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Biomedical subjects

M Taguchi

Publications and source records attributed to M Taguchi.

At least 37 records · Page 2Linked to original sources

Synthesis and antibacterial activity of thiazolopyrazine-incorporated tetracyclic quinolone antibacterials.

A novel series of 8-substituted-9,1-[(N-methylimino)methano]- 7-fluoro-5-oxo-5H-thiazolo[3,2-alpha]-quinoline-4-carboxylic acids 5a-q having a unique thiazolopyrazine-incorporated tetracyclic structure were synthesized, and the in vitro and in vivo activities were determined against Gram-positive and Gram-negative bacteria. All compounds 5a-q had more potent activity than ofloxacin (6), which is one of the most popular quinolones, against Gram-positive and Gram-negative bacteria. The 8-pyrrolidinyl, 5a-e, and 8-morpholino, 5p, derivatives showed the most potent activity against Gram-positive bacteria. It is also significant that these compounds, 5a-q, showed more potent antibacterial activity against methicillin-resistant Staphylococcus aureus isolates (MRSA) than ofloxacin (6). The combination of the morpholino group and this unique tetracyclic thiazolopyrazine skeleton contributes to the enhancement of the antibacterial activity against MRSA isolates. The in vivo antibacterial activities of these compounds, 5a-q, were limited and depended on the structure of the 8-substituent. The 8-(4-alkyl-1-piperazinyl) derivatives 5g, 5h, 5j, and 5n provided good oral efficacy and exhibited more potent activity than ofloxacin (6) against the systematic infection with S. aureus IID 803 in mice.

Animals

Continuous monitoring of mixed venous oxygen saturation for detecting alterations in cardiac output after discontinuation of cardiopulmonary bypass.

Although mixed venous oxygen saturation (SVO2) is related to the reciprocal of cardiac output (CO) if both arterial oxygen content and oxygen consumption remain constant, simultaneous alterations in the three variables may occur immediately after discontinuation of cardiopulmonary bypass (CPB). To examine if continuous monitoring of SVO2 using a fibreoptic pulmonary artery catheter would be useful for detecting alterations in CO immediately after discontinuation of CPB, we have examined the relationships between changes in SVO2, cardiac index (CI), oxygen consumption and haemoglobin concentration in 15 cardiac surgical patients. Changes in SVO2 correlated well with those in CI for 60 min after CPB (r = 0.75, P = 0.0001). A closer correlation between these two variables was noted in the patients with baseline CI of less than 2 litre min-1 m-2 (r = 0.87) than the patients with baseline CI of more than 2 litre min-1 m-2 (r = 0.66). However, changes in SVO2 did not correlate with either oxygen consumption or haemoglobin concentration. The current results suggest that continuous monitoring of SVO2 with the fibreoptic pulmonary artery catheter may be useful for detecting changes in CO after discontinuation of CPB in patients with compromised cardiac function.

Aged

Autocrine/paracrine function of transforming growth factor-beta 1 in porcine granulosa cells.

The present study was undertaken to investigate the effects of transforming growth factor (TGF)-beta 1 on ovarian steroidogenesis in immature or moderately mature porcine granulosa cells in vitro. TGF-beta 1 (0.01-10 ng/ml) significantly attenuated progesterone release from the basal and follicle stimulating hormone-stimulated porcine granulosa cells, and significantly increased DNA synthesis. TGF-beta 1 also significantly increased the extracellular accumulation of cyclic AMP, but did not change the production of inositol phosphate or the intracellular calcium concentration in these cells. Thus, TGF-beta 1 appears to have a direct effect on porcine granulosa cell function, regulating the differential synthesis of progesterone mainly via the intracellular signal transduction of the cyclic AMP-protein kinase A pathway. This growth factor may play a physiologically significant role in controlling differentiation of immature and moderately mature porcine granulosa cells via an autocrine/paracrine mechanism.

Animals

End-tidal sevoflurane concentration for tracheal intubation and minimum alveolar concentration in pediatric patients.

BACKGROUND: Sevoflurane is a new inhalational anesthetic agent having low solubility in blood and a relatively nonpungent odor. As such it should be useful as an inhalation induction in pediatric patients. The objectives of the study were to determine both the minimum alveolar concentration (MAC) and the concentration required for tracheal intubation (MACEI) of sevoflurane in pediatric patients. METHODS: The study group consisted of 36 ASA physical status 1 elective surgical patients, aged 1-9 yr. MACEI determination: After establishing and maintaining the end-tidal concentration for 15 min, tracheal intubation was attempted with an uncuffed tracheal tube without neuromuscular relaxants or other adjuvants. Each concentration at which tracheal intubation was attempted was predetermined according to the up-and-down method (with 0.5% as a step size). MAC determination: The patients examined were the same as those for MACEI determination except that for the exclusion of those to whom neuromuscular relaxants or other adjuvants drugs were administered. End-tidal sevoflurane concentration was determined according to the up-and-down method (with 0.5% as a step size) and held constant for at least 15 min before a skin incision. RESULT: MACEI of sevoflurane was 2.69% (95% fiducial limits: 2.23% and 3.37%); MAC of sevoflurane was 2.03% (95% fiducial limits: 1.51% and 2.53%); and the MACEI/MAC ratio was 1.33. CONCLUSION: Sevoflurane appears to be suitable for use in pediatric patients as an induction agent, permitting tracheal intubation without neuromuscular relaxants.

Anesthetics

End-tidal sevoflurane concentrations for laryngeal mask airway insertion and for tracheal intubation in children.

BACKGROUND: Sevoflurane, a new inhalational anesthetic agent characterized by a low blood-gas partition coefficient and nonpungent odor, appears suitable as an induction agent for children. The laryngeal mask airway is a new device for maintaining airway patency during anesthesia. This study was conducted to determine the sevoflurane concentrations required for insertion of a laryngeal mask (MACLMI) and for tracheal intubation (MACTI) in children. METHODS: Forty-two patients, aged 1-9 yr, scheduled for surgery during general anesthesia were randomly assigned into two groups: MACLMI (n = 21) and MACTI (n = 21). After the predetermined end-tidal concentration had been established and maintained for 20 min, laryngeal mask insertion or tracheal intubation was attempted without neuromuscular relaxants or other adjuvants. Each concentration at which laryngeal mask insertion or tracheal intubation was attempted was predetermined by the up-and-down method (with 0.5% as a step size). RESULTS: Sevoflurane MACLMI was 2.00 +/- 0.28%. Sevoflurane MACTI was 2.83 +/- 0.34%, significantly greater than MACLMI. CONCLUSIONS: Laryngeal mask insertion can be performed at a lesser sevoflurane concentration than that required for tracheal intubation.

Anesthesia

Aberrations of the tumor suppressor p53 gene and p53 protein in solar keratosis in human skin.

Aberrations of the p53 gene in 27 solar keratoses were examined by the polymerase chain reaction and single-strand conformation polymorphism and DNA sequencing analyses. In a series of Japanese patients, eight of 27 cases (30%) of solar keratosis showed structural abnormalities of the p53 gene. Six of eight aberrations of p53 gene were determined to be single nucleotide substitutions, and five of these were located at a dipyrimidine site. In solar keratosis, noticeable mutations were C to T in three cases, and one each of C to A and T to C nucleotide changes. p53 protein was detected immunohistochemically in the nuclei of six of 27 cases (22%) of solar keratosis. Nuclear staining for p53 protein was only significantly correlated with the presence of missense mutation of p53 gene (p < 0.01). Aberrations of the p53 gene in solar keratosis may be a marker to predict early cancerous lesions.

Base Sequence

[Polymerase chain reaction (PCR) method for the detection of Salmonella by using Chelex resin after enrichment culture].

Salmonella has been implicated as a important pathogen associated with acute gastroenteritis or food borne diseases in humans. Rapid and accurate diagnostic tests for Salmonella are needed by both the food industry and clinical laboratories. A pair of oligonucleotide primers from the phoE gene was used to develop a polymerase chain reaction (PCR) procedure to detect Salmonella spp. When Chelex-extracted DNA from the SBG enrichment culture were used as templates for the PCR amplification (E-Chx), the positive results were obtained with a few cells of Salmonella. This highly specific and sensitive technique gave an efficiency of 1.2 times (73 samples were positive) when tested against conventional culture method (62 samples were positive) using 125 fecal samples stored at 4 degrees C for 1-16 months. Based on the results obtained in this study, it appears that the enrichment-PCR method (E-Chx) using Chelex-extracted DNA described here can be useful to screen a large number of samples such as foods or environmental specimens for contamination of Salmonella.

Base Sequence

Determination of end-tidal sevoflurane concentration for tracheal intubation and minimum alveolar anesthetic concentration in adults.

The purpose of this study was to determine both the concentration of sevoflurane required for tracheal intubation (MACEI) and its minimum alveolar anesthetic concentration (MAC) in adults. The study group consisted of 86 elective surgical patients, ASA physical status I or II, aged 16-59 yr. There was no premedication administered. For MACEI determination, after establishing and maintaining the predetermined end-tidal concentration for 20 min, tracheal intubation was attempted using a cuffed tracheal tube without muscle relaxant or other adjuvants. Each concentration at which tracheal intubation was attempted was predetermined as follows: 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, and 7.0%. For MAC determination, the patients examined were basically the same as those for MACEI determination, except for those who received muscle relaxant or other adjuvants because they were "not intubated smoothly." After establishing and maintaining the predetermined end-tidal concentration for 20 min, skin incision was attempted. Each concentration at which skin incision was attempted was predetermined as follows: 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, and 3.0%. The MACEI of sevoflurane was 4.52% (95% confidence limits, 3.91%-5.21%), and the ED95 for tracheal intubation was 8.07%. The MAC of sevoflurane was 1.58% (95% confidence limits, 1.14%-1.98%), and the AD95 (anesthetic ED95) was 2.96%. The MACEI/MAC ratio was 2.86 (95% confidence limits, 2.63-3.43). Anesthesia induction followed by tracheal intubation can be accomplished in adults when sevoflurane is administered as a sole anesthetic, but in excess of 8% end-tidal concentration.

Adolescent

Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic acids.

A novel tetracyclic pyridone carboxylic acid with a thiazolidine ring, 1,2-dihydro-9,1-(epoxymethano)-7-fluoro-8-(4-methyl-1-piperazinyl)-5-oxo -5H- thiazolo[3,2-a]quinoline-4-carboxylic acid (4a), and variants with a nitrogen atom (4b) or carbonyl group (4c) in the place of the 10-position oxygen atom of 4a were prepared and tested for antibacterial activity and inhibitory activity on DNA gyrase from Escherichia coli KL-16. The in vitro antibacterial potency with regard to the 10-position atom was found to be of the following order; O > NCH3 = C = O. The IC50 values for DNA gyrase inhibition activity for the 4a, 4b, and 4c compounds were 0.33, 0.53, and 0.67 g/mL, respectively. The activity of 4a, in which the C-3 methyl group and C-5 of ofloxacin (2a) were connected with a sulfur atom to restrict the conformation of 2a, was more potent than that of 2a against both Gram-positive and -negative bacteria, except for Pseudomonas aeruginosa. Compared to the tetracyclic pyridone carboxylic acid 1a, which has a flat thiazole ring, compound 4a showed comparable or slightly more potent activity against both Gram-positive and -negative bacteria, except for P. aeruginosa.

Anti-Infective Agents

Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic acids.

A series of novel tetracyclic pyridone carboxylic acids replacing the 10-position oxygen atom of 9,1-(epoxymethano)-7-fluoro-8-(4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo [3,2-alpha]quinoline-4-carboxylic acid by imino groups (NR; R = Me, Et, c-Pr, allyl, Ph, benzyl), a sulfur atom, or a carbonyl group was prepared and evaluated for antibacterial activity and inhibitory activity on DNA gyrase isolated from E. coli KL-16. The in vitro antibacterial potency and DNA gyrase inhibitory activity were found to be in the following order: NMe > or = O > S >> C = O. Moreover, a methyl group was the optimal alkyl substituent at the 10-position nitrogen atom for antibacterial activity and for DNA gyrase inhibitory activity. 7-Fluoro-9,1-[(N-methylimino)methano]-8- (4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo[3,2-alpha]quinoline-4-carboxy lic acid (10-NCH3) showed potent in vivo antibacterial activity.

Animals

Immunohistochemical examination of tumor-suppressor gene p53 product and pyrimidine dimer in solar keratosis.

In order to find biomarkers to measure the effects of UV irradiation, we examined the accumulation of p53 protein and pyrimidine dimers in 18 solar keratosis specimens. Frozen or AMeX-fixed solar keratosis specimens were immunohistochemically stained by anti-p53 mouse monoclonal antibody, pAb1801 and polyclonal anti-(pyrimidine dimer) antibody. Nuclear accumulation of p53 protein was found in 5/18 (28%) solar keratosis lesions. The percentage of cases showing nuclear p53 protein varied according to the histological type; in the bowenoid type it was 4/7 (57%); in the atrophic type it was 1/7 (14%). Nuclear pyrimidine dimers were not stained in solar keratosis, although the skin of UV-irradiated nude mice was positive. Accumulation of p53 protein is a good marker for early precancerous change caused by UV exposure.

Aged

Endothelin-1 is an autocrine/paracrine regulator of porcine granulosa cells.

We studied whether a novel vasoconstrictor, endothelin-1 (ET-1), is synthesized by and released from porcine granulosa cells, and whether ET-1 acts directly on granulosa cells in an autocrine/paracrine fashion. The dilution curve of the conditioned medium from cultured porcine granulosa cells was parallel to a standard curve of ET-1 in RIA. Reverse-phase HPLC of the conditioned media from the granulosa cells revealed a major peak of ET-1-like immunoreactivity (ET-1-LI) coeluting with standard ET-1. ET-1-LI was released from cultured porcine granulosa cells as a function of time. Northern blot analysis demonstrated the expression of mRNA for prepro-ET-1 in the granulosa cells. We demonstrated the presence of ET-1 in the follicular fluid of porcine ovaries, and that the concentration of ET-1 in large follicles was higher than that in small-medium follicles. ET-1 dose-dependently stimulated cell growth and DNA synthesis in porcine granulosa cells. ET-1 inhibited the FSH- and hCG stimulated accumulation of progesterone in porcine granulosa cells in long-term incubation. These findings suggest that ET-1 produced by porcine granulosa cells may function as an autocrine/paracrine growth factor and modulator of steroidogenesis in ovarian granulosa cells.

Animals

Insulin-like growth factor II in follicular fluid of the patients with in vitro fertilization and embryo transfer.

OBJECTIVE: To investigate whether insulin-like growth factor II (IGF-II) is present in follicular fluids (FF) and whether IGF-II in FF plays an important role on human ovarian function. DESIGN, SETTING, PATIENTS: Insulin-like growth factor II concentrations were measured using an RIA technique in 46 samples of human FF obtained from 20 patients who were undergoing IVF and ET. The distribution profiles of unsaturated IGF-II binding protein were also investigated. Moreover, the effect of IGF-II on steroidogenesis by cultured granulosa cells (GCs) obtained simultaneously in the IVF-ET program was investigated. RESULTS: The IGF-II levels in FF (92.7 +/- 7.5 nmol/L) were approximately eight times greater than those of IGF-I (11.4 +/- 1.0 nmol/L), and significant positive correlations were observed between these IGFs in FF. By Sephadex G-150 gel-chromatography of FF, two apparent peaks of unsaturated IGF-II binding protein could be detected in the high molecular weight (MW) (150 kd) and low MW (approximately 36 to 38 kd) regions. Additionally, IGF-II dose dependently increased the release of P and E2 from the cultured human GCs. CONCLUSIONS: These findings suggest that the large quantity of IGF-II in FF may play possibly some roles in the ovarian steroidogenesis.

Adult

Pathological changes in epidemic porcine Pneumocystis carinii pneumonia.

An outbreak of epidemic porcine Pneumocystis carinii pneumonia on a "farrow-to-finish" pig farm was examined. The clinical disease was observed in weanling piglets, mostly in the seventh to eleventh weeks of life. Lesions of P. carinii pneumonia were detected histologically in the pigs at 36 to 75 days of age. These included pulmonary septal thickening, with mononuclear cell infiltration, swelling of the alveolar lining, an intra-alveolar exudate and the presence of P. carinii organisms. Focal pneumonia was seen at 36-43 days of age and diffuse pneumonia at 46-75 days. This outbreak resembled the infantile epidemic form of P. carinii pneumonia in man, in being age-related and in causing a non-suppurative intense inflammatory response in the lungs.

Animals

High levels of immunoreactive endothelin-1 in human follicular fluids.

Follicular fluids were obtained from 180 follicles of 15 women undergoing follicular aspiration for in-vitro fertilization. Follicular development was induced by a combination of buserelin acetate and human menopausal gonadotrophin. Endothelin-1 (ET-1) concentrations in human follicular fluids were determined by specific radioimmunoassay. ET-1-like immunoreactivity (ET-1-LI) ranged from 338 to 928 pg/ml. ET-1-LI concentrations in follicular fluids obtained from immature (< 15 mm) follicles were significantly higher than those from mature (15-25 mm) and post-mature (> or = 25 mm) follicles. No correlation was found between the concentration of ET-1-LI, on the one hand, and that of oestradiol, progesterone, testosterone, prolactin, luteinizing hormone, insulin-like growth factor-I, prostaglandin E2 or platelet activating factor on the other, in follicular fluids. However, a significant positive correlation was observed between ET-1-LI concentration and follicle stimulating hormone and IGF-II concentrations, respectively. These data suggest that the high concentration of ET-1 found in follicular fluids may play some physiological role in follicular development.

Buserelin

[Differentiation of cholera-enterotoxin producing Vibrio strains by polymerase chain reaction].

The pathogenic factor of Vibrio cholerae that induces a severe watery diarrhea in humans is cholera enterotoxin (CT). We have earlier reported on the use of a specific polymerase chain reaction method (PCR) for confirmation of CT-production. In our results, a few CT-producing V. mimicus strains were detected by the method. Here we report on the PCR method using 2-primer sets in the same tube for differentiation of toxigenic V. cholerae (O1 and non-O1) and toxigenic V. mimicus. One primer pair is for CT-gene (ctx), and the other pair is for the toxR gene which regulates the ctx gene of V. cholerae. ToxR genes were detected in all CT-producing V. cholerae (both O1 and non-O1). There were no isolates of the ctx gene positive and toxR gene negative in all V. cholerae strains. On the other hand, V. mimicus strain has not recognized toxR genes except one strain which is similar to the character of V. cholerae. These results indicates that the CT-producing V. cholerae strains are regulated by the toxR gene, but the ctx gene of V. mimicus is controlled by another different genome from toxR of V. cholerae.

Enterotoxins