[Overview of hemodialysis: characteristics, indications and recent progress].
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Biomedical subjects
Publications and source records attributed to Y Komatsu.
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We report cases of angina pectoris or minimal acute myocardial infarction accompanied by pulmonary edema, which were retrospectively studied with regard to their clinical characteristics, prognosis and treatment. Sixteen patients, 5 males and 11 females with a mean age of 72.6 years, admitted to the Cardiovascular Center of Sendai between January 1986 and June 1989, were studied. Ten had previous myocardial infarction. Hypertension, chronic renal failure and diabetes mellitus were found in 10, 7 and 7 patients, respectively. Electrocardiograms during cardiac ischemic attacks showed ST elevation in 8 and ST depression in the other 8 patients. Coronary arteriography which was performed in 6 patients revealed three-vessel disease in 5, and two-vessel disease in one. Mechanical ventilation was indicative of 7, and intraaortic balloon counterpulsation in 2 patients. Coronary artery bypass graft surgery was performed for 3 patients. All patients recovered from pulmonary edema and were discharged. During the mean 15-month-follow-up period, 8 patients died. The causes of death were sudden cardiac death in 3, acute myocardial infarction in one, congestive heart failure in one, post-surgical death in one, and non-cardiac death in 2.
About 100 derivatives of human recombinant granulocyte colony-stimulating factor (rhG-CSF) were created by various gene-mutagenic techniques, and KW-2228, in which amino acids were replaced at five positions of N-terminal region of intact rhG-CSF, was picked up and evaluated for its biologic and physicochemical properties in comparison with intact rhG-CSF. KW-2228 showed two to four times higher specific activity than that of intact rhG-CSF in mouse and/or human bone marrow progenitor cells by colony-forming unit assay in soft agar, and by cell-proliferation assay in liquid culture. KW-2228 showed a potency to increase peripheral neutrophil counts when it was administered to normal C3H/He mice by single intravenous injection. Increase of total leukocyte count and neutrophils was observed, with peak level at 8 to 12 hours at low doses (0.5 to 1.0 micrograms/mouse), and the highest level was maintained for 24 to 30 hours at high doses (5 to 10 micrograms/mouse). The granulopoietic effect of KW-2228 was examined by several doses of single course (once daily for 10 days) or multiple courses (twice daily injection for 5 days followed by cessation for 9 days on one cycle, 3 cycles in total) of treatment. KW-2228 showed higher activity than that of rhG-CSF, especially at sub-optimal doses of multiple courses of treatment. Furthermore, KW-2228 was found to be more stable physicochemically and biologically than intact rhG-CSF, especially under thermal conditions at 56 degrees C and in the human plasma at 37 degrees C, suggesting a protease resistancy. Pharmacokinetic study showed that plasma concentration of KW-2228 assayed for its bioactivity maintained a higher level than that of intact rhG-CSF for 60 minutes after intravenous injection of this protein to normal mice. Those results suggest that KW-2228 might show a superior in vivo hematopoietic effect to intact rhG-CSF due to its high specific activity to progenitor cells, and also due to its improved physicochemical, biologic, and pharmacokinetic stability in host animals.
Ultimobranchial calcitonins (CTs), known to stimulate cAMP production, inhibited the growth of a porcine kidney cell line LLC-PK1. This inhibition was accompanied by degenerative changes including vacuole formation and cell detachment. The electron microscopic study revealed marked swelling of rough endoplasmic reticulum (RER). Other cAMP-increasing agents such as human CT, arginine, vasopressin, and forskolin showed less growth inhibitory activities and no induction of the degenerative changes. These results indicate that the growth inhibition of LLC-PK1 by ultimobranchial CTs is mainly due to cellular death caused by the swelling of RER via a signalling pathway other than the cAMP-dependent event(s).
Yeast cells were frozen by plunging directly into liquid nitrogen (LN2) after exposure at 43 degrees C. Both the cells frozen without prior exposure to heat shock and those treated with cycloheximide showed almost 100% loss of viability during freezing and thawing. Heat exposure prior to freezing and thawing significantly increased the cell viability. This increase in cell viability was associated with the induction of heat shock protein synthesis, which was detected by gel electrophoresis. This protein may act by stabilizing the macromolecules and by increasing the hydrophobic interactions.
"Juzen-Taiho-To" (TJ-48), which is a kampo (Japanese herbal) medicine prepared by decocting a prescription of ten kinds of herbs, has several immunostimulating activities. In order to characterize the active substances for anti-complementary and mitogenic activities, TJ-48 was fractionated. Anti-complementary activity was observed in the water- and methanol-insoluble fraction (F-2) and the crude polysaccharide fraction (F-5), whereas mitogenic activity was only found in F-5. However, other low molecular mass fractions did not show both activities. Methylation analysis indicated that F-2 mainly contained amylopectin-like polysaccharides. Both Pronase digestion and periodate oxidation decreased the anti-complementary activity of F-2, and the beta-amylase-resistant fraction of F-2 still retained the potent anti-complementary activity. When F-5, which has the most potent of both activities, was further fractionated, only the major acidic polysaccharide fraction, F-5-2, showed potent mitogenic activity. Endo-alpha-(1----4)-polygalacturonase digestion showed that F-5-2 mainly contained pectic polysaccharides, and the endo-polygalacturonase treatment of F-5-2 reduced the mitogenic activity but not the anti-complementary activity. F-2 and F-5 each activated the complement system by a different mode of action.
Porin-deficient mutants of Pseudomonas aeruginosa PAO1 were selected by isolating latamoxef-resistant mutants following chemical mutagenesis. Highly latamoxef-resistant mutants had alterations in both the outer membrane proteins and penicillin-binding protein 3, a lethal target of latamoxef. Both of these alterations may be essential for cells to acquire high resistance to latamoxef. Many of the latamoxef-resistant mutants were also resistant to new quinolones and chloramphenicol. Resistance to these compounds was simultaneously co-transduced from one mutant into strain PAO1 when selection was made for transduction of ofloxacin resistance. Study of these transductants indicated that decreased amounts of outer membrane proteins C, D2, E1, and E2 lowered the outer membrane permeability and resulted in resistance. Three of these proteins were apparently identical to proteins previously reported to function as small pores. The results suggested that at least one of the four proteins was functioning as a porin for the antibacterial agents studied.
A 22-year-old man developed fat embolism syndrome. Although a computed tomographic (CT) scan of the brain showed nothing abnormal, a magnetic resonance imaging scan detected scattered spotty areas of low intensity on T1-weighted images and of high intensity on T2-weighted images. Magnetic resonance imaging is thought to be more sensitive than computed tomography in detecting cerebral fat embolism syndrome and correlates well with the clinical course.
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Although sonographically guided percutaneous ethanol injection therapy has been attracting a great deal of attention in the treatment of liver neoplasms, few reports regarding long-term results of this therapy have been published. We report here our 4-year experience, in which ethanol injection was performed 419 times on 108 lesions in 77 patients with hepatocellular carcinoma. Histopathologic examination performed in 14 cases after the therapy revealed that the lesion was completely necrotic in 10 cases, 90% necrotic in three cases, and 70% necrotic in the remaining case. Angiography performed after the therapy showed complete disappearance of tumor stain in 37 of 42 cases treated with ethanol injection. CT after the therapy showed no enhancement of the treated lesion in 55 of 56 cases. Elevated serum levels of alpha-fetoprotein decreased in 21 of 24 cases. Ethanol injection improved the long-term prognosis of the patients. Among the 50 patients in whom there were three or fewer lesions and all lesions were treated by ethanol injection, the 1-, 2-, 3-, and 4-year survival rates were 89%, 74%, 68%, and 60%, respectively. Factors that significantly affected the prognosis were the goal of the treatment, liver function, and size of the largest lesion. Serious complications rarely occurred even in patients with severe liver dysfunction. Percutaneous ethanol injection therapy appears to be valuable for treatment of hepatocellular carcinoma.
Abnormalities in albumin metabolism in nephrotic syndrome are still controversial. In an attempt to clarify the pathogenesis of the alteration in albumin metabolism in nephrotic syndrome. 131I-human serum albumin (131I-HSA) of 10 microCi loading was intravenously injected to 10 nephrotic (7 minimal change, 3 membranous nephropathy) and 3 non-nephrotic patients. Kinetic study was made by means of two compartment analysis following the 131I-HSA administration. The results were as follows: 1. Albumin synthesis decreased to some extent in nephrotic syndrome. 2. Absolute albumin catabolic rate decreased in nephrotic syndrome. 3. Fractional disappearance rate of albumin (FDR) and albumin turnover rate increased in association with progression of nephrotic syndrome. Both albumin escape into the extravascular pool and urinary excretion rate of albumin also increased. 4. In comparison of two types of nephrotic syndrome, minimal change and membranous nephropathy, it was found that, although renal and peripheral vascular permeabilities increased in both types, minimal change tended to show higher permeability than membranous nephropathy.
Effects of Juzen-taiho-toh (TJ-48) on the recovery of hemopoietic systems from radiation injury are analyzed. Female C57BL/6N mice (6-8 weeks old) were irradiated at doses of 1, 2, 3, 5, or 7 Gy from a 60Co source. After irradiation, the mice were given TJ-48 (1.25 g in 100 ml drinking water). Seven days after irradiation, the mice were sacrificed, and bone marrow (both femurs), thymus, spleen, and peripheral blood counts were made. The bone marrow cells were used for fibroblast colony-forming unit (CFU-f), spleen colony-forming unit (CFU-S), granulocyte-macrophage colony-forming unit (CFU-GM), erythroid colony-forming unit (CFU-E), and erythroid burst-forming unit (BFU-E) assays. No difference was observed between the experimental and control groups except for CFU-S counts. In the assay for day-14 CFU-S, the mice injected with TJ-48-treated bone marrow cells showed better general condition (including increased body weight) and heavier spleens with larger and more numerous colonies. The effect of TJ-48 does not seem to be elicited via the hemopoietic microenvironment, because mice that had been given TJ-48 before irradiation at 8 Gy and then injected with syngeneic bone marrow cells did not show enhanced day-14 CFU-S counts. These results suggest that TJ-48 manifests a radioprotective effect by increasing the number and size of day-14 CFU-S.
Neurosurgical patients with non-ketotic hyperosmolar diabetic coma (NHC) in our institution were analysed retrospectively. Seven cases were diagnosed as NHC being 0.47% of the number of inpatients in the last 5 years. The age ranged from 60 to 72 years old (mean 65) and there were 6 males and 1 female. Only 2 patients (29%) had a clear past history of diabetes mellitus. Prior to the NHC, systemic infection was present in 2 cases. Intravenous hyperalimentation (IVH) was performed in 5 cases, glycerol osmotherapy in 3 cases, diphenylhydantion therapy in 3 cases and tube feeding in 2 cases. The overall mortality rate in our series was 71% (5 cases), of which 2 cases died within 2 days due to cardiopulmonary failure, and 3 cases in the chronic stage died due to disseminated intravascular coagulopathy (DIC), or due to renal failure. The prognosis of NHC in neurosurgical patients is generally bad because of the presence of consciousness disturbance prior to the onset of NHC, which may mask the symptoms occurring from the NHC. Other predisposing factors could be systemic infection, IVH or tube feeding, and osmotic agents which are frequently used in neurosurgical patients. There was a tendency for NHC to occur predominantly in the chronic stage after the blood sugar had returned to normal range from the hyperglycemic state in the acute stage.(ABSTRACT TRUNCATED AT 250 WORDS)
To define the structure-function relationship, we have made a number of mutants of human granulocyte colony-stimulating factor (hG-CSF) by in vitro mutagenesis. The results indicate that most of the mutations located in the internal and C-terminal regions of the molecule abolished the activity, whereas the mutants without N-terminal 4, 5, 7, or 11 amino acids retained the activity. N-terminal amino acids were also altered by cassette mutagenesis using a synthetic oligonucleotide mixture. Among them, KW2228, in which Thr-1, Leu-3, Gly-4, Pro-5 and Cys-17 were respectively substituted with Ala, Thr, Tyr, Arg and Ser, showed more potent granulopoietic activity than that of intact hG-CSF both in vitro and in vivo.
We have previously reported that the combination of mitomycin C, carboquone, 5-fluorouracil and OK-432, including the intra-arterial administration of mitomycin C and carboquone (MQ-F-OK therapy), was effective in the treatment of advanced liver cancer. The Cooperative Study Group conducted a controlled study on MQ-F-OK therapy and the combination of mitomycin C, 5-fluorouracil and doxorubicin, including the intra-arterial administration of mitomycin C and doxorubicin (FAM therapy), against advanced liver cancer. Forty patients with advanced primary or secondary liver cancer were enrolled in this study and randomized into the MQ-F-OK group and the FAM group. Seventeen of the 21 cases in the MQ-F-OK group and 16 of the 19 cases in the FAM group were eligible for response evaluation in accordance with the criteria of the Japan Society for Cancer Therapy. There was no significant difference in the patient characteristics between the two groups. Three cases in the MQ-F-OK group and two in the FAM group showed partial response. There was, however, no significant difference in the response rates and the prolongation of life between the two groups. As for the side-effects, only anemia was observed more frequently in the FAM group than in the MQ-F-OK group. In conclusion, we could not preferentially recommend either MQ-F-OK therapy or FAM therapy for advanced liver cancer. The performance status of the patient was one of the most important factors in the treatment of advanced liver cancer because patients with poor performance status showed poorer results.
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Two new sulfur-containing amides, entadamide A (1) and entadamide B (2), isolated from the seeds of Entada phaseoloides, were synthesized by the addition reaction of methanethiol to propiolic acid (5) followed by condensation with ethanolamine by the use of dicyclohexylcarbadiimide. These compounds inhibited the 5-lipoxygenase activity of RBL-1 cells at 10(-4) g/ml. This finding suggests that entadamides A and B may be examples of a new type of antiinflammatory drug.
A case of congenital arteriovenous malformation (AVM) of the scalp containing a complex vascular network is described. The AVM was totally removed, together with its feeding artery and draining veins. Congenital AVM of the scalp is rare; only 21 other cases have been reported since 1973. All involved complex vascular networks, and about one half of the patients had red or purple birthmarks. These clinical features clearly differ from those of traumatic arteriovenous fistulae of the scalp. Although many treatment approaches have been tried, total excision appears to be the most appropriate.