The relationships between autonomic function and heart rate in essential hypertension

The circadian variation of blood pressure (BP) may be mediated at least in part by circadian variation of autonomic nervous system activity. In the present study power spectral analysis of hourly R-R intervals for 24 hours was done to obtain the low frequency variability (LF: 0.04 to 0.15Hz) and high frequency variability(HF: 0.15 to 0.40Hz) in 93 patients with untreated essential hypertension. LF/HF ratio and HF were considered to be an index of sympathetic nervous activity and parasympathetic nervous activity, respectively. The relationship between heart rate (HR) and systolic blood pressure (SBP), diastolic blood pressure (DBP), HF, and LF/HF was examined. Both SBP and DBP were correlated positively with HR(r = 0.28, p < 0.05 and r = 0.27, p < 0.05, respectively) in the daytime. HF was correlated negatively and significantly with HR in both daytime and nighttime (r = -0.40, p < 0.05, and r = -0.38, p < 0.05 respectively). After averaging for SBP of 24 hours, HR in the patients whose SBP was 135mmHg or more was significantly higher than that in the patients whose SBP was less than 135mmHg. These results suggest that the decreased parasympathetic nervous activity seems to be responsible for the rise in BP.     

Male with type II autosomal recessive cutis laxa

A 5-year-old boy, who had pre- and postnatal growth retardation, delayed motor development, cutis laxa, delayed closure of large fontanels, congenital hip dislocation and characteristic facies, is described. Disorders with cutis laxa are now divided into five types. The patient had clinical manifestations very similar to those of cutis laxa with bone dystrophy (type II autosomal recessive cutis laxa). Eighteen patients have been reported, the ratio of males to females being 5 to 14. This is the fifth case of this disorder occurring in a male, which provides further evidence for autosomal recessive inheritance.     

New medical education of laboratory medicine at Tohoku University

The purpose of this paper is to give an insight into the medical education program of our division at Tohoku University. Laboratory medicine in medical education is a field of learned basic clinical tests. Students have to learn the clinical laboratory through early clinical exposure in the first grade and try clinical technology through small-group learning in the fifth grade. Finally, they learn laboratory medicine such as infection control in our or another clinical hospital. The objects of our course are to encourage and promote the highest standards of training and post-graduate education of physicians and scientists at our university.     

Chronic myelogenous leukemia with a complex Ph1 translocation in an XYY male

We encountered a 38-year-old Japanese male patient with chronic myelogenous leukemia (CML), whose bone marrow and peripheral blood cells during the chronic and blastic phases contained a complex Ph¹ translocation and an extra Y chromosome [i.e., 47,XYY,t(9;22;13)(q34;q11;q14)]. A karyotypic analysis of PHA-stimulated lymphocytes showed the constitutional karyotype to be 47,XYY. Thus, it was considered that CML with a complex Ph¹ translocation developed in an XYY male; such a case has not been reported, so far. A B-lymphocyte cell line with the complex Ph¹ translocation was established by the procedure of Epstein-Barr virus transformation. The presence of the complex Ph¹ translocation in the B-lymphocyte cell line suggests that some of the B lymphocytes in this patient originated from the CML clone.     

Gastric juvenile polyposis associated with germline SMAD4 mutation

We treated a 39-year-old woman with hypoproteinemia and anemia who had profuse gastric polyposis. Radiographic and endoscopic examination showed numerous polyps restricted to the stomach. The patient had pulmonary arteriovenous malformations in the left lung. Histological examination of the resected stomach revealed the gastric polyposis to be composed of cystic dilatation of the glands with small areas of adenocarcinoma. These findings were compatible with gastric juvenile polyposis (GJP) accompanied by gastric cancer. Analysis of genomic DNA revealed that the patient had truncating mutation of SMAD4, a responsible gene for juvenile polyposis (JP). Our case suggests that SMAD4 is possibly a responsible gene for GJP.     

Effect of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes—A possible role of increased oxygen radicals generated by the neutrophils

Neutrophils from the synovial fluid (SFN) of 10 patients with active rheumatoid arthritis (RA) were investigated to determine the generation of oxygen intermediates (OI) (O2-, H2O2, OH .), chemiluminescence, and lysosomal enzymes (lysozyme and beta-glucuronidase). Lymphocytes from healthy individuals were cocultured at 37 degrees C for 17 hr with SFN from the patients and the number of OKT4+, OKT8+, and OKT3+ cells and the response to mitogens were determined. A markedly increased OI and slightly elevated lysosomal enzyme levels were observed in SFN from patients. Coculture of lymphocytes with SFN resulted in a decreased number of OKT4+ and OKT8+ cells and a greatly reduced response to Con A and mildly diminished response to PHA, while OKT3+ cells were not affected. The simultaneous addition of superoxide dismutase and catalase restored the impairment of monoclonal antibody reaction and lymphocyte responsiveness almost to control levels. It is suggested that the disturbed immunoreactivity of synovial fluid lymphocytes from RA patients may be due to increased OI generated by stimulated neutrophils.     

Effect of Azelastine Hydrochloride on Macrophage Chemotaxis and Phagocytosis in Vitro

Azelastine, a newly synthesized anti-allergic agent, was tested for its effects on guinea pig macrophage chemotaxis and phagocytosis. As specific macrophage chemo-attractants, we used macrophage chemotactic factors a and c; separated and highly purified from inflamed skin sites. Macrophage chemotaxis induced by skin extract or chemotactic factors was significantly suppressed by a low concentration of the agent (1 microgram/ml); the effect was dose-dependent. The inhibition of chemotaxis was reversible, because chemotactic activity was restored when the agents was removed by washing cells before chemotactic assay. Inactivation of chemotactic factors was not detected by mixing azelastine and factors a and c. Azelastine may directly interact with macrophages to decrease their chemotactic responsiveness. beta-Glucuronidase activity in the medium and macrophages after phagocytosis of polystyrene latex particles was not affected by this agent at concentrations ranging from 1 to 10 micrograms/ml. The phagocytosis of latex particles or sheep red blood cells opsonized with IgG antibodies (EA) and anchoring of macrophages to substrate were not inhibited and azelastine did not damage the macrophages as determined by lactate dehydrogenase (LDH) release assay.     

Computational studies on acquisition and adaptation of ocular following responses based on cerebellar synaptic plasticity

To investigate how cerebellar synaptic plasticity guides the acquisition and adaptation of ocular following response (OFR), a large-scale network model was developed. The model includes the cerebral medial superior temporal area (MST), Purkinje cells (P cells) of the ventral paraflocculus, the accessory optic and climbing fiber systems, the brain stem oculomotor network, and the oculomotor plant. The model reconstructed temporal profiles of both firing patterns of MST neurons and P cells and eye movements. Model MST neurons (n = 1,080) were set to be driven by retinal error and exhibited 12 preferred directions, 30 preferred velocities, and 3 firing waveforms. Correspondingly, each model P cell contained 1,080 excitatory synapses from granule cell axons (GCA) and 1,080 inhibitory synapses. P cells (n = 40) were classified into four groups by their laterality (hemisphere) and by preferred directions of their climbing fiber inputs (CF) (contralateral or upward). The brain stem neural circuit and the oculomotor plant were modeled on the work of Yamamoto et al. The initial synaptic weights on the P cells were set randomly. At the beginning, P cell simple spikes were not well modulated by visual motion, and the eye was moved only slightly by the accessory optic system. The synaptic weights were updated according to integral-differential equation models of physiologically demonstrated synaptic plasticity: long-term depression and long-term potentiation for GCA synapses and rebound potentiation for inhibitory synapses. We assumed that maximum plasticity was induced when GCA inputs preceded CF inputs by 200 ms. After more than 10,000 presentations of ramp-step visual motion, the strengths of both the excitatory and inhibitory synapses were modified. Subsequently, the simple spike responses became well developed, and ordinary OFRs were acquired. The preferred directions of simple spikes became the opposite of those of CFs. Although the model MST neurons were set to possess a wide variety of firing characteristics, the model P cells acquired only downward or ipsilateral preferred directions, high preferred velocities and stereotypical firing waveforms. Therefore the drastic transition of the neural representation from the population codes in the MST to the firing-rate codes of simple spikes were learned at the GCA-P cell synapses and inhibitory cells-P cell synapses. Furthermore, the model successfully reproduced the gain- and directional-adaptation of OFR, which was demonstrated by manipulating the velocity and direction of visual motion, respectively. When we assumed that synaptic plasticity could only occur if CF inputs preceded GCA inputs, the ordinary OFR were acquired but neither the gain-adaptation nor the directional adaptation could be reproduced.     

Hydrogen peroxide-induced Ca responses in CNS pericytes

Objective: The aims of the present study were to elucidate the interaction of reactive oxygen species (ROS) and Ca²⁺ response in central nervous system (CNS) pericytes. Methods: The intracellular Ca²⁺ concentration was measured using fluorescent Ca²⁺ indicator, fura-2, in cultured CNS pericytes. Results: Hydrogen peroxide evoked a dose-dependent increase in cytosolic Ca²⁺, which was completely inhibited by catalase. Removal of external Ca²⁺ or addition of nicardipine (1 μM) during application of hydrogen peroxide did not affect Ca²⁺ response. Incubation of the cells in Ca²⁺ free solution did not abolish but slightly reduced Ca²⁺ response by hydrogen peroxide. Ca²⁺ response to hydrogen peroxide was not altered by the depletion of intracellular Ca²⁺ by thapsigargin (1 μM). Pretreatment of the cells with tyrosine kinase inhibitor genistein (100 μM) or tyrphostin A47 (30 μM) significantly reduced Ca²⁺ increase by hydrogen peroxide. Conclusions: These results indicate that hydrogen peroxide evokes Ca²⁺ increase predominantly by release from intracellular Ca²⁺ store, which may be regulated by tyrosine kinases.     

A new balloon catheter for selective cerebral perfusion

Selective cerebral perfusion (SCP) is a better method than hypothermic circulatory arrest for brain protection in aortic arch surgery because of fewer time limitations; however; it is more troublesome during surgery. We developed a new catheter for SCP, the SP Stud catheter, with a rib-surface balloon to reduce slipping to eliminate the need for snaring or clamping. To evaluate the slipping resistance of the new catheter, we compared it with two different balloon catheters; a Foley balloon catheter with a smooth-surface balloon as long as the SP Stud catheter, and a Retro-TH catheter with a smooth-surface balloon of discoid shape half as long as the SP Stud catheter. The “draw-strength”, which refers to the slipping resistance, was measured in 20 autopsy carotid arteries in the three groups. The average draw-strengths of SP Stud catheter, foley balloon catheter, and Retro-TH catheter were 92.3±4.0, 20.8 ±1.5, and 17.9±0.8g, respectively, in sclerotic carotid arteries. The SP Stud catheter demonstrated approximately four times more resistance to slipping than the Foley balloon or Retro-TH catheters. The SP Stud catheter demonstrated a higher slipping resistance than conventional catheters, which may allow selective cerebral perfusion without snaring or clamping the carotid arteries, minimize the change of cerebral embolism, and clear the operative field.