Gadolinium interaction in GdBa2Cu3Oy compounds.
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Biomedical subjects
Publications and source records attributed to T Tamura.
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We previously demonstrated that there existed extremely abundant NH2-terminal big gastrin immunoreactivity (NT G-34-IR) in human urine. This report describes the purification and sequence of NT G-34-IR from the urine of an achlorhydric patient. The purification was carried out by a combination of Sep-Pak C18 cartridges, Sephadex G-25, and HPLC steps using a radioimmunoassay specific for NH2-terminus of G-34 and ultraviolet absorption at 214 nm as monitors. Three peptides were isolated. The amino acid analysis, mass spectrometry, and sequence analysis confirmed the structures of urinary NT G-34 fragments being less than Glu-Leu-Gly-Pro-Gln-Gly-Pro-Pro, less than Glu-Leu-Gly-Pro-Gln-Gly- Pro-Pro-His, and less than Glu- Leu-Gly-Pro-Gln-Gly-Pro-Pro-His-Leu. NH2-terminal octapeptide of G-34 was the main component of urinary NT G-34-IR.
A mouse mAb, which recognized a rat T cell surface Ag responsible for the T cell activation, was produced by a regular hybridoma method using F344 rat T cells stimulated with PMA and a calcium ionophore, as the Ag. The mAb termed 1F4 (kappa-IgM) was reactive with rat T cells but not with B cells and immunohistochemically it stained rat thymus tissues strongly at medulla and weakly rat cortex. Addition of 1F4 mAb to a culture of T cells resulted in the proliferation of T cells by a help of PMA or a solid support. 1F4 mAb also caused the modulation of the corresponding Ag but not other T cell markers such as CD5, CD2, and OX-52-defined Ag. The 1F4 mAb immunoprecipitated a cell surface component having an apparent m.w. of 25,000 from rat T cells which could be associated with a disulfide-linked heterodimer (m.w. 92,000) consists of subunits having m.w. of about 52,000 and 43,000. These results strongly suggest that the 1F4 mAb recognizes a rat T cell Ag homologous to the human and mouse CD3.
Rat insulin-like growth factor-I (IGF-I), a serum polypeptide with growth promoting activity, was isolated from rat serum by a combination of acid/ethanol extraction, affinity chromatography, and a series of reversed phase high performance liquid chromatography, cation exchange, and reversed phase. All peptide fragments produced by chymotrypsin digestion of reduced and carboxymethylated rat IGF-I were amino acid sequenced and compared with the sequence of human IGF-I. Three out of 70 of the rat amino acid residues differed from those of human IGF-I as follows: Asp20----Pro, Ser35----Ile and Ala67----Thr. Purified rat IGF-I cross-reacted with polyclonal anti-human IGF-I antibody 75% as compared to human IGF-I, but it cross-reacted only 3% with monoclonal anti-human IGF-I antibody. Thus, it is possible to monitor the metabolic fate of human IGF-I, when injected into rats, without interference by endogenous rat IGF-I. Rat IGF-I showed 65% activity in the radioreceptor, 28.6% activity in the lipogenesis and 22.5% activity in the free fatty acid release inhibition assays as compared to human IGF-I on a protein quantity basis.
While protein kinase C (PKC) appears to play a role in the action of PTH in renal cells, direct evidence of activation by PTH is lacking. Rat PTH (1-34) caused a rapid, transient translocation of PKC in opossum kidney (OK) cells from a basal value of 0.09 to maximum of 0.24 at 10-15 sec. Both the time course and dose-response relationship of translocation matched a corresponding increase in cytosolic Ca2+. In contrast, PTH activation of cAMP-dependent protein kinase (PKA), while also rapid, was greater in magnitude (0.10 to 0.50), persistent, and occurred at a threshold level of 3 x 10(-10)M PTH, compared to 10(-8)M for PKC. Neither bPTH(3-34) nor bPTH(7-34) activated either protein kinase, while both antagonized rPTH(1-34)-induced PKC translocation more effectively than PKA activation. These differential effects of PTH agonist and antagonists further support the suggestion that PTH acts through two signal transduction mechanisms in which one or more receptors is linked in distinct ways to adenylate cyclase and phospholipase C.
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Based on a preclinical study demonstrating the synergistic antitumor effect of recombinant interleukin 2 (rIL-2) and beta-interferon (IFN-beta) on mouse tumors and previous results of a phase I study of rIL-2, a phase I study of combination therapy with human rIL-2 and IFN-beta was conducted in 26 patients with advanced malignancy. Patients were given rIL-2 by 24-h continuous i.v. infusion and IFN-beta by 2-h i.v. infusion for 5 days each week for 4 weeks. The common side-effects were fever, malaise, chills, appetite loss, and diarrhea. Leukocytosis and eosinophilia were observed in 56% and 69% of the patients, respectively. Transient leukopenia and thrombocytopenia were also observed in some patients. Dose-limiting manifestations were intolerable fatigue and liver dysfunction, and it was concluded that the maximum tolerated doses of rIL-2 combined with IFN-beta were 1.1 x 10(6) U/m2/day for rIL-2 and 6.0 x 10(6) IU/m2/day for IFN-beta. No patients achieved complete and partial response to therapy in this study. One patient with pulmonary metastasis from pharyngeal cancer showed a minor response. Natural killer (NK) and lymphokine-activated killer (LAK) activities increased during the 5 days of treatment and decreased during the 2-day intermission. The percentage of IL-2 receptor-positive cells increased markedly until Day 12, and gradually decreased thereafter. The percentage of OKT 4-positive cells and the OKT 4/OKT 8 ratio increased. In contrast, the percentage of Leu 7- or Leu 11-positive cells decreased over the 4-week treatment. A phase II study of this combination therapy is ongoing against head and neck cancer, and renal cell carcinoma.
We measured transiently-expressed beta-galactosidase activity by introducing the mouse myelin basic protein (MBP)-lacZ chimeric gene (MBP-lacZ) into the NG108-15 neuronal/glial hybrid cell line. Deletion studies of the promoter region of the MBP gene showed that the promoter region between -1318 bp and -254 bp might contain sequences that repress MBP promoter activity. Fine deletion analysis using BAL 31 exonuclease revealed sequences between bp -208 and -140, -139 and -118, and -89 and -75 which were critical for promoter activity in NG 108-15 cells. DNaseI footprinting analysis revealed a cellular factor(s) that bind to the promoter region between bp -127 and -106 with NG108-15 whole cell extracts. The SV40 promoter was activated by insertion of the sequences around the region protected in footprinting experiments, in a manner independent of its orientation in NG108-15 cells. This protected region is thought to be one of the critical cis-acting DNA elements for efficient transcription.
Physiological saline solution was infused in 9 normal subjects and 6 patients with central diabetes insipidus (DI). At 120 min after the start of infusion, arginine vasopressin (AVP) was injected (i.m.). Urine was collected every 30 min fraction. The urinary excretion of kallikrein-like activity (KAL-A) (S-2266 hydrolysis activity) was significantly lower in patients with DI than in normal subjects, without showing the differences of plasma renin activity (PRA), plasma aldosterone concentration (PAC), creatinine clearance (Ccr) and blood pressure between the two groups, except a marked water-diuresis in DI. The urinary excretion of KAL-A correlated positively with the urinary excretion of AVP. AVP administration significantly increased the urinary excretion of KAL-A. After overnight fasting, an acute oral water-loading was carried out for 15 min in 6 normal subjects. Concomitant with a significant suppression of the level of plasma AVP from the first 30 min, a slight, but significant, decrease in urinary excretion of KAL-A was observed in the first 30 min fraction after loading, compared with the control period. Afterwards, the urinary excretion of KAL-A increased prominently with an increase in urine flow. KAL-A in the urine decreased promptly from the first 30 min fraction and then gradually until 120 min after loading. Urine volume and free-water markedly increased except the first 30 min fraction, compared with the control period. Thus it is suggested that AVP is one of factors which actually regulate the secretion of renal kallikrein in man.
A new compact high-performance instrument for monitoring the oxygenation state of the human newborn are developed. First we applied this instrument to the rat head, and next to the human arm. We could confirm that the volume of Oxy-Hb, Deoxy-Hb and total blood volume were well monitored by using our instrument. Now we started to apply this technique to the human newborn. Furthermore, we started the experiments of the near-infrared tomography for the small animals on the basis of this technique.
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The c-fms protooncogene encodes the receptor for the colony-stimulating factor 1 of macrophages. Its transforming counterpart, the v-fms oncogene has previously been recognized as the transforming gene of the McDonough strain of feline sarcoma virus. We have isolated rabbit antisera against a 115-kDa recombinant polypeptide containing the 926 carboxy-terminal amino acids of the v-fms protein. All antibodies recognized the cytoplasmic domain of the v-fms protein, which is 95% homologous to the corresponding domain of human c-fms proteins. These sera were applied in a survey of various human cancer cell lines, such as peripheral blood mononuclear (HL60) and choriocarcinoma (BeWo) cells, as well as leukemic cells from 58 patients with acute myelocytic, chronic myelocytic or acute lymphocytic leukemias (AML, CML, ALL). Significantly enhanced levels of fms-specific tyrosine kinase activity were detected in 12-O-tetradecanoylphorbol-13-acetate-induced HL60 and in BeWo cells, and in 7 out of 24 samples from AML patients, whereas no activity could be detected in 9 ALL or in 25 CML cell preparations. The AML cells were classified according to the FAB criteria. The highest incidence of increased fms activity was found in cells assigned to the M4 class (four out of five cases). While no activity was found in material belonging to FAB classes M2 or M3, one of the two cases of the M5 class was kinase-positive. Interestingly, two out of seven cases of the M1 class cells exhibited enhanced levels of fms kinase. These data suggest that the determination of the fms kinase may be useful to subdivide the M1 class of the FAB classification into monocytic and non-monocytic precursor leukemia cells.
The pharmacokinetics of (glycolato-0,0')-diammine platinum (II) (254-S; NSC 375101D), one of the new platinum analogues, was examined in a phase I study of this drug and compared with that of cisplatin and carboplatin. All drugs were given in short-term (30-min) i.v. drip infusions; the doses of 254-S, cisplatin, and carboplatin were 100, 80, and 450 mg/m2, respectively. Platinum concentrations in whole plasma, plasma ultrafiltrate, and urine were determined by atomic absorption spectrometry. After the infusion, the plasma concentration of total platinum for the three agents decayed biphasically. Ultrafilterable platinum in plasma decreased in a biexponential mode after infusions of 254-S and carboplatin, whereas the free platinum of cisplatin showed a monoexponential disappearance. The peak plasma concentrations and AUC for free platinum were 5.31 micrograms/ml and 959 micrograms/min per ml for 254-S, 3.09 micrograms/ml and 208 micrograms/min per ml for cisplatin, and 19.90 micrograms/ml and 3446 micrograms/min per ml for carboplatin, respectively. The mean ratio of plasma ultrafilterable platinum to total platinum were calculated, and the results showed that the protein-binding abilities of 254-S and carboplatin were almost identical. More than 50% of the 254-S was excreted in the urine within the first 480 min after its administration. Thrombocytopenia was reported as a dose-limiting toxicity for both 254-S and carboplatin. This similarity in side effects may mainly be due to the comparable pharmacokinetic behavior of these two platinum compounds.
We monitored serum zinc and copper levels for 4 months in six patients treated with continuous ambulatory peritoneal dialysis (CAPD). Zinc and copper fluxes were studied during a single dialysis exchange and over a 3-day period. Routine oral trace element supplements were then discontinued for 2 months. Serum zinc levels declined but serum copper levels remained unchanged. One month after oral supplements had been restarted, serum zinc levels returned to normal and serum copper levels rose above initial values. Zinc and copper concentrations in dialysis exchange indicated that the patients absorbed zinc and lost copper in significant amounts. The patients had poor dietary intakes of both minerals. These data suggest that patients treated with CAPD benefit from oral zinc supplementation.
Normal rat kidney (NRK) cells transformed by the v-sis oncogene of simian sarcoma virus (SSV) were treated with the glucosidase I inhibitor castanospermine. The inhibitor did not change cell morphology, but specific growth parameters such as serum- and anchorage-independence were lost.
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Two patients who had common atrioventricular valvular regurgitation associated with right isomerism, univentricular heart of the right ventricular type, transposition of the great arteries, pulmonary stenosis, and both systemic and pulmonary venous anomalies underwent common atrioventricular valvular annuloplasty. They also underwent bilateral, bidirectional cavopulmonary shunt. A Carpentier's ring was used in patient 1 and a polytetrafluoroethylene tube was used in patient 2 to reduce the diameter of the common atrioventricular annuli. Postoperative catheterization confirmed complete elimination of regurgitation of the common atrioventricular valve in both patients.
1. The effect of sodium fluoride (NaF) on gastrointestinal tracts of rats was investigated. 2. Blood flow rate in rat stomach mucosa was only 30% of the initial rate during 30-60 min after a single oral dose (300 mg/kg) of NaF. 3. The addition of NaF (final NaF concentration: 50 and 100 ppm) in vitro gave the reduction of 10 and 28%, respectively, of initial free calcium ion levels in rat blood. 4. These results indicate that oral ingestion of excess amount of NaF caused dilatation of blood vessel and greatly decreased blood flow rate to accumulate the circulating blood in the mucosa of gastrointestinal tract to cause redness.