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.     

Inhibition of in vivo tumorigenicity and invasiveness of a human glioblastoma cell line transfected with antisense uPAR vectors

Our previous studies showed that glioblastomas express increased urokinase-type plasminogen activator receptors (uPARs) in comparison to low-grade gliomas (Yamamoto et al., Cancer Res., 54, 5016-5020, 1994). To explore whether downregulation of uPAR inhibits tumor formation and invasiveness, a human glioblastoma cell line was transfected with a cDNA construct corresponding to 300 bp of the human uPAR's 5¢ end in an antisense orientation, resulting in a reduced number of uPA receptors. Co-culture studies with tumor spheroids and fetal rat brain aggregates showed that antisense SNB19-AS1 cells expressing reduced uPAR failed to invade fetal rat brain aggregates. Intracerebral injection of SNB19-AS1 stable transfectants failed to form tumors and were negative for uPAR expression in nude mice. Thus uPAR appears in this model to be essential for tumorigenicity and invasion of glioblastomas in vivo.     

Moving Mesh Method for Reconstructing Some Spread Sources in the Brain

The purpose of this paper is to propose a new algorithm for the analysis of biomagnetic field data obtained from magnetoencephalography (MEG) measurements. This new method overcomes two major problems faced by the current method of data analysis. The first problem is the need to determine the number of sites of brain activity before calculations can be performed. The second problem is inability of the analysis to provide any information regarding the volume of the brain activity. The new data analysis method, called the Moving Mesh Method (MMM), is capable of analyzing MEG data without the need to determine the number of sources beforehand. In addition, the MMM determines the location of brain activity as a three dimensional volume, instead of as a point source of activity. The MMM uses an iterative method of calculating the position of the sources to achieve greater accuracy, and a regularized g-inverse matrix to stabilize its solution. The feasibility of the MMM was examined by two methods. First, a computer simulation was used to confirm the MMM's capability to analyzing MEG data. In the second experiment, the MMM was applied to analyze somatosensory evoked fields obtained using a new imaging system (Shimadzu Biomagnetic Imaging System, Model-100). From the interpretation of the results, we have concluded that the MMM is a feasible method of biomagnetic data analysis.     

Differential effect of brain-derived neurotrophic factor on high-threshold mechanosensitivity in a rat neuropathic pain model

We investigated the effect of the systemic infusion of brain derived neurotrophic factor (BDNF) on the behavioral response in a rat neuropathic pain model. One microgram per hour infusion of BDNF significantly attenuated mechanical hyperalgesia tested by the pin-prick test, however, 20 microg/h-BDNF infusion, on the contrary, enhanced the response. Neither 0.5 nor 10 microg/h-BDNF infusion influenced the mechanical hyperalgesia. Mechanical allodynia and thermal hyperalgesia, tested using a von Frey filament (23.0 mN) and the plantar test, were not influenced by BDNF treatment. These data suggest that systemic BDNF treatment can specifically alter high-threshold mechanosensitivity.     

Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer

Prostate cancer is a major cause of cancer death among elderly men in America, Europe, and Japan. However, the molecular mechanism of carcinogenesis is not yet well characterized. Frequent loss of heterozygosity (LOH) on chromosome 10q was reported in prostate cancer, and a candidate tumor suppressor gene, PTEN, was isolated on chromosome band 10q23.3. To investigate the genetic alterations of PTEN, we examined 45 primary prostate cancer specimens. LOH at the PTEN locus was observed in two (11.1%) of 18 tumors. However, no mutations were observed in any of the primary prostate cancers. These data suggest that mutation of the PTEN gene does not play a major role in prostate carcinogenesis of Japanese patients. Received: February 6, 1998 / Accepted: July, 3, 1998