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Biomedical subjects

T Iwai

Publications and source records attributed to T Iwai.

At least 19 recordsLinked to original sources

Effects of regression of cardiac hypertrophy on myocardial contractility and ventricular myosin isoenzymes.

The effects of regression of cardiac hypertrophy on myocardial contractility and ventricular myosin isoenzymes were investigated in rats with renovascular hypertension. Six-week-old male Wistar rats were made hypertensive by constriction of one renal artery with a silver clip. Regression of cardiac hypertrophy was induced following the lowering of blood pressure by nephrectomy on the affected side 5-6 weeks after constriction of the renal artery and was maintained for 5-6 weeks. In contrast, myocardial hypertrophy was induced by 10-11 weeks of the hypertensive state. Isometric developed tension of isolated left ventricular papillary muscles was measured, while they were being perfused with Tyrode solution. Left ventricular myosin isoenzymes were separated by pyrophosphate gel electrophoresis. The ventricular to body weight ratio of the nephrectomized group was significantly lower than that of the hypertensive group, although it was greater than that of age-matched normal control rats. There were no significant differences in the isometric developed tension among three groups, the nephrectomized, hypertensive, and normal control rats. However, dT/dtmax tended to decrease in the hypertensive rats and recovered to normal in the nephrectomized rats. The left ventricular myosin isoenzyme pattern was shifted toward VM-3 in hypertensive rats and was shifted back toward VM-1 again in nephrectomized rats.

Animals

Evaluation of the measurement of the intraoperative transcutaneous partial pressure of oxygen (PtcO2) as a prognostic indicator in vascular reconstruction.

The intraoperative transcutaneous partial pressure of oxygen (PtcO2) was used to monitor 58 vascular reconstructive surgery procedures in 54 patients. The study comprised three groups: Group A (24 limbs without any ischemic symptoms or signs), Group B (45 limbs with intermittent claudication), and Group C (12 limbs with ischemic rest pain, ulceration, and gangrene). In addition in 31 patients the chest wall was monitored simultaneously as a control. The results showed that the PtcO2 values increased immediately and significantly to varying degrees and at varying speeds after unclamping. The controls had higher values than Group A (P > 0.05), Group B (P < 0.05), and Group C (P < 0.05) patients. Further study showed that there were no significant differences between the maximal values in the limbs with good distal vessel run-off in Groups A, B, and C, and in the controls (P > 0.05). It is thus concluded that effective vascular reconstruction in the limbs is indicated by a rapid and marked increase of both the PtcO2 value and the response value, while with a slow and low increase of the value, early graft failure and poor distal vessel run-off should be suspected. We believe that this monitoring method dynamically reflects the functional state during vascular reconstruction and is clinically valid.

Adult

Expression of adult T-cell leukaemia-derived factor, a human thioredoxin homologue, in the human ovary throughout the menstrual cycle.

An immunohistochemical study of the expression of adult T-cell leukaemia-derived factor (ADF), a human thioredoxin homologue, was performed in the normal human ovary throughout the menstrual cycle. Primordial follicles were negative for ADF. Both granulosa cells and theca interna cells at the stages of preantral and antral follicles contained ADF. The staining intensity of these cells was very strong in the preovulatory dominant follicle. After ovulation, both granulo-lutein and theca-lutein cells were positive for ADF. During pregnancy, the theca-lutein cells revealed very intense ADF staining. The theca interna cells of the atretic follicles showed ADF staining, while the granulosa cells of such follicles did not. These results suggest that ADF localizes in the ovarian steroidogenic cells which have the binding sites of either luteinizing hormone or follicle-stimulating hormone, and that ADF expression is closely associated with the activity of the ovarian steroidogenic cells.

Adult

Expression of c-erbB-2 protein and epidermal growth factor receptor in normal tissues of the female genital tract and in the placenta.

The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor receptor that has molecular homology with the epidermal growth factor receptor (EGFR). To investigate the relationship between the expression of c-erbB-2 protein and EGFR in the tissues of the human female genital tract and in the placenta, we examined the immunohistochemical reactivity of monoclonal antibodies against both of these proteins. In the müllerian-derived genital tract, epithelial cells of the fallopian tube, endometrium, and endocervix showed reactivity for c-erbB-2 protein, whereas reactivity for EGFR was distributed mainly in the stromal cells throughout the menstrual cycle and during pregnancy. In addition, the staining intensity for EGFR in the endometrial stroma increased with its decidualization. In the exocervical squamous epithelium, basal cells were c-erbB-2 protein-negative and EGFR-positive, but the more differentiated squamous cells of the intermediate layer were c-erbB-2 protein-positive and EGFR-negative. In the placental tissues, cytotrophoblasts and syncytiotrophoblasts of the chorionic villi were c-erbB-2 protein-negative and EGFR-positive. In contrast, intermediate trophoblasts in the extravillous space were c-erbB-2 protein-positive and EGFR-negative. Thus, there is an inverse relationship between the expression of c-erbB-2 protein and EGFR in the tissues of the female genital tract and in the placenta. This suggests that there may be a regulatory mechanism(s) for the expression of both proteins that is associated with the differentiation and/or function of cells in the female genital tract and the placenta.

ErbB Receptors

Immunohistochemical localization of c-erbB-2 protein and epidermal growth factor receptor in normal surface epithelium, surface inclusion cysts, and common epithelial tumours of the ovary.

The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor receptor showing molecular homology with the epidermal growth factor receptor (EGFR). We examined the immunohistochemical reactivity of monoclonal antibodies against both of these proteins in normal surface epithelium, surface inclusion cysts, and common epithelial tumours of the ovary. The ovarian tumours were classified as benign (16), borderline malignant (2), and malignant (19). Normal surface ovarian epithelium was weakly positive for both c-erbB-2 protein and EGFR. In surface inclusion cysts, however, the epithelial cells lining the lumen exhibited stronger staining for c-erbB-2 protein, but no staining for EGFR. All 16 benign ovarian tumours and the 2 borderline malignant ovarian tumours were positive for c-erbB-2 protein and negative for EGFR. Of the ovarian carcinomas, 13 of the 19 (68.4%) were positive for c-erbB-2 protein and negative for EGFR, while 4 showed positivity for both c-erbB-2 protein and EGFR. Two cases were negative for both proteins. Expression of both c-erbB-2 protein and EGFR was found in endometrioid carcinoma with squamous differentiation and in clinically advanced poorly differentiated serous carcinomas. Expression of c-erbB-2 protein appears to be increased and that of EGFR is reduced in the early stage of epithelial ovarian oncogenesis. The expression of EGFR with c-erbB-2 protein in ovarian carcinoma is related both to histological differentiation and/or advanced clinical stage.

Adolescent

A case of popliteal cystic degeneration with pathological considerations.

Adventitial cystic degeneration of the popliteal artery is seldom encountered; only 39 cases have been reported up to now in Japan. The pathogenesis of this disease remains controversial, and the authors describe a case in which the pathological findings differed from cases reported in the previous literature. The subject was a 74-year-old man admitted to our hospital complaining of intermittent claudication. The characteristic findings of cystic degeneration of the popliteal artery were uncovered by contrast-enhanced computed tomography (CT) and duplex sonography. The contrast-enhanced CT showed a low-density area and duplex sonography revealed a multi-lobulated low-echoic lesion. The Doppler signal of the low-echoic lesion could not be detected. While some cysts were found in the adventitia, they were mainly located in the media. The media also showed a remarkable decrease of smooth muscle cells and a prominent mucinous degeneration that had occurred circumferentially. These findings suggest that the medial degeneration noted had occurred prior to cystic formation. Because of this and other findings, we recommend the use of the term cystic degeneration of the popliteal artery in addition to the term cystic adventitial disease of the popliteal artery.

Aged

Role of wrapping in concomitant intra-abdominal aneurysm and colorectal carcinoma. Report of three cases.

The therapeutic measure against concomitant intraabdominal aneurysm and colorectal carcinoma is still a dilemma. Here we report the clinical courses of three cases of colorectal carcinoma coincidental with moderate-sized abdominal aortic or iliac artery aneurysm in those who underwent operations during a recent three-year period. Resection of malignant lesion and wrapping of aneurysm were carried out in all three patients simultaneously. Carcinoma was staged by Dukes classification as A in one patient and B in two patients. All tolerated surgery well without any signs of complications. Two-year or three-year follow-up shows that they have continued to do well, with no further symptoms of abdominal aortic aneurysm, peripheral vascular disease, or recurrence of colorectal carcinoma. We conclude that, if the aneurysm is not about to rupture and the carcinoma is in an advanced stage, then the carcinoma should be resected, associated with interim aneurysmal wrapping. However, both lesions need to be resected eventually for long-term survival.

Aortic Aneurysm, Abdominal

Effect of opioids on delayed neuronal death in the gerbil hippocampus.

The effect of opioids on delayed neuronal death was evaluated in the gerbil hippocampus. Male Mongolian gerbils were subjected to transient forebrain ischemia and neuronal density was evaluated in the hippocampus 7 days following ischemia. When hypothermia during and after ischemia was prevented, treatment with morphine, U-50488H, or naloxone provided no significant protection. In contrast, a spontaneous drop in rectal temperature to 32 degrees C at the end of ischemia produced near-complete protection of CA1 pyramidal neurons. No opioids modulate the protective effect of hypothermia.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

Effects of isoprenaline and ouabain on cytosolic calcium and cell motion in single rat cardiomyocytes.

OBJECTIVE: The aim was to develop a novel system to measure changes in cytosolic free calcium concentration ([Ca2+]i) and cell motion simultaneously in a single beating myocyte by digital imaging microscopy. METHODS: Indo-1 was selected as a fluorescent calcium indicator. The particular feature of our digital imaging microscopy is that, in order to avoid cell movement artifacts, two indo-1 fluorescence images of different wavelengths are obtained at the same time at 16.7 ms intervals using two SIT cameras. Isolated ventricular myocytes were used, prepared from hearts of male Sprague-Dawley rats, weighing 350 to 400 g. RESULTS: In continuously beating cells contracted by electrical field stimulation, we can visualise changes in [Ca2+]i and cell shape during contraction with pseudocolour images of the fluorescence ratios, and it was found that the onset of the calcium transient preceded that of the shortening of cell length. Both isoprenaline and ouabain enhanced the magnitudes of the calcium transient and cell contraction. Furthermore, isoprenaline shortened the half decay time of the calcium transient. CONCLUSIONS: Our data suggest that the newly developed system is useful for measuring rapid changes in [Ca2+]i in relation to cell motion, and is particularly suitable for measuring the calcium transients in a beating cardiomyocyte.

Animals

Catalytic properties of yeast protein kinase C: difference between the yeast and mammalian enzymes.

With bovine myelin basic protein as a model common substrate, protein kinases C (PKC) purified from yeast (Saccharomyces cerevisiae) and mammalian tissue (rat brain) were shown to exhibit clearly different catalytic properties. The major sites of phosphorylation in bovine myelin basic protein by the yeast PKC were identified: Thr-19, Thr-34, and Thr-65. These sites are distinctly different from those for the mammalian PKC: Ser-8, Ser-46, Ser-55, Ser-110, Ser-132, Ser-151, and Ser-161, which were previously identified [Kishimoto, A., Nishiyama, K., Nakanishi, H., Uratsuji, Y., Nomura, H., Takeyama, Y., & Nishizuka, Y. (1985) J. Biol. Chem. 160, 12492-12499]. The results suggest that the yeast and mammalian enzymes may play distinct roles in cellular regulation. No evidence is available, however, that a yeast-type PKC exists in mammalian tissues. An oligopeptide containing the sequence around Thr-19 of bovine myelin basic protein, Lys-Tyr-Leu-Ala-Ser-Ala-Ser-Thr(19)-Met-Asp-His-Ala, can be used as a substrate for selective assaying of the yeast PKC.

Amino Acid Sequence

The effect of DHAS on steroidogenesis of the human corpus luteum.

To examine whether or not dehydroepiandrosterone sulfate (DHAS) is a substrate for steroidogenesis in the corpus luteum, we studied 17 women in the luteal phase, the follicular phase, and after castration. Following suppression of adrenal function with dexamethasone, DHAS was administered intravenously and the serum levels of DHAS, dehydroepiandrosterone (DHA), androstenedione (ADS), testosterone (T), 17 beta-estradiol (E2) and progesterone (P) were measured serially for 24 h. An obvious increase in the serum levels of all steroids except for E2 and P was observed in each subject for at least 8 h after DHAS administration. To evaluate the effect of DHAS on the serum levels of the steroid hormones, the integrated response area (IRA) was calculated for each hormone in all the subjects. The IRA values for ADS, T and E2 (at 2 and 4 h) in the luteal phase group were significantly higher than in the other DHAS treated groups, and the IRA values for DHA and P tended to be higher than in the other groups. These results suggest that the corpus luteum utilizes serum DHAS as a substrate for steroidogenesis.

Adult

[Conservative treatment of acute deep vein thrombosis of lower extremities].

To evaluate conservative treatment for acute deep vein thrombosis (DVT) of lower extremities, 56 limbs of 53 patients (29 men and 24 women, age ranging 20 to 77 years, mean age of 50.1 years) were reviewed. Only three patients underwent thrombectomy of restricted iliac venous regions by Fogarty catheter within 24 hours of the onset and their symptoms were relieved immediately after operation with good follow-up condition. Forty-five limbs were treated conservatively. Among 45 limbs, 15 limbs were treated within 7 days of symptom's onset using heparin and urokinase for 6-10 days followed by oral anticoagulant. Forty-seven percent of the patients were freed from their symptoms within one year. However 30 limbs received conservative therapy after 7 days of the onset showed 23% recovery from their symptoms within one year and in extensive thrombosis recovery was only 14%. We concluded that conservative treatment for DVT was effective if it was started within 7 days of the onset, and thrombectomy of ilio-femoral regions might be more effective than conservative treatment under the same condition.

Acute Disease

Immunohistochemical analysis of estrogen receptors, progesterone receptors, Ki-67 antigen, and human papillomavirus DNA in normal and neoplastic epithelium of the uterine cervix.

To investigate the relationship between the sex steroid receptor (estrogen receptor [ER] and progesterone receptor [PR]) status and the cell proliferation kinetics during the menstrual cycle in normal and neoplastic epithelium of the uterine cervix, immunohistochemical localization of ER, PR, and cell proliferation-associated antigen, Ki-67, was investigated in 35 normal cervical specimens, 3 condylomas, 26 cervical intraepithelial neoplasia (CIN) samples, and 22 invasive squamous carcinoma samples. The presence of human papillomavirus (HPV) DNA was also studied. In the normal cervix, basal cells were usually ER positive, PR negative, and Ki-67 negative throughout the menstrual cycle. Parabasal cells were ER positive and PR negative in the follicular phase, but ER negative and PR positive, and Ki-67 positive in the luteal phase, and Ki-67-positive cells increased in number in the luteal phase. In contrast, PR positivity was observed in the cells of condyloma (2 of 2 cases), CIN (19 of 26 cases), and invasive squamous carcinoma (13 of 22 cases) irrespective of the menstrual phase. Moreover, most neoplastic cells containing HPV DNA type 16/18 were ER negative, whereas several lesions containing HPV DNA type 31/33/35 were weakly ER positive. Many Ki-67-labeled cells were observed in the neoplastic lesions. These results suggest that reduced ER expression and increased PR expression are associated with the proliferation of normal cervical squamous epithelium, and this proliferation-related receptor status, which is probably induced by HPV infection, is usually expressed in neoplastic cervical squamous cells.

Adult

Effects of long term treatment with an alpha 1 adrenoceptor blocker on cardiac hypertrophy, contractility, and myosin isoenzymes in spontaneously hypertensive rats.

STUDY OBJECTIVE: The aim was to investigate the effects of long-term treatment with an alpha 1 blocker, bunazosin hydrochloride, on blood pressure, heart weight, myocardial contractility, and ventricular myosin isoenzyme pattern in spontaneously hypertensive rats (SHR). DESIGN: Bunazosin hydrochloride was given orally in a dose of 10 mg.kg-1.d-1 for 8-9 weeks. Isometric tension development was measured in isolated left ventricular papillary muscles. The left ventricular myosin isoenzyme pattern was determined by pyrophosphate gel electrophoresis. SUBJECTS: 14 male SHR (seven treated and seven untreated rats) aged 23 to 24 weeks were studied. MEASUREMENTS AND MAIN RESULTS: The blood pressure of the bunazosin treated rats was approximately 14% lower than that of the untreated rats at the end of the treatment period. The ventricular weight of treated SHR was significantly lower (around 8%) than that of untreated rats, but there were no significant differences between the two groups in the mechanical data obtained from isolated left ventricular papillary muscles. The myosin isoenzyme pattern of the left ventricle was significantly shifted toward VM-1 in the bunazosin treated SHR, the VM-1 concentration in the treated group being 38% greater than in the untreated group. CONCLUSIONS: These results indicate that long term treatment with bunazosin hydrochloride reduces blood pressure and leads to the regression of cardiac hypertrophy in SHR. Myocardial energetics (as represented by the myosin isoenzyme pattern) were affected, but there was no influence on myocardial tension development.

Adrenergic alpha-Antagonists

Isolation of chicken-bek and a related gene; identification of structural variation in the ligand-binding domains of the FGF-receptor family.

cDNA clones carrying the chicken-bek gene and a related gene were isolated. Deducing the amino acid sequence of chicken-bek allowed us to predict that it encodes for a receptor tyrosine kinase related to the fibroblast growth factor (FGF) receptor, and that the chicken-bek gene and Cek3 are closely related. However, a significant structural difference was identified between chicken-bek and Cek3 within the putative extracellular region, in such a manner that the structure of the immunoglobulin-like domain was conserved. A probe specific to the altered structure detected mRNA in the tissues as did a probe common to bek and Cek3, indicating heterogeneity in the FGF-receptor family in a novel manner. Furthermore, another bek-like gene was isolated and the expressions of its mRNA and protein product were analysed in tissues and cultured cells.

Amino Acid Sequence

Duplicate origin of left vertebral artery.

A verified case of duplicate origin of the left vertebral artery in association with a large aneurysm arising from the aortic arch immediately distal to the left subclavian artery is presented. An anomalous left vertebral artery arises directly from the aortic arch between the left common carotid and subclavian arteries, and joins with the normal left vertebral artery in the transverse foramen of the fifth cervical vertebra.

Aged

Surgical treatment of juxtarenal aortic occlusion.

From 1974 to 1976, four patients with juxtarenal aortic occlusion were operated upon with no surgical mortality. Thromboendarterectomy (TEA) of the aorta with renal revascularization was performed in one patient, and TEA with grafting in three. Intraoperative renal protection was particularly important, since suprarenal aortic clamping was often required in these cases. Possible renal embolism developed in one patient postoperatively. In order to prevent renal embolism and to minimize ischemic insult to the kidney, the value of the following procedures was stressed; (a) irrigation of aortic lumen with saline after TEA under suprarenal aortic clamping with renal arteries kept occluded, and (b) re-application of aortic clamp below the renal arteries after irrigation. Since the most distal level of occlusive process was the common femoral artery in our series, the patient with this disease entity should be treated more actively.

Aged