Near-triploidy and near-tetraploidy in hematological malignancies and mutation of the p53 gene.

Hyperdiploidy of > or =58 chromosomes is reported in 0.5-3% of hematological malignancies, but reports of near-triploidy (58-80 chromosomes) and near-tetraploidy (81-103 chromosomes), are few. We examined these chromosome abnormalities and analyzed the relationship with the mutation of the p53 gene. Thirty-one of 979 adult patients (3.2%) with hematological malignancies were identified as having near-triploid or near-tetraploid (tri-/tetraploid) chromosomes. These included 11 with B-cell neoplasms, seven with Hodgkin's lymphoma, five with T-cell neoplasms, four with myelodysplastic syndromes and four with acute myeloid leukemias. All patients had concurrent complex chromosome aberrations. Deletion of one allele of the p53 gene was found in two patients and a point mutation of the p53 gene was detected in five patients. Although abnormalities of the p53 gene have been reported in about 10% of hematological malignancies, these were found in seven of 31 (23%) patients with tri-/tetraploidy. These findings suggest that the abnormality of the p53 gene may be closely related with tri-/tetraploidy. The four myelodysplastic syndrome (MDS) patients with tri-/tetraploidy had a significantly worse prognosis than those with diploid cytogenetics (n = 35; P < 0.002). In B-cell neoplasms (n = 3), triploidy was associated with a worse prognosis than tetraploidy (n = 8) and diploidy (n = 130; P < 0.02).

[Skeletal muscle T-cell lymphoma following hemophagocytic syndrome].

A 43-year-old man was admitted to our hospital because of hemophagocytic syndrome (HPS) in August, 1998. A CT scan, gallium scintigraphy, gastrofiberscopy and colonofiberscopy showed no evidence of malignant lymphoma. Virus-associated HPS was suspected because of an increased titer of anti-Epstein-Barr (EB) virus antibody (EBV VCA IgG 2,560x, EBV EA IgG 40x, EBNA 20x). The HPS resolved spontaneously for 40 hospital days, but two weeks into the period of HPS remission, the patient developed pain and marked swelling of the right thigh muscle, and pectoral, biceps brachii, quadriceps femoralis and masseter muscles. Otherwise, CT scan and gallium scintigraphy showed no abnormal findings. A biopsy of the right quadriceps femoralis muscle revealed non-Hodgkin's lymphoma with muscle infiltration. Immunohistologic examination confirmed T-cell type (CD3, CD43, CD45, CD45RO) lymphoma, and Southern blot analysis for T-cell receptor revealed a rearranged band. The lymphoma cells were negative for EBV genome monoclonality. The patient responded well to CHOP therapy and achieved a complete remission. This is considered a very rare case of T-cell lymphoma infiltrating multiple skeletal muscles following an episode of hemophagocytic syndrome.

[Right middle cerebral artery occlusion during endovascular embolisation of cerebral aneurysm by Guglielmi detachable coil: a case report].

Right middle cerebral artery embolism by thrombus occurred in 63-year-old female during endovascular embolisation of cerebral aneurysm by Guglielmi detachable coil. Middle cerebral artery occlusion lasted for 60 minute, and haemodynamics was stable during this period. Middle cerebral artery occlusion was detected only by digital subtraction angiography and information from neurosurgeons. Middle cerebral artery blood flow was restored with thrombolytic agents. After tracheal extubation, transient confusion and seizure occurred, but cerebral infarction was not seen in postoperative CT and there was no complication. In case of endovascular embolisation of cerebral aneurysm by Guglielmi detachable coil, systemic heparinization is necessity to decrease the risk of embolism by thrombus, and anesthetist is required to pay attention to cerebral angiography to maintain, close relationship with neurosurgeons and to take measures for cerebral protection.

Heart rate and plasma cyclic AMP responses to isoproterenol infusion and effect of beta-adrenergic blockade in patients with postural orthostatic tachycardia syndrome.

To clarify the pathophysiological mechanism of postural orthostatic tachycardia syndrome (POTS). the responses of heart rate and the plasma cyclic AMP (cAMP) level to isoproterenol infusion in the supine position were evaluated in 10 POTS patients and 10 age-matched controls. Also, the effect of beta-adrenergic blockade on POTS was assessed using the headup tilt test. The POTS patients consisted of two men and eight women, with a mean age of 19.7 years (range. 15-28 years). An exaggerated increase of both heart rate and the plasma cAMP concentration after isoproterenol infusion at a low dose (1 microg/min) was observed in the POTS patients, but not in control subjects. Seven POTS patients received oral beta-blocker therapy. In five of these, symptoms were abolished and there was a smaller heart rate increase during the head-up tilt test. These data suggest that POTS may be more prevalent in young women and that beta-adrenergic hypersensitivity may play a role in the mechanisms of this syndrome. However, a larger series of patients need to be studied in the future.

Tomographical description of tennis-loaded radius: reciprocal relation between bone size and volumetric BMD.

Effects of long-term tennis loading on volumetric bone mineral density (vBMD) and geometric properties of playing-arm radius were examined. Paired forearms of 16 tennis players (10 women) and 12 healthy controls (7 women), aged 18-24 yr, were scanned at mid and distal site by using peripheral quantitative computerized tomography. Tomographic data at midradius showed that tennis playing led to a slight decrease in cortical vBMD (-0.8% vs. nonplaying arm, P < 0. 05) and increase both in periosteal and endocoritcal bone area (+15. 2% for periosteal bone, P < 0.001; and +18.8% for endocortical bone, P < 0.001). These data suggest that, together with an increase in cortical thickness (+6.4%, P < 0.01), cortical drift toward periosteal direction resulted in improvement of mechanical characteristics of the playing-arm midradius. Enlargement of periosteal bone area was also observed at distal radius (+6.8%, P < 0.01), and the relative side-to-side difference in periosteal bone area was inversely related to that in trabecular vBMD (r = -0.53, P < 0.05). We conclude that an improvement of mechanical properties of young adult bone in response to long-term exercise is related to geometric adaptation but less to changes in vBMD.

Endothelial Gi protein expression is markedly low in human coronary microvessels.

Gi protein functionally mediates endothelium-dependent relaxations in large epicardial coronary arteries but not in small coronary arteries, which suggests a different involvement of Gi protein in the endothelium-dependent relaxations between large and small coronary arteries. We previously showed that endothelial Gi protein is present in human epicardial coronary artery. In the present study, we examined the expression of endothelial Gi protein in human coronary microvessels. Immunohistochemical staining with a specific antibody against human Gi protein was performed in intramyocardial coronary microvessels and vasa vasorum from 34 autopsy cases. The immunoreactive levels of the endothelial Gi protein were semiquantitated into four grades (none, 0; slight, +1; moderate, +2; high, +3), and the mean value of the ratings of all endothelial cells was then used as an index of the endothelial Gi protein expression of the vessel. The immunoreactive levels of the endothelial Gi protein were extremely low in intramyocardial coronary microvessels and in vasa vasorum, irrespective of the age of the patients, the presence or absence of coronary risk factors, or the influence of medical treatments. These results may therefore explain in part why endothelium-dependent relaxations in coronary microvessels are not functionally mediated by Gi protein.

Differential changes in alpha- and beta-adrenoceptors in the cerebral cortex and hippocampus of the Mongolian gerbil after unilateral brain ischemia.

BACKGROUND AND PURPOSE: Changes in adrenoceptors in the cerebral cortex and hippocampus of Mongolian gerbils after brain ischemia were investigated. METHODS: Twenty-four hours after unilateral occlusion of the common carotid artery, alpha 1-, alpha 2-, and beta-receptors of the membrane fraction of the cerebral cortex or the hippocampus were analyzed by binding assay with the use of [3H]prazosin, [3H]p-aminoclonidine, and [125I]cyanopindolol as radioligands, respectively. RESULTS: In the cerebral cortex, the number of binding sites (Bmax) and the dissociation constant (Kd) of [3H]prazosin were not altered, whereas the Bmax value of [3H]p-aminoclonidine binding was decreased by 30% and that of [125I]cyanopindolol binding by 16% without a change in Kd values for the ligands. In the hippocampus, the Bmax values of [3H]prazosin, [3H]p-aminoclonidine, and [125I]cyanopindolol bindings were decreased by 21%, 53%, and 19%, respectively, but there was no change in the Kd values for the ligands. The bindings of [3H]prazosin and [3H]p-aminoclonidine of the contralateral side of the cerebral cortex and the hippocampus were not altered by ischemia, but that of [125I]cyanopindolol was decreased when compared with normal tissues. CONCLUSIONS: These results show that ischemia results in a decrease in brain alpha 1-, alpha 2-, and beta-adrenoceptors to various degrees, depending on the brain area and the types of receptors, and suggest that vulnerability of the brain to ischemia is different depending on brain areas and that the regulatory mechanisms of alpha 1-, alpha 2-, and beta-receptors are different.

Effect of lidocaine on alpha 1-adrenoceptors in cultured neonatal rat cardiocytes.

The effect of lidocaine on alpha 1-adrenoceptors in cultured neonatal rat ventricular cardiocytes was studied by binding assay. When the cells were cultured in the presence of lidocaine, the binding of (+/-)-beta-([125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone to the cells increased in a concentration- and time-dependent manner. The effect was due to an increase in maximum binding but not due to a change in the dissociation constant for the ligand. The increased number of alpha 1-adrenoceptors returned to the control level after culturing the cells without lidocaine. The stimulating effect on the number of alpha 1-adrenoceptors of lidocaine was also observed in the presence of norepinephrine. Other class I antiarrhythmic drugs such as procainamide. disopyramide, mexiletine and flecainide increased the number of alpha 1-adrenoceptors in the cells. These results suggest that cardiac responsiveness mediated by alpha 1-adrenoceptors is increased by class I antiarrhythmic drugs.

Lidocaine increases the number of beta-adrenoceptors in neonatal rat cardiocytes in culture.

Some physiological functions of the heart are modulated through cardiac beta-adrenoceptors. In acute myocardial infarction, ventricular arrhythmias occur frequently and class I antiarrhythmic drugs such as lidocaine are often administered continuously over long period. The aim of this study was to investigate the effects of long-term treatment with lidocaine on cardiac beta-adrenoceptors. Ventricular cardiocytes from 2-day-old Wistar rat were cultured in the presence or absence of lidocaine, and beta-adrenoceptors of the membrane fraction of the cells were measured with a binding assay using [125I]-iodocyanopindolol ([125I]CYP) as a radioligand. When the cells were cultured in the presence of lidocaine at clinical or toxic concentrations, the binding of [125I]CYP to the cells increased in a concentration (10(-5) mol/l-10(-3) mol/l)--and time (12-72 h)--dependent manner. The effect was due to an increase in maximum binding and was not due to a change in the dissociation constant for the ligand. The stimulation of adenylyl cyclase activity in the cell membrane by 1 mumol/l isoproterenol increased in lidocaine-treated cells. The increased number of receptors returned to the control level when the cells were cultured without lidocaine for a further 24 h. These results indicate that lidocaine up-regulates cardiac beta-adrenoceptors at both clinical or toxic doses during the period of treatment. Other antiarrhythmic drugs such as disopyramide (Ia), mexiletine (Ib) and flecainide (Ic) also increased the number of beta-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Antidepressant effect of lithium in patients with systemic lupus erythematosus and cerebral infarction, treated with corticosteroid.

Two depressive patients with systemic lupus erythematosus (SLE) and cerebral infarction, while being treated with corticosteroid, are described. In both cases, lithium was remarkably effective and no severe side-effects occurred. These findings suggest that lithium can be a useful antidepressant agent in the treatment of depressive SLE patients.

Receptors for C-type natriuretic peptide in cultured rat glial cells.

To characterize sites of action of C-type natriuretic peptide (CNP) in the glial cells, the effect of CNP on cGMP accumulation and the binding of [125I]CNP in rat astrocyte RCR-1 cells were studied. CNP stimulated cGMP accumulation in the cells from 10(-9) M in a dose-dependent manner, but ANP (atrial natriuretic peptide) had a negligible effect on cGMP accumulation in the cells. [125I]CNP was bound to the cells and its Kd value was 2 orders of magnitude lower than that of the ED50 value for stimulation of cGMP accumulation in the cells. Not only CNP but also ANP displaced [125I]CNP binding to the cells. These results suggest that RCR-1 cells have a B-receptor which contains a guanylate cyclase domain and is preferentially activated by CNP, and that they also have a C-receptor which does not contain a guanylate cyclase domain that reacts with both ANP and CNP.

Cell-cell contact modulates expression of cell adhesion molecule L1 in PC12 cells.

The effect of cell contact on the expression of cell adhesion molecule L1 was investigated. The rat pheochromocytoma cell line PC12 cells were cultured at various densities in the presence or absence of the nerve growth factor. The addition of the nerve growth factor promoted the expression of L1. The expression of L1 was higher when the cells were cultured at high density than when done at low density both in the presence or absence of the nerve growth factor. Immunohistochemical staining of L1 showed that the expression of L1 was higher in the cells contacting each other. These results show that cell interaction affects the expression of cell adhesion molecule L1 in the PC12 cells.

Veratridine causes the Ca(2+)-dependent increase in diacylglycerol formation and translocation of protein kinase C to membranes in cultured bovine adrenal medullary cells.

Our previous studies suggested that protein kinase C is involved in the veratridine (an activator of voltage-dependent Na+ channels)-induced phosphorylation and activation of tyrosine hydroxylase as well as the synthesis of catecholamines in adrenal medulla (Uezono et al. 1989). In the present study, we investigated whether treatment of cultured bovine adrenal medullary cells with veratridine causes the accumulation of diacylglycerol, a physiological activator of protein kinase C and the translocation of protein kinase C from cytosol to membrane, a process required for protein kinase C activation. Veratridine (100 mumol/l) increased diacylglycerol level about 2.2 fold in a monophasic manner, with peaking at 5 min and declining toward the basal level within 20 min. Veratridine also increased membrane protein kinase C from 15.6% to 26.9% of total protein kinase C in a time-course similar to that of diacylglycerol accumulation. Both stimulatory effects of veratridine were inhibited by tetrodotoxin and not observed in Ca(2+)-free, EGTA-containing medium. Amiloride, an inhibitor of Na+/Ca2+ and Na+/H+ exchange, did not alter veratridine-induced events. These results suggest that veratridine-induced Ca2+ influx contributes to the accumulation of diacylglycerol and the activation of protein kinase C in adrenal medullary cells.

Subtypes of protein kinase C in rat cerebral microvessels.

Protein kinase C in rat cerebral microvessels was characterized. By hydroxyapatite column chromatography, protein kinase C in the soluble fraction was resolved into two major peaks corresponding to type II and III enzymes, in the proportion of 57% and 38%, respectively. Since each subtype is considered to have a distinct role, the high proportion of type II enzyme found in this study suggests that this type may be involved in specific functions of the cerebral microvessels.

Evaluation of autoSCAN-W/A automated microbiology system for the identification of non-glucose-fermenting gram-negative bacilli.

We evaluated the ability of the autoSCAN-W/A (MicroScan Division, Baxter Healthcare Corporation, West Sacramento, Calif.), in conjunction with the dried colorimetric Neg ID type 2 panel (DCP) and new rapid fluorometric Neg ID panel (RFP), to identify non-glucose-fermenting gram-negative bacilli by challenging the system with 310 previously identified reference strains. Of these 310 isolates, 286 organisms were in the DCP data base and 269 were in the RFP data base. Use of the DCP panels resulted in 118 (41.3%) correct and 64 (22.4%) incorrect first choice identifications at greater than or equal to 85% probability, 61 (21.3%) low-probability identifications, and 43 (15.0%) reports of unidentified organisms. The RFP system reported 135 (50.1%) correct and 25 (9.3%) incorrect identifications at greater than or equal to 85% probability and 109 (40.5%) low-probability identifications. Unidentified isolates (DCP system only) and isolates producing low-probability first choice identifications (both systems) required supplementary biochemical testing. Over half (37 of 64 [57.8%]) of the DCP misidentifications were due to four commonly isolated, saccharolytic organisms (Alcaligenes xylosoxidans subsp. xylosoxidans, Pseudomonas putida, Pseudomonas fluorescens, and Xanthomonas maltophilia), while 7 of 25 (28%) of misidentifications in the RFP system were due to P. fluorescens. Of note, the RFP system identified non-glucose-fermenting gram-negative bacilli within 2 h of panel inoculation, allowing additional conventional biochemical tests to be set up the same day on low-probability isolates, whereas only 13.5% of the DCPs could be read at 18 h, with the remainder requiring 42 h of incubation before reading. When organism identifications were recalculated with the updated RFP data base and revised software, only 8.1% of all 310 isolates were misidentified at greater than or equal to 85% probability while 77.1% of the isolates were now correctly reported at this same high probability.

Protein kinase C subtypes in tissues derived from neural crest.

Subtypes of protein kinase C were determined in tissues derived from neural crest. The bovine adrenal medulla and rat superior cervical ganglia contained type III enzyme as the major subtype with a small amount of type II enzyme. In PC12 cells, treated with or without nerve growth factor, type III was the major subtype but a minor peak which is distinct from types II and III was observed. These results show that the type III enzyme is prevalent in various differentiation stages of neural crest and suggest that the enzyme relevant to the regulation of catecholamine synthesis and release in these cells is type III.

Sustained-release diltiazem in patients with effort angina and severe coronary artery sclerosis.

Two case histories are presented. Patient 1 was an agricultural worker, aged 63 years, whose attacks of chest pain, diagnosed as effort angina, were relieved by sublingual nitroglycerin. An exercise test revealed ST segment depression of 2 mV in lead V5 of the electrocardiogram. Coronary arteriography disclosed 99% stenosis with delay in segments 7 and 14, 90% stenosis in segment 10, and 25% stenosis in segment 1. Treatment with 100 mg of sustained-release diltiazem relieved some of the symptoms; when the dose was increased to 200 mg daily, no further chest pains were experienced. Patient 2 was a restaurant owner, aged 61 years, who reported attacks of chest pain during physical work. An exercise test revealed ST segment depression of 2 mV in lead aVF; coronary arteriography showed 99% stenosis in segment 7, 75% stenosis in segment 9, and 50% stenosis in segment 10. No attacks of chest pain were experienced after treatment with 200 mg of sustained-release diltiazem daily. Blood pressure, heart rate, and the rate-pressure product fell in both patients after diltiazem treatment.