor activities. We conducted a Phase I study of CPT-11 combined with carboplatin in previously untreated solid cancers, especially advanced lung cancer. The aim of the study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities in this regimen. In addition, we prospectively evaluated the Chatelut formula for predicting carboplatin clearance. Patients with advanced cancer were treated with CPT-11 (days 1, 8, and 15) and carboplatin (day 1) of a fixed-target area under the concentration-time curve (AUC) of 5 mg x min/ml. Carboplatin dose was determined by multiplying the AUC by the clearance predicted using the Chatelut formula. The CPT-11 dose was escalated from 40 mg/m2 to the MTD by 10 mg/m2. A total of 27 patients, 26 lung cancer patients and 1 colon cancer patient, were enrolled in this study. Dose-limiting leukoneutropenia, thrombocytopenia, and diarrhea, including one treatment-related death, were observed at 60 mg/m2 CPT-11, indicating that this level was the MTD. In 11 patients, the actual AUCs of carboplatin almost achieved the target AUC of 5. Fifteen (60%) of 25 evaluable patients showed an objective response, with an 85% response rate [11 of 13 patients (complete response, 31%; partial response, 54%)] in small cell lung cancers and a 36% response rate (4 of 11 patients) in non-small cell lung cancers. Neutropenia, thrombocytopenia, and diarrhea were the dose-limiting toxicities in this regimen. CPT-11 (50 mg/m2) under the carboplatin target AUC of 5 using the Chatelut formula was the recommended dose for further Phase II study, and this regimen seems to be active for small cell lung cancer.

Adult↗
PubMed1999

[Mycoplasma].

Explore the source record for details and available documents.

Antibodies, Bacterial↗
PubMed1999

Ability of teicoplanin and vancomycin to induce contraction of, and histamine release from, pulmonary tissue of humans, monkeys and guinea pigs.

To assess the safety of teicoplanin and vancomycin with respect to airway tissue, we evaluated whether these two antibiotics induce pulmonary tissue contraction and histamine release in human, monkey and guinea pig specimens in vitro. The effects of these drugs on the release of histamine from monkey blood leucocytes and mouse bone marrow-derived mast cells (BMMC) were also studied. Neither teicoplanin nor vancomycin (10(-6)-10(-3) g/mL) induced contractions of guinea pig trachea or lung parenchyma. Similarly, these drugs induced no appreciable change in the resting tonus of cynomolgus monkey bronchus or lung parenchyma. The tonus of monkey trachea was not influenced by teicoplanin, whereas 10(-3) g/mL vancomycin caused contraction. The spontaneous tonus of human lung parenchyma was not altered by teicoplanin or vancomycin, and that of the bronchus was not influenced by teicoplanin; however, 10(-3) g/mL vancomycin elicited obvious contraction of the bronchus. Neither drug promoted the release of significant amounts of histamine from these pulmonary tissues or from monkey blood leucocytes and BMMC. These results suggest that, compared with vancomycin, teicoplanin may be associated with a lower risk of inducing bronchospasm when used for inhalation therapy.

Animals↗
PubMed1998

A leukotriene receptor antagonist, ONO-1078, modulates drug sensitivity and leukotriene C4 efflux in lung cancer cells expressing multidrug resistance protein.

ONO-1078 is a new class of peptide leukotriene receptor antagonist, and multidrug resistance protein (MRP) is a membrane tranporter of multiple anticancer drugs and endogenous leukotriene C4 (LTC4). We investigated the effects of ONO-1078 on drug sensitivity and LTC4-efflux in MRP-expressing lung cancer cells. Drug sensitivity, intracellular vincristine accumulation, and intracellular and extracellular LTC4 concentrations were measured with or without ONO-1078. The effect of ONO-1078 on MRP-mediated calcein-efflux was determined by flow cytometry. ONO-1078 (1 to 10 microM) dose-dependently enhanced the sensitivity of NCI-H520 cells to vincristine with the reduced accumulation, and also enhanced the sensitivity to doxorubicin and etoposide. ONO-1078 inhibited both LTC4- and calcein-efflux from the cells with increased intracellular accumulations. Our findings indicate that ONO-1078 modulates multidrug resistance and inhibits LTC4-efflux in lung cancer cells, by inhibition of MRP function.

ATP-Binding Cassette Transporters↗
PubMed1998

Facilitation of adrenal sympathetic efferent nerve activity induced by mechanical stimulation of teeth in the rat.

The effects of afferent signals from the periodontal mechanoreceptors and muscle spindles of jaw-closing muscles on adrenal nerve activity were examined using anesthetized rats. The adrenal nerve activity increased with pressure stimulation of the teeth and by biting a wooden stick. However, after denervation of the periodontal ligament, the facilitation due to the stick-biting was not observed. These results indicate that periodontal afferents facilitate adrenal nerve activity.

Adrenal Glands↗
PubMed1998

HTLV-I-associated myelopathy associated with multi-organ inflammatory disease: a case report.

We report a 73-year-old man with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) complicated with multi-organ inflammatory disease, including Sjögren's syndrome, interstitial cystitis, and uveitis. The presence of HTLV-I proviral DNA in peripheral blood mononuclear cells (PBMC), cerebrospinal fluid, salivary gland, mucosa of urinary bladder, and aqueous humor was confirmed by polymerase chain reaction using HTLV-I pX region primer. Western blot analysis revealed the presence of anti-HTLV-I antibodies in serum, CSF, saliva, and urine, suggesting replication of HTLV-I in each tissue. A high load of HTLV-I proviral DNA (20 copies out of 100 PBMC) was present, associated with increased spontaneous proliferation of peripheral blood lymphocytes (24,747 cpm). Our results suggest that the high load of HTLV-I in patients with HAM may potentially induce systemic inflammation in several organs.

Aged↗
PubMed1998

Immunological competence and nutritional status in patients with lung cancer.

The rate of infection in patients with malignant disease is significantly higher than in patients with benign disease. To investigate whether immunological competence is impaired in patients with lung cancer, we assessed neutrophil function (chemotaxis, phagocytosis, bacterial killing activity, and superoxide production), monocyte function (phagocytosis and killing activity), lymphocyte subsets using flow cytometry, and proliferation of lymphocytes stimulated by phytohemagglutinin, concanavalin A, and pokeweed mitogen. Studies were performed on 22 untreated patients with lung cancer and 21 age-matched healthy volunteers. Nutritional status was assessed by Niederman's nutritional index. In patients with lung cancer neutrophil chemotaxis, monocyte phagocytosis and killing, proliferation of lymphocytes stimulated by phytohemagglutinin and concanavalin A, but not pokeweed mitogen, and the number of natural killer cells were significantly lower than in healthy volunteers, whereas gammadelta T cells were increased (p < 0.05). The mean score on Niederman's nutritional index was worse in patients than in healthy volunteers (p < 0.001). Our results suggest that the impaired immunological competence and undernutrition may be among the mechanisms causing increased susceptibility to infection in patients with lung cancer.

Adenocarcinoma↗
PubMed1998

Development of pollen-induced allergic rhinitis with early and late phase nasal blockage in guinea pigs.

OBJECTIVE AND DESIGN: Development of nasal blockage and sneezing during repeated inhalation challenges with Japanese cedar pollens was evaluated in guinea pigs. SUBJECTS: Male Hartley guinea pigs. TREATMENT: Guinea pigs were sensitized by intranasal instillation of cedar pollen extracts + Al(OH)3 2 times a day for 7 days. The animal was then forced to inhale the pollens for challenge, which was restrictively trapped in the upper airways, once a week. METHODS: Change of specific airway resistance (sRaw), sneezing frequency, and titers of anaphylactic antibodies in the serum were measured after each of the 30 challenges. RESULTS: At the first challenge, no obvious increase in sRaw was observed. However, the second and third challenges to the animals caused modest biphasic elevations of sRaw, with peaks at the first and the fourth to sixth hour. At the fourth to tenth challenges, marked elevations of sRaw were observed. However, with repetition of the inhalation challenge, the early and the late responses became almost indistinguishable because of partial overlapping as the responses expanded. All guinea pigs sneezed immediately after each pollen inhalation challenge. Apparent increases of both circulating gamma1 and IgE antibodies were seen after the seventh challenge. CONCLUSIONS: These results indicate that the experimental allergic rhinitis established in the present study can be a valuable model for analyzing the pathogenesis of the disease and developing new therapeutic drugs.

Aluminum Hydroxide↗
PubMed1998

Cytogenic studies of Hynobiidae (Urodela). XIV. Analysis of the chromosome of a Chinese salamander, Batrachuperus pinchonii (David).

The chromosome number of a Chinese salamander, Batrachuperus pinchonii, was re-examined Adults and embryonic specimens had a diploid number of 66, with 33 bivalents during meiosis, in contrast to previous reported results. Furthermore, when C-banding analysis was performed with embryos, chromosomes with banding patterns homoeologous to those of Salamandrella keyserlingii and Hynobius species were found. It appears, therefore, that Batrachuperus, Salamandrella and Hynobius might be derived from a common ancestral species in eastern Asia.

Animals↗
PubMed1998

Identification of a single nucleotide insertion polymorphism in the upstream region of the insulin promoter factor-1 gene: an association study with diabetes mellitus.

Insulin promoter factor 1 (IPF1) is a key factor both for the regulation of insulin gene expression and for the development of the pancreas. In this study 88 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were diagnosed as diabetic at less than 40 years of age, 55 patients with insulin-dependent-diabetes (IDDM), and 67 normal control subjects were analysed for variants in the upstream region of the IPF1 gene by direct sequencing. A novel single nucleotide insertion polymorphism was found in a guanine triplet at 108 bp upstream of the translation start site. The G insertion allele (G4 allele) was found to be common in the Japanese population, at a frequency of 0.50. The prevalence of G3 homozygotes was higher in IDDM patients (35%) and lower in NIDDM patients (17%) than in normal control subjects (28%, p=0.049). In the NIDDM group, the ratio of insulin treatment tended to be higher in subjects homozygous for the G3 allele, although the genotype was not significantly associated with basal C-peptide levels. The polymorphism is unlikely to be a major contributor to the insulin deficiency of diabetes. However, the polymorphic locus, or an unknown mutation which is in linkage disequilibrium with the polymorphism, could be involved in the pathophysiology of diabetes. The high heterozygosity may be useful for genetic linkage studies of other mutations within and near the IPF1 gene.

Adolescent↗
PubMed1998

Highly repetitive DNA sequences that are restricted to the germ line in the hagfish Eptatretus cirrhatus: a mosaic of eliminated elements.

The New Zealand hagfish, Eptatretus cirrhatus, is known to eliminate parts of its chromosomes during embryogenesis from presumptive somatic cells. Electrophoresis of germ line and somatic DNAs of this species, after treatment with the restriction endonucleases DraI and EcoRI, revealed three fragments of DNA that were restricted to the germ line. DNA filter hybridization experiments demonstrated that these fragments were present almost exclusively in the germ line DNA of E. cirrhatus and that they were highly and tandemly repeated. Thus, these DNA fragments appeared to be eliminated during embryogenesis. Moreover, one fragment (a DraI fragment) cross-hybridized with the germ line DNA from other species of hagfish, namely, Eptatretus okinoseanus and Paramyxine atami. Molecular cloning and sequence analysis revealed that the DraI fragment was composed mainly of closely related sequences of 85 bp in length and that this sequence was about 75% homologous to the sequence of EEEo2 (eliminated element of E. okinoseanus 2) which is a germ line-restricted and highly repetitive sequence that was isolated previously from E. okinoseanus. The other two fragments were composed of three families of closely related sequences that were 172 bp long (designated EEEc1), 61 bp long (EEEc2) and 54 bp long (EEEc3). Fluorescence in situ hybridization experiments revealed that each eliminated element was distributed on several chromosomes that are limited to germ cells. EEEo2 was dispersed on 12 C-band-positive chromosomes. EEEc1 and EEEc3 were dispersed on all C-band-positive and several C-band-negative chromosomes. By contrast, EEEc2 was located to terminal regions of several C-band-negative chromosomes. These results suggest that the eliminated chromosomes in hagfish are mosaics of highly repeated, germ line-restricted families of DNA sequences.

Animals↗
PubMed1998

Bleomycin-induced pulmonary fibrosis in rat is associated with increased expression of collagen-binding heat shock protein (HSP) 47.

Increased accumulation of collagens in extracellular matrix (ECM) is mainly responsible for bleomycin-induced pulmonary fibrosis in rats. This study was designed to assess whether increased collagen accumulation in bleomycin-induced pulmonary fibrosis is associated with heat shock protein (HSP) 47, a molecular chaperone for collagen biosynthesis. We investigated the expression of type I and type III collagens and HSP47 in bleomycin-induced pulmonary fibrosis. Fifteen male Wistar rats were divided into two groups; group I: bleomycin-induced pulmonary fibrosis; group II: PBS-treated age-matched control rats. Pulmonary fibrosis was induced by injecting a single dose of bleomycin sulphate (5 U/kg body weight) intratracheally. Three bleomycin-treated rats and two age-matched control rats were sacrificed at the end of each of the 1st, 2nd and 4th weeks of the experiment. In bleomycin-treated rats, histological examination revealed pulmonary fibrosis, which increased with time. Increased type I and type III collagen desposition was observed in the lungs of all the bleomycin-treated rats. Weak immunostaining of HSP47 was noted in the control lungs. In contrast, strong immunostaining for HSP47 was seen in all the bleomycin-treated fibrotic lungs. In addition, increased numbers of phenotypically altered myofibroblasts (alpha-smooth muscle actin immunopositive) and fibroblast (vimentin immunopositive) were seen in bleomycin-treated lungs and found to express HSP47. Parallel increase of collagens and their molecular chaperone HSP47 expression was found in the bleomycin-treated lungs, and their co-localization could be detected by double immunostaining. Overexpression of HSP47 may play a significant part in the excessive assembly of collagens and could contribute in this way to the fibrosis found in bleomycin-treated rat lungs.

Animals↗
PubMed1998

Acinar cell carcinoma of the pancreas associated with hypoglycemia: involvement of "big" insulin-like growth factor-II.

Apart from insulinomas, pancreatic tumors are rarely complicated by hypoglycemia and some may produce insulin-like growth factor II (IGF-II). To our knowledge, IGF-II-producing pancreatic tumors associated with hypoglycemia have not been reported previously. We describe what we believe to be the first case of "big" IGF-II-producing pancreatic acinar cell carcinoma. A 68-year-old man presented with a history of recurrent hypoglycemia. Abdominal computed tomography scan and magnetic resonance imaging showed a mass, approximately 5 cm in diameter, in the tail of the pancreas and two low-density areas in the liver. Low serum glucose was associated with low insulin levels and high levels of hormones (i.e., glucagon and IGF-II) that are functionally opposite to insulin. Although serum IGF-II level was within the normal range, most IGF-II was of the high molecular weight form, as determined by Western immunoblot analysis. Based on these findings, a diagnosis of hypoglycemia induced by IGF-II-producing pancreatic tumor was made. Surgery was not possible because of the patient's poor general condition. The patient ultimately died as a result of malignant cachexia. At autopsy, a yellowish-white tumor was found in the tail of the pancreas, and a histopathologic diagnosis of acinar cell carcinoma was made. Immunohistologically, the tumor cells contained IGF-II in an irregular staining pattern, suggesting that the hypoglycemia was caused by a pancreatic tumor producing "big" IGF-II.

Aged↗
PubMed1998

The effect of aging and ovariectomy on mandibular condyle in rats.

STATEMENT OF PROBLEM: It is important for dentists to understand the effect of systemic hormonal change on the osseous oral structures. PURPOSE: This study examined the effect of aging and ovariectomy on rat mandibular condyle. MATERIAL AND METHODS: Seventy-two 120-day-old female Fischer rats were killed at 7, 14, 30, and 60 days after bilateral ovariectomy or sham surgery. As the baseline control group, eight animals were killed on day 0 without surgeries. Changes in the bone mineral density and bone marrow area were detected through dual-energy x-ray absorptiometry and soft x-ray photography, respectively. RESULTS: No significant difference of bone mineral density was found between the bilateral ovariectomy and sham surgery groups with dual-energy x-ray absorptiometry, probably because the thickness of cortical bone obscured any possible changes in trabecular bone. Age-related osteosclerotic changes were found in the sham group with soft x-ray photography. In contrast, the bilateral ovariectomy group showed little change in bone marrow area in relation to time course; on the other hand, the value of their bone marrow area became significantly larger than that of the sham surgery group from 14 days after ovariectomy onward. CONCLUSIONS: It was inferred that estrogen deficiency caused the significantly large marrow area found in the rat mandibular condyle. Although much more research is necessary, this study allowed us to speculate that osteoporotic changes may occur in the mandibular condyle of postmenopausal women.

Absorptiometry, Photon↗
PubMed1998

Effects of methylenechloride-soluble fraction of Japanese angelica root extract, ligustilide and butylidenephthalide, on pentobarbital sleep in group-housed and socially isolated mice.

We previously showed that the extract of Japanese angelica root (JAR-E) reversed the decrease in pentobarbital (PB) sleep induced by isolation stress and yohimbine and methoxamine, stimulants of central noradrenergic systems, in mice. Here, we tested the effects of several fractions from JAR-E and ligustilide and butylidenephthalide, phthalide components of JAR-E, on PB sleep in isolated mice to elucidate the mechanism of the action of JAR-E. Methanol-soluble (Met-S) and -insoluble (Met-IS) fractions were obtained from JAR-E. Methylenechloride-soluble (MC-S) and -insoluble fractions (MC-IS) were prepared from Met-S. MC-S (11.4-76 mg/kg, p.o.) reversed the isolation stress-induced decrease in PB sleep, but neither Met-IS (0.8-2.4 g/kg, p.o.) nor MC-IS (0.7-2 g/kg, p.o.) had the same effect. The i.p. administration of MC-S exhibited a similar activity to that observed after the p.o. administration of the same fraction. Ligustilide (5-20 mg/kg, i.p.) and butylidenephthalide (10-30 mg/kg, i.p.) reversed PB sleep decrease in isolated mice. Both components (20 mg/kg, i.p.) attenuated the suppressive effects of yohimbine (30 nmol, i.c.v.), methoxamine (200 nmol, i.c.v.) and a benzodiazepine inverse agonist FG7142 (10 mg/kg, i.p.) on PB sleep in group-housed mice. These results suggest the contribution of ligustilide and butylidenephthalide to the effect of JAR-E on PB sleep in isolated mice, and implicate central noradrenergic and/or GABA(A) systems in the effects of these components.

4-Butyrolactone↗
PubMed1998

Correlation between alcohol-induced asthma and acetaldehyde dehydrogenase-2 genotype.

BACKGROUND: Alcohol-induced asthma, a phenomenon characteristic of Asians, is due to differences in alcohol metabolism, particularly acetaldehyde metabolism. We investigated the effect of polymorphism in acetylaldehyde dehydrogenase 2 (ALDH2) gene on the response to alcohol challenge testing in a group of Japanese asthmatic subjects and normal subjects. METHODS: Subjects were 32 asthmatic subjects and 30 healthy individuals. We measured the change in FEV1 after ingestion of 30 gm of ethanol. Blood ethanol, acetylaldehyde, and histamine concentrations were determined. ALDH2 gene type was established by polymerase chain reaction. RESULTS: Ethanol provocation test results were positive in 15 (47% responders) asthmatic subjects. The blood ethanol concentration was similar in responders and nonresponders. The fall in FEV1 was associated with a rise in blood acetaldehyde and histamine concentrations. The response to oral ethanol challenge was positive in three (19%) of 16 patients with normal homozygote ALDH2 genotype, 10 (71%) of 14 patients with type mutant heterozygote, and two (100%) of two patients with type mutant homozygote ALDH2 genotype. CONCLUSIONS: Alcohol-induced asthma is probably caused by increased blood acetaldehyde concentration resulting from abnormalities of ALDH2 enzyme activity based on ALDH2 genotype differences.

Acetaldehyde↗