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To study myocardial contractility in hypertensive hearts with normal wall motion, we examined left ventricular end-systolic wall stress-dimension relationships (ESWDR) during a baseline period (CS: control stage) and in the eighth week after induction of systemic hypertension by Page's method (HS: hypertensive stage) in unanesthetized dogs. The mean aortic blood pressure increased from 94 +/- 11 to 142 +/- 26 mmHg (p less than 0.01). The end-diastolic left ventricular posterior wall thickness increased significantly during the HS (9.4 +/- 1.3 vs 7.3 +/- 1.3 mm; HS vs CS), and its dimension was significantly (p less than 0.05) smaller than it was during the CS (37.0 +/- 4.2 vs 39.9 +/- 4.6 mm; HS vs CS). There were no significant differences between the 2 stages in left ventricular fractional shortening (31.9 +/- 5.0 vs 32.6 +/- 2.8; HS vs CS), in end-systolic meridional left ventricular wall stress (75.3 +/- 10.8 vs 68.3 +/- 15.6 10(3) dynes/cm2; HS vs CS), or in the ESWDR slopes (98.6 +/- 17.7 vs 94.0 +/- 19.7; HS vs CS). The ESWDR dimension intercepts significantly decreased from 2.0 +/- 0.3 to 1.8 +/- 0.3 cm during the HS; that is, the relationship shifted to the left with no significant change in the slope. At autopsy, the ratio of left ventricular weight to body weight of the hypertensive dogs was significantly (p less than 0.01) greater than that of sham-operated control dogs (6.0 +/- 0.9 vs 4.3 +/- 0.5 g/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

The development of nocturnal sleep of 79 mentally retarded children and adolescents (from 6 months to 20 years of age) was studied. Polygraphic recordings were carried out while the subject was in bed, and routine sleep parameters were measured. Total sleep time and percentage of Stage REM (rapid eye movements) decreased and awake time tended to increase with age. These values were similar to those previously found for age-matched nonretarded subjects. Results showed that the basic function of the sleep-waking system of retarded children seems to develop normally with age.

Right ventricular function was assessed at rest and during exercise in patients with chronic obstructive pulmonary disease (COPD). Right ventricular ejection fraction (RVEF) was measured by first-pass radionuclide angiography using ultrashort-lived radionuclide krypton-81m. The half-life of this nuclide is only 13 sec, and it is completely expired from the lungs. These properties allow measurement of RVEF without correcting for background activity. In 30 patients with cardiac or pulmonary disease, RVEF was first measured by krypton-81 m scintigraphy (Kr-RVEF), then by technetium-99m (Tc-RVEF), without changing the patients' positions. In eight of the 30 cases, right ventricular cineangiography (RVG) was performed within 72 hrs after the radionuclide study, and RVEF was measured according to the Chapman's rule (RVG-RVEF). Kr-RVEF correlated significantly with Tc-RVEF (r = 0.87), and also with RVG-RVEF (r = 0.80). In 10 patients with stable COPD, who had severe hypoxemia (PaO2 less than or equal to 60 mmHg) and pulmonary hypertension [mean pulmonary arterial pressure (mean PAP) greater than or equal to 20 mmHg], and in seven normal control subjects, radionuclide angiographic and hemodynamic monitoring were performed at rest and during supine ergometer exercise. Kr-RVEF at rest was 47.6 +/- 5.4% (mean +/- SD) in patients with COPD and was 54.1 +/- 4.8% in normal subjects. Kr-RVEF during exercise was 51.8 +/- 7.3% in the patients, and 62.3 +/- 3.2% in the normal subjects. Hemodynamically, mean PAP and pulmonary vascular resistance (PVR) increased significantly during exercise, but the RV end-diastolic volume index (RVEDVI) did not change. There was inverse correlation between Kr-RVEF and mean PAP (r = -0.51) or PVR (r = -0.47) as an index of RV afterload. However, there was no correlation between Kr-RVEF and RVEDVI as an expression of RV preload. These findings suggest that a poor response by RVEF during exercise in patients with COPD is associated with elevation of afterload. Thus, right ventricular imaging techniques using the ultrashort-lived nuclide krypton-81 m allow noninvasive, serial and accurate assessments of right ventricular function in patients with COPD.

To determine the mechanism for prolongation of pre-ejection period (PEP) in the hypertensive heart with normal systolic function, cardiac catheterizations, echocardiograms, and electrocardiograms were performed at the baseline period (CS, control stage) and eight weeks (HS, hypertensive stage) after the induction of systemic hypertension by Page's method in unanesthetized dogs. Mean aortic blood pressure increased significantly (96 +/- 12 to 137 +/- 26 mmHg) (p less than 0.05). Diastolic aortic pressure also increased significantly (80 +/- 12 to 118 +/- 24 mmHg) (p less than 0.01). Left ventricular (LV) PEP of HS was significantly prolonged (72 +/- 12 vs. 87 +/- 22 ms, CS vs. HS). The ratio of LV pre-ejection period to ejection time (PEP/ET) also increased significantly (0.33 +/- 0.04 to 0.42 +/- 0.07) (p less than 0.05). LV end-diastolic wall stress as an index of preload decreased significantly (7.7 +/- 2.5 vs. 5.9 +/- 1.8 10(3) dynes/cm2, CS vs. HS). Heart rate, mean velocity of circumferential fiber shortening (VCF) and end-systolic wall stress of HS did not change. That is, myocardial contractility in the hypertensive heart of HS most likely is not depressed. At autopsy, left ventricle to body weight ratio of HS was significantly (p less than 0.01) greater than the sham-operated dogs (5.7 +/- 0.8 vs. 4.3 +/- 0.5 g/kg). From these findings, there are two possible factors responsible for prolongation of PEP of HS. First, elevated diastolic aortic pressure may influence PEP. Second, the prolonged PEP is possibly caused by the decrease of preload.(ABSTRACT TRUNCATED AT 250 WORDS)

A 56-year-old Japanese man was admitted to the hospital with a large mass in his right axilla. Histological investigation revealed that it was a Burkitt's lymphoma. Ultrastructures of the tumor cells showed immature lymphoid features with frequent lipid droplets within the cytoplasms. Virological studies before the treatment revealed that the lymphoma was closely related to EB virus infection, being positive for EBNA (more than 95% of all tumor cells) and IgG antibodies to VCA (X 5,120), EA (X 640), and EBNA (X 160). The tumor cells exhibited low levels of cytoplasmic IgM and other properties of B cells. They were positively stained with L26, L27, Leu 14, and HLA-DR MAb. In cultured tumor cells, L25 and CALLA antigens were demonstrated, but no surface Ig was shown. In contrast, the tumor cells were negative for T cell markers including AcP, E-receptor, and Leu 1, 2, and 3. Cytogenetic studies demonstrated that the karyotype of the tumor cells was 46, XY, dup (1q), t(2;8)/46, X, -Y, t(2;8), +mar. VEMP therapy was immediately conducted. However, following a two-month partial remission, a relapse with bone marrow infiltration occurred. Thus, a case of Japanese Burkitt's lymphoma with EBNA (+) and t(2;8) properties is described, and the relationships among primary sites, phenotypes, and genotypes are discussed.

The effects of 1,2-benzisoxazole-3-methanesulfonamide (zonisamide, AD-810, CI-912), an antiepileptic compound, on the cardiovascular, visceral, renal and blood functions were compared with those of carbamazepine and, in part, acetazolamide in experimental animals. 1. Zonisamide (30 mg/kg i.v.) transiently lowered the blood pressure and decreased the blood flows in the carotid and femoral arteries in anesthetized dogs. The effects were 3 times less potent than those of carbamazepine, Zonisamide, when orally administered, did not affect the blood pressure even at 300 mg/kg in conscious rats. 2. Zonisamide little affected the autonomic nervous system even at high doses. In anesthetized cats, contractions of the nictating membrane by electrical stimulation of the cervical sympathetic nerve, pressor responses to norepinephrine, and depressor responses to acetylcholine, all were not modified with zonisamide (100 mg/kg i.v.). In isolated guinea-pig ileum, contractions induced by acetylcholine, histamine and bradykinin were not affected by zonisamide up to a concentration of 10(-3) g/ml zonisamide, although those by serotonin and nicotine were depressed with high concentrations over 10(-5) g/ml. 3. With 100 mg/kg p.o., zonisamide decreased the gastric juice volume and pH in pylorus ligated rats, and depressed gastric emptying in rats, but did not inhibit the intestinal transit of charcoal meal in mice. These effects were less potent than those of carbamazepine. 4. Zonisamide increased the urine volume, pH, and Na+ and K+ concentrations in rats and anesthetized dogs. The renal blood flow and glomerular filtration rate were little changed with the high doses of zonisamide.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of 1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine (alacepril, DU-1219), an orally active angiotensin converting enzyme inhibitor, on the central nervous and sensory systems and on several other functions were compared with those of captopril in the experimental animals. Alacepril at the high oral dose of 600 mg/kg prolonged the hexobarbital sleeping time and potentiated the reserpine-induced hypothermia in mice. However, alacepril at the same dose did not affect the general behavior, convulsions induced by maximal electroshock, pentetrazol and strychnine, active avoidance in mice and body temperature in rats. In addition, alacepril (200 mg/kg i.v.) has little effect on general behavior in mice. Captopril at over 107 mg/kg p.o. produced eyelid closure and at 320 mg/kg prolonged the hexobarbital sleeping time. A metabolite of alacepril, desacetylalacepril (DU-1227) (200 mg/kg i.v.), caused salivation in mice. Alacepril and DU-1227 at 60 mg/kg i.v. were without effect on flexor reflex and spontaneous electroencephalogram (EEG) in cats, while captopril at the equimolar dose depressed the flexor reflex and showed a tendency to increase the beta 2-band relative power of the cortical EEG. Alacepril and captopril neither affected the writhing syndrome induced by acetic acid nor that by phenylquinone in mice. Local anesthetic and irritant activities in rabbits and effect on neuromuscular junction in anesthetized rats were not observed with the two compounds. Alacepril at the oral dose of 0.1 mg/kg potentiated the carrageenin-induced edema in rats. However, the effect was one third that of captopril. Alacepril and captopril did not affect the increased vascular permeability by acetic acid in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

The immune response to bovine insulin (BI) in the rat is controlled by the major histocompatibility complex (Mhc)-linked immune response gene (Ir-BI) and immune suppression gene (Is-BI). In the present study, we investigated the low responsiveness to BI in the WKAH rat (RT1k) and attempted to explore the functional link between Is-BI and Mhc class II molecules. Lymph node cells (LNC) from the low responder (WKAH) rats responded well to BI when a large amount of antigen was added to the culture in vitro or after OX8-bearing (OX8+) T cells were eliminated. These LNC, after the elimination of OX8+ cells, could show the RT1.Dk-restricted proliferative response upon in vitro challenge with BI, BI-B chain, or pork insulin. In addition, OX8+ T cells, which were activated with BI and antigen-presenting cells (APC) in vitro, suppressed the anti-BI response of W3/25-bearing proliferating T cells from BI-immunized rats. The results have demonstrated that proliferating T-cell repertoires do exist to BI, which recognize BI-B chain in the context of RT1.Dk molecules in the WKAH rat, and that the state of low responsiveness is mediated to a great extent by antigen-specific OX8+ suppressor T (Ts) cells. Furthermore, the elimination of APC or the addition to RT1.Bk-specific monoclonal antibody in the in vitro secondary activation culture of Ts cells diminished the suppressive activity of OX8+ Ts cells. In the induction phase of Ts cells it therefore seems to be necessary for these cells to recognize BI together with RT1.Bk molecules on APC.

Characterization of beta-thalassemia mutations were attempted for 29 Japanese families clinically diagnosed as having beta-thalassemia. Following the identification of a mutation by cloning and sequencing, all families were screened for this particular mutation, using biotinylated allele-specific oligonucleotide probes. Seven different mutations were detected in 17 families: Six families had the frameshift mutation at codons 41/42, resulting from a 4 nucleotide deletion (TTCTTT----TT); four had the deletion at codons 127/128 (CAGGCT----CCT); and three had the TATA box mutation at nucleotide -31 (A----G). Four additional families had mutations at codon 24 (GGT----GGA), codon 26 (GAG----AAG), IVS-II-654 (C----T) and codon 110 (GTG----CCG), respectively. The newly discovered deletion mutation at codons 127/128, and mutations at nucleotide -31, and at codon 110 are peculiar to Japanese, and have not been found in any other ethnic group. The haplotypes of the beta-globin gene cluster were also determined. Some of the haplotypes and beta-thalassemia mutations are identical to those reported in the Chinese population. However, it is noteworthy that nearly half of the beta-thalassemia mutations were unique to Japanese.

Spontaneous extracranial metastases of glioblastoma multiforme in the absence of previous surgery have been rarely reported (Table 1). We presented an autopsy case of glioblastoma multiforme which spontaneously metastasized to the lungs, bronchial lymph nodes, liver, kidney, heart and spleen. A 68-year-old man was admitted to the Department of Neurosurgery at our hospital with chief complaints of right sided weakness in July 1984. He was well until November 1983, when he noticed weakness of right lower extremity followed one month later by the weakness in the right arm. He was treated at another hospital under the diagnosis of cerebral infarction, but his right sided weakness gradually progressed. In June 1984, a diagnosis of brain tumor was made by the neurological findings and CT scan, and he was transferred to our hospital for further evaluation and treatment. Neurological examination revealed disorientation, bilateral papilledema, right hemiparesis, right hyperreflexia and right hemisensory disturbance. CT scan revealed abnormal low density area in the left fronto-parietal lobe (Fig. 1) with irregular enhanced lesions on contrast CT scan (Fig. 2). Chest x-ray showed abnormal shadow in the right middle and lower lobe (Fig. 3) and a diagnosis of pulmonary infarction was suspected. The clinical states of this patient took downhill course and he expired on July 13, 1984 by the complication of disseminated intravascular coagulation syndrome. The brain weight was 1400 gr. Dura mater and falx cerebri were tightly adherent to the left parietal lobe (Fig. 4). Primary brain tumor was found in the left fronto-parietal region. The tumor was poorly defined with necrosis and hemorrhage (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS)

A beta+-thalassemia mutation at codon 24 (GGT----GGA) was discovered in a Japanese; this is the third type of beta-thalassemia found in this population. The case, as well as the data from DNA sequencing analysis, are presented.

In recent years, because of advances in diagnostic techniques and therapy for malignant tumors, it is not rare to encounter cases of primary multiple malignant neoplasms. However, triple cancer is still rare. We report a case of triple cancer--gastric cancer, sigmoid colon cancer and malignant fibrous histiocytoma. To our regret, we could not make a diagnosis while the patient was alive. Careful examination of a cancer patient is important because malignant tumors may develop at any time.

The effects of 1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine (alacepril, DU-1219) an antihypertensive compound with angiotensin converting enzyme inhibitory activity, and its metabolite, desacetyl-alacepril (DU-1227), on the cardiovascular and autonomic nervous systems and on the blood were compared with those of captopril in the experimental animals. Alacepril and DU-1227 at the i.v. dose of 10 mg/kg gradually lowered the diastolic blood pressure in pentobarbital anesthetized dogs. Captopril showed similar effects. However, the former two compounds showed triphasic effects on the carotid blood flow, i.e., transient increase immediately after the injection, second increase 2 min later, and gradual decrease 20-30 min later. The second increase by DU-1227 was more potent than that by alacepril. Alacepril, DU-1227 and captopril did not affect the pressor responses induced by norepinephrine in anesthetized cats. The contractions of the nictitating membrane in cats induced by electrical stimulation of the cervical sympathetic nerve or epinephrine were depressed with high doses of these three compounds. Captopril potentiated the contractions induced by bradykinin in isolated guinea-pig ileum, while alacepril and DU-1227 were without effect. These three compounds neither affected the resting tension of isolated ileum in guinea-pigs and rabbits nor the contractions induced by acetylcholine, histamine, serotonin and nicotine of isolated guinea-pig ileum. Alacepril at the oral dose of 60 mg/kg decreased the total acidity in pylorus ligated rats, and at higher doses depressed the intestinal charcoal meal passage in mice. Alacepril at comparatively low doses decreased the urine volume with slight reduction of Na+ and K+ excretions in saline-loaded rats.(ABSTRACT TRUNCATED AT 250 WORDS)