Modulation of the control of muscle sympathetic nerve activity during severe orthostatic stress

We tested the hypothesis that arterial baroreflex (ABR)-mediated beat-to-beat control over muscle sympathetic nerve activity (MSNA) is progressively modulated as orthostatic stress increases in humans, but that this control becomes impaired just before the onset of orthostatic syncope. In 17 healthy subjects, the ABR control over MSNA (burst incidence, burst strength and total MSNA) was evaluated by analysing the relationship between beat-to-beat spontaneous variations in diastolic blood pressure (DAP) and MSNA during supine rest (control) and during progressive, stepwise increases in lower body negative pressure (LBNP) that were incremented by −10 mmHg every 5 min until presyncope (nine subjects) or −60 mmHg was reached. (1) The linear relationships between DAP and burst strength and between DAP and total MSNA were shifted progressively upward as LBNP increased until the level at which syncope occurred. The relationship between DAP and burst incidence, however, gradually shifted upward from control only to LBNP =−30 mmHg; there was no further upward shift at higher LBNPs. (2) Although the slope of the relationship between DAP and burst strength and between DAP and total MSNA remained constant at all LBNPs tested, except at the level where syncope occurred, the slope of the relationship between DAP and burst incidence was reduced at LBNPs of −40 mmHg and higher ( versus control). (3) In syncopal subjects, the slopes of the relationships between DAP and burst incidence, burst strength, and total MSNA were all substantially reduced during the 1–2 min period prior to the onset of syncope. Taken together, these results suggest baroreflex control over MSNA is progressively modulated as orthostatic stress increases, so that its sensitivity is substantially reduced during the period immediately preceding the severe hypotension associated with orthostatic syncope.     

Radiotelemetry recording of electroencephalogram in piglets during rest

A wireless recording system was developed to study the electroencephalogram (EEG) in unrestrained, male Landrace piglets. Under general anesthesia, ball-tipped silver/silver chloride electrodes for EEG recording were implanted onto the dura matter of the parietal and frontal cortex of the piglets. A pair of miniature preamplifiers and transmitters was then mounted on the surface of the skull. To examine whether other bioelectrical activities interfere with the EEG measurements, an electrocardiogram (ECG) or electromyogram (EMG) of the neck was simultaneously recorded with the EEG. Next, wire electrodes for recording movement of the eyelid were implanted with EEG electrodes, and EEG and eyelid movements were simultaneously measured. Power spectral analysis using a Fast Fourier Transformation (FFT) algorithm indicates that EEG was successfully recorded in unrestrained piglets, at rest, during the daytime in the absence of interference from ECG, EMG or eyelid movements. These data indicate the feasibility of using our radiotelemetry system for measurement of EEG under these conditions.     

Roles of p38 mitogen-activated protein kinase,NF-kappaB,and protein kinase C in proinflammatory cytokine mRNA expression by human peripheral blood leukocytes,monocytes, and neutrophils in response to Anaplasma phagocytophila

Anaplasma phagocytophila, an obligately intracellular bacterium of granulocytes, causes human granulocytic ehrlichiosis. Within 2 h after addition of A. phagocytophila, interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and IL-6 mRNAs are induced in human peripheral blood leukocytes (PBLs) or monocytes in vitro. However, neutrophils generate only IL-1beta mRNA. In the present study, signaling pathways for induction of these three cytokines were examined. TNF-alpha and IL-6 mRNA expression by PBLs was inhibited with SB 203580 (a p38 mitogen-activated protein kinase [MAPK] inhibitor), MG-132 (a proteasome inhibitor), and SN-50 (an NF-kappaB inhibitor). Activation of p38 MAPK and NF-kappaB mRNAs in monocytes was detectable within 15 to 30 min after addition of A. phagocytophila. Expression of these two cytokine mRNAs in PBLs and monocytes was also dependent on protein kinase C (PKC), protein kinase A (PKA), and protein tyrosine kinase (PTK). IL-1beta mRNA expression by neutrophils was not dependent on p38 MAPK, and p38 MAPK was not activated in neutrophils incubated with A. phagocytophila. IL-1beta mRNA induction by PBLs, monocytes, and neutrophils was dependent on PKC and PKA. Neutrophil expression of IL-1beta mRNA was dependent on transglutaminase, phospholipase C, and PTK, all of which are also required for internalization of A. phagocytophila. However, monocyte expression of IL-1beta mRNA was less dependent on these enzymes. These results suggest that A. phagocytophila transduces different signals between its host neutrophils and monocytes for proinflammatory cytokine generation.     

Education of medical technologists in North America

The increasing complexity of diseases and advancing medical technologies have recently raised the number of test items and their use. This has caused each department to ask for clinical support by medical technologists, including consultation services on clinical laboratory tests in Japan. Under these circumstances, we think it is necessary to consider a Japanese education system for medical technologists to foster people with advanced ability capable in providing adequate clinical support. It is important that we study medical technologist systems and education systems superior to than ours. Therefore, to investigate the state of the Japanese education system for medical technologists, we conducted a comparison between the medical technologist systems and education systems in foreign countries and those of Japan. The social background in which medical technologists are positioned, their scope of work, and the education systems overseas are different from Japan on many points and we were given many suggestions for what a system in Japan should be like.     

Antioxidant enzyme systems in skeletal muscle atrophied by immobilization

To clarify the mechanism of oxidative stress in skeletal muscle atrophied by immobilization, we investigated the change of antioxidant enzyme activities in a typical slow red muscle, the soleus. Atrophied soleus muscles were collected from male Wistar rats (16 weeks old), one ankle joint of which had been immobilized in the fully extended position for 7 days. Also, soleus muscles were collected from intact age-matched rats as control. The activities of Mn-containing superoxide dismutase (Mn-SOD), Cu,Zn-containing superoxide dismutase (Cu,Zn-SOD), Se-dependent glutathione peroxidase (Se-GSHPx), glutathione S-transferase (GST), catalase, and glutathione reductase (GSSGRx) were measured. The activities of Cu,Zn-SOD, GST, and GSSGRx were significantly higher in atrophied muscles, while the others were unchanged. Increased Cu,Zn-SOD and unchanged Mn-SOD levels might reflect increased generation of superoxide anions in the cytoplasm rather than in the mitochondria. Owing to the enhancement of Cu,Zn-SOD and the unaltered Se-GSHPx and catalase activities, hydrogen peroxide is thought to be increased in the cytoplasm. Because there is also an increase of iron in the microsomes of atrophied muscles, the production of hydroxyl radicals, the most aggressive of radicals, might consequently be elevated.     

Effect of short physical exercise on the levels of zinc and carbonic anhydrase isoenzyme activities in human erythrocytes

Summary Studies of the influences of physical exercise of short duration (bicycle ergometer, 200 W for 30 min) on the activities of carbonic anhydrase isoenzymes (CA-B and CA-C types) and zinc concentration in erythrocytes were made on 5 untrained healthy male volunteers. The subjects were rested for 30 min after the exercise. There were significant decreases in the levels of zinc, CA-B, total carbonic anhydrase activity and CA-B-dependent activity immediately after exercise, but after 30 min of rest they all returned to their pre-exercise levels. No significant change in CA-C level or CA-C-dependent activity was found after exercise. Immediately after exercise, total carbonic anhydrase activity and CA-B-dependent activity following the addition of Zn²⁺ showed significant increases, compared with their respective activities without Zn²⁺ addition. However, no such effects were observed just before exercise or after rest; the addition of Zn²⁺ had no effect on CA-C-dependent activity at any time. A significant correlation was found between the changes in concentration of zinc and CA-B-dependent activity after exercise (r=0.711). The findings of the present study suggest that active CA-B enzymes are converted in part to inactive enzymes during acute physical exercise, possibly by decreased zinc binding. Moreover, the change in CA-B-dependent activity correlated well with the changes in pH and HCO₃ concentrations in venous blood (r=0.853 and r=0.718, respectively). One may speculate that an adaptive decrease in CA-B-dependent activity in erythrocytes occurs with increased acidification in blood during heavy physical exercise of short duration.The present study was presented to the Fifth International Symposium on the Biochemistry of Exercise, Boston, June 1–5, 1982     

Effect of skin temperature on the ion reabsorption capacity of sweat glands during exercise in humans

The effect of skin temperature on the ion reabsorption capacity of sweat glands during exercise in humans is unknown. In this study, eight healthy subjects performed a 60-min cycling exercise at a constant intensity (60% VO_2max) under moderate (25°C) and cool (15°C) ambient temperatures at a constant relative humidity of 40%. The sweating rate (SR), index of sweat ion concentration (ISIC) by using sweat conductivity, esophageal temperature (Tes), mean skin temperature, and heart rate (HR) were measured continuously under both ambient temperatures. The SR and ISIC were significantly lower at the cool ambient temperature versus the moderate temperature. There were no significant differences in the changes in HR and esophageal temperature between these ambient temperature conditions, while the mean skin temperature was significantly lower at the cool ambient temperature by almost 3°C (P<0.05). The slopes of the relationships between Tes and the SR and ISIC were significantly lower and the thresholds of these relationships were significantly higher at the cool ambient temperature (P<0.05). The ion reabsorption capacity of the sweat glands was significantly lower (P<0.05) in a cool environment (0.21±0.04 vs. 0.52±0.06 mg/cm²/min at 15 and 25°C, respectively) as evaluated using the relationships for SR and ISIC. The results suggest that the ion reabsorption capacity of the sweat glands is influenced by skin temperature during exercise in humans.     

Carcinoid Tumor of the Middle Ear Containing Serotonin and Multiple Peptide Hormones A Case Report and Review of the Pathology Literature

A 69-year old man complaining of longstanding hearing loss and mild otorrhea was found to have a mass obliterating the external auditory canal and polypous tympanic mucosa with accompanying absence of the tympanic membrane and ossicular chain. Tumors excised from the external auditory canal and tympanum showed histologic features essentially characteristic of a carcinoid tumor: a ribbon or festoon arrangement of tumor cells, formation of anastomosing cords and glandular spaces, presence of numerous argyrophilic as well as argentaffin secretory granules within many of the tumor cells, and ultrastructur-al evidence of neurosecretory granules in the tumor cell cytoplasm. Immunohistochemically, the tumor was found to contain not only neuronal marker substances such as neuron-specific enolase, S 100 protein and chromogranin A, but also serotonin and multiple peptide hormones such as pancreatic polypeptide, glucagon, cholecystokinin and leucine-enkephalin. A review of the pathology of 17 previous cases of carcinoid of the middle ear suggested that this type of carcinoid may have a variegated hormone profile among carcinoids of foregut origin, and hormonally may resemble ileal carcinoid arising from the midgut, although their histogenetic origins may differ, because of frequent production of serotonin. Acta Pathol Jpn 42: 614–620, 1992.