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Biomedical subjects

M Koga

Publications and source records attributed to M Koga.

At least 343 records · Page 19Linked to original sources

Amyloid fibril formation in the rough endoplasmic reticulum of plasma cells from a patient with localized A lambda amyloidosis.

Evidence for amyloid fibril formation in rough endoplasmic reticulum (RER) of plasma cells from the duodenum of a 62-year-old man with localized A lambda amyloidosis is described. The inclusions in RER of plasma cells were composed of tightly packed, regular arrays of fibrils cut in both longitudinal and cross-sections. The fibrils within the inclusions, measuring 10 nm in width, were oriented parallel to the long axis of the inclusions. By immunoelectron microscopy with an antihuman A lambda antiserum, gold particles labeled the fibrils located both in the RER of plasma cells and in the extracellular space. In addition, electron-dense material in the dilated RER was occasionally labeled. These findings suggest that at least some amyloid fibrils are unequivocally created in the RER of plasma cells.

Amyloid↗

[A case report of atrial septal defect with quadricuspid pulmonary valve].

We reported the successful case of valvuloplasty on the quadriscuspid pulmonary valve which had pulmonary regurgitation. A 38-year-old woman was admitted with the complaint of palpitation. Atrial septal defect and pulmonary regurgitation were revealed preoperatively by the cardiac catheterization and doppler echocardiography. The malcoaptation of the pulmonary valve and pulmonary dilatation were diagnosed in echocardiography. At operation, the pulmonary valve was found quadricuspid and each cusp was same in size. The patient underwent the valvuloplasty on the abnormal cusps and the remarkable improvement of the coaptation was examined postoperatively. The patient had good clinical course for three years after operation.

Adult↗

[The amount of nitrogenous oxygen demand (NOD) in BOD--study on effluents and influent from biological treatment plants and river waters in Kitakyushu area].

BOD (Biochemical Oxygen Demand) is utilized widely as an index of water quality. However, nitrification is a cause of significant errors in measuring BOD, particularly when a large population of nitrifying organisms are existing in water such as effluents from biological treatment plants. In this case, the use of a nitrification inhibitor is recommended, but it is not used commonly. In order to investigate the amount of nitrogenous oxygen demand (NOD) which is caused by nitrification, BOD with and without inhibitor was measured as samples in the Kitakyushu area. About 70 percent of BOD from the effluents of biological treatment plants was NOD. In the case of influent of biological treatment plant and river waters, 0-39 percent of NOD was contained in BOD.

Japan↗

Effect of retinoic acid on proliferation of estrogen-responsive transformed murine Leydig cells in serum-free culture.

B-1 F cells, one of the sublines established from mouse Leydig cell tumor, have been found to be maintained as an estrogen-responsive cell line under the serum-free culture conditions. Reported results that retinoids have action mechanisms similar to those of estrogen prompted us to examine the effect of retinoids on the proliferation of B-1 F cells. Stimulation of B-1 F cell growth by retinoic acid in a dose-dependent manner was observed, whereas retinoic acid did not promote but inhibited the proliferation of MCF-7 cells (estrogen- and retinoic acid receptor-positive human breast cancer cells). To elucidate the mechanism of retinoic acid-dependent cell growth, simultaneous treatment with retinoic acid and estradiol was carried out. The result did not show the additive effect on B-1 F cell growth. Hydroxytamoxifen, a potent antiestrogen, inhibited not only estradiol-dependent but also retinoic acid-dependent cell growth. However, retinoic acid failed to be associated with estrogen receptor, suggesting that retinoic acid induced enhancement of B-1 cell growth through its interaction with retinoic acid receptor. Northern blot analyses of polyadenylated RNA with complementary DNA probes for human retinoic acid receptor alpha, beta, and gamma revealed the presence of transcripts encoded by retinoic acid receptor alpha gene in B-1 F cells. These results would suggest that enhancement of the B-1 F cell growth is mediated through interaction of retinoic acid with retinoic acid receptor alpha. This stimulatory activity is inhibited by estrogen receptor complexed with hydroxytamoxifen.

Animals↗

Differential effects of phorbol ester on epidermal growth factor receptors in estrogen receptor-positive and -negative breast cancer cell lines.

A previous study from this laboratory (Koga et al., Cancer Res., 48: 2734-2739, 1988) demonstrated that the growth inhibitory effect of 1,25-dihydroxyvitamin D3 in human breast cancer cells in vitro was associated with a decline in the concentration of epidermal growth factor receptor (EGF-R). In the present study experiments were undertaken with the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), an agent known to decrease EGF-R binding, in order to further define the relationship between changes in EGF-R binding and changes in growth rates in 10 human breast cancer cell lines. Treatment with TPA decreased the rate of cell proliferation in all cell lines except BT 474 in which a slight increase in proliferation rate was observed. Sensitivity to TPA was unrelated to estrogen receptor (ER) status and a wide spectrum of sensitivities was apparent. The concentrations of TPA that produced a 25% decrease in cell number ranged from less than 0.25 nM for MCF 7M and BT 20 cells to greater than 10 nM for the HBL 100, T 47D, and ZR 75-1 cell lines. Growth inhibition was associated with a block in cell cycle progression in the G1 and G2 + M phases of the cell cycle. In all cell lines studied, except BT 474, TPA treatment resulted in a reduction in the ability of cells to bind EGF. Saturation analysis revealed marked differences between the effects of TPA on EGF binding in ER+ and ER- cell lines. In ER+ cell lines, 2-h treatment with 10 nM TPA resulted in a marked reduction in the number of high affinity EGF-R sites and a significant decrease in binding affinity. Among this group of cell lines there was a significant positive correlation between the ability of TPA to decrease cell growth and the TPA-induced decrease in the number of EGF-R sites/cell (r = 0.82, P less than 0.03). In ER- cell lines, TPA-induced growth inhibition and the minor changes in EGF-R concentration were unrelated. However, growth inhibition was negatively correlated with TPA-induced changes in apparent affinity of the EGF-R (r = 1.00, P less than 0.003) and in the same rank order as the EGF-R concentration in control cells. These data demonstrate differential relationships between TPA-induced changes in growth and EGF-R binding in ER+ and ER- breast cancer cells, thus supporting the view that growth regulatory pathways are markedly different in these two subtypes of human breast cancer.

Breast Neoplasms↗

Progesterone receptor regulation by retinoic acid in the human breast cancer cell line T-47D.

Data are presented which document the first known effect of retinoic acid on progesterone receptor (PR) gene expression. Treatment of T-47D human breast cancer cells with retinoic acid for 48 h resulted in a marked concentration-dependent decrease in the level of PR mRNA and immunoreactive protein which was similar to the known effect of progestins on these parameters. Retinoic acid, however, did not bind to PR, nor did it cause the previously demonstrated increase in PR molecular weight observed after progestin exposure. When T-47D cells were treated with retinoic acid for 6 h rather than 48 h, no reduction in the level of PR protein was noted at any retinoic acid concentration whereas the effects of retinoic acid on PR mRNA at 6 and 48 h were the same. Examination of the time course of the effects of retinoic acid revealed a rapid decrease in PR mRNA levels detectable 1 h after and maximal 6 h after treatment of T-47D cells with retinoic acid. These effects of retinoic acid contrasted with previously demonstrated progestin effects on PR mRNA which were not apparent until 3 h after and were not maximal until 12 h after treatment. As expected, the PR protein concentration was unaffected for at least 6 h but was maximally decreased 24-48 h after retinoic acid treatment. In summary, retinoic acid treatment of T-47D cells caused a decrease in the cellular PR concentration by decreasing levels of receptor mRNA and protein, suggesting that retinoic acid is capable of modulating sensitivity to progestins in human breast cancer cells.

Blotting, Northern↗

Effects of estrogen on cell proliferation and leukotriene formation in transformed mouse Leydig cells cultured under serum-free conditions.

B-1 F cells from mouse Leydig cell tumor (T 124958-R) were maintained in serum-free culture. Estrogen enhanced the growth of the cells, and this growth was suppressed by antiestrogens such as 4-hydroxytamoxifen or TAT, a newly developed antiestrogen. Since the growth of B-1 F cells was recently found to be inhibited by the metabolites of arachidonic acid, we examined the relationship between this metabolism and the enhancement of cell growth by estrogen. Among the modulators affecting the metabolism of arachidonic acid, 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoqu inone, an inhibitor of 5-lipoxygenase, reproducibly stimulated the growth of the cells, whereas the cyclooxygenase inhibitor indomethacin had only the marginal growth-stimulatory effects. Phorbol ester had no growth-modulating effect. 17 beta-Estradiol and 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoqu inone had some additive effects especially in terms of restoration of antiestrogen-induced inhibition. Moreover, the inhibition of DNA synthesis elicited by the addition of arachidonic acid in concentrations of 0.05 to 0.5 micrograms/ml was partly blocked by estrogen. Analyses of extracts of media and cells by high-pressure liquid chromatography and radioimmunoassay showed that 17 beta-estradiol inhibited the synthesis of leukotrienes B4, C4, D4, and E4 and this inhibition could be restored by antiestrogen. These results suggest that the enhancement of B-1 F cell growth by estrogen is at least partly mediated through its ability to inhibit leukotriene synthesis.

Animals↗

[Injuries of the sigmoid colon following radiation therapy of carcinoma of the uterine cervix--a method of estimating the radiation dose to the sigmoid colon].

Grade 2 or 3 injuries of the sigmoid colon were observed in 4 out of 42 patients with carcinoma of the uterine cervix who were treated by radiation therapy. The irradiation was planned as the combination of the external irradiation (whole pelvic 30 Gy and 20 Gy with central shielding by 25 fractions, 5 weeks) and the intracavitary irradiation (RALS, 19 Gy at point A by 3 fractions). To analyze the causes of the radiation sigmoiditis, we have investigated the following factors: age, dose at point A, dose at point C, grade of tandem dislocation, uterine angle, obesity score, evidence of previous surgery to the pelvic cavity and hypertension. The dose at point C and the grade of tandem dislocation were determined from the confirming X-Ps at RALS therapy and external irradiation. The superimposition of these films was performed with corrections for the angle between the projection direction of the X-Ps and the vertical magnification factor of the central shielding area. Point C was defined as a point 2 cm anterior to the intersection of the tandem axis and a curvilinear line 1 cm outside from the margin of central shield on the X-Ps. Grades of tandem disclocation were decided as the number of tandem tips which were outside of the central shielding area on X-Ps. As the results, the doses at point C showed very high statistical significance (p less than 0.001) with the evidence of radiation sigmoiditis. All the cases with radiation sigmoiditis were received over 1290cGy at point C. Age had also some significance (p less than 0.05) with radiation sigmoiditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Bilateral intrahepatic lithiasis without extrahepatic bile duct stones.

Bilateral intrahepatic lithiasis is a rare condition, and for this reason a nationwide survey was conducted. Reports on 675 patients with bilateral intrahepatic lithiasis over a 10-year-period were collected. Among these, 258 patients with bilateral intrahepatic lithiasis having no extrahepatic bile duct stones were analyzed. The peak incidence was seen in the fourth to sixth decades. Males and females were equally effected. The stones removed were mainly calcium bilirubinate stones (75.6%). The main clinical symptoms were abdominal pain, fever and jaundice. Charcot's triad was seen in 29.7%, while 12.4% of the patients had no symptoms. Visualization of each segmental duct of the liver by direct cholangiography was excellent in this survey and ranged from 88 to 97.3% of the patients. The most frequent site of stones was the left hepatic duct (60.1%). The site of bile duct dilatation coincided with the location of stones. The most common sites of stenosis were the central part of the lateral segmental duct (32.5%) and the left hepatic duct (37.6%). Hepatic resection was employed in 49.2% of the patients, and drainage procedures were added in 95.6%. Follow-up studies of 236 patients treated by surgery revealed good results in 67.4%, fair in 13.6%, and poor in 7.6%. In these patients, however, endoscopic lithotomy was often employed intra- and/or post-operatively. Conducting hepatic resection, with adequate biliary drainage procedure and cholangiofiberscopic lithotomy may help to improve the therapeutic results of bilateral intrahepatic lithiasis.

Adult↗

A possible Japanese male case of Pelizaeus-Merzbacher disease.

A boy with an abnormal auditory brain stem response showing only a wave I-II pattern, congenital nystagmus, psycho-motor retardation, pyramidal tract signs and muscular hypotonia was reported. The auditory brain stem response, short latency somatosensory-evoked potential, somatosensory-evoked potential and visual-evoked potential indicated an intramedullary disorder of conduction. Magnetic resonance imaging revealed marked high signal intensity of the cerebral white matter in T2-weighted images, suggesting hypomyelination. A muscle biopsy specimen showed neurogenic changes with mild myogenic changes.

Brain↗

Persistence of Gnathostoma hispidum in chronically infected rats.

Gnathostomiasis by Gnathostoma hispidum has occurred mainly in southern and western areas of Japan since 1980. In all cases, patients had eaten live loaches, freshwater fish imported from southeast Asia. Chief symptoms were creeping linear skin eruptions and eosinophilia, both of which disappeared in most patients within three months after the onset, and never recurred thereafter. In order to study how gnathostome larvae may survive and behave in humans, rats were infected with gnathostome larvae. Loaches were purchased in city markets in Fukuoka. Gnathostome larvae (G. hispidum) were recovered from the fish and fed to rats. They were killed at intervals of one and six months and one, two and three years postinoculation. Encysted larvae were found in the muscles of all rats and recovered larvae were all viable. A migrating larva was observed in muscle tissue from one rat that was killed three years postinoculation. In histological sections, walls around encysted larva were much thinner in a rat killed three years postinoculation than in a rat killed one month postinoculation.

Animals↗

Cardiovascular anomalies of cephalothoracopagus synotus. A case report and review of the literature of 23 Japanese autopsied cases.

A case of cephalothoracopagus female twins is reported, and the anatomical and pathologic features are described in detail. The central nervous systems were completely double. However, there were three eyeballs, two on the well-formed face and one in the cranial base, forming a saddle-shaped ridge of orbital plates. The latter was supplied by optic nerves of both individuals. On the other hand, there was a single esophagus, stomach and duodenum, but the intestine was shared equally at the jejunum by the two individuals. The larynges, tracheae, lungs, hearts, livers, pancreases, spleens and urogenital organs were also duplicated. Previously unreported abnormalities of the hearts are described, and a comparison with similar autopsy cases reported previously in Japan is given.

Blood Vessels↗

Active drainage of cardiac lymph in relation to reduction in size of myocardial infarction: an experimental study.

Active drainage of cardiac lymph using hyaluronidase was attempted in dogs. The results were satisfactory and the ischemic myocardium was salvaged. The infarct risk area (I/R) ratio decreased after drainage. Regional myocardial ischemia and infarction were provided by means of ligature of the left coronary artery for 120 and 240 minutes respectively. Cardiac lymph was collected by conventional procedures. Enzymes released from the myocardium increased significantly in the cardiac lymph. The volume of cardiac lymph gradually increased after ligature of the coronary artery. Administration of hyaluronidase further increased the cardiac lymph flow and significantly decreased the I/R ratio as determined by triphenyl tetrazolium chloride (TTC) and methylene blue staining. Drainage of the cardiac lymph salvaged the ischemic myocardium. Reduction of interstitial edema and augmentation of cardiac lymph flow with the hyaluronidase prevented the development of the infarction. This is the first documentation of the effect of active drainage of cardiac lymph on the development of infarction through observation of the I/R ratio.

Animals↗

Ultrastructural alterations of right and left ventricular myocytes in tetralogy of Fallot.

We examined the ultrastructure of right and left ventricular myocardial biopsies obtained prior to cardiopulmonary bypass in fourteen patients undergoing total correction of tetralogy of Fallot (TOF). Twelve patients were undergoing primary one-stage repair and two patients had had a previous Blalock-Taussig shunt operation. The ages of the patients ranged from 3 to 35 years. In left ventricular (LV) myocytes, the sarcolemma often formed pouches filled with mitochondria and the muscle fibers showed a disoriented arrangement. In addition, the myofibrils showed hypercontraction and the Z-bands were thickened; the degree of the myofibril contraction was more severe than that in right ventricular (RV) myocytes. These ultrastructural findings are similar to those observed in myocytes under hypoxic conditions. The number of lysosomes in LV myocytes, but not in RV myocyte increased in the older patients. While we have not established a causal relationship between the ultrastructural findings and clinical features in our cases, our observations are consistent with the possibility that early total correction of TOF may be required to prevent the development of hypoxic changes and degeneration of heart muscle.

Adolescent↗

Inverse relationship between estrogen receptor and epidermal growth factor receptor mRNA levels in human breast cancer cell lines.

Epidermal growth factor receptors (EGF-R) are present in a number of human breast cancer cell lines and tumor biopsies. Furthermore, it has been suggested that EGF-R levels are higher in estrogen receptor negative (ER-) than in ER+ human breast tumors and that EGF-R status may be a prognostic indicator in breast cancer. The present study was undertaken to establish whether there is a quantitative relationship between EGF-R and ER mRNA concentrations in a series of 10 well-characterized human breast cancer cell lines. All cell lines expressed detectable quantities of EGF-R mRNA by Northern analysis but the relative abundance of EGF-R mRNA varied more than 50-fold. Two transcripts corresponding to the 10.5- and 5.8-kb mRNAs described in other cell types were present but in different relative proportions in different cell lines. When these lines were divided into an ER+ and an ER- group based on their ability to bind estradiol, ER- cell lines were shown to express significantly higher concentrations of EGF-R mRNA than did ER+ cell lines (p less than 0.005). Furthermore, linear-regression analysis revealed a significant inverse relationship between ER and EGF-R mRNA concentrations both within the group of 10 human breast cancer cell lines as a whole (r = 0.66) and within the 6 functionally ER + lines (r = 0.77). This demonstration of a significant (p less than 0.005) inverse relationship between the concentrations of ER and EGF-R mRNAs in ER + cell lines raises the possibility of reciprocal regulation of the expression of these genes in human breast cancer.

Blotting, Northern↗

[Sweet's syndrome in patient with refractory anemia during recombinant human granulocyte colony stimulating factor therapy].

We present a patient with refractory anemia (RA) who developed Sweet's syndrome during the treatment of recombinant human granulocyte colony-stimulating factor (rhG-CSF). A 30-year-old man was admitted to the hospital for evaluation of anemia. He was diagnosed as MDS (RA). As a phase II study in MDS, rhG-CSF therapy was begun. Fever associated with cutaneous lesion developed over the left shoulder. Antibiotics showed no effects. Skin biopsy revealed Sweet's syndrome. This skin lesion disappeared thoroughly with discontinuance of G-CSF and administration of prednisolone. To examine whether Sweet's syndrome was related to the G-CSF therapy, we analyzed the effect of G-CSF on the function of patient's neutrophils. However, the function of patient's neutrophils was not activated by G-CSF administration.

Adult↗

[A case of thymolipoma on the cervicomediastinal area].

Thymolipoma is a very rare mediastinal tumor. We reported a case of 52-year-old female with thymolipoma which was located in the cervicomediastinal area. The chest X-ray film revealed an abnormal shadow in the superior mediastinum. Computed Tomography (CT) clearly showed the existence of a large mass in the left side of the trachea. The angiogram showed that there was a stenosis on the left brachiocephalic vein. On June 13, 1988, median sternotomy was performed. A large tumor, about 5.5 x 13 x 5.5 cm, was found arising from the left cervical area. This tumor was excised completely and thymolipoma was diagnosed histopathologically. The post-operative course was very satisfactory.

Female↗