PBRM1 loss in porocarcinoma arising from poroma.
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Letter↗
Biomedical subjects
T Kawamura
Publications and source records attributed to T Kawamura.
Gene expression of metalloproteinase and its inhibitor in mesangial cells exposed to high glucose.
To clarify the roles of metalloproteinases and their inhibitor (TIMP) in diabetic glomerulopathy, we studied the effect of a high glucose concentration on the gene expression of metalloproteinase transin and TIMP as well as collagen type IV and laminin in cultured rat mesangial cells (MCs). In the high glucose group, collagen type IV, laminin, and TIMP mRNA levels were all elevated in a concentration-dependent manner, whereas transin expression was suppressed. Osmotic control of high glucose with mannitol selectively stimulated TIMP expression. We hypothesize that high glucose decreases matrix-degrading activity as well as increases matrix productivity in MCs.
Animals↗
[Radiation therapy of Graves' ophthalmopathy].
During the decade from 1978 to 1987, 20 patients with Graves' ophthalmopathy were treated with irradiation of 2000 cGy to the orbital tissue. We examined the effects of the therapy on 17 such patients. Exophthalmos tended to decrease. When the degree of deviation of the exophthalmic eye was small, the effect of therapy tended to be better than when it was large. Two cases that showed an increase in retrobulbar fatty tissue without thickening of the extraocular muscles did not respond as well as those that had thickening of the extraocular muscles. Diplopia tended to improve both subjectively and objectively. Ocular movement improved in 11 of the 17 patients. There were no serious radiation injuries after the radiation therapy, except for some transient swelling of the eyelid.
Adult↗
Purification and cDNA cloning of a novel factor produced by a human T-cell hybridoma: sequence homology with animal lectins.
We have purified a novel immunoregulatory factor (BMPG: bone-marrow proteoglycan) produced by a T-cell hybridoma, with a monoclonal antibody column. Using an oligonucleotide probe corresponding to the partial amino acid sequence of BMPG, we cloned, sequenced, and expressed a cDNA for BMPG. BMPG has 222 amino acid residues with a 16 N-terminal signal sequence, so the mature form has 206 amino acid residues. BMPG was found to have unique characteristics: it has three types of sugar chains and it shows a marked homology with animal lectins including the human asialoglycoprotein receptor, chicken hepatic lectin and the homing receptor of lymphocytes.
Amino Acid Sequence↗
Charybdotoxin, dendrotoxin and mast cell degranulating peptide block the voltage-activated K+ current of fibroblast cells stably transfected with NGK1 (Kv1.2) K+ channel complementary DNA.
The blocking actions of the K+ channel toxins charybdotoxin, dendrotoxin and mast cell degranulating peptide were studied in B82 mouse fibroblast cells transformed to express NGK1 (Kv1.2) K+ channels. All three toxins were potent blockers of the K+ current in these cells, with KD values of 1.7, 2.8 and 185 nM, respectively. The toxin block exhibited a weak voltage-dependence with the degree of inhibition decreasing at positive membrane potentials. For charybdotoxin and dendrotoxin, reducing [K+]i did not increase the fractional block, demonstrating that the relief of block at positive membrane potentials is not due to displacement of the toxin molecules by outward flow of K+ ions. A voltage-jump protocol was used to determine the rates of binding and unbinding of dendrotoxin and mast cell degranulating peptide; binding of charybdotoxin was too rapid to be quantitatively evaluated in this manner. The binding rates (dendrotoxin, approximately 5 x 10(7)/M per s; mast cell degranulating peptide, approximately 0.8 x 10(7)/M per s) were largely voltage-independent, suggesting that association of the toxin molecules with the channel is diffusion limited. The rates of unbinding (dendrotoxin, approximately 0.3/s; mast cell degranulating peptide, approximately 3/s at +60 mV) of both toxins increased e-fold per approximately 40 mV change in membrane potential, thus accounting for the voltage-dependence of the equilibrium block. Internal perfusion with the three toxins failed to affect the K+ current (in contrast to internal tetraethylammonium which strongly blocked the current), indicating that the toxins exert their blocking action by binding to extracellular sites.
Ampicillin Resistance↗
Blood pressure-independent effect of angiotensin inhibition on vascular lesions of chronic renal failure.
Previous studies in experimental models of progressive renal failure have shown that the capacity of antihypertensive drugs to protect glomeruli from sclerosis is often unpredictable from their effect on systemic blood pressure. The present study was undertaken to ascertain whether this systemic blood pressure-independent structure-preserving effect of antihypertensives, particularly angiotensin II converting enzyme inhibitors (ACEI), is confined to the glomerulus or not, as well as whether this effect is mediated via angiotensin II (Ang II). The following experimental drug regimens were used in the rat model of subtotal nephrectomy (sNPX): so-called triple therapy [TRX; a combination of reserpine 5 mg/liter drinking water (DW), hydralazine 80 mg/liter DW and hydrochlorothiazide 25 mg/liter DW], or ACEI (either captopril, CPL, 600 mg/liter DW, enalapril, ENL, 400 mg/liter DW or lisinopril, LSL, 200 mg/liter DW), or a novel Ang II receptor antagonist (Ang IIR, L-158,809, 20 mg/liter DW). These dosages were identified in pilot studies to be the minimum required to control systemic blood pressure in the early phase up to 12 weeks. In addition, a separate group was treated with a higher dose of L-158,809 (80 mg/liter DW) with equipotent systemic pressor effect. Treatment was initiated eight weeks after subtotal nephrectomy following renal biopsy, and animals were sacrificed at 16 weeks. In ACEI treated rats, carotid arterial wall thickening (WT), defined as ratio of media thickening to radius of outer vessel wall, was similar to normal age-matched control (0.073 in all ACEI treated rats, vs. 0.074 in normal control) and significantly less than with TRX (ratio 0.118) or untreated sNPX (0.130). Even more remarkably, coronary arteriole WT in ACEI-treated rats averaged 0.139, a value less than one half and one third of TRX (0.298) and untreated sNPX control (0.388), respectively. Similar results were obtained for mesenteric artery WT. These findings were closely paralleled by changes of glomerular sclerosis. In untreated sNPX control rats, glomerular sclerosis increased from biopsy to autopsy specimens by an average of 458%. Although TRX dampened the degree of increase in sclerosis to on average 212%, this protective effect was far less than that achieved by ACEI. In the latter, sclerosis increased on average only 65% from biopsy to autopsy. Although all ACEIs were more effective than TRX, captopril and lisinopril groups showed greatest benefit at these doses. Ang IIR also protected renal and extrarenal structures with 34% increase of sclerosis index in low dose and WT 0.088, 0.117 and 0.112, respectively in carotid, mesenteric and coronary arteries.(ABSTRACT TRUNCATED AT 400 WORDS)
Angiotensin Receptor Antagonists↗
Molecular evolution of phosphoenolpyruvate carboxylase for C4 photosynthesis in maize: comparison of its cDNA sequence with a newly isolated cDNA encoding an isozyme involved in the anaplerotic function.
Molecular events associated with the evolution of an enzyme for C4 photosynthesis were investigated. In maize, at least three isozymes of phosphoenolpyruvate carboxylase [EC 4.1.1.31] are known: the C4-form, the C2-form and the root-form, being named according to their physiological roles and pattern of tissue distribution [Ting, I.P. & Osmond, C.B. (1973) Plant Physiol. 51, 448-453]. A cDNA clone which presumably encodes the C3-form isozyme was newly isolated and analyzed. Comparison of the sequences of the C3-form and C4-form isozymes revealed that (i) the homologies in the nucleotide and deduced amino acid sequences were 71 and 77%, respectively, and (ii) the gene for the C4-form isozyme evolved under strong G/C pressure. The genes for these isozymes were found to be located apart on different chromosomes. A phylogenetic tree was constructed using 8 amino acid sequences of phosphoenolpyruvate carboxylases from various sources. The topology of the tree indicated that, at least in monocots such as maize and sorghum, the genes for the C4-form and C3-form isozymes diverged from their common ancestral gene earlier than the monocot-dicot divergence (about 2 x 10(8) yr ago), though the divergence of maize (C4 plant) from wheat (C3 plant) is supposed to have occurred much later (6 x 10(7) yr ago).
Amino Acid Sequence↗
Generation and characterization of a human monoclonal antibody that neutralizes diverse HIV-1 isolates in vitro.
OBJECTIVE: The purpose of this study was to develop and characterize human monoclonal antibodies (HuMAb) that neutralize HIV-1. DESIGN: Based upon previous studies involving the generation of HuMAb that neutralize other enveloped viruses, we thought it feasible to generate HuMAb that might neutralize HIV-1. METHODS: A HuMAb was generated by fusing splenic B-cells from an HIV-positive patient with a mouse myeloma cell line. Flow cytometry was used to determine surface reactivity of the HuMAb on HIV-infected and non-infected cells. Radioimmunoprecipitation was employed to elucidate the antigen recognized by the HuMAb. A cell survival assay was used to determine the ability of the HuMAb to neutralize divergent isolates of HIV-1 in the presence or absence of complement. A gp120-CD4 inhibition enzyme-linked immunosorbent assay (ELISA) was developed in order to initiate studies to determine the mechanism of neutralization by the HuMAb. RESULTS: An anti-HIV HuMAb was generated that neutralized two HIV-1 isolates (IIIB and MN) without complement and which neutralized one divergent isolate (RF) and one clinical isolate in the presence of complement. This HuMAb, designated S1-1, was found, by flow cytometric analysis, to react with the surface of HIV-1-infected but not with uninfected cells. Radioimmunoprecipitation analysis demonstrated that S1-1 binds to native HIV gp120, but not dithiothreitol (DTT)-treated gp120. In addition, HuMAb S1-1 did not bind to denatured HIV antigens in Western blot analysis. HuMAb S1-1 effectively inhibited the binding of gp120 to soluble CD4 in ELISA. CONCLUSIONS: These results suggest that the epitope recognized by S1-1 is conformational and conserved among diverse HIV-1 isolates and may represent an uncharacterized HIV neutralizing domain within or close to the CD4 binding domain on gp120. HuMAb S1-1 might have a role to play in vaccine development or passive immunotherapy.
Antibodies, Monoclonal↗
Chronic human skin graft rejection in severe combined immunodeficient mice engrafted with human PBL from an HLA-presensitized donor.
Mice with severe combined immunodeficiency (C.B-17 scid [SCID]) accepted xenografts of adult human peripheral blood leukocytes injected intraperitoneally as evidenced by production of human immunoglobulin (IgG and IgM), and circulation of human leukocytes in peripheral blood. SCID mice also accepted human split-thickness skin xenografts. Passenger leukocytes present in small numbers in such skin grafts could also recirculate in host peripheral blood and make detectable levels of human immunoglobulin. To test the immunocompetence of the transferred human PBL, SCID mice received a human skin xenograft from a second donor (HLA-mismatched with the PBL donor) either before (n = 6) or after (n = 23) xenografting of PBL. Skin was monitored daily for signs of rejection, and rejection was scored by histology 3-4 weeks after the second graft (PBL or skin) was placed. Of 19 SCID injected with PBL from an HLA presensitized patient (L.G.), 7/19 (37%) rejected a subsequent HLA-mismatched skin xenograft. Two of six SCID (33%) rejected a previously established skin xenograft when PBL were administered afterward. The rejection of the human skin was chronic, of relatively late onset (3-4 weeks), and was characterized grossly by contraction, glassy surface, and thickening. Histopathologic examination showed lymphocyte infiltration into the dermis with endothelial cell cuffing and destruction of capillaries, as well as lymphocyte tagging of the basal epidermis, hyperkeratosis, lymphocyte exocytosis and single epidermal cell necrosis. Immunostaining with monoclonal antibody to human CD2 or mouse CD3 revealed that human, but not mouse T lymphocytes were tagging the dermis/epidermis junction and infiltrating the epidermis of rejecting skin grafts. We conclude that a form of human skin graft rejection may be reproduced in an SCID mouse. The immune status of the transferred cells (sensitized vs. normal) and the lymphocytes ability to recirculate in SCID peripheral blood appear to be factors limiting the rejection process.
Animals↗
Imidazo[1,2-alpha]pyridines. III. Synthesis and bradycardic activity of new 5-imidazo[1,2-alpha]pyridin-6-ylpyridine derivatives.
Structural modification of the cardiotonic agent, loprinone (E-1020, 1), suggested by data that it has a less positive chronotropic effect than milrinone (15), led us to find novel bradycardic agents that were structurally different from homoveratryl amine derivatives. Alkyl-oxy, -thio, and -amino derivatives at the 2-position of the pyridine ring of 1 produced bradycardic activity without a significant effect on blood pressure and myocardial contractility. Aryloxy analogues also decreased heart rate, and members with an electron-withdrawing group at the ortho position of the phenyl ring showed higher activity. Replacement of the imidazo[1,2-alpha]pyridine with pyridine resulted in diminished activity. The mechanism of bradycardic activity of these compounds seems to be direct action on the sinus node.
Animals↗
The level of serum granulocyte colony-stimulating factor in cancer patients with leukocytosis.
The level of serum granulocyte colony-stimulating factor (G-CSF) obtained from patients with leukocytosis (greater than 10,000/microliters) between May 1989 and April 1991 was measured by enzyme immunoassay. Studied were 18 patients with malignant neoplasms (median age, 64 years) and 14 patients with hematologic disease (median age, 59 years). Increased serum G-CSF values ranging from 70 to 374 pg/ml were noted in 7 of 15 lung cancer cases, a case of malignant thymoma and a blastic crisis of chronic myelogenous leukemia. The rest of the cases showed a normal value (less than 60 pg/ml). There was no correlation between the neutrophil count and G-CSF level. In lung cancer cases with high G-CSF values, neither a characteristic histologic type nor common elevation of tumor markers could be seen. The neutrophil alkaline phosphatase score was significantly increased and hypercalcemia was presented in high G-CSF cases. G-CSF may contribute at least in part to unknown leukocytosis observed in malignant neoplasms, especially in lung cancer.
Adult↗
Serum interleukin-2 receptor and interferon-alpha levels in a patient with allergic granulomatous angiitis (Churg-Strauss).
A patient with allergic granulomatous angiitis accompanied by increases in serum interleukin-2 receptor (IL-2R) and interferon-alpha (IFN-alpha) levels is reported. Laboratory findings revealed leukocytosis with eosinophilia and increased serum IgE and IgG. The serum IL-2R and IFN-alpha were increased. The serum immune complex, interferon-beta, -gamma and complements remained at normal levels. The serum IgE, IgG, IL-2R and IFN-alpha correlated with disease activity. Immunofluorescent studies using frozen sections obtained from the dermal lesion showed no immunoglobulin or complement deposits on vascular walls. Measurements of serum IL-2R and IFN-alpha might be considered reliable serologic indicators of disease activity.
Adult↗
[A case report: occurrence of bladder carcinoma in the defunctionalised bladder in a patient after operation of left ureteral carcinoma].
An eighty year-old woman was diagnosed as left ureteral carcinoma and right dysfunctional kidney in 1984. Left partial ureterectomy, partial cystectomy, and left ureterocutaneostomy were performed and her bladder was left behind after the operation. In 1990 (72 months after the operation), she was aware of bleeding from the urethra. A bladder wash was performed, demonstrating malignant cells on cytological examination, and cystoscopy revealed a papillary tumor in the defunctionalized bladder. Total cystectomy was performed and the histological findings of the surgical specimen showed transitional cell carcinoma, grade 2, pTaNoMo. This case shows the need for periodic examinations of the defunctionalized bladder, because renal pelvic and ureteral carcinoma tends to recur in the bladder within two years after operation and because tumors rarely developed in the defunctionalized bladder.
Adenocarcinoma↗
Smooth muscle myosin light chain phosphatase.
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Animals↗
[Efficacy of nicorandil on myocardial protection during coronary artery bypass grafting--a comparison with diltiazem].
Diltiazem (DTZ), a calcium slow channel blocker, is estimated to be highly effective for myocardial protection and the prevention of perioperative coronary spasms (PCS). However, the use of high doses of DTZ sometimes results in difficulty in coming off cardiopulmonary bypass due to negative chronotropic activity. Nicorandil (NCD) has remarkable coronary vasodilating effect but possesses little negative chronotropic activity. The purpose of this study was to compare NCD with DTZ with respect to effect on myocardial protection during coronary artery bypass grafting (CABG). As parameters, excess lactate (delta XL), redox potential (delta Eh), left and right ventricular stroke work indices (LVSWI, RVSWI), cardiac index (C.I.), systemic vascular resistance index (SVRI.), myocardial isoenzymes (CK-MB, LDH1), number of PCS and recovery time of chronotropic action were used. delta XL, delta Eh, LVSWI, RVSWI, C.I., SVRI, CK-MB, LDH1 were measured at 0, 1, 3, 6, 9, 18 and 24 hours after the removal of aortic cross clamping. The degree of chronotropic action was evaluated by the length of the recovery time to self beat or normal sinus rhythm after the removal of aortic cross clamping. Forty patients who underwent CABG with retrograde cold blood cardioplegia between Dec. 1989 and May 1991 were divided into the NCD group (n = 20), in which 1.1 micrograms/kg/min NCD was continuously administered from the beginning of the operation and the DTZ group (n = 20), in which the initial St. Thomas cardioplegia containing 5 mg/L and subsequent cold blood cardioplegia solution contained DTZ 3.5 mg/L, for a total DTZ dose of less than 10 mg.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardioplegic Solutions↗
[Plasma lipid peroxides in the operation of esophageal cancer].
Lipid peroxides are formed by autooxidation of polyunsaturated fatty acids found primarily in cell membranes. An increase level of lipid peroxides in the tissue therefore reflects membrane damage. We reported that water immersion restraint rats caused significant increase of gastric mucosal lipid peroxide which reflected on gastric mucosal injury. The gastric mucosal injury is also known as the post-operative complication due to physical stress. So we studied plasma lipid peroxide and its related substances in the operation of esophageal cancer. Lipid peroxide levels increased significantly in pre- and post-operation but temporal decrease was found during the operation. Vitamin E is thought to be an important structural component of biologic membranes and is believed to act as a free radical scavenger in lipid peroxidation. Vitamin E also increased in the patients of esophageal cancer and decreased significantly during the operation. Superoxide dismutase changed frequently during the operation but there was no deficit tendency in its changes. Catalase levels also changes frequently and showed temporal but statistical elevation after the operation. These results indicated that lipid peroxidation may contribute to the development of organic damage in the operation of esophageal cancer.
Catalase↗
Effect of drug therapy on the relapse of peptic ulcers. 1st communication: the effect of acute therapy.
The following study was conducted in order to investigate the effect of drug therapy on the relapse of peptic ulcers. Acute therapy with pirenzepine (Gastrozepin, CAS 28797-61-7) (100 mg/d) or cimetidine (CAS 51481-61-9) (800 mg/d) was given to 402 patients with peptic ulcers using the envelope method. Subsequently, 1-year maintenance therapy with pirenzepine (75 mg/d) or placebo was carried out in a double-blind study in 251 patients who had been cured within 3 months. During the study period, an endoscopic examination was repeated regularly to study the relapse of ulcers. When the results were stratified and analyzed by Cutler-Ederer's life table method to see changes in relapse over time, it was noted that the acute therapy for active ulcers did have an influence on the course of relapse after the ulcer lesions had been cured. Pirenzepine, a M1 antagonist, was superior to cimetidine, a H2 antagonist, in the prevention of relapse of ulcers after they had been cured. The results suggest that the prevention of relapse of peptic ulcers should be started at the stage of acute therapy for active ulcers and that care should be taken in selecting drugs. The results also suggest that the natural history of peptic ulcers with respect to their relapse can be modified to a certain extent by drug therapy although the period for such cannot be specified.
Cimetidine↗
Effect of drug therapy on the relapse of peptic ulcers. 2nd communication: the effect of maintenance therapy.
One-year maintenance therapy with pirenzepine (Gastrozepin, CAS 28797-61-7) (75 mg/d) or placebo was performed in a double-blind fashion in 251 patients to investigate the relapse by means of endoscopic examinations repeated every 3 months. Enrolled were the patients who had been cured within 3 months by acute therapy with either pirenzepine or cimetidine randomly given by the envelope method. When the results were analyzed by Cutler-Ederer's life table method to monitor manifestation of relapse, the maintenance therapy with pirenzepine did not show any significant difference from placebo in all the patients enrolled. However, stratified analysis according to various combinations of background factors revealed that there was significant difference in 1-year cumulative non-relapse rates between the pirenzepine maintenance therapy group and the placebo group, suggesting prophylactic effect of the maintenance therapy with pirenzepine on relapse. An increase of daily dose more than 75 mg in maintenance therapy may be expected to display the prophylactic effect of pirenzepine on ulcer relapse in a definite manner.
Cimetidine↗