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Biomedical subjects

I Hayashi

Publications and source records attributed to I Hayashi.

At least 181 records · Page 10Linked to original sources

Role of high molecular weight (HMW)-kininogen in inflammatory exudation: evidence with the studies of the HMW-kininogen deficient rat.

Role of the kallikrein-kinin system in inflammation has been studied in rat model of inflammation, such as paw edema and pleurisy. Previous works suggested involvement of HMW-kininogen and activation of plasma kallikrein system in the carrageenin-induced rat pleurisy at early phase. This study clearly demonstrates the involvement of HMW-kininogen in carrageenin-induced rat paw edema and carrageenin-induced rat pleurisy by using congenitally deficient rat strain in plasma HMW-kininogen. Conclusion is the followings: 1. Significantly less reactivity was noticed in the deficient strain, B/N-Ka, in comparison with normal strain, B/N-Ki, when carrageenin-paw edema or carrageenin- and kaolin-pleurisies were induced. 2. Pretreatment with captopril enhanced the paw swelling as well as pleural fluid accumulation in normal strain but no enhancement was observed in the deficient strain. These results indicate that HMW-kininogen is responsible to inflammatory exudation. 3. T-kinin may not be involved in these inflammations, since the deficient strain owns normal plasma level of T-kininogen.

Animals↗

Changes of T-kininogen levels in plasma and liver during development of rats.

T-kininogen levels of plasma and liver were measured in rats during development by RIA. We found that higher levels of T-kininogen in plasma and liver of neonates and of the mother rats at around term. The plasma level of mature male rats was as low as 1/5 to 1/2 of that of mature female rats. T-kininogen levels in male and female rats increased after treatment with estradiol, indicating that sex hormones may regulate the physiological level of T-kininogen in rats.

Aging↗

Kaolin-induced writhing in mice, a new model of possible bradykinin-induced pain for assessment of analgesic agents.

Kaolin induced a clear and reproducible writhing reaction when intraperitoneally injected into mice. A simultaneous injection (i.p.) of soybean trypsin inhibitor (SBTI) significantly suppressed the kaolin-induced writhing reaction. This writhing reaction was markedly potentiated by a simultaneous injection (i.p.) of captopril. In an in vitro experiment kaolin caused kinin-release in mouse plasma, possibly through the activation of prekallikrein. This activation of plasma prekallikrein and kinin-release were inhibited in the presence of SBTI. Some non-steroidal anti-inflammatory agents inhibited the kaolin-induced writhing reaction dose-dependently. These results suggest that kaolin-induced writhing reaction may be caused by the released bradykinin through activation of the plasma kallikrein-kinin system. This model is a novel and simple tool for assessment of analgesic agents.

Acetylcholine↗

The policy of surgery for small carcinoid tumors of the rectum.

In this report, we discuss the current policy of surgery for small carcinoid tumors of the rectum, with reference to our own cases and also to those reported in the literature. Ten cases of rectal carcinoid tumors were surgically treated at the National Kyushu Cancer Center over a period of sixteen years and three months. The tumors ranged in size from 0.2 to 1.0 cm, with an average of 0.5 cm, and all were confined to the submucosa. The lesions were treated by local excision in eight patients and by low anterior resection in the other two cases, where transanal or transsacral excision was considered difficult. No lymph node involvement was found in these two cases. All patients are alive and well without recurrence, after an average follow-up time of three years and six months. According to the literature, the incidence of metastasis from rectal carcinoid tumors smaller than 1 cm is very low, ranging between 1.7 to 3.4 per cent, and it therefore seems that most such lesions can be treated by local excision alone. If, however, any muscle invasion or lymphatic vessel invasion is demonstrated, then radical surgery is recommended.

Adult↗

Elevation of a novel pituitary protein (7B2) in the plasma in small cell carcinoma of the lung.

7B2 is a new protein isolated from human pituitary glands and distributed widely, particularly with high concentrations in the neuroendocrine tissues in the rat. We measured plasma 7B2 concentrations in 333 normal subjects, 20 patients with benign pulmonary disease and 111 patients with primary lung cancer (21 small cell carcinoma, 90 non-small cell carcinoma). A normal range for plasma 7B2 concentrations was defined as less than the mean + 3 S.D. value (110 pg/ml) based on plasma 7B2 concentrations in 333 normal subjects. Elevation of the plasma 7B2 concentration over the normal range was observed in 15 of 21 patients (71.4%) with small cell carcinoma, eight of 90 (8.9%) with non-small cell carcinoma and four of 20 (20%) with benign pulmonary disease. Plasma 7B2 concentrations correlated with the clinical course on chemotherapy in some patients with small cell carcinoma. Immunocytochemical studies revealed numerous 7B2-positive cells in the small cell carcinoma specimen, while 7B2 staining was not observed in the non-small cell carcinoma and the normal lung specimens. These findings suggest that 7B2 is secreted by the small cell carcinoma of the lung, which caused elevation of plasma 7B2 in these patients. 7B2 might be a possible plasma tumor marker for the small cell carcinoma of the lung.

Adult↗

Pharmacological demonstration of inflammatory mediators using experimental inflammatory models: rat pleurisy induced by carrageenin and phorbol myristate acetate.

Rat pleurisy induced by carrageenin or phorbol myristate acetate (PMA) was utilized for examination of the plasma exudation process of inflammation. Chemical mediators responsible for induction of vascular permeability increase were examined. In carrageenin-induced pleurisy, kinin and PGl2 were demonstrated as the main mediators, and in PMA pleurisy histamine, PGI2 and platelet-activating factor were the main mediators. These results indicate that different stimuli may activate different enzymatic processes to produce different mediators, but they may result in similar inflammatory reactions by action of these multiple mediators simultaneously released.

Animals↗

Differentiation of kinin fractions in ureter urine and bladder urine of normal and kininogen-deficient rats.

Like human kininogens-deficiency, the ureter urine of Brown Norway (B/N) Katholiek rat, a congenitally deficient strain in plasma high molecular weight (HMW)- and low molecular weight (LMW)-kininogen, showed no detectable kinin in the peptide fraction of gel chromatography, whereas normal ureter urine (B/N-Kitasato rat) expressed kinin in the peptide fraction, when assayed by bradykinin enzyme immunoassay (EIA). However there was immunoreactive substance in the higher molecular weight fraction in both strains of rat. The nature of this substance is not known, but it may give rise to a wrong estimate for kinin if rat urine is allowed to immunoassay directly, and peptide fraction of urine is not resolved into its components by gel chromatography. Kinin degrading activity in rat urine is so potent that kinin could be mostly degraded when stored in the bladder, since kinin was found in the peptide fraction of fresh ureter urine but not in that of bladder urine of the normal strain.

Animals↗

Kaolin-induced writhing response in mice: activation of the plasma kallikrein-kinin system by kaolin.

A mechanism of writhing reaction induced by kaolin, a known activator of factor XII, was studied. Kaolin induced a distinct writhing response, when injected intraperitoneally into mice (2.5 mg/mouse). The response disappeared in 15 min, but it was reproduced by intraperitoneal injection of captopril, 20 micrograms, into mice who had received the injection of kaolin 60 min before. This later response as well as the early one was not produced when mice were pretreated with bromelain (10 mg/kg, intravenously), 30 min before the kaolin administration. Therefore we determined if bromelain, a known depleter of plasma prekallikrein and a high molecular weight (HMW) kininogen, depletes those in mice. Plasma was collected from mice with or without pretreatment of bromelain, and kinin release of these plasma samples was examined by action of kaolin. The bromelain-treated mouse plasma released kinin amount of less than detection limit when activated with kaolin, whereas normal plasma released about 300 ng/ml of kinin of bradykinin equivalent as assessed by rat uterus contraction. Furthermore, activation of prekallikrein by kaolin was observed in mouse plasma as amidase activity to produce fluorescence from the synthetic substrate. It was completely diminished in the presence of soybean trypsin inhibitor. These results suggest that bromelain could deplete the HMW-kininogen in mouse plasma in the same way as in rat plasma. Furthermore, it is assumed that the kinin released from HMW-kininogen by kaolin could be responsible for inducing the writhing response.

Animals↗

Experimental approach to a role of the increased T-kininogen level in carrageenin-induced pleurisy of rats.

In order to elucidate the biological role of T-kininogen, it's levels in plasma, exudate, and liver were measured by radioimmunoassay in rats following the induction of carrageenin pleurisy. T-kininogen level in the liver microsomes was increased markedly at 8-24 hr after the carrageenin injection, and its plasma level increased at 24-48 hr with a delay. Pretreatment with dexamethasone suppressed the pleural exudate accumulation almost completely, but inhibited the T-kininogen level in plasma or liver only partially. When rats were pretreated with carrageenin injection into a paw 2 days prior to intrapleural injection of carrageenin, the pretreatment did not affect the pleurisy development, even though the plasma level of T-kininogen was greatly increased. Increased level of T-kininogen correlated well with the thiol protease inhibitor activity found in the plasma and exudate. These results indicate that an increase in the T-kininogen level does not influence the exudation, but might act as an inhibitor of thiol proteases that could be released at the inflammatory site.

Animals↗

Thiosemicarbazide used after periodic acid makes methenamine silver staining of renal glomerular basement membranes faster and cleaner.

The periodic acid-methenamine silver staining technique, which is frequently used for demonstrating the renal glomerular basement membrane, requires a high degree of skill, and in some cases it may be difficult to obtain a good result. To overcome such difficulty and inconsistency, we have improved the method by performing methenamine silver staining after oxidation with periodic acid and subsequent application of thiosemicarbazide. In this procedure, this semicarbazide enhanced the reaction of methenamine silver with the glomerular basement membrane and the reaction was completed within a shorter time in comparison with the conventional method. This modification also eliminated any nonspecific reaction with the surface of the glass slide and the solution container and yielded excellent and reproducible results irrespective of the fixation method and material employed. It was also found to stain the renal glomerular basement membrane of rabbits, which is demonstrable only with difficulty by the conventional method.

Animals↗

[Changes in retention strength of luting cements by repeated loading].

The retention of crowns cemented on abutment tooth model was examined for three types of luting cements when compressive loads of 2.5 to 10.0 kg were repeatedly applied to the occlusal plane. The chamfer type Ni-Cr alloy crown and abutment tooth model were prepared, and their surfaces to be cemented were sandblasted with glass beads. Loads were applied 7,200 times a day for 1, 3, or 7-day period after cementing. The polycarboxylate and zinc phosphate cements showed higher crown retentions than glass ionomer cements. Although retention strength of glass ionomer cements was significantly increased by storing the cemented specimen in water for 7 days, repeated loading tended to decrease retention. In polycarboxylate cements and one brand of zinc phosphate cement employed, retention strengths were decreased when stored in water over 3 days. However, their highest levels were maintained or even positively impacted by repeated loading for 7 days.

Crowns↗

[Isolation perfusion chemotherapy using cisplatin in malignant tumors of the extremities].

Since 1960 isolation perfusion chemotherapy has been performed as a preoperative procedure combined with surgery in 226 patients with malignant tumor of the extremities in our department. In this report we presented the result of isolation perfusion chemotherapy using cisplatin (CDDP) for 27 patients since 1983. The histologic classification of the malignant tumor was osteosarcoma in 17 patients, malignant fibrous histiocytoma (MFH) of bone in 8, and other tumor in 2. The extremity was perfused with CDDP (100 micrograms/ml) for 60 minutes. Of 27 patients, 11 were treated with hyperthermic isolation perfusion. The two-year survival rate of the 15 patients with osteosarcoma was 80%, and that of the 7 patients with MFH of bone 71%. The tumor was microscopically analyzed, and the ratio of necrotic to viable tumor cells was calculated. The degree of tumor necrosis was classified as excellent (greater than or equal to 95%), good (80-94%), fair (50-79%), and poor (less than 50%). Of 16 patients, 7 were excellent, 5 good, 3 fair and 1 poor. We concluded that isolation perfusion chemotherapy using CDDP is an effective procedure combined with surgery for malignant tumor of the extremities.

Adolescent↗

[Development of a cancer of the large bowel following radiotherapy for cancer of the uterine cervix].

Eight patients with a colorectal cancer, following radiotherapy for a cervical cancer have been analyzed. A total of 9 lesions in the large bowel were found. Four were located in the rectum. The average interval between radiation and the diagnosis of a second tumor was 9 years and 6 months. Four patients had had a post-irradiation interval of more than 10 years. In 7 resected specimens, histologic alterations were seen, such as atrophy or the erosion of the mucosal layer around the tumor. Radiotherapy may have contributed to the development of the colorectal cancer in some of these patients. Thus, attention should be paid to monitoring patients who have received radiotherapy for a cervical cancer, since the development of a colorectal cancer after pelvic radiotherapy may occur.

Aged↗

[Usefulness of radioisotope (RI) deconvolution analysis with Tc-99m-DTPA in transplanted kidney].

In 50 renal transplant recipients, we performed radioisotope (RI) deconvolution analysis, as reported by O'Reilly, in 179 renograms from dynamic renal scanning with Tc-99m-DTPA and obtained MTT (mean transit time) and H0 (initial height) values. We found characteristic features of various graft conditions using the combination of MTT and H0. The mean H0 value was greater in normally functioning grafted kidneys than in kidneys with other states. The mean MTT in the normal group was about 2 min. In the acute rejection group, the mean H0 value was lower and the mean MTT was more prolonged compared with the normal group. In ATN group, the mean MTT was similar to that in the acute rejection group, whereas the mean H0 value was lower. In the chronic rejection group, the mean MTT was similar to that in the normal group, but the mean H0 value showed a lower one. The hydronephrosis group had an extremely prolonged MTT. This study indicated that the combination of H0 and MTT obtained from RI deconvolution analysis is a valuable means of understanding the condition of renal grafts.

Graft Rejection↗

[Intraoperative ST-T changes resembling myocardial ischemia due to accidental myocardial cooling].

During the mitral valve replacement on a 48-year-old male with mitral valve stenosis, ST-T changes (ST elevation and T inversion) suddenly appeared just before the start of cardiopulmonary bypass. Myocardial ischemia was suspected before we noticed the cardioplegic solution (about 10 degrees C) had been dripping on the surface of the right ventricle by mistake for about five minutes. After pouring warm saline over the myocardial surface, the EKG returned to normal within ten minutes. In this case, there appeared the elevation of the J point which is characteristic of profound hypothermia and is easily mistaken as myocardial ischemia because of ST segment elevation. It is very important to observe even a trivial intraoperative action which is not directly related with the operative procedure.

Accidents↗

Developmental and sexual differences of T-kininogen levels in rat plasma and liver.

T-kininogen levels in plasma and liver microsomes were measured by radioimmunoassay in female and male rats of various ages. High levels of T-kininogen were found in plasma and liver of 1-day to 1-week old male and female rats and their mothers. The levels in newborns gradually decreased along with their development. In mature male rats the levels were as low as 1/5-1/2 of those in mature female rats. Treatment with estradiol increased the plasma and the liver levels of T-kininogen significantly in both sexes, but testosterone decreased the level in female rats and had no effect in male rats. These results suggest that sex hormones may regulate the physiological level of T-kininogen in rats.

Aging↗

Purification and characterization of rat T-kininogens isolated from plasma of adjuvant-treated rats. Identification of three kinds of T-kininogens.

Two T-kininogens (TI- and TII-kininogens) found in plasma of Freund's adjuvant-treated rats were purified by several chromatographic procedures. The isolated TI- and TII-kininogens showed different mobilities on polyacrylamide gel electrophoresis in the absence of sodium dodecyl sulfate, but were indistinguishable in the presence of sodium dodecyl sulfate. They were also indistinguishable in amino acid composition and antigenicity, but differed in sialic acid content. The NH2- and COOH-terminal sequences were determined. In the 30 NH2-terminal residues, 2 were different. The kinin regions in the COOH-terminal portions of the two kininogens have sequences that demonstrate TI-kininogen contains a mixture of two kinin-containing regions, with substitution of 4 amino acid residues, one of which is identical to the COOH-terminal portion of alpha 1-major acute phase protein (Cole, T., Inglis, A. S., Roxburgh, C. M., Howlett, G. J., and Schreiber, G. (1985) FEBS Lett. 182, 57-61) and the other to the COOH-terminal portion of TI-kininogen (Furuto-Kato, S., Matsumoto, A., Kitamura, N., and Nakanishi, S. (1985) J. Biol. Chem. 260, 12054-12059), both predicted from cDNA sequences. The amino acid sequence of the kinin-containing region from TII-kininogen is the same as the COOH-terminal portion of TII-kininogen predicted from the cDNA. These results indicate that T-kininogens from the plasma of adjuvant-treated rats consist of a family of kininogens, that is, TI- and TII-kininogens (separable on DEAE-Sephadex A-50), and that TI-kininogen consists of at least two variants (TI alpha and TI beta) which correspond to the alpha 1-major acute phase protein reported by Cole et al. and TI-kininogen reported by Furuto-Kato et al., respectively. Immunoblotting studies with plasmas from non-inflamed and adjuvant-treated rats also indicate that T-kininogen which was previously isolated from non-inflamed rat plasma corresponds to TI-kininogen and that TII-kininogen is newly generated after treatment of rats with adjuvants.

Adjuvants, Immunologic↗

Purification and characterization of two kinds of low molecular weight kininogens from rat (non-inflamed) plasma. One resistant and the second sensitive to rat glandular kallikreins.

Two kinds of low molecular weight kininogens (identified as A and B) were isolated from pooled plasma of Sprague-Dawley rats. They show a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence and absence of 2-mercaptoethanol, and the molecular weights are 68,000 for low Mr kininogen A and 73,000 for low Mr kininogen B. Although the molecular weights and amino acid compositions of the low Mr kininogens are similar, rat submaxillary and urinary kallikreins released bradykinin from low Mr kininogen B, whereas low Mr kininogen A was resistant to these enzymes. The COOH-terminal portion of low Mr kininogen A was isolated after cyanogen bromide treatment, and the amino acid sequence of the COOH-terminal 55 residues including the T-kinin (Ile-Ser-bradykinin) was determined. The COOH-terminal portion consists of two sequences with substitution of 4 residues. One peptide corresponds to alpha 1-major acute phase protein (Cole, T., Inglis, A. S., Roxburgh, C. M., Howlett, G. J., and Schreiber, G. (1985) FEBS Lett. 182, 57-61) and the other to the TI-kininogen predicted from a cDNA study (Furuto-Kato, S., Matsumoto, A., Kitamura, N., and Nakanishi, S. (1985) J. Biol. Chem. 260, 12054-12059). The results demonstrate that there exist at least two kinds of low Mr kininogens with clearly different function in rat plasma: one of them, low Mr kininogen A, is a precursor of T-kinin and is resistant to kallikreins, and the second, low Mr kininogen B, is sensitive to tissue kallikreins and shares properties with bovine and human low Mr kininogens. The results also demonstrate that T-kininogen is a mixture of two isoproteins which correspond to alpha 1-major acute phase protein or TI-kininogen, respectively. We could not detect the low Mr kininogen corresponding to the TII-kininogen predicted from the cDNA study of Furuto-Kato et al.

Amino Acid Sequence↗