Search PubMed⌕ Search

Biomedical subjects

M Taguchi

Publications and source records attributed to M Taguchi.

At least 109 records · Page 6Linked to original sources

Studies on topical antiinflammatory agents. V. 17-(Alkylthio)- and methoxyalkanoates of corticosteroids.

As part of our search for new topical antiinflammatory agents, a series of corticosteroid 17-(alkylthio)- and methoxyalkanoate derivatives was prepared and tested for vasoconstrictive activities. Several compounds were proved to have activity superior or comparable to that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV). Among these compounds, 21-chloro-11 beta-hydroxy-17 alpha-(methylthio)acetoxy-4-pregnene-3,20-dione (5Aa) was found to have the most potent activity, being more active than BV. The structure-activity relationships of the series revealed that introduction of a (methylthio)acetate function into the 17-position as well as the 21-position of corticosteroids was effective for enhancing the topical antiinflammatory activity.

Administration, Topical↗

Studies on topical antiinflammatory agents. IV. 21-(Alkylthio)acetates and (methylthio)methoxides of corticosteroids.

A series of 21-(alkylthio)acetates and 21-(methylthio)methoxides of corticosteroids were synthesized and examined for vasoconstrictive activities. The activities of seven compounds were equal to or greater than that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV). Among them, betamethasone 21-(methylthio)acetate 17-propanoate (2Ca) was found to have the most potent activity, which is superior to that of BV. A structure-activity relationship study revealed that substitution of the 21-hydroxy group of corticosteroids with the (methylthio)acetate function is a useful approach for obtaining potent activity.

Administration, Topical↗

[Tuberculosis sequelae: secondary bacterial infections].

Bacterial infections is one of the most important complications in the patients with pulmonary tuberculosis. We reported the causative microorganisms in these cases with special reference to various clinical features and presented the recommended treatment and prophylaxis against respiratory bacterial infections in the patients with pulmonary tuberculosis sequelae. In 1988 and 1989, 63 patients with tuberculosis sequela were demonstrated to have been infected with respiratory pathogenic bacteria by the quantitative sputum culture method (greater than or equal to 10(7)/ml) in Tokyo National Chest Hospital. The male/female ratio of these patients was 3.5, and their average age was 62.5 years. Causative microorganisms of the secondary infections in the patients with tuberculosis sequela were essentially similar in those with other lower respiratory tract infections, i.e., chronic bronchitis, bronchiectasis, diffuse panbonchiolitis, chronic pulmonary emphysema, etc. Pseudomonas aeruginosa, other glucose-nonfermentative Gram-negative bacilli (GNF-GNB), and glucose-fermentative Gram-negative bacilli (GF-GNB) were the major pathogenic bacteria responsible for the chronic respiratory failure and/or fatal outcome in the post-tuberculous patients. Patients with complications, including aspergillosis, atypical mycobacteriosis, bronchial asthma, and so forth, showed no specific causative microorganism for the secondary infections except frequent isolation of Haemophilus influenzae. Our clinical observations clearly demonstrated that there were differences between the causative microorganisms in patients hospitalized during 1988 to 1989 and those in patients without admission. Gram-negative bacilli, including P. aeruginosa, GNF-GNB and GF-GNB, and Staphylococcus aureus were predominant in hospitalized patients. On the contrary, Streptococcus pneumoniae, H. influenzae, and Branhamella catarrhalis were major pathogenic bacteria in patients without hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Inhalation therapy of antibiotics].

We produced experimental murine Klebsiella pneumoniae pneumonia by air-borne infection using exposure apparatus (LD50: 9.7 X 10 C.F.U./lung). The MIC value of cefazolin was 1.56 micrograms/ml, and that of gentamicin was 0.39 micrograms/ml. We treated this murine pneumonia with aerosolized antibiotics. The infected mice received inhalation of 50 mg (5 mg/ml), 100 mg (10 mg/ml), 200 mg (20 mg/ml) and 400 mg (40 mg/ml) gentamicin were alive. Survival rate of the infected mice treated with inhalation of 1000 mg (100 mg/ml) cefazolin was low, but that of them received inhalation of 500 mg (50 mg/ml) cefazolin was high. On the basis of these experiments it is suggested that aerosol of 50 mg/ml cefazolin gets to alveoli, and inhalation therapy of low level of cephems is proper for bacterial respiratory infections. Inhalation therapy of 50 mg/ml cephem for chronic bronchitis had a marked clinical effect. This proves that aerosol of cephem gets to infected bronchi.

Administration, Inhalation↗

Developmental physiology of cardiac contraction in the Japanese newt in vivo and in vitro.

Development and differentiation of whole hearts of larvae of an experimental amphibian species, the Japanese newt (Cynops pyrrhogaster), were studied in vitro and in vivo with particular reference to cardiac contraction, its temperature sensitivity and morphology. Hearts cultured in the solid or flat state in plastic flasks for 27 days developed from stage 35 to stage 55 and corresponded closely to in vivo developing hearts with respect to morphologic criteria and temperature sensitivity of cardiac contraction. The peak rate of contraction at room temperature occurred after 20 days, both for cultured hearts in vitro and for in vivo hearts, which had reached stage 50 to 52 of development. Excised fractions of heart continued to beat at reduced rates for extended periods. Hearts cultured at late stages (50 to 55) continued to beat for 282 days, though the rate decreased to 1 bpm. Although cardiac contraction rate gradually declined during long-term culture, the sensitivity of this tissue to temperature change remained constant for 250 days. Thus, culture of the heart of this species should prove useful to the investigation of factors related to induction and developmental regulation of contractility.

Animals↗

Development of the heartbeat during normal ontogeny and during long-term organ culture of hearts of the newt, Cynops pyrrhogaster.

Development of cardiac contraction was investigated in the newt, Cynops pyrrhogaster, during normal development and in hearts maintained in long-term organ culture. In the embryos the heart began beating as early as stage 33. The heart rate increased up to stage 52 and then gradually decreased to the adult rate by stage 60. The heart rate showed a logarithmic temperature dependence. In organ-cultured hearts the pattern of heart rate depended on the stage at which the heart was explanted; cultured embryonic hearts showed a pattern of increase and decline similar to that seen in vivo, and hearts explanted near metamorphosis showed only a slow decline.

Animals↗

[Studies on bacterial agents in acute diarrheal disease (1985-1987)].

A three-year epidemiological study (from January 1985 to December 1987) was carried out on sporadic cases of acute diarrhea. A total of 2889 fecal specimens in Cary-Blair transport medium were examined for bacterial enteric pathogens, and 832 strains of fifteen species were isolated from 739 specimens, 73 patients having two or more pathogens. C. jejuni shared 51.7%, Salmonella spp. 18.3%, V. parahaemolyticus 10.3%, and Aeromonas spp. 15.7% of total fecal specimens. Isolation rates of C. jejuni and Salmonella spp. in children under the age of fifteen years (19.3%, 6.4%) were higher than those of older years (9.8%, 3.9%), respectively. Isolation of C. jejuni decreased to 24% (12/50) during 2-4 days storage at room temperature in Cary-Blair transport medium, which showed the necessity of rapid plating for isolation of C. jejuni from fecal specimens. Incidence of A. caviae in children up to ten years of age was significantly higher as compared with those of other Aeromonas species. Desoxycholate-hydrogen sulfide-xylose-agar (DHXA) was used for direct plating technique and for plating after enrichment with alkaline peptone water (without NaCl), which was found suitable as an enrichment medium for Aeromonas spp. Enterohemorrhagic E. coli (EHEC) O157:H7 was isolated from 3 patients by using desoxycholate-hydrogen sulfide-sorbitol-agar (DHSA).

Acute Disease↗

Studies on topical antiinflammatory agents. II. Synthesis and vasoconstrictive activity of 21-substituted corticosteroids with sulfur-containing moieties.

As part of the search for new topical antiinflammatory agents, various 21-substituted corticosteroids having sulfur-containing moieties were prepared and tested for vasoconstrictive activity in humans. A structure-activity relationship study revealed that substitution of the 21-hydroxy group with a lower alkyl-thio group enhanced the activity. The activities of the 21-methylthio (3Ad) and the 21-ethylthio (3Ae) compounds were more potent than that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeroyloxy-1,4- pregnadiene-3,20-dione (betamethasone 17-valerate, BV).

Administration, Topical↗

Studies on topical antiinflammatory agents. III. Synthesis of 17 alpha-acyloxy-9 alpha-fluoro-11 beta-hydroxy-16 beta-methyl-1,4-pregnadiene-3,20-dione 21-thio derivatives and related compounds.

A series of 21-thio derivatives of 9 alpha-fluoro-11 beta,17 alpha-dihydroxy-16 beta-methyl-1,4-pregnadiene-3, 20-dione 17-esters and related compounds were synthesized and evaluated as topical antiinflammatory agents. These compounds were prepared by the reaction of 9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-16 beta-methyl-1,4-pregnadiene-3, 20-dione (betamethasone, I) 17-ester derivatives and various mercapto compounds. A structure-activity relationship study revealed that the structural combination of a thio group at the 21-position and an ester group at the 17-position contributed to vasoconstrictive activity. Among these compounds, the 21-methylthio 17-propanoate compound (6) was found to have the most potent activity, being more potent than betamethasone 17-valerate (BV).

Administration, Topical↗

[Clinical evaluation of I-131 metaiodobenzylguanidine (MIBG) imaging in suspected neuroblastoma].

Twenty neuroblastoma and 4 nonneuroblastoma patients were studied by 131I-MIBG imaging. The primary tumor was detected in 89% of patients (8/9) before therapy. Bone marrow metastasis was also visualized in 4 of the 8 patients with primary positive scan. True negative results were obtained in 4 nonneuroblastoma patients. After therapy, of 10 tumor-bearing patients, eight showed positive scans and 9 of 12 lesions (75%) were visualized. The accuracies of presence or absence of neuroblastoma were compared between 131I-MIBG imaging and several tumor markers. The accuracies before and after therapy were as follows: 131I-MIBG imaging; 92% (12/13), 88% (15/17), serum NSE; 80% (4/5), 93% (13/14), serum LDH; 92% (11/12), 76% (13/17), urinary VMA; 54% (7/13), 56% (9/16), and urinary HVA; 77% (10/13), 56% (9/16). It appears that 131I-MIBG imaging is useful for both locating and excluding neuroblastoma. In addition, 131I-MIBG imaging appears to be the most efficient diagnostic and follow up study for neuroblastoma when it is combined with measurements of serum NSE.

3-Iodobenzylguanidine↗

Immunoregulatory effects of interleukin 2 and interferon on syngeneic murine malignant glioma-specific cytotoxic T-lymphocytes.

The effects of interleukin 2 (IL2) and interferon (IFN) on the generation and lytic activation of syngeneic murine malignant glioma (a methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin, 203-glioma)-specific cytotoxic T-lymphocyte (G-CTL) were investigated. The surface marker analysis showed that G-CTLs from both intracranial and s.c. tumor-bearing mice were composed of thymectomy-resistant (mature) Lyt-1-.2.3+ and thymectomy-sensitive (immature) Lyt-1+.2.3+ CTLs, which markedly decreased concurrently with increased intracranial pressure. G-CTLs were confirmed to be activated with target specificity by both factors in a different way. The CTL activation by IL2 (20 units/ml) remained for a longer time, although a lag time of 5 days after initial culture was required. IL2 influenced Lyt-1+.2.3+ CTLs to proliferate and develop the lytic potential. In contrast, even a 3-h incubation with IFN (1000 units/ml) could enhance the cytotoxicity, but the augmenting effects were observed no longer than 5 days later. IFN activated Lyt-1-.2.3+ CTLs and increased their proportion of the total cell population with a simultaneous decrease of Lyt-1+.2.3+ CTLs. Therefore, it was suggested that IL2 may provide a growth of CTL populations and that IFN can accelerate recruitment of new effectors, causing activation of the lytic process.

Animals↗

Effects of thyroid-stimulating hormone, carbachol, norepinephrine, and adenosine 3',5'-monophosphate on polyphosphatidylinositol phosphate hydrolysis in dog thyroid slices.

TSH (10-250 mU/ml), carbachol (100 nM to 10 microM), and norepinephrine (10-100 microM) stimulated in a dose-dependent manner the accumulation of [3H]glycerophosphoinositol, [3H]inositol monophosphate, [3H]inositol bisphosphate, and [3H]inositol triphosphate in dog thyroid slices prelabeled with myo-[2-3H]inositol. The maximal effect of carbachol was considerably greater than that of TSH and norepinephrine. Carbachol stimulation of [3H]inositol phosphates (InsPs) was present by 5 min of incubation, while that of TSH required at least 30 min. Neither the basal level of [3H]InsPs nor the stimulation by carbachol (1 microM) or norepinephrine (500 microM) was affected by forskolin (10 microM) or cAMP analogs [8-bromo-cAMP or (Bu)2-cAMP; 1 mM]. A maximal amount of TSH (250 mU/ml) had ergistic effects on submaximal carbachol (1 microM)- and additive effects on maximal norepinephrine (500 microM)-induced accumulation of [3H]InsPs. Since not all of the effects of TSH on the thyroid can be explained by activation of the adenylate cyclase system, these data indicate that TSH may also regulate thyroid function through the polyphosphatidylinositol phosphate pathway. In addition, stimulation of the adenylate cyclase-cAMP system does not modify the effects of carbachol or norepinephrine on [3H]InsPs accumulation in dog thyroid slices.

8-Bromo Cyclic Adenosine Monophosphate↗

Biodistribution and in vivo kinetics of iodine-131 lipiodol infused via the hepatic artery of patients with hepatic cancer.

The biodistribution and in vivo kinetics of [131I]lipiodol infused into the hepatic artery were studied to estimate the potential of internal radiotherapy of hepatic cancer in five patients. It accumulated only in the vascular tumors and adjacent hepatic tissue (AHT) supplied by the infused artery, and to a lesser extent in the lung throughout 8 days imaging sequence. Iodine-131 lipiodol appeared to lead to oil embolization of the tumor and AHT followed by secondary embolization to the lungs and finally the activity was mainly excreted into urine. Four tumors had rapidly and slowly decreasing components, while the AHT activity decreased exponentially from the beginning. The effective half life in tumors was longer with the slow component (mean +/- s.d.: 5.7 +/- 1.2 days) than the AHT (3.7 +/- 0.6 days). The tumor/AHT concentration ratio in three patients at 2 hr was estimated to be 7.5-21. The activity was lower in the lungs than in the AHT in four patients. Iodine-131 lipiodol thus may be used as an intra-arterial infusion agent to treat certain vascular hepatic cancers.

Adenoma, Bile Duct↗