Biomedical subjects
Publications and source records attributed to M Nishikawa.
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A 57-year-old woman was admitted to our hospital because of further examination of anemia in November, 1978. She was diagnosed as having aplastic anemia, which was not associated with any atypical findings. Treatment with oxymetholone had been effective. However, she developed pancytopenia in January, 1988. A bone marrow aspiration revealed a hypocellular marrow with 75.6% blasts. Following two courses with low dose cytosine arabinoside and vitamin D3, the leukemia improved although she needs red cell transfusions at intervals of one to two months because of persistent pancytopenia. We present a patient with aplastic anemia who developed a hypoplastic leukemia at the tenth year of the disease.
YNK01 (a daily oral dose of 450 mg) was administered for 22 days to a 58-year-old-female with Ph1-positive acute unclassified leukemia. Leukemia cells were negative for peroxidase and esterase, but were positive for CD19, CD13, CD34, CD9, HAL-DR, CD25, and TdT. Complete remission was obtained and continued for at least a month. The main side effects noted were diarrhea and melena. The administration of YNK01 resulted in plasma ara C levels that ranged between 15.4 to 23.0 ng/ml, which appear to be nearly equivalent to dose achieved during continuous IV infusion of a low dose (20 mg/m2/day) of ara C.
We reported a 33-year-old woman with thrombasthenia (type II) in whom 1-deamino-8-D-arginine vasopressin (DDAVP) was available for the hemostasis control during breast tumor resection. She has had recurrent nasal bleeding and purpura since 2 years old. On the first admission to our hospital because of hematuria at 18 years old, she was diagnosed as thrombasthenia (type II) from hemostatic studies. At 20 years old, she had a healthy baby by the cesarean section with transfusion of fresh blood and platelet concentrates. On the 5th admission for the breast tumor resection, defect of glycoprotein II b-III a of her platelets was confirmed by using SDS gel electrophoresis. Recently, there are some reports on availability of DDAVP for hemostatic control in platelet dysfunction of various etiologies as well as mild hemophilia and von Willebrand disease. So, DDAVP (0.4 microgram/kg) was used for hemostasis control. After 1 hour, the bleeding time was shortened from over 10 to 4 min, platelet adhesiveness to glass beads increased from 1.8 to 37%. Furthermore, the levels of Ristocetin cofactor and von Willebrand factor antigen (especially large multimer) also increased. But platelet aggregation with various inducers remained unchanged before and after infusion. Breast tumor (fibroadenoma) resection.
Iodinated oil (Lipiodol Ultra-Fluid) emulsified by non-ionic contrast material (Iopamidol) featuring much iodine and surface activity, was developed for computed tomography (CT) of the liver and spleen. The stability study revealed that Lipiodol-Iopamidol Emulsion (LIE, 1-6 microns in diameter) stored 2 weeks under refrigeration showed no visible change in globule size distribution. The biodistribution study in six rabbits revealed that LIE injected into the vein was accumulated in the liver, spleen, and lung, which have reticuloendothelial cells, however not accumulated in the brain, kidney, and serum, which have no reticuloendothelial cells. The disruption to the blood brain barrier (BBB) was assessed using Evans' Blue dye as a visual marker. After the coarse emulsion (larger than 8 microns in diameter) was injected into the internal carotid artery of three rats, the permeability of BBB increased. However, after the injection of LIE, no increased permeability of BBB was noted. Our results suggest that LIE will have a clinical application in the detection of focal hepatic and splenic lesions.
Described herein are two brothers with 21-hydroxylase deficiency (21-OHD) associated with adrenal tumors, and these possible mechanisms are discussed. A 34-year-old male was admitted on Jan. 9, 1984 because of an enlarged and tender left breast. Physical examination revealed short stature (152 cm, 76.5 kg), gynecomastia and shortening of metacarpal bone. His testes were small (2.6 X 1.6 X 1.9 cm). Urinary excretion of 17-OHCS was within normal range (5.9 mg/day), but those of 17-KS, 17-KGS and pregnanetriol were markedly increased (44.4, 110 and 22.6 mg/day, respectively). Plasma concentrations of progesterone and ACTH and urinary excretions of estrone, estradiol and estriol were also increased. Urinary excretions of 17-KS were decreased to 11.7 mg/day and 17-KGS to 22.3 mg/day after the ingestion of 2 mg/day dexamethasone for two days. The computed tomography and a scintigraphy with 131I-Adosterol revealed a tumor in the left adrenal gland, and the adrenal arteriography revealed a neovascularity and a tumor stain in the tumor. These data indicated that the patient was suffering from both 21-OHD and the left adrenal tumor. At this point, adenoma or adenocarcinoma of the adrenal gland was suspected. The left adrenal tumor (85 g) was resected on April 10, 1984, and the pathological diagnosis was adrenal adenoma. The patient's endocrinological abnormalities, however, did not improve after the operation. Urinary excretions of 17-KS and KGS were increased to 57.9 and 108.5 mg/day, respectively, in the patient's elder brother, and 63.3 and 127.9 mg/day, respectively, in his younger brother, indicating that they also had 21-OHD. Interestingly, an adrenal tumor was diagnosed by abdominal computed tomography in the elder brother who had the same HLA typing as the present case. The three brothers had 21-OHD, and two of them had both 21-OHD and adrenal tumor. To our knowledge, this is the first report documenting the co-existence of adrenal tumors in brothers with 21-OHD. This suggests that adenoma can be one of the complications of 21-OHD, probably due to the chronic stimulation by ACTH, and that a possible linkage to HLA may exist in such cases.
The analysis of stimulants in urine using a headspace gas chromatography system equipped with an in-column sample trifluoroacetylation unit was investigated. A 5-ml aliquot of urine containing stimulants was pipetted into a 20-ml autosampler vial together with 3.5 g of potassium carbonate. The vial was sealed and heated for 20 min at 80 degrees C, then 0.8 ml of the headspace gas and N-methylbis(trifluoroacetamide) gas were injected simultaneously into the gas chromatograph equipped with a flame ionization detector and a fused-silica capillary column (DB-1, 30 m x 0.32 mm I.D., film thickness 0.25 micron), with a gas-tight syringe. Calibration graphs prepared by the absolute calibration curve method showed good linearity over the concentration range of 0.04 to 50 micrograms/ml for methamphetamine hydrochloride and amphetamine sulphate. The detection limits were 0.03 micrograms/ml for both of these compounds.
Parathyroid hormone (PTH) -degrading activity was studied using osteoblast-like UMR-106 cells. PTH-degrading activity was assessed by the amount of PTH fragments produced in the medium after exposure of intact human PTH-(1-84) to UMR-106 cells. PTH immunoreactivity recovered in trichloroacetic acid-soluble products of the medium and in fractions eluted from reverse-phase high-performance liquid chromatography (HPLC) was measured by radioimmunoassay using an antibody specific for the mid-region and C-terminus of PTH. In this study, intact UMR-106 cells but not extracellular enzymes cleaved human PTH(1-84) into fragments which were released into the medium (in a time- and temperature-dependent fashion). HPLC analysis of the PTH fragments depicted three immunoreactive peaks (peaks 1, 2 and 3) besides intact PTH, indicating a limited PTH-hydrolyzing activity of the cells. Furthermore, a 1000-fold molar excess of either hPTH-(3-34) or [Nle8,Nle18,Tyr34]hPTH-(3-34)amide inhibited PTH-degrading activity by 63% and 80% of control, respectively, whereas neither calcitonin, vasopressin nor growth hormone suppressed it. Additionally, HPLC analysis of the samples treated with [Nle8,Nle18,Tyr34]hPTH-(3-34)amide showed a reduction of the three peaks, suggesting an involvement of PTH receptor in the production of PTH fragments. This PTH-degrading activity was strongly inhibited by phenylmethylsulfonyl fluoride and chymostatin, but not by soybean trypsin inhibitor, elastatinal or inhibitors of cysteine, aspartic or metalloproteinases, indicating that it is due to a seryl chymotrypsin-like endopeptidase. Chymotrypsin-like activity seems to be solely responsible for PTH-degrading activity in intact UMR-106 cells, since all three PTH fragments were predominantly suppressed in the presence of chymostatin. Further analysis of chymotrypsin-digested products of hPTH-(1-84) eluted from HPLC exhibited five fragments detected by ultraviolet absorbance at 210 nm, three of which were measurable by PTH radioimmunoassay, each corresponding to the three PTH fragments produced by UMR-106 cells. To explore the cleavage sites of PTH further, amino acid analysis of chymotrypsin-cleaved products was performed. The results strongly support the view that the chymotrypsin-like enzyme in UMR-106 cells cleaved the hormone between residues 23-24 and 34-35, to produce, at least, hPTH-(24-84) and -(35-84). Our present study indicates that a chymotrypsin-like endopeptidase is solely responsible for limited hydrolysis of PTH by intact UMR-106 cells.
A case report is presented of a 73-year-old male who was seen with fever, jaundice, abdominal pain and central nervous system depression. He failed to respond to intensive antibiotic therapy, and subsequently acute obstructive suppurative cholangitis fully developed. Upon laparotomy, the patient's gallbladder was found to be enlarged with the bile from the gallbladder and bile duct itself containing a high pus content. Its cultured organism revealed non-0-1 Vibrio cholerae. To our knowledge, no prior case of acute obstructive suppurative cholangitis in a non-0-1 Vibrio Cholerae biliary carrier has been reported in Japan.
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A case with severe pulsatile tinnitus of the left side caused by occlusion of the right common carotid artery was reported. Tinnitus in this case was supposed to be due to the rich blood flow of the external carotid systems developed as collateral routes resulting from the occlusion of the right common carotid artery. It subsided with the establishment of a bypass using a vein graft between the ascending aorta and the residual patent portion of the right common carotid artery.
We hereby report a case of a laterally situated sinus pericranii, which is rare. According to the articles regarding this kind of lesion, carotid angiograms revealed no pathological findings, and venograms taken with direct injection of contrast medium into the mass were useful. It should be stressed that the lesion could be demonstrated in the late phase of carotid angiograms, and digital subtraction angiography was especially useful for diagnosis. The literature is also reviewed.
During monocyte-macrophage differentiation of HL-60 cells by 12-O-tetradecanoyl phorbol 13-acetate, the intracellular globular(G)-actin and polymerized(F)-actin increased 3-fold and 1.7-fold, respectively. Time course studies showed that these changes of actin levels were nearly coincident with the development of macrophage characteristics, including adhesiveness, positive reactivity against OKM-1 antibody and elevated lysozyme activity. When exposed to 5 nM TPA, these different properties of differentiation were detectable as early as 12 h after TPA treatment and reached a maximum by 24 h. Phosphorylation of 17 K and 27 K proteins, induced by TPA, occurred early (within 30 min) during TPA-induced differentiation. On the other hand, HL-60R cells, which are resistant to TPA in terms of the development of adhesiveness and differentiation, showed no change in both G- and F-actin levels, after the TPA treatment. TPA did not induce phosphorylation of these proteins in the HL-60R cells. In the presence of the protein kinase inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7, 20 microM) and staurosporine (10 nM), the increase in actin levels induced by TPA was inhibited as well as other later evidence of differentiation. These results suggest that the phosphorylation of specific proteins is closely associated with the process of differentiation of HL-60 cells into macrophages.
A series of analogues of N-(cyclohexylcarbonyl)-D-phenylalanine (5) have been synthesized and evaluated for their hypoglycemic activity. Relationships were studied between the activity and the three-dimensional structure of the acyl moiety, which was characterized by high-resolution 1H NMR spectroscopy and MNDO calculations. The role of the carboxyl group of the phenylalanine moiety was also studied by comparing the activities of the enantiomers, the decarboxyl derivative, the esters, and the amides of the phenylalanine derivatives. Thus, the structural requirements for possessing hypoglycemic activity was elucidated and a highly active compound, N-[(trans-4-isopropylcyclohexyl)carbonyl]-D-phenylalanine (13) was obtained, which showed a 20% blood glucose decrease at an oral dose of 1.6 mg/kg in fasted normal mice.
To evaluate the effect of a thyroid stimulator on thyroid function in the sera of normal pregnant women, we measured thyroid-stimulating activity (TSA) using a highly sensitive bioassay based on cAMP accumulation in cultured rat FRTL-5 thyroid cells. Serum was pretreated with 10% polyethylene glycol (PEG), and the supernatant (PEG-pretreated serum) was then used in the following studies. FRTL-5 cells were preincubated in 5H medium and incubated for 2 h with PEG pretreated serum, and cAMP was measured. All 11 patients with untreated hyperthyroid Graves' disease with strongly positive thyroid-stimulating antibody activity had normal TSA, because only 5.6% of their immunoglobulin G was recovered in the PEG-pretreated serum. In 32 normal pregnant women, 29 (91%) had positive TSA. Their TSA showed statistically significant positive correlations with serum hCG and free T4 levels, and a negative correlation with serum TSH levels. Moreover, when hCG was absorbed from sera by incubation with the solid phase anti-HCG monoclonal antibody, a significant positive correlation was observed between the rate of decrease in hCG and that in TSA. In conclusion, 1) TSA exists in the sera of normal pregnant women, which reflects hCG itself; and 2) thyroid glands of normal pregnant women may be stimulated by TSA to induce a slight suppression of TSH but not sufficient to induce overt hyperthyroidism.
To investigate the pathophysiology of patients with autoimmune thyroid diseases, we measured serum thyroid stimulating antibody (TSAb) activity and thyroid stimulation blocking antibody (TSBAb) activity by determining the radioiodine (125I) uptake into FRTL-5 cells. FRTL-5 cells were pre-incubated for seven days with 5H medium and then incubated for 48 hours with patients' crude IgG prepared by polyethylene glycol precipitation. In order to measure TSBAb, 10 microU/ml TSH was also added. 125I was added one hour before the end of the 48 hour incubation period. After the incubation, the medium was aspirated, and the radioactivity in the cells was counted. In patients with untreated hyperthyroid Graves' disease, TSAb was detectable in 18 of 20 patients, the detectability being 90%, and activity showed a statistically significant positive correlation with TSAb activity determined by c-AMP accumulation. Out of 41 patients with hypothyroidism, TSBAb determined by 125I uptake was positive in six cases, the detectability being 14.6%. The inhibition of 125I uptake by one of these six IgGs was suggested to be at the TSH receptor level because it inhibited TSH induced c-AMP accumulation and showed positive thyrotropin binding inhibitor immunoglobulin (TBI I) activity, but did not inhibit the forskolin- and (Bu)2cAMP-induced 125I uptake. Inhibition of another IgG was suggested at the post-receptor level because it did not inhibit TSH induced cAMP accumulation and showed negative TBI I activity, but inhibited forskolin- and (Bu)2cAMP-induced 125I uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
A sensitive bioassay for TSH employing a practical extraction method was developed, and the bioactivities in patients with chronic renal failure receiving hemodialysis were compared with those in normal subjects. Serum samples were obtained from 12 normal subjects and 12 patients with chronic renal failure receiving hemodialysis. TSH was extracted from the serum using anti-human TSH monoclonal antibody coated tubes, followed by elution with 2.0 mol/l guanidine-HC1 solution (pH 3.2). After the eluate had been dialyzed against phosphate buffered saline (pH 7.4) and again against TRIS-HC1 solution (pH 7.4) and then lyophilized, it was reconstituted with hypotonic Hanks' solution. Bioassay for TSH was performed by measuring the levels of cAMP released into the medium from cultured FRTL-5 cells incubated with the extract. The mean immunoreactive recovery rates of TSH from the serum in normal subjects and patients with chronic renal failure were about 42% (+/- 6) and 40% (+/- 2), respectively. The present bioassay was sufficiently sensitive to detect a serum TSH level of 1.0 mU/l when 3.0 ml of serum was used. Extracts from standard sera at concentrations ranging from 1.0 to 10 mU/l added to the culture medium caused significant linear increases in cAMP production. Based on analysis of covariance the regression line between the immunoreactivities and bioactivities of serum TSH in patients with chronic renal failure (y = 0.90x + 0.3, r = 0.92) was not significantly different from that in normal subjects (y = 1.04x + 0.1, r = 0.93).(ABSTRACT TRUNCATED AT 250 WORDS)
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