Biomedical subjects

T Kawabata

Publications and source records attributed to T Kawabata.

At least 109 records · Page 6Linked to original sources

PubMed1994

Metabolic effect of PGE1 analogue 01206.alpha CD on nerve Na(+)-K(+)-ATPase activity of rats with streptozocin-induced diabetes is mediated via cAMP: possible role of cAMP in diabetic neuropathy.

We investigated the dose-dependent effects of prostaglandin E1 (PGE1) analogue, OP1206.alpha CD (OP), on motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and Na(+)-K(+)-ATPase (ATPase) activity in streptozocin-induced diabetic rats. At 10 micrograms/kg/day, OP ameliorated MNCV and NBF, but no ATPase activity, whereas at 30 micrograms/kg/day it increased MNCV and ATPase activity, but not NBF. These results suggested a possible direct metabolic effect of OP, at least at a certain dose, on ATPase activity independent of NBF. Since PGE1 exerts an effect on nerve cAMP content, we conducted an in vitro study to clarify the relationship of cAMP to the modulation of ATPase activity in diabetic nerves. We studied sciatic nerves isolated from 53 rats with streptozocin-induced diabetes that had exhibited hyperglycemia for 6 wk. OP increased the activity of ATPase and the accumulation of cAMP in a dose-dependent manner. Dibutyryl cAMP, a cAMP analogue, and aminophyline, which increases nerve cAMP content, enhanced ATPase activity in a dose-dependent manner. In addition, the increased activity of ATPase in diabetic nerves produced by OP was suppressed by a protein kinase inhibitor, H8. These results suggest that ATPase activity in diabetic nerves might be regulated or modified by cAMP and, possibly, by protein kinase A, a finding that is important for clarifying the pathogenesis of diabetic neuropathy and for developing new approaches to treatment.

Alprostadil↗

PubMed1994

N-nitroso compounds in two nitrosated food products in southwest Korea.

Gastric cancer is the commonest malignant neoplasm in Southwest Korea. The possibility of carcinogenic dietary factors led to the investigation of exposure to N-nitroso compound precursors among residents of the City of Chonju and of two outlying rural townships in North Cholla Province. Two traditional and widely consumed home-prepared food products, salted pickled cabbage (kimchi) and salted seafood sauce (chut-kal) were analysed (a) for nitrite, nitrate, total secondary amines and pH in these food products prior to nitrite incubation and (b) for volatile nitrosamines and total N-nitroso compounds before and after incubation with nitrite in simulated human stomach conditions. Nitrate levels were significantly higher in kimchi (median 1550 mg/kg) than in chut-kal (median 140 mg/kg) (P < 0.001). Secondary amine levels in non-nitrosated samples of kimchi (median 5.5 mg/kg) were significantly lower than secondary amine levels in non-nitrosated chut-kal (median 56 mg/kg) (P = < 0.001). Analyses of nitrite-incubated kimchi revealed high levels of total N-nitroso compounds (median 1173 micrograms/kg); the increase with nitrosation was significant (P = 0.001). The concentration of N-nitroso compounds in nitrite-incubated kimchi was significantly greater than that found in nitrite-incubated chut-kal (P = 0.015). The combination of high levels of nitrate in the kimchi, the demonstration of high levels of total N-nitroso compounds in this food after nitrosation, and the volume of kimchi consumed in the traditional diet suggest that salted pickled cabbage may play a role in gastric carcinogenesis in Southwest Korea.

Amines↗

PubMed1994

The identification of chemicals with sensitizing or immunosuppressive properties in routine toxicology.

In the context of this paper, immunotoxicity is taken to encompass immunosuppression/immunopotentiation and allergy. Over the last 10 to 15 years, well characterized methods for the assessment of altered immune competence have been reported. This has led to proposals for tiered testing schemes. This review examines the suitability of immunotoxicity parameters for inclusion in routine 28-day studies and comments on methods that have been proposed for incorporation within the guidelines issued by the US FDA and US EPA and OECD. It is recommended that the existing OECD Guideline 407 is modified to incorporate total and differential blood cell counts, spleen and thymus weight and histopathology, and draining and distal lymph node histopathology for Tier I level testing. Data so generated will provide a reliable and accurate means of identifying at an early stage potential immunotoxic effects. Tier II testing should be carried out on a case by case basis and only assuming positive results are obtained at Tier I. An increasingly sophisticated understanding of the nature of immune responses to chemical allergens has facilitated the design of novel predictive methods for the identification of sensitizing activity. Opportunities which arise from these new developments in allergy testing such as the local lymph node assay, mouse ear swelling test, and the mouse IgE test should be monitored closely.

Adjuvants, Immunologic↗

PubMed1994

Effects of natural antioxidant ginkgo biloba extract (EGB 761) on myocardial ischemia-reperfusion injury.

Recently, it was reported that Ginkgo biloba extract (EGb 761), which is known to have antioxidant properties, also has antiarrhythmic effects on cardiac reperfusion-induced arrhythmias. In the present study, effects of EGb 761 on cardiac ischemia-reperfusion injury were investigated from the point of view of recovery of mechanical function as well as the endogenous antioxidant status of ascorbate. Isolated rat hearts were perfused using the Langendorff technique, and 40 min of global ischemia were followed by 20 min of reperfusion. EGb 761 improved cardiac mechanical recovery and suppressed the leakage of lactate dehydrogenase (LDH) during reperfusion. Furthermore, EGb 761 diminished the decrease of myocardial ascorbate content after 40 min of ischemia and 20 min of reperfusion. Interestingly, EGb 761 also suppressed the increase of dehydroascorbate. These results indicate that EGb 761 protects against cardiac ischemia-reperfusion injury and suggest that the protective effects of EGb 761 depend on its antioxidant properties.

Analysis of Variance↗

PubMed1994

Right atrial pressure and ANP release during prolonged exercise in a hot environment.

To investigate the relationship between right atrial pressure (RAP) and atrial natriuretic peptide (ANP) release during prolonged exercise in a hot environment (30 degrees C, 20% relative humidity), we studied with a Swan-Ganz catheter five male volunteers exercising on a cycle ergometer at 60% of peak aerobic power for 50 min. The ANP level increased from 14 +/- 3 (SE) to 69 +/- 10 pg/ml (P < 0.001) during the first 10 min of exercise as RAP rose from 4.3 +/- 0.8 to 6.9 +/- 1.1 mmHg (P < 0.001). The 10-min ANP level was significantly correlated with RAP (r = 0.88, P < 0.05) but not with heart rate, pulmonary arterial blood temperature, plasma norepinephrine, or plasma epinephrine. The 10-min RAP value was inversely correlated with blood volume (r = -0.98, P < 0.01) and also with stroke volume (r = -0.96, P < 0.01). In the next 20 min of exercise, ANP continued to increase to 101 +/- 12 pg/ml (P < 0.02 vs. 10 min) and remained at this level until 50 min of exercise, whereas RAP decreased and reached a level not significantly different from baseline at 50 min (5.7 +/- 1.0 mmHg; P < 0.01 vs. 10 min). This dissociation of ANP and RAP may have been related to the significant increases from the 10-min values of heart rate, blood temperature, norepinephrine (all P < 0.01), and epinephrine (P < 0.02) during the same period. These results suggest that ANP release is primarily controlled by atrial distension at the onset of exercise but that other stimulators may be involved thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Cloning of cDNAs for cecropins A and B, and expression of the genes in the silkworm, Bombyx mori.

cDNA clones coding cecropins A and B were isolated from a cDNA library constructed from the fat body of immunized Bombyx mori larvae. The cloned cDNAs had an open reading frame of 63 amino acids, indicating the primary translated peptides were processed to form mature cecropins of 35 amino acid residues. The homology in the coding regions of cecropins A and B was 73%. In immunized fat body, the expression of both cecropin A and B genes reached the maximal level 5 h after the injection of soluble peptidoglycan, and the high level was maintained until 9 h after immunization. The cecropin A and B genes were expressed at high levels in fat body and hemocytes, at lower but significant levels in malpighian tube, slightly in midgut, and none in silk gland.

Amino Acid Sequence↗

PubMed1994

[Hilar type squamous cell carcinoma confined within the bronchial wall with hilar lymph node metastasis: a case report].

A 60-year-old male patient visited our hospital for evaluation of positive sputum cytology. A chest X-ray film revealed no abnormal shadows. Bronchofiberscopy showed a protruding lesion at the spur between left B8 and B9. Histological findings indicated squamous cell carcinoma. Left lower lobectomy with hilar and mediastinal lymph node dissection was performed. The tumor did not infiltrate beyond the bronchial cartilage on postoperative histologic examination. However, hilar lymph node (#12 l) metastasis was identified. Surgical resection with lymph node dissection is mandatory even in the hilar type lung cancer confined within the bronchial wall.

Bronchi↗

PubMed1994

[Factors related to the degree of annoyance in school children caused by Shinkansen noise].

As part of a longitudinal study dealing with the effects of the noise from the Tohoku Shinkansen on the living environment of school children, social surveys were conducted on children in an elementary school near the Tohoku Shinkansen line in Saitama prefecture, by means of a questionnaire from July 1984 through February 1986. Between October and November in 1986, noise levels were also measured adjacent to the houses of subjects who lived within one hundred meters of the railroad track. The present paper is devoted to the examination by multiple regression analysis of factors related to the degree of annoyance at home resulting from the Tohoku Shinkansen noise expressed by subjects. The main results were as follows: 1. Multiple correlation coefficients between the degree of annoyance of the Tohoku Shinkansen noise at home and noise levels were less than 0.3. 2. When annoyance at school from the noise and the self-rated quality of sleep were incorporated in multiple correlations, the values of multiple correlation coefficients exceeded 0.5. These results suggest that so far as individual responses are considered, non-physical factors such as sensitivity to noise and quality of sleep account for a considerable part of the total variance of individual responses.

Child↗

PubMed1994

NMR study of lipoic acid binding to bovine serum albumin.

Evidence for the binding of lipoic (LA) and dihydrolipoic (DHLA) acid to bovine serum albumin (BSA) was sought as a feature for understanding the mechanism of their antioxidant activity and prevention of glycation. Experiments were performed by 1H high resolution NMR. The average binding ratio of LA, DHLA and tetranor LA to BSA were 10 +/- 2, 7.9 +/- 2 and 1.8 +/- 0.4 mol/mol BSA respectively. In this row the number of bound molecules lessens with the decrease of their hydrophobic interactions that correlates with their protective activity. Octanoic acid, the closest analog of lipoate, had a binding ratio of 4.7 +/- 0.5 mol. Lipoic acid was able to replace bound octanoic acid which points out that lipoate occupies the same binding site on BSA. Lipoate had no binding to low density lipoproteins extracted from human plasma which corresponds to its low protection of LDL against glycosylation and oxidative modification. This study indicates that lipoic acid molecules experience strong hydrophobic attraction and binding to BSA which is important part of lipoate protective mechanism.

Animals↗

PubMed1994

[Knowledges of foodstuffs in relation to adult diseases in Japanese students--results from Japan Know Your Body Study].

As part of developing the Know Your Body (KYB) program for Japan, a questionnaire survey was administered assessing knowledge, attitudes, and behavior regarding cigarette smoking, alcohol drinking, dietary lifestyle and exercise. The subjects, about 13,000 in total, were students in elementary, junior and senior high schools in 9 prefectures. The main results concerning knowledge of foods that cause or prevent adult diseases are as follows: 1) Correct responses on the relationship of excessive salt intake and hypertension were made by 39% of males and 41% of female in the fifth grade of elementary school. In the third grade of junior high school, the percentage of correct answer for the same question increased to 80% of males and females, and in the third grade of senior high school, it rose to 90% of males and 91% of females. No clear sex difference was seen in all the grades of school. 2) Less than 23% of the students from the first to fourth grade of elementary school knew the word "cholesterol" and could distinguish high cholesterol foods. In the sixth grade of elementary school, more than 50% of students knew the word "cholesterol". In the third grade of junior high school, more than 50% of students could distinguish high cholesterol foods correctly and recognized the relationship of excessive cholesterol intake to heart disease. These results provide a basis for determination of the age for introducing nutrition education. 3) The percentage of correct answers for distinguishing green-yellow vegetables, showed a clear sex differential. The percentage of correct answers concerning dietary fiber was 75% for males and 81% for females in senior high school.

Adolescent↗

PubMed1994

[Basic studies on combination effects of arbekacin and beta-lactam antibiotics on methicillin-resistant Staphylococcus aureus].

Combination effects were studied with arbekacin (ABK) and beta-lactam antibiotics including imipenem/cilastatin (IPM/CS), flomoxef (FMOX), and cefotiam (CTM) for bactericidal activities, post-antibiotic effects (PAE's) and bactericidal activities of beta-lactam antibiotics after removal of ABK using methicillin-resistant Staphylococcus aureus (MRSA) strain 1936. The following results were obtained. 1. When ABK was administered in combination with IPM/CS, FMOX or CTM against MRSA strain 1936, low FIC index was not obtained. 2. Higher bactericidal activity was observed when ABK was given before beta-lactam than when beta-lactam was given before ABK. 3. Combination of ABK and each of beta-lactam antibiotic led a longer PAE than ABK alone. 4. When each beta-lactam antibiotic was administered after a treatment and removal of ABK, greater bactericidal activity and growth inhibition were observed than when administered each beta-lactam alone. These findings basically demonstrated that ABK was effectively bactericidal against MRSA when administered in combination with beta-lactam antibiotic such as IPM/CS, FMOX or CTM, even when the FIC index did not indicate a favorable effect.

Aminoglycosides↗

PubMed1993

An animal model of chronic ischemic neuropathy with proliferative changes of nerve microvessel wall.

In order to produce a model of ischemic neuropathy with neural microvascular alterations, sodium laurate was injected into a femoral artery and saline into the contralateral artery at the mid-thigh level in Sprague-Dawley rats aged 11 weeks. In view of the dose-related findings, 0.3 mg sodium laurate dissolved in 0.1 ml saline was used for the main experiment. The laurate-injected leg showed paresis during the experimental period. On day 1-7, various stages of Wallerian degeneration and acute microvascular changes were found. At 1 month, regenerating myelinated nerve fibers (MNFs) were found at the central or total fascicular area mainly in the distal tibial nerve. Morphometric analyses suggested that MNFs other than regenerating fibers are atrophic ones. The proliferative changes of nutrient microvascular walls were striking. The percent of closed epineurial microvessels was significantly larger on the laurate-injected sides and inversely associated with the diameter of MNFs. At 7 months, the attenuation of MNFs was more prominent and microvascular alterations were persistently observed. These pathological findings resemble those of chronic ischemic neuropathy including diabetic neuropathy, suggesting that this neuropathy model might provide some valuable and useful clues for clarifying the pathogenesis of chronic ischemic neuropathy.

Animals↗

PubMed1993

The effect of dehydration level on the NaCl concentration chosen by rats.

The relationship between the level of dehydration (3%, 6%, and 8% body weight) and the preference for water and saline in the rehydration were assessed in rats for 15 h. At the 6% and 8% dehydration levels, rats provided with tap water and 0.9% NaCl solution simultaneously consumed more water than NaCl solution (calculated Na concentration was about 57 mEq/l) within 3 h and then consumed more NaCl solution than water (about 116 mEq/l). The shift of the Na concentration of fluid occurred when about 107% of lost cations and 82% of lost fluid were regained. Urine output and urinary Na output were about 14% of the ingested fluid during the initial 4 h; after that, the output was in amounts almost equal to the ingestion. However, the 3% dehydrated rats consumed almost equal amount of tap water and NaCl solution (about 68 mEq/l) throughout the 15 h. The result indicates that at more than 3% dehydration level, rats initially choose hypotonic NaCl solution, and the volume loss of body fluid is then regained by the consumption of almost isotonic Na solution.

Animals↗

PubMed1993

Purification and processing of rat liver procathepsin B.

In order to characterize the intracellular processing event of lysosomal cathepsin B, the proenzyme was purified from the rat liver microsomal contents using a Con A-Sepharose column, a Sepharose-Gly-Phe-GlySc column, and an anti-cathepsin B IgG column. The purified proenzyme gave a single protein band of 39 kDa on SDS/polyacrylamide gel electrophoresis. The proenzyme showed no appreciable enzymatic activity. When the purified proenzyme was incubated with the cathepsin B-free tritosomal contents, prepared by treatment of the tritosomal contents with anti-cathepsin B IgG Sepharose, at pH 3.0, 30 degrees C, a remarkable increase of enzymatic activity was observed. Immunoblot analysis showed that the proenzyme was completely converted to the active intermediate form of 31 kDa after 1 h incubation. These processing and activation events were blocked in the presence of pepstatin. When the proenzyme was incubated with the cathepsins B- and D-free tritosomal contents, prepared by treatment of the cathepsin B-free tritosomal contents with anti-cathepsin D IgG Sepharose, the processing and activation did not occur. These results indicate that cathepsin D is involved in the processing and activation of procathepsin B in rat liver lysosome. In the NH2-terminal sequence analysis of the 31 kDa form, the terminal was assigned as proline (66th residue). Since the NH2-terminus of the mature single-chain form of cathepsin B (29 kDa) ends at leucine (80th residue), the NH2-terminus of the 31 kDa form is 14 amino acid residues longer than that of the single-chain form.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Transforming growth factor-alpha expression of renal proximal tubules in Wistar rats treated with ferric and aluminum nitrilotriacetate.

A high incidence of renal adenocarcinoma has been observed in rats treated with ferric nitrilotriacetate (Fe-NTA) but not in rats treated with aluminum nitrilotriacetate (Al-NTA). Transforming growth factor (TGF)-alpha is one of the several cytokines that is known to be expressed in human and rat renal adenocarcinomas. However, its role in neoplastic transformation is still questionable. Therefore, we investigated the effect of repeated Fe-NTA and Al-NTA administration on renal TGF-alpha expression. Male Wistar rats were given Fe-NTA (n = 16, 5-10 mg Fe/kg) and Al-NTA (n = 19, 1-2 mg Al/kg) i.p., three times a week for 3 or 12 weeks. Another group of rats (n = 4) was given Fe-NTA (5-10 mg Fe/kg) three times a week for 12 weeks and then left untreated for one year. Immunoreactivity for TGF-alpha was positive in the collecting ducts and on the apical surface of proximal tubules in the outer stripe of the outer medulla in all the animals including NTA-injected control animals. However, TGF-alpha immunoreactivity in the regenerative proximal tubular epithelium was observed only in the animals treated with Fe-NTA for 12 weeks. Northern blot analysis also showed expression of TGF-alpha mRNA only in animals treated with Fe-NTA for 12 weeks. The expression of TGF-alpha mRNA in the kidney was stronger than that in the liver or brain. TGF-alpha was also positive in renal cell carcinoma found in animals treated with Fe-NTA for 12 weeks and left untreated for one year. These results suggest that TGF-alpha expression may play an important role in renal carcinogenesis and that it may be a sensitive marker during the induction stage of renal cell carcinoma.

Animals↗

PubMed1992

The role of the C-terminal region of rat brain natriuretic peptide in receptor selectivity.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have different C-terminal tail structures compared with the rather conservative ring structures which consist of 17 amino acid residues. To examine the different effects of the tail structures of ANP and BNP on their interaction with receptors, we synthesized several peptide analogs and measured their biological actions in three different assay systems. Deletion of the C-terminal tail from rat BNP did not effect the vasorelaxation activity against rat aorta, but it promoted cGMP production in cultured rat aortic smooth muscle cells (RASMC). Deletion of the C-terminal tail from rat ANP diminished both vasorelaxant and cGMP producing activities. In a binding competition assay with RASMC and [125I]rat ANP-(1-28), the competition activities of both ANP and BNP were greatly reduced by C-terminal deletion. In addition, we obtained agonists with novel receptor selectivity.

Animals↗

PubMed1992

Increased plasma post-heparin diamine oxidase activity and plant sterol levels in streptozotocin diabetic rat.

Plasma post-heparin diamine oxidase (DAO) activity and plasma levels of plant sterols were examined in streptozotocin diabetic rats fed with chow containing plant sterols, to investigate the enzyme activity in relation to the morphological changes of small intestine as well as sterol absorption in the diabetic rats. Diabetic rats showed increased small intestinal mass and surface area compared with control rats. Plasma post-heparin DAO activity and plant sterol level were also increased more than 2.5-fold in the diabetic rats. Insulin treatment improved these abnormalities. Plasma DAO activity correlated to both the small intestinal hyperplastic change and plasma plant sterol levels. These results indicate that plasma post-heparin DAO activity may be used as a marker of intestinal hypertrophy as well as ability to absorb dietary sterols.

Amine Oxidase (Copper-Containing)↗

PubMed1992

A combination of the aldose reductase inhibitor, statil, and the prostaglandin E1 analogue, OP1206.alpha CD, completely improves sciatic motor nerve conduction velocity in streptozocin-induced chronically diabetic rats.

In view of the possible implication of multifactorial mechanisms in the pathogenesis of diabetic neuropathy, the aldose reductase inhibitor (ARI), Statil, which ameliorates abnormal sorbitol or myo-inositol metabolism in diabetic nerves, and the prostaglandin E1 (PGE1) analogue, OP1206.alpha CD (OP), which improves diabetic vascular derangements, were administered simultaneously for 2 months to streptozocin (STZ)-induced diabetic rats with 5 months' duration of diabetes, and the effects on sciatic motor nerve conduction velocity (MNCV), Na(+)-K(+)-adenosine triphosphatase (ATPase) activity, and morphology of myelinated nerve fibers (MNF) were compared with the effects of a monotherapy with OP. The combination regimen ameliorated abnormal nerve sorbitol and myo-inositol levels and normalized decreased MNCV and enzyme activity. In contrast, neither sorbitol nor myo-inositol metabolism was ameliorated, and only insufficient improvement of MNCV and morphology of MNF was obtained with a monotherapy with OP. In addition, the combination therapy reversed both a decrease in the percent of large MNF and an increase in the percent of small MNF in diabetic rats, whereas a monotherapy with OP reversed only a decrease in the percent of large MNF. The results might suggest that a multiple-drug therapy with different mechanisms of action has greater effects on diabetic neuropathy than a single-drug therapy and is worthy of clinical consideration.

Aldehyde Reductase↗