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Biomedical subjects

K Nakada

Publications and source records attributed to K Nakada.

At least 73 records · Page 4Linked to original sources

Plasma beta-endorphin around parturition and its relationship to cortisol level and resumption of pituitary and ovarian functions in dairy cows.

The objectives were to evaluate the concentrations of beta-endorphin in peripheral circulation around parturition and to investigate their relationship to the concentrations of cortisol and postpartum resumption of pituitary and ovarian functions in dairy cows. Subjects were 21 Holstein-Friesian cows in late pregnancy. Blood samples were collected from these animals from day 270 in pregnancy until the first ovulation after calving. Average immunoreactive (IR) beta-endorphin concentrations in cows with dystocia (n = 8) in periparturient period (from day 270 of pregnancy until 24 h after calving) were slightly higher than those in cows with normal calving (n = 13) in the same period although the difference was not significant. During the periparturient period, the peak level of IR beta-endorphin was seen at the time of rupture in cows with normal calving and it was observed at the time of parturition in cows with dystocia. The trend of IR beta-endorphin secretion appeared to be concomitant with cortisol secretion in the periparturient period but not in postpartum period (from 24 h after calving until the first ovulation). Average IR beta-endorphin concentrations in cows with dystocia in the postpartum period were not significantly different from those in cows with normal calving. There was no significant association between average IR beta-endorphin concentrations in early postpartum period (from 24 h until 7 days after calving) and the responsiveness of luteinising hormone (LH) to exogenous GnRH administered on day 7 postpartum. However, a negative correlation (r = -0.593; n = 21; P = 0.004) was observed between average IR beta-endorphin concentrations and LH concentrations during the period from day 1 until the first ovulation in the 21 cows. In addition, a positive correlation (r = 0.498; n = 21; P = 0.020) was seen between the beta-endorphin concentrations and time to the first ovulation after calving. The results from this study suggest that beta-endorphin may release into peripheral blood differently from cortisol and that it may be involved in regulating LH secretion and thus the resumption of ovarian cyclicity in postpartum dairy cows.

Animals↗

Processing and release of tumor necrosis factor alpha.

Tumor necrosis factor alpha (TNFalpha) is synthesized as a transmembrane precursor form that is proteolytically processed and released as the soluble mature form. In human monocytes and monocytic cell lines, the production, processing, and release of TNFalpha are co-induced by certain activators, such as lipopolysaccharide. To investigate the mechanism of TNFalpha processing and release, we established a cell line which constitutively produced TNFalpha, by transfecting the TNFalpha precursor form cDNA into NIH/3T3 cells. In these cells, the processing and release of TNFalpha were augmented by phorbol 12-myristate 13-acetate (PMA), mediated through a protein kinase C (PKC) signalling pathway. Various protease inhibitors were tested and it was found that matrix metalloproteinase (MMP) inhibitors blocked the processing and release of TNFalpha both in the absence and presence of PMA. This result is compatible with the recent reports that MMP are involved in the processing and release of TNFalpha. In contrast, 3,4-dichloroisocoumarin, N alpha-p-tosyl-L-phenylalanine chloromethane, iodoacetamide, and o-phenanthroline inhibited the processing and release of TNFalpha only in the presence of PMA, suggesting that serine proteases requiring SH for their activity, a combination of serine proteases and cysteine proteases, or MMP, may be involved in the PKC-mediated induction of TNFalpha processing and release.

3T3 Cells↗

Stratification of treatment of stage 4 neuroblastoma patients based on N-myc amplification status. Study Group of Japan for Treatment of Advanced Neuroblastoma, Tokyo, Japan.

BACKGROUND: It has been shown that children aged more than 12 months with stage 3 and 4 neuroblastoma with N-myc amplification do worse than those without amplification. Development of an innovative chemotherapeutic protocol for patients in such an extremely poor-risk group was the purpose of this study. PROCEDURE: Since March 1991 a new protocol for the treatment of advanced neuroblastoma was started. When N-myc was amplified more than 10-fold, patients received regimen A3, in which cyclophosphamide 1,200 mg/m2 was given on days 1 and 2; hence the dose of cytotoxic drugs was doubled. Patients with fewer than 10 copies of N-myc received regimen new A1, which is very similar to regimen A1 that had been used until March 1991 for all patients with advanced neuroblastoma with/without N-myc amplification. The efficacy of regimen A3 was evaluated. RESULTS: The relapse-free survival rate at 1 and 2 years for stage 4 patients older than 12 months of age with N-myc amplification of more than 10-fold was 43% and 29%, respectively, with regimen A1 and that for the same subgroup of patients treated with regimen A3 since March 1991 was 79% and 49%, respectively; the difference is statistically significant. On the other hand, there were no differences in the relapse-free survival rate at 1 year and 2 years for stage 4 patients with fewer than 10 copies of N-myc between those treated with regimen A1 and those treated with new A1 since March 1991. CONCLUSIONS: Stratification based on N-myc amplification into new A1 and A3 treatment protocols is of significant clinical importance. Regimen A3 was well tolerated and showed an improvement in clinical results in stage 4 patients with N-myc amplified more than 10-fold.

Antineoplastic Combined Chemotherapy Protocols↗

Efficacy of exogenous fibronectin in wound healing in malnourished rats.

BACKGROUND/PURPOSE: Fibronectin (FN) plays an important role in fibrin matrix formation during the wound healing process. The authors investigated whether exogenous FN increases the bursting strength (BS) of surgical wounds in malnourished rats. METHODS: Ninety rats were grouped according to three nutritional conditions (n = 30 in each group). All animals underwent a transverse celiotomy after 3 weeks of feeding, and FN (2 mg/body/day) was given postoperatively to 15 rats in each of the three groups. Wound BS was measured on postoperative days (PODs) 3, 5, and 7 after removal of the sutures. RESULTS: BS in normally nourished rats (group N; 142.6+/-23.4 mmHg) was significantly higher than that in protein malnourished rats (group PM, 110.2+/-11.2 mm Hg) and protein/ calorie (Cal)-malnourished rats (group PCM, 76.5+/-10.7 mm Hg) on POD 7 (P<.01). However, BS values for groups PM + FN (147.0+/-21.1 mmHg) and PCM + FN (115.1+/-28.9 mm Hg) were intensified significantly in comparison with groups PM and PCM (P<.01). Plasma FN levels in rats of the three FN nontreated groups were similarly decreased on POD 3 or 5, but returned to the preoperative level on POD 7, whereas those for the other three FN-treated groups increased after POD 3. CONCLUSION: Intravenous administration of FN might strengthen the weakened wounds of malnourished animals.

Abdominal Injuries↗

Skeletal muscle regeneration induced by chorio-allantoic grafting.

To examine whether the expression pattern of fast-muscle type troponin-T (TnT) isoforms was fixed in cell lineage, breast muscle pieces (pectoralis major) from chick embryos and young and adult chickens were grafted on to chorio-allantoic membrane of 9-day-old chick embryos and cultured until the host embryos hatched out. Muscle fibre formation of the grafts was investigated by histological and immunohistochemical methods with anti-fast-muscle type and anti-slow-muscle type TnT sera, and the expression of fast-muscle type TnT in the grafts from chick embryos and young chickens was studied by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional SDS-PAGE, and immunoblotting. In the chorio-allantoic grafting, the breast muscle initially degenerated forming pyknotic nuclei and hyaline cytoplasm. The surviving cells, which were supposed to be satellite cells, regenerated new muscle fibres of the same type as those of the grafted muscle in respect of TnT isoform expression. Therefore, we considered that the ability to express specific isoforms of TnT was fixed in the satellite cells, and that chorio-allantoic grafting was a useful technique for studying muscle differentiation.

Allantois↗

Antigenic and genetic diversities of Babesia ovata in persistently infected cattle.

Exploring the antigenic and genetic diversities of Babesia ovata, we obtained several field isolates from grazing cattle in the Okushiri island, Japan. Parasite isolation was greatly facilitated by using bovine red blood cell-substituted SCID mice (Bo-RBC-SCID mice), into which the blood samples of the cattle were inoculated. Isolates from different individuals within a herd of cattle were compared in immunoblot analysis with an anti-B. ovata serum and also in Southern blot analysis with a probe for the small subunit ribosomal RNA gene. In both analyses, the isolates exhibited banding patterns that were significantly different from each other. We were also able to obtain a series of parasite isolates from a single cow in different seasons of a nine months period, including winter when active vector ticks were not in the field environment. Different seasonal isolates showed different banding patterns in both immunoblot and Southern blot analyses. By contrast, these analyses detected little difference among the parasites that had been passed various times in Bo-RBC-SCID mice, where no specific immune responses should be generated. These results indicate that individual animals within a herd of cattle were infected with antigenically and genetically diversified populations of B. ovata, and that the parasites could persistently infect a single animal with dynamic change in their predominant subpopulations.

Animals↗

Thallium-201 scintigraphy to predict therapeutic outcome of iodine-131 therapy of metastatic thyroid carcinoma.

UNLABELLED: We studied the relationship between 201Tl uptake and the efficacy of radioiodine therapy in thyroid carcinoma. METHODS: Forty-four patients with metastases of well-differentiated thyroid carcinoma received 201Tl scintigraphy within the 2 mo before their initial 131I therapy. Patients were classified into two groups according to the tumor-to-background (T/B) ratio on the late 201Tl scan: high 201Tl uptake (T/B > or = 2.1) and low 201Tl uptake (T/B < 2.1). The therapeutic outcome was judged by the percent reduction in the tumor diameter at 6 mo after the treatment. The treatment was defined as effective when the tumor showed more than 50% reduction in the tumor diameter. The patients in whom radioiodine was ineffective were followed up to determine if the tumor showed further growth. RESULTS: Of the 44 patients, 25 had high 201Tl uptake and 19 had low 201Tl uptake. The therapy was effective in 15 patients and was ineffective in 29. All the patients in whom radioiodine was effective had low 201Tl uptake. On the other hand, 25 of 29 patients in whom radioiodine was ineffective had high 201Tl uptake. Eight patients, in whom radioiodine was ineffective despite good 131I uptake, had high 201Tl uptake. There were no significant differences in the positive predictive value and the negative predictive value for effective treatment between 201Tl scintigraphy and therapeutic dose 131I scintigraphy. Among the 25 patients in whom radioiodine was ineffective and who had high 201Tl uptake, the tumor diameter increased in 7 (28%). However, none of the tumors with low 201Tl uptake increased in size during the follow-up period. CONCLUSION: Thallium-201 scintigraphy has a high predictive value for the efficacy of radioiodine therapy in metastatic thyroid carcinoma. Thus, it is helpful in determining the indication for radioiodine therapy and it seems to be an adjunct to tracer dose 131I scintigraphy.

Adenocarcinoma, Follicular↗

Natural occurrence of fast- and fast/slow-muscle chimeric fibers in the expression of troponin T isoforms.

Rhomboideus, one of the back muscle tissues, and its single fibers were studied in chickens by immunostaining with antisera against fast- and slow-muscle-type troponin T isoforms. Nonuniform distribution of slow-muscle-type isoforms was for the first time detected in single fibers isolated from the muscle, although fast-muscle-type troponin T isoforms were distributed over the whole length of the fiber. Based on these observations, we conclude that fast- and fast/slow-muscle chimeric fibers exist in normal skeletal muscle tissue and that the existence of chimeric fibers is direct evidence showing that myonuclei subjected to different determination in troponin T isoform expression can together form a single muscle fiber.

Aging↗

Sequential change of BMIPP uptake with age in spontaneously hypertensive rat model.

UNLABELLED: Changes in myocardial perfusion and metabolism are often associated with myocardial hypertrophy, but there are few reports describing the serial assessment of fatty acid metabolism in hypertrophic myocardium. The aim of this study is to assess fatty acid metabolism serially in hypertrophic myocardium in spontaneously hypertensive rats (SHR) with 125I-BMIPP, a branched fatty acid analog. METHODS: SHR and Wistar-Kyoto rats (WKY) as the control were divided into 4 groups (12, 15, 18 and 51 weeks after birth). The heart was extracted 10 minutes after intravenous injection of 125I-BMIPP and 201Tl at the same time. The accumulation of each radiotracer in the myocardium was counted with a well gamma counter. In addition, 125I-BMIPP uptake was corrected by 201Tl uptake (B/T). RESULTS: The heart weight/body weight ratio was significantly higher in SHR than that in WKY (p < 0.001). In SHR, this ratio increased up to 18 weeks (12 weeks; 0.266 +/- 0.005, 18 weeks; 0.281 +/- 0.006: mean +/- SE, p < 0.05). The 125I-BMIPP uptake tended to be significantly reduced in SHR (12 weeks; 2.373 +/- 0.212, 18 weeks; 1.380 +/- 0.047; mean +/- SE, p < 0.05). Such a difference in BMIPP uptake was more evident when BMIPP uptake was corrected by Tl uptake (B/T), but no regional difference or heterogeneity of BMIPP distribution was observed in the hypertrophic myocardium in SHR. CONCLUSION: A change in fatty acid metabolism with age was observed in association with myocardial hypetrophy in this hypertensive rat model, which was well demonstrated with 125I-BMIPP and 201Tl.

Aging↗

Digestive tract disorders associated with asplenia/polysplenia syndrome.

The authors reviewed experience gained over a 20-year period of asplenia or polysplenia syndrome, focusing on patients with associated digestive tract disorders (DTDs). Eleven of 27 patients (40%) with asplenia/polysplenia had associated DTDs. The DTDs comprised malrotation of the intestine in nine, both preduodenal portal vein and gastric volvulus in three, esophageal hiatal hernia in two, and biliary atresia in one. Laparotomy was carried out on four patients with symptoms of acute bowel obstruction and on one patient with biliary atresia. One patient with both malrotation and gastric volvulus, and another with only associated malrotation survived. Nine patients died, eight of cardiac insufficiency and one because of hepatic insufficiency. When infants are diagnosed with heterotaxia, they should be examined for other combined DTDs, because they may have a chance for survival if they undergo surgery when their condition is still stable.

Biliary Atresia↗

Two cases of torsion of the gallbladder diagnosed preoperatively.

BACKGROUND: The authors experienced two cases of torsion of the gallbladder, both of which were correctly diagnosed preoperatively. METHODS: Two boys, aged 4 and 5 years, were transferred to Yokohama City Seibu Hospital because of their acute abdominal disorders. Diagnostic imaging demonstrated acute inflammatory changes in the gallbladder with an abnormal arrangement of the gallbladder and common bile duct in both cases. Laparotomy findings showed torsion of the gallbladder by 180 degrees and 360 degrees, respectively, at the cystic ducts, resulting in gangrenous change. RESULTS: Both children recovered uneventfully after cholecystectomy. The diagnostic imaging criteria are (1) collection of fluid between the gallbladder and the gallbladder fossa of the liver, (2) a horizontal rather than vertical arrangement of the long axis of the gallbladder, (3) the presence of a well-enhanced cystic duct located on the right side of the gallbladder, and (4) signs of inflammation including marked edema with thickening of the wall. CONCLUSIONS: The authors report the clinical characteristics of this uncommon condition, and discuss the significance of accurate preoperative diagnosis of these acute surgical disorders.

Child, Preschool↗

Influence of combined use of selenious acid and SH compounds in parenteral preparations.

The influence of the combined use of selenious acid and SH compounds (glutathione (GSH) and cysteine (Cys), or ascorbic acid (Asc)) on cultured venous vascular cells was investigated experimentally. When cultured human umbilical venous vascular endothelial cells were exposed to 10 microM of selenious acid combined with 0.5 mM-GSH or 0.5 mM-Cys, the release rates of [3H]-adenine and lactate dehydrogenase (LDH) from cells into the medium increased significantly as compared with after exposure to selenious acid alone, and damage to the vascular endothelial cells was found to be intensified. Addition of 1 microM of selenious acid simultaneously with 0.5 mM-GSH or 0.5 mM-Cys showed no differences in toxicity for the vascular endothelial cells as compared with the addition of selenious acid alone. On the other hand, simultaneous exposure to 10 microM of selenious acid and 1 mM-Asc induced no significant differences in the release rates of [3H]-adenine and LDH, and no damage was observed to the vascular endothelial cells. These results suggest that simultaneous addition of selenious acid together with GSH or Cys, which have the SH-group, may cause damage to the vascular endothelial cells. Therefore careful attention is warranted in total parenteral nutrition (TPN).

Ascorbic Acid↗

Incidence and clinical significance of linear defects ascribed to interrenuncular septa on 99Tcm-DMSA SPET.

99Tcm-dimercaptosuccinic acid (99Tcm-DMSA) planar and single photon emission tomographic images from 100 children were reviewed to analyse whether linear defects corresponding to anatomical characteristics of interrenuncular septum (IRS) could be seen. Thirty sites in 30 kidneys (20 right, 10 left) from 27 patients were determined as showing IRS. They were seen less frequently in patients less than 7 years of age. The prevalence of IRS in the patients with vesico-ureteric reflux (VUR) was not significantly different from that in the patients without VUR. The interrenuncular septum was never seen on planar images and was most clearly demonstrated on conventional coronal tomographic images. The linear defects ascribed to IRS on 99Tcm-DMSA scintigrams were of a similar incidence to that reported previously. However, IRS is still an unestablished structure, and there is no evidence that these linear defects actually correspond to the structure described as the interrenuncular septum.

Child↗

Imaging of recurrent intestinal carcinoma with indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody CEA102.

CEA102 is a mouse immunoglobulin G1 monoclonal antibody (mAb) that detects an epitope of carcinoembryonic antigen (CEA). The biodistribution and imaging characteristics of indium-111-labeled (111-In)-mAb CEA102 were studied in 1 primary and 9 extrahepatic recurrent intestinal carcinoma patients. Evaluation included antibody pharmacokinetics and assessment of antibody distribution in surgical specimens, in comparison with whole body imaging using a gamma camera, and imaging with single photon emission computed tomography. Selective mAb CEA102 localization to tumor tissue was demonstrated in 7 patients with tumors over 2 cm in size, and the external images correlated well with the results of surgical inspection, pathological examination, and tissue radioactivity measurements. Tumor:serum ratios ranged from 0.20:1 to 3.22:1, and serial biodistribution study of "regions of interest" also demonstrated a high radioactivity in the tumor. These results indicated the potential exploitability of the 111-In-labeled mAb CEA102 in radioimmunodetection of primary and extrahepatic recurrence of CEA-positive intestinal carcinomas.

Adult↗

Postpartum adrenal, pituitary and ovarian functions in dairy cows.

Postpartum stress and the resumption of pituitary and ovarian functions were investigated in 29 dairy cows during the first month after calving. Adrenocorticotropic hormone (ACTH, 25 i.u., IM) challenge tests for adrenal function at 8 and 22 days postpartum and gonadotropin releasing hormone (GnRH, 50 micrograms IM) challenge tests for pituitary function at 7 and 21 days postpartum were conducted. Ovarian function, particularly the interval to first ovulation, was evaluated through weekly rectal palpation and ultrasonographic examination, as well as thrice weekly milk progesterone levels. Elevated basal cortisol levels were found in 24.1% and 20.7% of cows at 8 and 22 days postpartum, respectively. Adrenal response to ACTH was similar at 8 and 22 days postpartum with low, medium and high peak responses in 13.8%, 62.1% and 24.1% of cows, respectively. A moderate correlation was observed between basal and peak cortisol levels. Peak pituitary luteinizing hormone (LH) response was low in 65.5%, medium in 27.6% and high in 6.9% of cows at 7 days postpartum. Pituitary responsiveness improved by day 21 with low in 34.5%, medium in 37.9% and high in 27.6% of cows. About a week after calving, a negative correlation between peak cortisol and peak LH levels was observed. First ovulation occurred in 28%, 48% and 17% of postpartum cows during the second, third and fourth week, respectively. These results indicate a negative effect of peak cortisol levels on pituitary responsiveness to GnRH stimulation during the first week, altered adrenal and pituitary function in a third of the cows until the third week and restoration of ovarian function in most cows (93%) a month after parturition.

Adrenal Glands↗