[A case of typical diffuse alveolar septal pulmonary amyloidosis involved by multiple myeloma].
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Biomedical subjects
Publications and source records attributed to S Abe.
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A 51-year-old man with recurrent gastric cancer was treated by combined administration of Cisplatin and Carmofur. The target sites were the abdominal lymph nodes and the area of invasion to the stomach. Cisplatin (50 mg/body/day) was given for 3 days, while Carmofur (400-800 mg/body/day) was administered daily in 1 course. After 1 course of administration, the target tumor was reduced in size and the therapy was continued. A complete response was confirmed by upper gastrointestinal roentgenography, endoscopy and echography after 8 courses of Cisplatin administration. The patient has survived for 2 years 6 months in a state of CR. This case suggests that a combination therapy of Cisplatin and Fluoropyrimidine derivatives might be effective for gastric cancer.
The effects of systemic administrations of immune complex, complement activators, and insoluble particles on endogenous production of tumor necrosis factor (TNF) were investigated in mice. Production of serum TNF was triggered by i.v. injection of OK-432, a streptococcal preparation, and measured by in vitro L-929 cytotoxicity assay. Intravenous injection of IgG-opsonized sheep red blood cells (10(8)/mouse) enhanced OK-432-triggered TNF production significantly. This effect was maximal (about 30-fold enhancement) 1.5 to 3 h after the injection and disappeared within 10 h. Complement activators other than immune complex also possessed this activity. Zymosan (0.1 mg/mouse) enhanced OK-432-triggered TNF production maximally (about 25-fold) 3 to 6 h after its i.v. injection, its effect lasting for 10 h, and disappearing within 24 h. Heat-aggregated IgG and cobra venom factor also had similar enhancing effects. In addition, systemic pretreatment with insoluble particles enhanced OK-432-triggered TNF production. The enhancement by latex beads (2 microliters volume of solid/mouse) was maximal (about 60-fold) 3 to 6 h after their i.v. injection, was sustained for at least 20 h, and disappeared within 48 h. Glass beads, dextran beads, alum, silica, and carbon particles all had similar enhancing effects. Based on these results, the in vivo scavenger function of macrophages, as well as direct activation with cytokines, may participate in priming for endogenous production of TNF; alternatively, particles or macromolecules which can be scavenged by macrophages may activate macrophages and prime for TNF production.
A sensitive high-performance liquid chromatographic method has been developed for the determination of dolichyl phosphate homologs in tissues. Dolichyl phosphates were methylated and derivatized with 3-(9-anthryl)-diazo-2-propene to yield methyl 3-(9-anthryl)-2-propenyl dolichyl phosphates. As an internal standard, 2,2-didecaprenylethyl phosphate was used. The derivatives were separated on a reversed-phase column using isocratic elution, and detected fluorometrically. The method with fluorescence detection was sufficiently sensitive to measure the concentration of dolichyl phosphate homologs in tissues.
The results of surgical treatment of gastric cancer were reviewed retrospectively for 135 atomic bomb survivors and 377 control patients. The mean age was significantly higher in the survivors than in the controls. Otherwise, both groups were quite comparative especially in terms of the stage of the disease. Histopathologically, the rates of poorly differentiated or undifferentiated types of carcinoma and secondary lymph node involvements were significantly lower in the survivors than in the controls. There were no significant difference between the two groups in postoperative morbidity and mortality rates and long-term survival rate. The incidence of second primary malignancies, however, was apparently higher in the survivors than in the controls.
Frozen sections of eight primary malignant lymphomas of the brain were examined by the immunohistochemical methods using a panel of monoclonal and heterologous antibodies to B lymphocyte (immunoglobulins, BA-1, Leu-12 and HLA-DR), T lymphocyte (OKT-11 and Leu-1) and monocyte (OKM-1) surface markers. Paraffin sections were also used in the examination of cytoplasmic immunoglobulins. Surface and/or cytoplasmic immunoglobulins (Ig) were observed in seven cases, four of which were shown to be distinctly monoclonal and the other three less so. The remaining 1 case showed no distinct staining for Ig. BA-1, Leu-12 and HLA-DR stainings were positive in four, four and five cases, respectively. The marker phenotypes of (BA-1, Leu-12, HLA-DR) were shown to be (+, +, +) in one lymphoma, (+, -, -) in three, (-, +, +,) in three, and (-, -, +) in one. Thus, it was demonstrated that the present lymphoma cases showed a marked immunological heterogeneity, and it was shown that all of them including the Ig-negative case revealed one or more of these three additional B cell markers, indicating B cell lineage of these cases. Examination of T cell and monocyte markers revealed positive staining in normal or reactive lymphoid cells distributed around blood vessels or sporadically in tumor tissues, but not in lymphoma cells. Epstein-Barr virus (EBV)-associated nuclear antigen was not demonstrated in the seven cases examined, making it unlikely that these lymphomas were related with EBV infection.
Myocardial protective effects of intracoronary administration of relatively small doses of propranolol were examined and compared with systemic administration in 20 open-chest dogs. In group 1 (n = 6) rate-pressure-product (R X P) did not change during 5-minute left anterior descending artery (LAD) perfusion with deoxygenated Krebs-Henseleit solutions (KHS). However, R X P decreased by the same degree in group 2 (n = 7), which received perfusion with KHS containing 0.4 or 0.8 mg/dl of propranolol, and in group 3 (n = 7) given LAD perfusion with original KHS and systemic administration of 0.02 to 0.04 mg/kg of propranolol. Total administered doses of propranolol were the same for groups 2 and 3. Transmural biopsy after 5 minutes of perfusion revealed less severe metabolic deterioration of hypoxic myocardium in group 2 when compared with that in group 1, as evidenced by higher ATP (adenosine triphosphate) (2.81 +/- 0.35 versus 2.23 +/- 0.45 mumol/g, p less than 0.05) and lower lactate content (5.62 +/- 1.44 versus 9.01 +/- 2.62 mumol/g, p less than 0.05). On the other hand, significant metabolic preservation was not noted in group 3. Sequential changes in regional myocardial contraction did not differ among the three groups. In conclusion, intracoronary administration of propranolol showed myocardial protective effects that were not mediated by the changes in hemodynamics and myocardial contraction.
Viruses were recovered from HeLa S3 cells and African green monkey kidney (AGMK) cells transfected with an infectious cDNA clone of poliovirus vaccine Sabin 1 strain. The viruses recovered from the different DNA-transfected cells were tested for the biological characteristics of temperature sensitivity (rct marker), plaque size, and bicarbonate concentration dependency (d marker). The results revealed that the above properties were similar to those obtained from tests on the Sabin 1 vaccine reference strain. The recovered viruses and the vaccine reference virus were passaged in AGMK cells at an elevated temperature of 37.5 degrees, and the passaged isolates were tested for the rct marker. The virus recovered from AGMK cells had the most stable rct phenotype while the virus from HeLa S3 cells had a similar stability to that of the reference virus, suggesting that the virus from AGMK cells would be more suitable as a vaccine strain than the other two viruses. Furthermore, an infectious cDNA clone of high specific infectivity, constructed by introducing SV40 large T antigen into the plasmid, was used for production of high titers of virus after transfection. The results of in vitro biological tests on the recovered virus suggested that virus produced in the transfected AGMK cells also had the high quality that is desirable in vaccine stocks. Monkey neurovirulence tests performed with these recovered viruses revealed that the recovered viruses were weakly neurovirulent, similar to the vaccine reference virus. The infectious cDNA clone of the poliovirus vaccine strain could therefore be used to generate a possible inoculum of the oral polio live vaccine. Our findings strongly suggest that an infectious cDNA clone of poliovirus RNA may be used to preserve the constancy and quality of the present seed viruses of the Sabin 1 vaccine strain.
Silver-stained nucleolar organizer regions (Ag-NOR) in bone marrow cells and/or phytohemagglutinin-stimulated peripheral blood lymphocytes were compared between six normal healthy persons as controls and 22 Philadelphia chromosome (Ph)-positive chronic myelocytic leukemia (CML) patients, to examine if any disease associated changes occur in the expression of Ag-NOR. Although the frequency of Ag-NOR-positive cells and the number of Ag-NOR per cell were generally greater in lymphocytes than in bone marrow cells in both controls and CML patients, the Ag-stainability of these cell types in CML patients was considerably heterogeneous, compared with that found in controls. The peripheral lymphocytes of CML patients in the chronic phase, but not in the blastic phase, exhibited a significantly lowered Ag-stainability when compared with those of controls. while no such difference was observed between bone marrow cells of controls and leukemia patients in both phases of CML. In the blastic phase, however, the occurrence of Ag-NOR on the Ph of CML bone marrow cells was significantly less than expected. The present findings are discussed in relation to the existing data on the Ag-NOR expression in both normal and neoplastic cells.
Arachidonic acid (AA), a prostaglandin precursor, significantly potentiated sister-chromatid exchange (SCE) induction in vitro by benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene (DMBA) in the aryl hydrocarbon hydroxylase (AHH)-inducible human hepatoma C-HC-4 cells, and to a lesser extent in the non-inducible rat tumor AH66-B and R1 and Chinese hamster Don-6 cells, all of which were less sensitive to these compounds than C-HC-4 cells. Indomethacin (IM), an inhibitor of prostaglandin endoperoxide synthetase (PES), moderately suppressed SCE induction by BP or DMBA in AH66-B and R1 cells, but it exerted no such effect in C-HC-4 and Don-6 cells. In C-HC-4 cells, however, IM completely eliminated the potentiating effect of AA on SCE induction by both BP and DMBA. The above findings suggest that PES in prostaglandin biosynthesis may also be involved in the metabolic activation of polycyclic aromatic hydrocarbons to genotoxic forms capable of inducing SCEs, in addition to AHH system.
Cytotoxic activity of recombinant human TNF (rHu-TNF) on various human cell lines was examined in vitro. rHu-TNF exerted a cytostatic effect on various types of human tumor cells such as carcinoma, sarcoma, leukemia, melanoma and other types. When the cytocidal effect was examined on the tumor cells which were cytostatically susceptible to rHu-TNF, the cytocidal effect of rHu-TNF was also noticed on many of these tumor cells. However, some tumor cells were affected cytostatically only. Human diploid cells were not affected cytostatically or cytocidally by rHu-TNF. WI-38 VA13 cells which are an SV-40-transformed derivative of WI-38 diploid cells, were affected both cytostatically and cytocidally by rHu-TNF. These results suggest that rHu-TNF exerts cytostatic and cytocidal effects against a broad spectrum of human tumor cells, and its cytotoxic activity is tumor-specific.
Numerical calculations were done of the indoor exposure rate due to the cosmic rays. Only muons were considered, and the calculations were done within a two-dimensional framework under the non-scattering approximation. The effects of various structural parameters on the level and the distribution of the exposure rate were studied by a case control method. It was shown that a building's dimensions and the floor thickness were important in all cases. However, the effect of partition walls would become significant only when the partition number is large. The effect of neighboring buildings would be especially important in the lower floors of tall buildings. In such a case, attention is necessary not only to the buildings' internal structures but also to the relationship between that particular building and its neighborhood. The maximum amplitude of the possible variation of the exposure rate due to the change of any single structural parameter would be 30% in ordinary Japanese housing conditions.
Calmodulin antagonists, trifluoperazine, chlorpromazine, calmidazolium, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), strongly inhibited the electrofusion of barley (Hordeum vulgare L. cv Moor) protoplasts with a marked increase of broken fusion products, after 60 minutes of incubation. W-5, a dechlorinated analog of W-7, was found less effective for the inhibition than W-7. Ethyleneglycol-bis(beta- aminoethylether)-N,N'-tetraacetic acid a Ca(2+) chelator, La(3+), a surface Ca(2+) antagonist, and verapamil, a Ca(2+) channel blocker, also inhibited electrofusion. Dielectrophoresis was inhibited by La(3+). A microtubule inhibitor, vinblastine, inhibited electrofusion strongly while colchicine, slightly. A microfilament inhibitor, cytochalasin B, promoted fused cells to become spherical while phalloidin did not affect electrofusion.
Seven different recombinant viruses from the virulent Mahoney and the attenuated Sabin parental strains of type 1 poliovirus were constructed in vitro by using infectious cDNA clones. Monkey neurovirulence tests (lesion score, spread value, and incidence of paralysis) using these recombinant viruses revealed that the loci influencing attenuation were spread over several areas of the viral genome, including the 5' noncoding region. In vitro phenotypic marker tests corresponding to temperature sensitivity of growth (rct marker), plaque size, and dependency of growth on bicarbonate concentration (d marker) were performed to identify the genomic loci of these determinants and to investigate their correlation with attenuation. Determinants of temperature sensitivity mapped to many areas of the viral genome and expressed strong but not perfect correlation with attenuation. Recombinant viruses with Sabin-derived capsid proteins showed a small-plaque phenotype, and their growth was strongly dependent on bicarbonate concentration, suggesting that these determinants map to the genomic region encoding the viral capsid proteins. Plaque size and the d marker, however, were found to be poor indicators of attenuation. Moreover, virion surface characteristics such as immunogenicity and antigenicity had little or no correlation with neurovirulence. Nevertheless, viruses carrying Sabin-derived capsid proteins had an apparent tendency to exhibit less neurovirulence in tests on monkeys compared with recombinants carrying Mahoney-derived capsid proteins. Our results suggest that the extent of viral multiplication in the central nervous system of the test animals might be one of the most important factors determining neurovirulence. Moreover, we conclude that the expression of the attenuated phenotype of the Sabin 1 strain of poliovirus is the result of several different biological characteristics. Finally, none of the in vitro phenotypic markers alone can serve as a good indicator of neurovirulence or attenuation.
Clinicopathological studies of 89 cases of idiopathic membranous glomerulonephritis was carried out to investigate the clinical and histopathological characteristics of the disease. The results were compared with those of previous published reports to observe whether any difference between Japanese and caucasian patients exists. There were no obvious differences as to main clinical features, although an apparently better prognosis in our data was observed during long term follow up. In renal biopsy findings, especially glomerular capillary wall injuries, the prevalence of advanced electron microscopic stages (stages III and IV) was higher in the Japanese cases. A higher rate of clinical remission was observed in the treated group. It was concluded that Japanese cases had an obviously better prognosis despite having more advanced histological findings than the caucasian patients.
To compare genetic and environmental factors that determine lung function and dimensions, chest radiographs and pulmonary function were measured in 17 pairs of nonsmoking twin adolescent boys (12 monozygotic pairs and 5 dizygotic pairs). Genetic factors dominated in tracheal width and lung dimensions (height, width, and apicofissural and fissurodiaphragmatic distances) at residual volume. Genetic factors also affected forced vital capacity, functional residual capacity, forced expiratory volume in 1 s, maximum expiratory flow at 25% vital capacity, and maximum flow at 50% vital capacity-to-forced vital capacity ratio. Peak expiratory flow correlated with tracheal width at residual volume. Age correlated with lung dimensions (width and depth) but not with tracheal width. These results indicate that genetic factors determine the dimensions and function of central airways, peripheral airways, and lung parenchyma in adolescent males. The effects of genetic factors on some functional measurements (airway resistance, closing volume-to-vital capacity ratio, and phase III in single-breath N2 washout) may be masked because of poor reproducibility of the tests.