Smoking and adult T-cell leukemia/lymphoma.
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Biomedical subjects
Publications and source records attributed to Y Shimamoto.
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We investigated effects of three kinds of putative protein kinase C (PKC) inhibitors, calphostin C, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), and stauro-sporine, on aortic muscle contractions induced by KCl, phenylephrine, 12-O-tetradecanoylphorbol-13-acetate (TPA), and phorbol 12, 13-dibutyrate (PDBu). Calphostin C noncompetitively inhibited TPA-induced contractions in a concentration-dependent manner. At 10(-6) M, calphostin C completely abolished responses to TPA and also effectively inhibited PDBu-induced contractions. Such a concentration of calphostin C had no effect on KCl-induced contractions but decreased the maximal tension of phenylephrine-induced response curve by 35.3 +/- 6.6% H-7 (10(-5) M had little effect on TPA-induced contraction but significantly inhibited contractile responses to phenylephrine and KCl. Staurosporine (10(-8) M, 3 x 10(-8) M) inhibited contractile responses to KCl, phenylephrine, and TPA. We suggest that staurosporine and H-7, which are known to act on the catalytic domain of PKC carrying high degree of sequence homology with other protein kinases, are relatively nonselective for PKC. On the other hand, calphostin C acting on the regulatory domain of PKC, which is distinct from other protein kinases, may serve as a relatively more selective PKC inhibitor.
A IgG-kappa-type plasmacytoma secreting salivary-type amylase ectopically is reported in a patient with smouldering adult T-cell leukemia(ATL). The patient had plasmacytomas in the distal region of the right femur, the proximal region of left tibia, and the left paranasal sinus. Both his serum and urine contained high levels of amylase. The presence of IgG-kappa and S-type amylase in the plasmacytoma cells was confirmed immunocytochemically. In addition, he was also positive for the antibody against the human T-cell leukemia virus type I (HTLV-I), and had abnormal lymphocytes with convoluted nuclei (ATL cells) in the peripheral blood. The monoclonal integration of HTLV-I proviral DNA was demonstrated in the leukemic cells of the peripheral blood, but not in the plasmacytoma cells. Our case suggested that not only can HTLV-I infection play a role in the development of ATL, but may also induce a B-cell malignancy in an indirect manner, and even an ectopic amylase producing plasmacytoma.
An unusual case of CD4+ helper T-cell lymphocytic leukaemia is reported in a 67-year-old Japanese woman. CD4+ cells showed convoluted nuclei and dense cytoplasmic granules, features usually present in CD8+ large granular lymphocytes and disorders of this particular cell type. Serum did not show antibodies to HTLV-I and HTLV-I proviral DNA integration was not evident by Southern blot analysis or after PCR. A monoclonal rearrangement of the TCR-beta chain gene was evident when hybridization methods were used. The patient died 11 months after diagnosis. No skin involvement, or splenomegaly was evident. Serum LDH levels were markedly elevated but serum calcium levels were within normal limits. The case is discussed and compared to other T-cell lymphoid leukaemias. The heterogeneity in the morphology of CD4+ T cell leukaemias is stressed.
The gastrointestinal (GI) tract is the common extranodal site for non-Hodgkin's lymphoma (NHL), and primary lymphoma of GI tract are mostly of B-cell origin. We have treated 16 patients with primary lymphoma of GI tract between 1981 and 1991, of whom 10 (62%) were of B-cell origin, while 6 (38%) were of T-cell origin. The incidence of T-cell phenotype in our hospital was considered to be much higher than that of previous reports and these 6 patients with primary T-cell lymphoma of GI tract were carefully studied. The primary sites were stomach in 4, ileocecum in 1, and duodenum in 1 case. Their T-cell nature was confirmed by immunohistochemical methods. All were peripheral T-cell lymphomas; one was CD 3+ 4- 8- and the other 5 were CD 3+ 4+ 8-. The antibody against human T-cell leukemia virus type I (HTLV-I) was positive in 3 cases (HTLV-I associated), but negative in 3 (HTLV-I non-associated). The integration of HTLV-I proviral DNA in HTLV-I associated patients was demonstrated by Southern blot analysis after DNA amplification by means of polymerase chain reaction (PCR). The clinical features of the HTLV-I associated and HTLV-I non-associated primary T-cell lymphoma of the GI tract were quite different. HTLV-I associated patients showed leukemic manifestations and tumor involvement of the skin at a later stage of the disease. These observations indicated that HTLV-I can play an important role in the occurrence of primary T-cell lymphoma of GI tract.
A case of acquired FVIII inhibitor in a nonhemophilic, 80 year-old man who had no underlying disorder, is presented. The level of inhibitor was 13.3 Bethesda unit/ml, and the antibody was IgG, with lambda light chain. The antibody reacted with the 92 kD fragment of non-treated human FVIII, and the 44 kD fragment of thrombin treated FVIII when analysed by the immunoblot analysis.
We analyzed the vasoconstrictor effects of arginine vasopressin (AVP) on regional arteries before and after ganglionic blockade with hexamethonium. Simultaneous measurements of mean arterial pressure and regional flows were obtained in conscious rats, using chronically implanted electromagnetic flow probes. Regional vascular resistance was calculated as mean arterial pressure divided by regional flow. AVP was applied intravenously as a bolus, at doses ranging from 5 x 10(-11) to 5 x 10(-8) g/kg. AVP increased mean arterial pressure, decreased superior mesenteric, renal and terminal aortic flows (supplied mainly for the hindquarter vascular area), and increased superior mesenteric, renal and terminal aortic (hindquarter) resistances in a dose-dependent manner. Ganglionic blockade decreased mean arterial pressure and renal resistance significantly, whereas there were no significant differences between changes in resistance before and after ganglionic blockade in superior mesenteric or terminal aortic areas. This suggested the presence of basal sympathetic vasoconstrictor tone in the renal area. After ganglionic blockade, the pressor effect of AVP was enhanced significantly. The increase in renal resistance induced by AVP was augmented after ganglionic blockade, whereas increases in superior mesenteric or terminal aortic resistance remained unchanged following ganglionic blockade. Our data suggest that the vasoconstrictor effect of AVP on renal vascular area is reduced by a mechanism which inhibits renal sympathetic basal tone.
Rauwolscine, a selective alpha-2 adrenoceptor antagonist, elicited a sustained contraction in the dog mesenteric artery precontracted with 20 mM KCl or 10(-9) M endothelin-1. Cumulative concentration-response curves to rauwolscine were not shifted by spiperone, propranolol, pindolol, mianserin, ketanserin, prazosin or phenoxybenzamine at the concentration of 10(-6) M. The pA2 values against rauwolscine were 8.34 +/- 0.32 for methysergide, 8.52 +/- 0.22 for methiothepin and 5.84 +/- 0.27 for phentolamine, which were in good agreement with the pA2 values for those antagonists against 5-hydroxytryptamine (5-HT) in the dog mesenteric artery precontracted with 20 mM KCl. Contractile responses to 5-HT after pretreatment with 20 mM KCl were antagonized in an apparently competitive manner by 10(-5) M rauwolscine. In the absence of precontraction, rauwolscine also shifted 5-HT-induced contractions in a parallel manner. These data suggest that rauwolscine is a partial agonist with a lower intrinsic activity than 5-HT and acts at the same 5-HT1-like receptors as 5-HT, most probably 5-HT1D receptors, in the dog mesenteric artery precontracted with KCl.
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We analyzed the relationship between autoantibody and dermatosis in 22 patients with myelodysplastic syndrome (MDS). These MDS patients consisted of five cases with refractory anemia (RA), three RA with ringed sideroblasts (RARS), eight RA with excess of blasts (RAEB), four RAEB in transformation (RAEB-t), and two chronic myelomonocytic leukemia (CMMoL) according to the FAB classification of MDS. The autoantibody was detected in seven patients, of whom four had rheumatoid factor (RF) and three had antinuclear antibody (ANA). Neither RF-positive nor ANA-positive MDS patients had other autoantibodies. Dermatosis was observed in nine cases of these 22 MDS patients. Five of 7 MDS patients (71%) with autoantibody developed dermatosis in their clinical course, as did four of 15 MDS patients (27%) without autoantibody. All four MDS patients with RF had dermatosis such as anaphylactoid purpura, xerotic dermatitis, thrombophlebitis, ephelides, and genital herpes. One of three MDS patients with ANA had pruritus senilis. The four MDS patients without autoantibody had dermatosis such as erythema nodosum, ichthyosis vulgaris, Sweet syndrome, and thrombophlebitis. Three of four MDS patients with RF had normal liver function tests, while three MDS patients with ANA showed liver dysfunction. Our studies presented here suggested that the dermatosis could develop frequently in MDS patients with autoantibody and that RF was closely related to development of dermatosis in MDS patients, although the dermatosis is not specially fixed.
Hyperkalaemia with renal tubular dysfunction by oral therapy of sulfamethoxazole-trimethoprim (co-trimoxazole) is described in 2 elderly Japanese patients with lymphoid malignancy, who developed Pneumocystis carinii pneumonia and improved. A high dose of cotrimoxazole induced hyperkalaemia with the elevation of serum creatinine and blood urea, and increased urinary N-acetyl glucosaminase after several days of the drug administration in these patients; one patient became unconscious. Discontinuation of co-trimoxazole normalized serum potassium level and symptoms. A repeated low dose of the drug induced hyperkalaemia. Before the treatment of co-trixomazole, their serum levels of creatinine showed upper limits of normal ranges. In the present study, our cases suggested that patients receiving a high dose of co-trimoxazole should be evaluated for these potential complications during a course of treatment, particularly in elderly patients with preexisting renal dysfunction.
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Spontaneous remission in a 50-year-old woman with adult T-cell leukemia (ATL) is presented. The patient was referred to our hospital because of generalized lymphadenopathy and the appearance of abnormal lymphocytes with convoluted nuclei in the peripheral blood. She was diagnosed as ATL because of the characteristic morphological ATL cells, cell surface marker analysis and the presence of serum antibody to human T-cell lymphotropic virus type-I (HTLV-I). However during the following weeks before admission, her leukocyte count and ATL cells in the peripheral blood decreased in number even though she received no therapy. After admission, abnormal lymphocytes in the peripheral blood disappeared and lymphadenopathy decreased in size, LDH level was normalized. Spontaneous remission had continued ten months without chemotherapy, but she developed recurrence thereafter and died two years later after onset with progressive disease. Gene analysis study by Southern blot analysis showed monoclonal integration of HTLV-I proviral DNA at the same positions both before regression and after recurrence. In this case, the trigger of spontaneous remission was unclear.
To assess influences of intra-aortic balloon pumping (IABP) on superior mesenteric flow, 15 postoperative patients were examined, in whom distal aspects of balloons were distal to the superior mesenteric artery. Superior mesenteric flow velocity-time integral in systole (IntS), that in diastole (IntD), and the sum of IntS and IntD (IntS+IntD) were determined on and off IABP (IABP ON-OFF test). The same parameters were obtained with balloon inflating on every other beat (IABP 1:2 test). The cardiac cycle with balloon inflation during diastole was defined as "1:2 ON," and the cardiac cycle without balloon inflation during diastole was defined as "1:2 OFF." (1) IABP ON-OFF test. IABP increased IntS (p less than 0.01), IntD (p less than 0.01), IntS+IntD (p less than 0.01), and cardiac output (p less than 0.05). The increments in IntS, IntD and IntS+IntD on IABP are attributed largely to an increased in cardiac output. (2) IABP 1:2 test. IntS during 1:2 OFF was greater than IntS during 1:2 ON (p less than 0.01), whereas IntD during 1:2 OFF was smaller than IntD during 1:2 ON (p less than 0.01). There was no significant difference in IntS+IntD between 1:2 ON and 1:2 OFF. These data suggest that juxtamesenteric balloon placement did not interrupt the arterial inflow of a superior mesenteric artery.
The mitral inflow method of measuring cardiac output with pulsed Doppler two-dimensional echocardiography was developed and validated against the thermodilution technique in 42 patients. A mitral inflow method combined the velocity of left ventricular inflow at the mitral annulus (apical long-axis view) with the cross-sectional area of the annulus calculated from its diameter (parasternal long-axis view). A good correlation was observed between thermodilution and Doppler measurements of cardiac output (r = 0.93). The ratio of Doppler measurements to thermodilution measurements will be between 0.76 and 1.15 for about 95% of cases. There was a good correlation between percentage change in thermal cardiac output and those in Doppler cardiac output (r = 0.95); the limits of agreement were -11.5% to 10.5%, suggesting that this method can be most useful for assessing relative changes in cardiac output.
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1. Calphostin C at 10(-6) M was shown to be selective and highly effective in inhibiting contractile responses of rat aortae to 12-o-tetradecanoylphorbol-13-acetate, while it had no effect on contractile responses to elevated KCl. 2. In the rat aorta, endothelin-1 (ET-1) developed a sustained tonic contraction dose-dependently in both normal Ca(2+)-containing Krebs and Ca(2+)-free Krebs containing 1 mM EGTA. Calphostin C (10(-6) M), a selective protein kinase C inhibitor, antagonized the maximal tensions for cumulative addition of 10(-8) M ET-1 by 13.2% in Ca(2+)-containing medium and 25.8% in Ca(2+)-free Krebs containing 1 mM EGTA. 3. In both Ca(2+)-containing medium and Ca(2+)-free Krebs containing 1 mM EGTA, precontraction with 10(-8) M ET-1 had no effects on the contractile response to subsequently added 10(-6) M 12-o-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C. 4. In Ca(2+)-free Krebs containing 1 mM EGTA, precontraction with 10(-6) M TPA potentiated the contractile response to subsequently added 10(-8) M ET-1, whereas this potentiation was abolished by pretreatment with 10(-6) M calphostin C. The mechanism of the TPA-induced potentiating effect remains to be determined. 5. These results suggest that the participation of protein kinase C in the 10(-8) M ET-1-induced contraction may be 13.2% and 25.8% in the presence and absence of extracellular Ca2+, respectively, and that mechanisms other than protein kinase C may be predominantly responsible for ET-1-induced tonic contraction.