Search PubMed⌕ Search

Biomedical subjects

H Kai

Publications and source records attributed to H Kai.

At least 127 records · Page 7Linked to original sources

Effects of anticholinergic bronchodilators on mucociliary transport and airway secretion.

The effects of atropine, ipratropium and oxitropium on the mucociliary clearance were studied in pigeons and rabbits. The normal mucociliary transport (MCT) in pigeons was inhibited after the treatment by any of the three drugs at concentrations of 10(-4) to 10(-3) g/ml. These three drugs markedly inhibited eserine-induced MCT acceleration at a lower concentration than ACh-induced acceleration. The normal airway secretion was inhibited only by atropine in rabbits. The results indicate that neither oxitropium nor ipratropium depress the normal mucociliary clearance, but atropine may depress it under some conditions. Additionally, we suggest that these anticholinergic drugs might selectively affect the mucociliary transport modulated by endogenous ACh.

Acetylcholine↗

Effects of nicorandil on cytosolic calcium concentrations in quin2-loaded rat aortic vascular smooth muscle cells in primary culture.

We made use of quin2 microfluorometry to observe the effects of nicorandil (2-nicotinamidoethyl nitrate) on cytosolic Ca++ concentrations [( Ca++]i) in rat aortic vascular smooth muscle cells in primary culture. Regardless of whether cells were at rest, in a state of Ca++-depletion or at K+-depolarization, nicorandil rapidly and dose-dependently decreased [Ca++]i to the lower steady-state level. Nicorandil dose-dependently inhibited norepinephrine-induced Ca++ transients in physiological salt solution containing 1 mM Ca++. Nicorandil accelerated the reduction of [Ca++]i observed when the cells were exposed to Ca++-free solution. When the cells were treated with nicorandil in Ca++-free solution, Ca++ transients induced by the first application of caffeine were little affected, but those induced by subsequent repetitive caffeine applications were reduced strongly and progressively. In contrast, pretreatment with nicorandil markedly inhibited Ca++ transients induced by the first application of norepinephrine, in Ca++-free solution. These effects of nicorandil on [Ca++]i and Ca++ transients were similar to those seen with nitroglycerin. The denitrated compound of nicorandil, N-(2-hydroxyethyl)nicotinamide, had no such effect. Thus, it is apparently the nitrate moiety of the chemical structure by which nicorandil actively and strongly reduces [Ca++]i in vascular smooth muscle cells. The reduction of [Ca++]i by nicorandil may result in a decrease in Ca++ in the norepinephrine-sensitive store; hence, the reduction of [Ca++]i elevation by norepinephrine.

Aminoquinolines↗

[Antitussive effects of Bakumondô-tô and codeine in bronchitic guinea-pigs].

Antitussive effects of Bakumondô-tô and codeine were examined in bronchitic guinea-pigs made by an exposure to SO2. Bakumondô-tô significantly depressed the cough reflex induced by mechanical and chemical stimulations in the bronchitic but not in the normal animals. Repeated administration of Bakumondô-tô significantly suppressed the increased spontaneous discharge of the superior laryngeal nerve in bronchitic animals. On the other hand, the antitussive action of codeine in bronchitic animals was significantly weaker than that in normal animals. Moreover, repeated administrations of codeine significantly potentiated the increased spontaneous discharge of the superior laryngeal nerve. The results suggest that Bakumondô-tô, unlike codeine, has a notable antitussive activity in bronchitic rather than in normal guinea-pigs.

Animals↗

Preoperative hyperthermia combined with radiotherapy and chemotherapy for patients with incompletely resected carcinoma of the esophagus.

Two hundred eighty-nine patients with squamous cell carcinoma of the esophagus underwent subtotal esophagectomy from December 1965 to June 1986. Resection of esophageal carcinoma was absolutely noncurative in 64 patients (20%) due to invasion to the surrounding structures. These 64 patients were subdivided as follows into three groups based on the type of preoperative treatment: Group I included 16 patients without preoperative treatment; Group II included 38 patients with preoperative radiotherapy combined with chemotherapy (average doses: radiation 37.3 Gy, 1-(2-tetrahydrofuryl)-5-fluorouracil [tegafur] 8.4 g); Group III included 10 patients who underwent preoperative hyperthermia (42 degrees C to 45 degrees C) combined with chemotherapy and radiotherapy (average doses: radiation 33 Gy, bleomycin 33.9 mg, or cis-diamine dichloroplatinum 75 mg, hyperthermia 6.2 times). There were no significant differences in terms of postoperative therapy among the three groups. The median survival times for patients in Groups I, II, and III were 6, 7.5 and 11 months, respectively. The 2-year survival rates for patients in Groups I, II, and III were 0, 15.6%, and 34.3%, respectively. The prognosis in Group III was superior to that for Group I (P less than 0.05) and Group II. These results suggest that preoperative hyperthermia combined with radiotherapy and chemotherapy could prolong survival even in patients who have had noncurative resection.

Carcinoma↗

20-Hydroxyecdysone accelerates the flow of cells into the G1 phase and the S phase in a male accessory gland of the mealworm pupa (Tenebrio molitor).

The cells of the bean-shaped accessory glands of mealworms proliferate through the first 7 days of the 9-day pupal stage. Immediately after larval-pupal ecdysis, 25-27% of the cells were in the G1 phase, 60-65% were in the G2 phase, and the balance were in S phase. Over the first 4 days of normal development, the S fraction gradually increased, to reach its highest level in the mid-pupa at the time of the major ecdysteroid peak (Delbecque et al., 1978). Thereafter, the S fraction declined until over 95% of the cells had accumulated in G2 on Day 8. When 0-day pupal glands were explanted into Landureau's S-20 medium for 6 days, the G1 fraction remained fairly constant (25-30%) while S and the G2 fractions fluctuated. On the first day in vitro, the G2 fraction declined and the S fraction rose. On the second day in basal media, the S fraction fell and G2 rose correspondingly until 70% of the cells reached G2 when cycling stopped on the third day. With addition of 20-hydroxyecdysone to 0-day cultures, the S fraction increased quite sharply. It remained large for all 6 days of the experiment in the continuing presence of hormone. A 1-day pulse of hormone produced a transient increase in S. We blocked cell cycling with hydroxyurea in a stathmokinetic experiment and showed that 20-hydroxyecdysone accelerated the flow of cells from the G2 phase to the G1 phase by 2.5-fold. An increase in the G1 fraction was detected within 10 hr of hormone administration and the effect was dose-dependent with an ED50 of 5 X 10(-7) M for 20-hydroxyecdysone. We conclude that 20-hydroxyecdysone acts at a control point in the G2 phase. Incubation of the glands with 20-hydroxyecdysone for only 30-60 min followed by washout stimulated the flow from G2 to G1 and the effect persisted after transfer of the tissues to hormone-free media. Dose-dependent stimulation also occurred with ponasterone A (ED50 3 X 10(-9] but not with cholesterol.

Animals↗

Heat, drugs, and radiation given in combination is palliative for unresectable esophageal cancer.

From April 1966 to April 1986, 101 men and women with unresectable squamous cell carcinoma of the esophagus were treated in our clinic. Since 1983, 21 were treated with a combination of hyperthermia, chemotherapy, and radiotherapy (group I). Before 1983, for another 80 patients, radiation plus chemotherapy had been prescribed (group II). Nine of 21 patients in group I had an unresectable carcinoma due to an advanced tumor, 9 had an associated severe clinical status, and 3 refused surgery. Out of 80 in group II, 50 had a far advanced tumor, 21 had a poor clinical condition, and 9 refused operation. With regard to staging, for 21 in group I, 6 were classified as Stage I, 5 as Stage II, 7 as Stage III, and 3 as Stage IV. As to the 80 in group II, those in Stage I, II, III, and IV accounted for 8, 22, 39, and 11, respectively. The median doses of each modality, for patients in group I, were 6 times of hyperthermia at 42-45 degrees C for 30 minutes, 40 Gy of X ray and 30 mg of bleomycin. For patients in group II, a median dose of 56 Gy of X ray was given. Response rates determined by esophagograms and endoscopies for the patients in groups I and II were 76.2% (16/21; 4 CRs, 12 PRs) and 39.2% (31/79; 2 Crs, 29 PRs), respectively (p less than 0.001). The effective rates determined by improvement in quality of life (relief of pain and dysphagia) for groups I and II were 61.9% and 37.2%, respectively. A longer survival was obtained for patients in group I (median survival: 9 months vs 6 months). Especially for the patients classified as Stage I, a significantly longer survival was obtained with a combination of hyperthermia, chemotherapy, and radiotherapy (p less than 0.01).

Aged↗

Lethal effect of hyperthermochemoradiotherapy on cultured transformed cells.

Hyperthermia alone had a lethal effect on V-79 cells. Temporary exposure to hyperthermia resulted in substantial decreases in cell growth, in a time (20-120 min)- and temperature (39-44 degrees C)-dependent manner. A precipitous fall in cell growth occurred when cells were incubated at temperatures between 42 and 43 degrees C. Concomitant application of hyperthermia, bleomycin and irradiation (hyperthermochemoradiotherapy) led to a maximal effect, compared with findings in cells treated with a single or two modalities, in vitro as well as in vivo and in clinical cases. To produce a similar situation of tumor cell growth in vivo, multicellular tumor spheroids (MTS) were developed by culturing tumor cells on soft agar. The effect of various treatments on the cells was then determined. Hyperthermia had a greater effect on the inner layer (hypoxic state) of MTS than on the outer layer, while radiotherapy was more effective on the outer layer (aerobic state). The synergistic effect of the combination with hyperthermia and irradiation was exhibited in all layers of MTS. Hyperthermochemoradiotherapy may prove to be an effective and safe form of adjuvant therapy for treating clinical carcinoma.

Animals↗

[Clinical studies on effect of cefbuperazone on surgical infections].

We conducted clinical studies on the efficacy and safety of cefbuperazone (CBPZ) on surgical infections with the following results. 1) In evaluable 32 patients, CBPZ was evaluated to be clinically effective in 23 (71.9%) and the efficacy rate was better in those who were administered 4 g/day of CBPZ (87.5%, 14/16) than in those who were given 2 g/day (57.1%, 8/14). 2) Antibacterial activity of CBPZ was evaluated in 41 isolated bacterial strains. Pathogen eradication rate by bacterial species was 75.6% (31/41). CBPZ exerted excellent antibacterial effects on Escherichia coli (100%, 8/8) and anaerobic bacteria such as Bacteroides (88.9%, 8/9). Resistant bacteria to CBPZ were Enterococcus faecalis and Pseudomonas aeruginosa. 3) No serious side effects were noted in any of the 34 patients who entered in this study. Abnormal laboratory test results were noted in 2 patients (5.9%) and they were transient elevation of transaminases and alkaline phosphatase. From the results shown above, CBPZ appears to be a highly useful antibiotic for the treatment of surgical infection.

Adult↗

8-Bromoguanosine 3':5'-cyclic monophosphate decreases intracellular free calcium concentrations in cultured vascular smooth muscle cells from rat aorta.

The effects of 8-bromoguanosine 3':5'-cyclic monophosphate (8-Br cGMP) on intracellular free calcium concentrations ([Ca2+]i) in cultured rat aortic vascular smooth muscle cells (VSMCs) loaded with fura-2 were recorded microfluorometrically. Irrespective of whether VSMCs were at rest (in 5 mM K+ PSS), under Ca2+ depletion (in Ca2+-free medium for 10 min) and K+ depolarization (in high K+ PSS), [Ca2+]i was actively reduced and reached a new and lower steady-state level with the application of 8-Br cGMP. This may be the first and direct evidence that cGMP, a putative mediator of various vasodilators, actively reduces [Ca2+]i in VSMCs.

Animals↗

Intra-epithelial carcinoma concomitant with esophageal squamous cell carcinoma.

A review of 222 cases of squamous cell carcinoma of the esophagus revealed 67 (30.2%) with intra-epithelial carcinoma, contiguous with the main lesion. The incidences of such lesions were 10.9% and 68.0% in those given and not given preoperative irradiation, respectively. The 222 tumors were grouped into five categories, according to depth of invasion of the main lesion, those restricted to the mucosa, submucosa, proper muscular layer, and those invading the adventitia and neighboring structures. The rates of occurrence of intra-epithelial carcinoma were 87.5, 65.0, 26.9, 18.8, and 17.7%, respectively. Of the 67 with intra-epithelial carcinoma, the incidences of both proximal and distal location of such lesions were 85.7% in mucosal carcinoma, 84.6% in submucosal carcinoma, 71.4% in cancer restricted to the proper muscular layer, 50.0% in cancer invading the adventitia, and 9.1% in cancer invading the neighboring structures. Intra-epithelial carcinoma may thus originate from field carcinomatous transformation rather than from an intra-epithelial spread of the main lesions. These observations also support the concept of the field origin of carcinogenesis in the esophagus.

Carcinoma in Situ↗

Adenosine decreases intracellular free calcium concentrations in cultured vascular smooth muscle cells from rat aorta.

Using an intracellularly trapped dye, quin 2, effects of adenosine on intracellular free calcium concentrations ([Ca2+]i) were recorded, microfluorometrically, using rat aortic medial vascular smooth muscle cells (VSMCs) in primary culture. Regardless of whether cells were at rest (in 5 mM K+), at K+-depolarization (in 55 mM K+) or at Ca2+ depletion (in Ca2+-free media), adenosine induced a rapid reduction of [Ca2+]i, following which there was a gradual increase to pre-exposure levels, in cells at rest and in the case of Ca2+ depletion. Only when the cells were depolarized (55 mM K+) did adenosine induce a new steady [Ca2+]i level, lower than the pre-exposure value. These findings indicate that decrease in [Ca2+]i by adenosine is one possible mechanism involved in the adenosine-mediated vasodilatation, and that adenosine decreases [Ca2+]i by direct extrusion, by sequestration, or by inhibiting the influx of Ca2+ into VSMCs.

Adenosine↗

Two-stage operation for poor-risk patients with carcinoma of the esophagus.

We have devised a two-stage operation for poor-risk patients with carcinoma of the thoracic esophagus. The first-stage operation consists of a right thoracotomy, subtotal esophagectomy, and lymph node dissection. Two to three weeks later, the second-stage operation of esophageal reconstruction with gastric tube is performed under laparotomy. During this 3-week period of no esophagus, the nutritional status can be adequately maintained by intravenous hyperalimentation. We describe herein the technique, postoperative complications, and mortality of our two-stage operation as compared with events during an ordinary one-stage operation for carcinoma of the thoracic esophagus.

Adult↗

Effect of azelastine on the release and action of leukotriene C4 and D4.

The effect of azelastine on the release of leukotriene C4 and D4 (LTC4 and LTD4), and the antagonistic action of the drug against the leukotrienes were determined by using in vitro tests and compared with those of ketotifen and chlorpheniramine. Azelastine inhibited LTC4 and LTD4 release from guinea pig lung fragments passively sensitized with homologous anti-ovalbumin IgGl-b antibody. The 50% inhibitory concentration (IC50) of azelastine was 6.4 X 10(-5) M for a 15-min preincubation or 4.7 X 10(-5) M for a 30-min preincubation. Ketotifen and chlorpheniramine were inhibitory only at the highest concentration tested (3 X 10(-4) M), giving inhibitions of 35.6 and 21.3%, respectively. Azelastine also inhibited calcium ionophore A23187-induced release of leukotrienes from human polymorphonuclear leukocytes; the IC50 values were 3.6 X 10(-5) M for 15 min and 2.3 X 10(-6) M for 30 min of preincubation. Ketotifen and chlorpheniramine were inhibitory only after a 30-min preincubation, with IC50 values of 2.1 X 10(-5) and 5.9 X 10(-5) M, respectively. The potent inhibition by azelastine might be partly a result of the inhibition of 5-lipoxygenase, since 5-hydroxyeicosatetraenoic acid formation in rat basophilic leukemia cell homogenate was inhibited by azelastine. Pretreatment of guinea pig ileum with azelastine antagonized LTC4- and LTD4-induced contraction of the ileum with IC50 values of 7.0 X 10(-6) and 1.1 X 10(-5) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transnodal cancer chemotherapy for metastatic lymph nodes in rats.

The antitumor effects of transnodal cancer chemotherapy were studied using rat models. After inoculation of AH-66 tumor cells into the iliac lymph nodes (target lymph node), emulsionized bleomycin (BLM emulsion) or BLM water solution was injected into an intact popliteal lymph node and chronological changes in BLM levels in the target lymph node were measured. In the target lymph node of the iliac lymph node, the level of BLM emulsion continuously was greater than 2 micrograms/g for 9 hours after the injection, while the level of BLM water solution decreased rapidly. The antitumor effects were quantitatively estimated in the tumor of the target lymph node. The ratio of necrotic area in the BLM-emulsion-treated group was significantly greater than that in the emulsion- or saline-treated groups. Survival rate in rats treated with BLM emulsion was significantly higher than that in control groups and was slightly higher than that in the group given BLM water solution iv. The concentration of BLM in the serum and lung in case of transnodal administration of BLM was much lower than that in rats given an iv administration of BLM water solution. These findings suggest that transnodal administration of BLM emulsion is an effective and safe treatment for metastatic lymph nodes, at least in rats.

Animals↗

Secretomotor and mucolytic effects of mabuterol, a novel bronchodilator.

Action of mabuterol, a novel bronchodilator, on the respiratory secretion system was investigated, and the following effects were confirmed: 1) increase of output volume, amounts of protein and pulmonary surfactant in respiratory fluid; 2) decrease of sputum viscosity; 3) fragmentation of the sputum structure and 4) promotion of the mucociliary transport of particles. The results in the present study may, at least partly, substantiate clinical efficacy such as improvement of pulmonary function, favourable effects on expectoration and amelioration of symptoms observed in patients with chronic obstructive pulmonary disease.

Adrenergic beta-Agonists↗

Survival rates of women with carcinoma of the esophagus exceed those of men.

Postoperative complications, mortality and survival rates and nuclear deoxyribonucleic acid (DNA) content of cancer cells for 212 male and 47 female patients with carcinoma of the esophagus were studied. There were no differences in age, site and length of carcinoma, histologic type, invasion to the adventitia, metastases to the lymph node, staging and postoperative complications. However, survival time for female patients was significantly longer than in males. In studies of cell nuclear DNA content, the incidence of more favorable DNA type (relatively regular in DNA distribution) was relatively high while the incidence of the unfavorable DNA type (widely scattered DNA distribution) was relatively low in female patients when compared with male patients. These findings suggest that tumor factors warrant attention when studying the clinical differences in males and females with carcinoma of the esophagus.

Carcinoma, Squamous Cell↗

Prognostic factors of esophageal carcinoma: univariate and multivariate analyses.

The correlation of 5-year survival rate with various clinical and histopathological factors was studied using univariate and multiple analyses of 128 patients who had undergone resection for esophageal carcinoma between 1965 and 1978 in the Department of Surgery, Kyushu University Hospital. The depth of penetration, lymph node metastasis, lymphatic or vascular invasion, and INF had a significant correlation with 5-year survival in the univariate analysis; however, only depth of penetration and lymph node metastasis were prognostic factors with a significant difference, in the multivariate analysis. In 55 patients in whom the cell nuclear DNA content had been determined, the DNA pattern was the greatest prognostic factor (p less than 0.01), in multivariate analysis. We propose that the DNA distribution in the malignant cells should be examined as a most pertinent prognostic factor.

Adult↗