Biomedical subjects
Publications and source records attributed to T Katayama.
A new antitumor antibiotic, 3''-demethylchartreusin was isolated from the culture broth of Streptomyces chartreusis, as a minor component of crude chartreusin. It is structurally related to chartreusin, containing same aglycone of chartreusin, but different sugar moieties. 3''-Demethylchartreusin exhibits some potent inhibitory activities against murine tumors.
A case of cytomegalovirus (CMV) retinochoroiditis initially misdiagnosed as fungal endophthalmitis is reported. An 83-year-old man who was suspected of having cholangiocarcinoma presented uveitis in both eyes. Candida endophthalmitis was suspected on the basis of ophthalmic findings and past history, which included systemic corticosteroid administration and intravenous hyperalimentation. Intravenous treatment with miconazole was not effective. At autopsy, 3 months after the initial ophthalmological examination, the right eye was enucleated and examined histologically and histochemically. Light microscopic examination showed extensive retinal necrosis and numerous cytomegalic cells, so-called owl's eye cells, with intranuclear and intracytoplasmic inclusion bodies. CMV particles were seen by electron microscopy, and CMV-infected cells were observed by immunohistochemical staining by the direct method with fluorescein-labeled antibodies. These findings indicate that in suspected cases of fungal endophthalmitis various tests should also be carried out for CMV.
Between 1984 and 1990, a mass screening for prostatic diseases was carried out on men over 55 years old in cities, towns and villages in Toyama Prefecture, Japan. The total number of subjects examined in the primary study was 1,232, which was 17.7% of the males over 55 years old in these areas. The primary study consisted of inquiry concerning urination, digital examination of the prostate, transabdominal ultrasonography, and determination of tumor markers. A secondary study was indicated for 100 subjects (8.9%) suspected to have prostatic cancer and 169 (15%) suspected to have benign prostatic hypertrophy, but only 92 (35%) of them were actually examined. Prostatic cancer was histologically diagnosed in 3 subjects (0.3%), and benign prostatic hypertrophy was established in 56 subjects (4.5%), who were referred to urologists. Though a high percentage of the population was covered by the primary study the percentage of subjects who received the secondary study among those in whom it was indicated was low. This probably was a reason for the low detection rate of prostatic cancer. An improved system is considered to be needed to increase the efficiency of mass screening for prostatic diseases.
A 67-year-old man was admitted to our hospital because of cough and sputum. Chest X-ray revealed cavity and consolidation in the right upper lobe. Microscopical examination of stained specimens of sputum disclosed acid-fast bacilli (Mycobacterium tuberculosis). Cough and sputum resolved and cultures of sputum did not yield M. tuberculosis a month after administration of antituberculosis agents. However, a mass shadow in the right upper lobe was found 3 months later. Bronchofiberscopy revealed a polyp with a stalk at the orifice of right upper bronchus, which was elastic, soft in consistency, smooth surfaced, and movable. The pathological findings of the polyp showed non-specific inflammatory granulation which suggested to be inflammatory bronchial polyp. It was appeared in the healing process of bronchial tuberculosis.
Protein synthesis in mouse embryo fibroblastic (NIH-L1) cells was stimulated by addition of fibronectin (FN) to the culture medium as a soluble factor. This stimulatory activity of FN appeared only when the cells were cultured over their saturated density. A hexapeptide (GRGDSP) containing the RGDS cell attachment site of FN could not prevent the stimulation of protein synthesis. Moreover, activity of the stimulatory FN was not affected by inclusion of cytochalasin B, which is known to release FN from cell surface by disorganizing actin cytoarchitecture. These results suggest that the signaling of change in protein synthesis rate by FN may be distinct from signaling involving cell attachment and spreading.
In the preceding paper, we showed that fibronectin (FN) in solution has the ability to stimulate protein synthesis in NIH-L1 fibroblastic cells. We show here that FN stimulated protein synthesis also in other normal fibroblast cell lines, WI-38 and BALB/3T3, but did so only slightly in their transformed cell lines, L1-4NQOH10, WI-38 VA-13 and KN(7)8; and in rat hepatocytes in primary culture and rat liver epidermoid cells (GR-1) it hardly affected the synthesis. Augmentation of the protein synthesis rate was not attributable to stimulation of collagen synthesis. This stimulatory activity of FN was enhanced remarkably by proteolytic digestion of FN with trypsin.
The authors evaluated the efficacy of a daily administration of recombinant human alpha 2a interferon (IFN), given at a dose of 300MU for 12 consecutive days, in patients with steroid-nonresponsive or -dependent idiopathic thrombocytopenic purpura (ITP). Nine patients received courses of IFN therapy. Mean platelet counts rose from 1.39 to 10.9 x 10(4)/microliters and PAIgG decreased from 151.7 to 59.7 ng/10(7) cells. The maximum rise in platelet counts occurred from 10 to 42 days (mean 19.1) after the initiation of IFN. Complete response (CR) was achieved in 3 of 13 courses (23.1%), and partial response (PR) in 8 (61.5%). One CR case continued for longer than 20 months without further treatment, but intermittent IFN therapy was necessary for the other. The increment of the platelet counts was transient in all of the partial responders. No severe side effect requiring interruption of the course of IFN was experienced. Both serum IgG and PAIgG significantly correlated with the increment of platelet counts, therefore the mechanism of IFN on ITP was presumed to be associated with the inhibition of autoantibody production. Daily administration of IFN appears to be an effective and safe treatment protocol for refractory ITP.
The authors report a case of metastatic carcinoma to the retina. The patient was a 61-year-old man who had an operation for a well-differentiated adenocarcinoma of the rectum. Ophthalmoscopic examination disclosed a single, white, elevated mass lesion surrounded by serous retinal detachment located in the upper part of the macula of the right eye. A few retinal hemorrhages existed around the lesion. Fluorescein angiography revealed partially obscured retinal vessels due to compression by the tumor and arteriovenous anastomosis. Postmortem pathologic examination confirmed metastases to the brain, lung and retina. Microscopic examination showed a retinal lesion and tumor cells in the right eye. Tumor cells, similar to the carcinoma of the rectum, were present only in the neurosensory retina and did not invade the pigmented epithelium or choroid.
We measured the right ventricular ejection fraction (RVEF) before and during unilateral pulmonary artery occlusion test (UPAO) by thermodilution method. We also measured the right ventricular end-diastolic volume index (RVEDVI), right ventricular end-systolic volume index (RVESVI), and right ventricular stroke volume index (RVSVI). RVEF and RVSVI were significantly decreased by UPAO (p less than 0.05), but there were no obvious changes in RVEDVI and RVESVI. Some cases showed only a small decrease in RVEF by UPAO, even though their total pulmonary vascular resistance indices were over 700 dyne.sec.cm-5/m2 during UPAO. On the other hand, some cases had a decreased in RVEF of more than 10% by UPAO, even though their total pulmonary vascular resistance indices were under 400 dyne.sec.cm-5/m2 during UPAO. We consider that it is important to measure right ventricular functions such as RVEF together with pulmonary vascular hemodynamics in the pre-operative evaluation of cases of lung resection.
Clinical efficacy of oral high-dose cepharanthin (40-60 mg/day) was evaluated in nine patients with idiopathic thrombocytopenic purpura who were unable to discontinue the administration of adrenocorticosteroids or immunosuppressive drugs. Mean platelet counts significantly (p less than 0.05) rose from 4.5 +/- 0.9 x 10(4)/microliters to 8.9 +/- 4.2 x 10(4)/microliters without any side effects. Two to five months after the initiation of this therapy, 4 patients, including 3 who could discontinue adrenocorticosteroids, kept their platelet counts over 10 x 10(4)/microliters. It was suggested that the oral administration of cepharanthin could be a beneficial and safe strategy for ITP.
A 30-year-old female with effusive-constrictive pericarditis was admitted to our hospital because of dyspnea, ascites and edema. On examination, her blood pressure was 118/94 mmHg and her pulse rate was 90 bpm. Physical examination revealed pulsus paradoxus, markedly raised venous pressure and pericardial knock sound. Chest X-ray showed marked cardiomegaly and bilateral pleural effusion. After cardiac catheterization there was elevation of mean right atrial pressure, right ventricular end-diastolic pressure, pulmonary-capillary-wedge pressure, and their pressures during diastole were approximately 30 mmHg. After successful pericardiocentesis, their diastolic pressures still remained at 15 mmHg. Additionally, pressure wave of the right ventricle showed distinct diastolic dip and plateau pattern, and that of the right atrium showed deep x and y descents. The pressure pattern suggested that not only pericardial effusion but also decreased compliance of the pericardium was the main factor contributing to the cardiac diastolic dysfunction. Histological examination of the pericardium showed diffuse lymphocyte infiltration and fibrosis. These findings strongly suggested that there might have been viral infection.
A 38-year-old woman presented with ear pain and vertigo. No hepatosplenomegaly or lymphadenopathy were found, but her platelet counts markedly rose to 414 x 10(4)/microliters with an increase of megakaryocytes in the bone marrow (859/microliters). Cytogenetic assay revealed positive Ph1 chromosome and rearrangement of the break point cluster region (bcr). Although platelet counts remained under 100 x 10(4)/microliters after the administration of carboquone, a high fever and pancytopenia appeared 31 months later. Bone marrow biopsy showed marked myelofibrosis which was improved by low dose etoposide. This case was thought to be Ph1 positive ET, but it was more compatible with CML megakaryocytic predominance type according to the newly proposed "Hannover criteria for myeloproliferative disorders" and cytogenetic assay.
Seven cases of primary aldosteronism were experienced during the 12 years in the Toyama Medical and Pharmaceutical University Hospital. The majority of cases were between 32 and 64 years old with a mean of 51 years. Two cases were male and 5 were female. Hypertension was observed in 6 cases, but one case had normal blood pressure. Hypokalemia was recognized in 6 cases. The plasma level of aldosterone was high in all cases and all the cases showed low levels of plasma renin activity. Concerning the localization of the lesions, CT scan, magnetic resonance imaging and adrenal scintigraphy revealed an accuracy rate of 100%, each. Therefore, these imaging techniques are very useful tools for identifying the locality of the adenoma. On the other hand, the accuracy rates of adrenal venous aldosterone assay and ultrasonography were 83 and 60%, respectively. The cases with rather short duration of hypertension before surgery returned to normal in blood pressure earlier after the operation than the other cases.
From August 1990 to August 1991, sixteen patients with bullae or blebs (pneumothorax 9, giant bullae 5, bullous emphysema 2) were treated by CO2 laser ablation under limited thoracotomy. We found the irradiation of bullae or blebs by CO2 laser quite effective in eliminating these bullous lesions which were often multiple and inoperable by conventional methods. Histological examination revealed the wall of bullae where CO2 laser was applied became thick with dense fibrous tissues and degenerated collagen fibers which, however, were not disrupted. The procedure was safe and we were able to operate patients with disabling emphysema. Because CO2 laser can penetrate only 0.2-0.3 mm of tissue thickness, it is suitable for the ablation of bullous lesions which have thin walls and rapidly shrink and collapse by irradiation leaving thick walled scar tissues. Removing multiple bullae and blebs in patients with bullous emphysema can improve gas exchange by reducing dead spaces and elevating the diaphragm which is often flat and downward displaced because of hyperinflation in these patients. We are planning to incorporate thoracoscopy for this operation to make the procedure less invasive.
Serum-free conditioned medium of a rat mammary tumor cell line RMT-1, established from a rat mammary carcinoma induced by 7,12-dimethylbenz[a]anthracene (DMBA), produced the complete angiogenic response in both rabbit cornea and chick embryo chorioallantoic membrane assays. The angiogenic activity in the RMT-1 conditioned medium was separated into two fractions on a column of heparin-Sepharose; one was eluted with 0.1 M NaCl and the other with 0.5 M NaCl, which are referred to hereafter as rAF-1 and rAF-2, respectively. These two angiogenic factors were further purified separately by FPLC on a Superose 12 column. The partially purified rAF-2 had an apparent Mr of 30,000-50,000 and seemed to exhibit mitogenic activity toward Balb/c 3T3 cells, while the partially purified rAF-1, with an apparent Mr of 10,000-30,000 did not have a mitogenic effect on these cells. Both rAF-1 and rAF-2 were resistant to heat and acid treatment, and exhibited trypsin sensitivity, suggesting that they are heat and acid stable peptides. The two angiogenic factors did not stimulate the proliferation of cultured vascular endothelial cells. These results suggest that RMT-1 secretes two distinct angiogenic factors into the medium and that these two secretable angiogenic factors participate cooperatively in the induction of the angiogenic response produced by a DMBA-induced rat mammary tumor in vivo.
An enzyme-linked immunosorbent assay (ELISA) was developed for serological diagnosis of hepatitis C virus (HCV) infection, using HCV core protein (p22) synthesized by a recombinant baculovirus. Among 58 clinically well-defined chronic non-A, non-B hepatitis (NANBH) patients, 49 (84.5%) were positive for p22 antibody (anti-p22), whereas 42 (72.4%) were positive for C100-3 antibody (anti-C100-3), as measured by the present assay using the HCV nonstructural protein as antigen. Thirty-nine patients (67.2%) had both antibodies. No significant level of anti-p22 was detected in sera of chronic hepatitis B patients or normal blood donors. In typical post-transfusion NANBH patients, anti-p22 could be detected at, or even before, the first alanine aminotransferase peak. Anti-p22 was also detected in blood donors who were previously shown to be involved in transmitting HCV but in whose serum anti-C100-3 was not detectable. The ELISA detecting antibody to the HCV core protein expressed and properly processed in animal cells will be useful for mass screening of donor blood as well as for early diagnosis of hepatitis C.
Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. Herein, radioimmunoassay (RIA) for human EGF (hEGF) has been developed, using human recombinant EGF as reference standard and radioiodinated tracer and antibodies raised against hEGF. Its sensitivity was somewhat higher than that of RIAs reported formerly. This method had no cross reactivity with high molecular weight EGF. Urinary concentrations of hEGF in normal males and females were 30.2 +/- 13.0 ng/mg creatinine and 46.4 +/- 17.4 ng/mg creatinine, respectively. Urinary concentration of hEGF in patients with renal cancer was somewhat low. The patients with bladder cancer had lower urinary excretion of hEGF than normal adults (p less than 0.05). However, the role of hEGF in health and disease remains to be determined.
Mechanism of fibronectin (FN)-induced chemotaxis of fibroblastic cells has not been fully understood. The present study was performed to establish a molecular nature of the chemotactic region of rat plasma FN. The chemotactic dose-response pattern of intact FN for mouse embryo fibroblastic cells, NIH-L13 cells, which was represented as a "bell-shape" curve with a maximum activity at around 50 nM, changed to a "biphasic" mode through a proteolysis with thermolysin. Two distinct chemotactic components were isolated from the thermolytic fragments. One component, a fragment with a molecular mass of 110-150 kDa, was estimated to contain the central cell-binding domain and the carboxyl-terminal heparin-binding domain of the intact FN molecule. Cell migration stimulated by the 110-150-kDa fragment increased successively in a dose-dependent manner, and the capability to promote the migration was much higher than that of the intact FN (over 2-fold). The second chemotactic component, a fragment with a molecular mass of 21 kDa, was shown to reside in the carboxyl-terminal fibrin-binding domain. The 21-kDa fragment produced a bell-shape dose-response pattern, being consistent with the intact FN, whereas a maximum response occurred at a 100-fold lower concentration (0.5 nM) than that of the intact FN molecule. At higher concentrations, this fragment revealed an inhibitory activity for the cell migration in response to the 110-150-kDa fragment. No significant molecular interaction between these two active components was observed by polyacrylamide gel electrophoresis under nondenaturing conditions, suggesting that the 21-kDa fragment may act directly on the cell to inhibit the cell migration. These results suggest that rat plasma FN contains at least two chemotactically active components that regulate cooperatively chemotactic migration of fibroblastic cells.