Glycosaminoglycans in transplantable rat malignant fibrous histiocytoma.
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Biomedical subjects
Publications and source records attributed to T Saitoh.
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The therapeutic efficacy of the combination of cyproheptadine and bromocriptine was studied in 15 patients with active acromegaly showing incomplete GH suppression in response to bromocriptine therapy alone. The mean basal plasma GH was 31.3 +/- 5.5 micrograms/L, and it decreased to 19.0 +/- 3.9 micrograms/L during the single bromocriptine therapy (10 to 20 mg for 2 to 21 months). When cyproheptadine (12 to 16 mg for 8 to 52 months) was added to bromocriptine therapy, plasma GH decreased further (9.4 +/- 3.0 micrograms/L: vs pretreatment, P less than 0.001; vs bromocriptine treatment, P less than 0.005), and GH normalization was obtained in 8 patients. The plasma somatomedin-C levels in these 8 patients (0.3-1.8 U/ml) were within the normal range during the combination therapy. Plasma GH responses to TRH or GHRH were markedly suppressed in 6 patients during the combination therapy compared to pretreatment or during bromocriptine treatment. In addition, a clear reduction in the tumor size was observed in 4 of 7 previously untreated patients during the combination therapy. In conclusion, cyproheptadine has therapeutic efficacy in acromegalic patients who showed incomplete GH suppression in response to treatment with bromocriptine alone. Following the cyproheptadine and bromocriptine combination therapy tumor shrinkage was observed in some patients.
We studied the ratio of agreement between biopsy specimens and all-layer specimens in regard to growth pattern, histological classification, staging, grading, lymphatic invasion, intravenous invasion and infiltrating type of 42 cases in which it was possible to make a comparison among radical cystectomy cases treated between November 1976 and October 1988. The above 7 categories were studied according to the General Rule for Clinical and Pathological Studies on Bladder Cancer (Japanese Urological Association and Japanese Pathological Society). The result showed that the ratio of agreement between the biopsy specimens and the all-layer specimens was 90.5% according to growth pattern. The ratio of agreement was 85.7% according to histological classification but 76.2% according to staging. When grading was not based on the lower grade of cells occupying the major portion, but the higher grade of cells occupying the minor portion the ratio of agreement was 88.1%. The ratio of agreement was 76.2% according to lymphatic invasion. However, when lymphatic invasion was seen on the all-layer specimens, the ratio of agreement was 74.4% according to lymphatic invasion. The ratio of agreement was 76.2% according to intravenous invasion. However, when intravenous invasion was seen on the all-layer specimens, the ratio of agreement was 58.3% according to intravenous invasion. The ratio of agreement was 76.8% in regard to infiltrating type. Staging, grading, and vascular invasion are important prognostic factors in bladder cancer. According to our study, biopsy specimens alone are not enough to evaluate the staging and the presence of vascular invasion. For more accurate diagnosis, we must resect deep and multiple biopsy specimens.
Clinical symptoms of thoracic aortic aneurysm vary widely from symptoms resulting from its rupture to those due to compression of surrounding organs. Furthermore, the onset of symptoms is frequently followed by a fatal outcome unless emergency measures are taken. We have recently experienced a patient who developed respiratory insufficiency caused by an aneurysm of the descending thoracic aorta compressing the left primary bronchus and the right pulmonary artery, the former causing ventilatory failure in the left lung and the latter interfering with blood flow in the right lung. The patient underwent emergency prosthetic graft replacement and showed temporary symptom improvement. However, a postoperative complication of esophageal perforation due to ischemic necrosis occurred and eventually caused acute empyema followed by death. The patient was a 48-year-old male who presented with symptoms similar to bronchial asthma. Angiographic examination (iv-DSA) revealed compression of right pulmonary artery by an aneurysm of the descending thoracic aorta. Bronchoscopic findings included extramural stenosis of the left bronchus accompanied by arterial pulsation. As an emergency measure, artificial blood vessel replacement of the descending thoracic aorta was performed. However, the patient developed postoperative acute empyema and died on the 19th postoperative day. Autopsy revealed ischemic necrosis on the esophageal wall where the aneurysmal lesion had touched before operation. This seems to have formed a perforation into the left thoracic cavity and ultimately to have caused acute empyema. Since we believe that the pathogenesis and clinical course observed in this patient is rather rare, the case is reported in accompanied by relevant data from the literature.
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An 18-year-old male case in which multiple lung cysts with Aspergillus infection was diagnosed is reported. The case was recognized during the clinical course of bilateral pneumothorax, and chest X-ray showed cystic shadows in the middle field of the right lung. At first, bullectomy and partial cystectomy of the lung was performed, and Aspergillus fumigatus was cultured from the fluid in the cysts. The cysts were located in the right upper and middle lobe, so upper and middle lobectomy was performed in the second surgical operation. In this case, the check valve mechanism caused by the pneumothorax provided the conditions for Aspergillus infection. In cases of air-fluid levels shown by chest X-ray such as this, Aspergillus infection should be suspected.
The neurofibrillary tangle (NFT) is a pathological cytoskeletal structure found in diseased neurons of patients with Alzheimer's disease (AD). Immunocytochemical studies have revealed that the NFT contains cytoskeletal components which are excessively phosphorylated. It is not known if the overphosphorylation of cytoskeletal components is causally involved in the formation of NFT or if it is a simple reflection of abnormal cytoskeletal structure. A major pathological feature of AD is selective neuronal degeneration. Because neuronal survival is supported by the combined function of many growth factors which trigger various protein kinase reactions, some of the cascade reactions necessary for the survival of neurons may be aberrant in AD neurons. In fact, the concentration of Ca2+/phospholipid-dependent protein kinase (protein kinase C, PK-C) is lower in AD cortex than in control cortex. Furthermore, the endogenous phosphorylation reaction catalyzed by this kinase revealed diminished levels of phosphate incorporation into a major PK-C substrate, Mr 86,000 protein (P86). Is this aberrant PK-C system pertinent to NFT formation? The number of tangles does not correlate well with the degree of PK-C abnormality. Therefore, some other protein kinases may be involved in NFT formation. Under conditions where cAMP-dependent protein kinase (PK-A) and PK-C were not stimulated, the levels of in vitro phosphorylation of a Mr 60,000 protein (P60) by an endogenous kinase were found to be increased in AD cortex as compared to control. This increased P60 phosphorylation was not detected in AD patients without NFT, suggesting the involvement of P60 phosphorylation in the process of tangle formation. In fact, the degree of the P60 phosphorylation showed a positive correlation with tangle numbers. P60 phosphorylation was induced in neurons under various conditions where PK-C activity was impaired. Thus, it is possible that the aberrant P60 phosphorylation is consequential to aberrant PK-C. The other protein kinase relevant to NFT formation is casein kinase II (CK-II). CK-II concentration is reduced in AD cortex but its specific activity is increased. Immunohistochemical study of CK-II revealed a general decrease in its staining in AD neurons and a strong staining of NFT. Conversely, anti-paired helical filament antibody cross-reacted with partially purified CK-II. Thus, many protein kinases are affected in AD and some of them are associated with aberrant cytoarchitecture in AD neurons. Further study of protein phosphorylation in AD neurons should prove useful in elucidating the formation of pathological cytoarchitecture and eventual cell death in this disease.
A case of pneumonitis due to Serrapeptase was described. A 69-year-old man was treated with Serrapeptase for 16 days because of common cold, then fever, nonproductive cough and dyspnea developed and chest X-ray revealed diffuse fine granular shadows in bilateral lung fields. Once the administration of Serrapeptase was halted, symptoms, chest X-ray abnormalities and laboratory data improved markedly. The fraction of lymphocytes increased in bronchoalveolar lavage fluid and OKT4/T8 decreased. Microscopic examination of transbronchial lung biopsy showed interstitial pneumonia. Both leukocyte migration inhibition test and sensitized hemagglutination test were positive for Serrapeptase. Based on these findings, we diagnosed this case as Serrapeptase-induced pneumonitis.
Multidisciplinary treatment for advanced esophageal carcinoma, which is not resectable in many cases, has become an important subject to study. We have reported the effectiveness of thermotherapy in treatment of esophageal carcinoma by basic experiments using three cell strains of human esophageal carcinoma designated as SGF-3,4,5. Based on the results of the basic experiments, we have performed thermotherapy combined with radiotherapy, chemotherapy and immunotherapy on cases of advanced esophageal carcinoma since October 1985. As for the basic experiment, proliferation of SGF-3 was inhibited at more than 40 degrees C, SGF-4 at more than 41 degrees C and SGF-5 at more than 42 degrees C. We did not observe the recovery of the growth of SGF-3 after heating at 41 degrees C for 72 hours and 42 degrees C for more than 24 hours. And the growth of SGF-4 after heating at 42 degrees C for more than 48 hours did not recover either. No recovery of the growth of SGF-5 after heating at 42 degrees C for 72 hours was noted. Based on the data, combined therapy was performed in 12 patients with advanced esophageal carcinoma. The evaluation of the local response to the combined thermotherapy revealed CR in five cases, PR in five and NC in two.
It is well known that gastrin immunoreactive cells are observed in the fetal and postnatal rat pancreas. The role of the gastrin cells is unknown, however, it has been suspected that pancreatic gastrin may influence the development of pancreas and the gastrointestinal tract. The present study shows the localization of pancreatic gastrin cells and the ability of auto-proliferation of them in development. Gastrin cells were seen in 0-d to 2-wk-old rats in islet and in 0-d to 4-wk-old rats among exocrine cells. The ratio of gastrin cells to islet cells decreased in neonatal development and in rats older than 14-d gastrin cells were never observed in islet. Labeling indices of pancreatic gastrin cells after one injection of tritiated thymidine were 2.6% to 4.6% for 10 days after birth. It was suggested that gastrin cells have the ability of autoproliferation for 10 days after birth.
By light and electron microscopic examinations, histologic changes in the liver of mice with graft-versus-host reaction (GVHR) were analyzed. To induce GVHR, C57BL/6 (B6) spleen cells were injected into (B6Xbm1)F1, (B6Xbm12)F1, and (bm1Xbm12)F1 mice. In (B6Xbm12)F1 recipient mice, bile duct changes resembling chronic non-suppurative destructive cholangitis (CNSDC) and a formation of epithelioid granulomas were observed during the course of GVHR. An epithelioid granuloma in the liver of (B6Xbm1)F1 or (bm1.Xbm12)F1 recipients was not detected. By electron microscopy, the bile duct epithelia were seen to be in close contact with infiltrating cells, and marked alterations of their cytoplasm and microvilli were demonstrated; ie, vacuolation of the cytoplasm, deterioration of microvilli, and bleb formation were frequently observed in the liver of class II-disparate hosts. Concerning the basement membrane, no marked changes characteristic of primary biliary cirrhosis (PBC), such as many-layered basement membranes containing osmium positive substance, were detected. Because the major histocompatibility complex (MHC) class II-disparate system was used in our experimental system in the GVHR, the antigen expressed on the bile duct might be a target and be associated with the formation of the initial hepatic lesions in PBC such as CNSDC and epithelioid granuloma formation. Thus, GVHR across the MHC class II antigen is believed to play an important role in the development of PBC.
Sixty seven cases of stage D prostatic carcinoma were analyzed according to age, chief complaints, histopathological types, metastatic sites, and serum acid and alkaline phosphatase levels. In spite of metastasis, which were in 62 cases (92.5%) to bone, in 17 cases (25.4%) to lymph nodes, and in 3 cases (4.5%) to the lung, the most common chief complaints were symptoms related to the primary lesion, such as dysuria and urinary frequency. There was no significant correlation between the incidence of bone metastasis and histopathological type. However, higher incidence of lymph node metastasis was observed in the histological types of moderate and poorly differentiated adenocarcinoma than well differentiated type. When cases were divided into two groups by age, significant differences were observed between younger (64 less than or equal to years old) and older (greater than or equal to 65 years old) groups in the following points: 1) Histopathologically, well differentiated type was not recognized in the younger group, while three histological types of well, moderate and poorly differentiated adenocarcinoma, were equally distributed among the older one. 2) Although there was no significant difference in the incidence or the numbers of metastatic sites to bone between the two groups, the younger patients had less symptoms related to bone metastasis. The prominent symptoms in the younger group were complaints about voiding.
Effects of long-term administration of 1,2,3,4-tetrahydroisoquinoline (TIQ) on the striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were investigated in mice and rats. Striatal dopamine content significantly increased and DOPAC decreased after repeated administrations of TIQ at a dose of 50 mg/kg/day s.c. for 70 days in mice. In contrast, dopamine and DOPAC content did not show any significant change in rats. The ratio DOPAC/dopamine decreased significantly in mice treated with TIQ for 70 days. The results presented suggest that TIQ reduces the turnover rate of the nigrostriatal dopamine neurons after repeated administration for a long period in mice.
This is the first report on in vivo effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on mitochondrial respiration in mouse brain. C57/BL mice, injected with 40 mg/kg of MPTP subcutaneously, were sacrificed by cervical dislocation 5-6 h after the injection. Mitochondrial suspensions were prepared from whole brains. Mitochondrial respiration was studied polarographically. The state 3 respiration, i.e., the active respiration in the presence of tricarboxylic acid (TCA) cycle substrates and ADP with coupled phosphorylation of ADP to ATP, was significantly inhibited in mice treated with MPTP. This inhibition was prevented by pretreatment of mice with pargyline. Activity of mitochondrial NADH-ubiquinone oxidoreductase was also inhibited in mice treated with MPTP.
The amyloid beta protein peptide is a major constituent of amyloid plaque cores in Alzheimer's disease and is apparently derived from a higher molecular weight precursor. It is now shown that the core protein of a heparan sulfate proteoglycan secreted from a nerve cell line (PC12) has an amino acid sequence and a size very similar to those of the amyloid beta protein precursor and that these molecules are antigenically related. This amyloid beta protein precursor-related protein is not found in the conditioned medium of a variant cell line (F3 PC12) that does not secrete heparan sulfate proteoglycan. The synaptic localization and metabolism of this class of proteoglycans are consistent with its potential involvement in central nervous system dysfunction.
Characteristics of condensation and overall elongation of very-long-chain fatty-acyl-CoAs in swine cerebral microsomes were studied using radio high-performance liquid chromatography (RHPLC) and gas chromatography-mass spectrometry (GC-MS). The monounsaturated fatty-acyl-CoA depressed both the condensation and overall elongation activities of endogenous substrates and also of exogenous saturated fatty-acyl-CoA. The extent of the decrease of the elongation activity was dependent on the concentration and the chain length of the exogenous fatty-acyl-CoAs. The dependence of the condensation activity of monounsaturated fatty-acyl-CoA on the concentration of malonyl-CoA suggested that the non-Michaelis-Menten type kinetics was dominant for oleoyl-CoA, however, a normal kinetic pattern was obtained for endogenous palmitoyl-CoA and arachidonoyl-CoA with Km = 37 microM to malonyl-CoA. The condensation activity for icosanoyl-CoA (20:0-CoA) was inhibited by icosenoyl-CoA (20:1-CoA) in a non-competitive manner, which suggested that the condensation enzyme, or at least the active center of the enzyme for icosenoyl-CoA, was different from that for icosanoyl-CoA.
Protein kinase C (PK-C) levels were determined using [3H]phorbol-12,13-dibutyrate (PDB) binding and the in vitro phosphorylation of histone H I (III-S), in autopsied human frontal cortex of age- and postmortem time-matched normal and Alzheimer patients. PK-C levels in Alzheimer particulate fractions determined by both methods were about 50% of those in controls. PK-C levels in Alzheimer cytosol fractions were not significantly different from those in controls. In a parallel study, we measured the phosphorylation of a Mr 86,000 protein (P86), the major protein kinase C substrate in the cytosol fraction prepared from Alzheimer frontal cortex, and found it to be reduced to 43% of that in control brains. This reduction in P86 protein phosphorylation compared to controls was not detected in brain samples prepared from demented patients without Alzheimer's disease. We considered 3 extraneous factors (postmortem delay, age and sex) which may have affected the extent of P86 phosphorylation and concluded that the reduced P86 phosphorylation in the Alzheimer samples is not due to any of them. Reduced PK-C levels and Mr 86,000 protein phosphorylation may reflect a biochemical deficit related specifically to the pathogenesis of Alzheimer's disease.
The hydrogen transfer from NADPH was studied in the elongation of arachidoyl-CoA (20:0-CoA) and arachidonoyl-CoA (20:4-CoA) in swine cerebral microsomes. Previously, we showed that four deuterium atoms (2H) were transferred stereospecifically from (4S)-[4-2H1]NADPH in the elongation of 20:0-CoA to 24:0 (Yoshida, S., Takeshita, M. and Kawaguchi, A. (1984) Biochem. Biophys. Res. Commun. 124, 322-328), and that three deuterium atoms were transferred from 2H2O in the elongation of 20:4-CoA to 22:4. The deuteride transfer from (4S)-[4-2H1]NADPH was observed in the elongation of 20:4-CoA to 24:4, by the technique of mass fragmentography using the chemical ionization method, and, in this case, two 2H were transferred to 24:4. No deuteride was transferred from (4R)-[4-2H1]NADPH in the elongation of 20:0-CoA and 20:4-CoA. Moreover, the condensation product (3-keto-fatty-acyl-CoA) which was formed in the elongation without NADPH could be reduced by the addition of NADPH and sodium hydrosulfite, for the elongation of 16:0-CoA and 20:4-CoA, while the condensation product from 20:0-CoA could be reduced only by NADPH, but not by hydrosulfite. The hydrosulfite did not produce the final elongation products from 20:0-CoA, 16:0-CoA or 20:4-CoA. These results suggested that the hydride was transferred from NADPH stereospecifically only in the elongation of 20:0-CoA in the step of 3-ketoacyl-CoA reduction by the reductase which might be different from that for the elongation of 16:0-CoA and 20:4-CoA in which the proton exchange might occur via a water proton in the reduction of 3-ketoacyl-CoA. Accordingly, the hydride transfer might occur from NADPH in the step of 2,3-enoyl reduction in the elongation of 20:0-, 16:0- and 20:4-CoA.