Climatic adaptation in thermogenesis and thermal insulation in wood mice (Apodemus argenteus)

Wood mice (Apodemus argenteus) were trapped live at three different altitudes (below 1,000, 1,900, and 2,400 m) during a 1-year period (Feb. 1984-Jan. 1985). After remaining at the trapped locations for 10-14 days, they were transferred into a climatic chamber at an altitude of 610 m. Oxygen consumption (VO2) and colonic temperature (Tco) were measured at chamber temperatures (Ta) of five steps (30, 20, 10, 0, and -10 degrees C) in freely moving conditions. In response to Ta of 0 degrees C for the mice trapped in winter when their mean local habitat temperature (Te) were lower than 0 degrees C, there was a significant inverse correlation between VO2 and Te (r = -0.70, p less than 0.001) whereas no significant correlation (r = 0.23) was observed in the mice trapped in other seasons when Te was higher than 0 degrees C. The correlation between Tco and Te was significant (r = -0.66, p less than 0.001) over the entire range of Te. The pelt weight of the mice trapped at Te higher than 0 degrees C had a significant inverse correlation with Te (r = -0.65, p less than 0.001), but not in the mice trapped at Te lower than 0 degrees C. After measurement of VO2 and Tco at Ta of 0 degrees C, the mice who had lived in colder habitats (below 0 degrees C) showed 0% mortality, whereas the mortality of the populations which had lived in warmer habitats was 13%. These results suggest that, in wood mice, adaptation to severe cold is established by an enhanced thermogenesis and by an increased insulation of the pelt in moderate cold.     

Structure-activity relationship of mycoloyl glycolipids derived from Rhodococcus sp. 4306

Novel mycoloyl glycolipids with short carbon chains were isolated and purified from Rhodococcus sp. 4306, a soil origin of Actinomycetales. Their chemical structures were identified as trehalose 6,6'-dimycolate (TDM), trehalose 6-monomycolate, glucose 6-monomycolate, mannose 6-monomycolate and fructose 6-monomycolate. The length of carbon chains and number of double bonds of mycolic acids were C(34), C(36)and C(38)saturated, monoenoic and dienoic molecular species, which were much shorter than those of Mycobacterium tuberculosis (C(78-88)monoenoic and dienoic). Among them, only TDM could induce prominent granulomatous inflammation of the lung and spleen in mice. By contrast, other mycoloyl glycolipids induced mild lesions. The small-sized TDM of Rhodococcus possessed granulomatogenic activity, however, the toxicity was much lower than that of M. tuberculosis. Rhodococcal TDM was composed of mycolic acid with the shortest carbon chains, when compared to granulomatogenic TDM of Mycobacterium, Nocardia and Rhodococcus reported previously. Our results imply that rhodococcal TDM is a pathogenetic factor similar to that of M. tuberculosis, although rhodococcal TDM exhibits low toxicity.     

Exponential hyperbolic sine function fitting of heart rate response to constant load exercise

We attempted to fit heart rate (HR) changes induced by constant exercise loads of different intensities to an exponential hyperbolic sine curve by the least-squares method, and we compared the results with the fitting of the changes to exponential curves. Seven healthy male volunteers performed three different intensities of constant-load exercise on a bicycle ergometer. The exponential hyperbolic sine function adequately fitted the HR responses induced by all three different intensities of loads: low (30 W: correlation coefficient, r = 0.68 +/- 0.13, mean +/- SD), moderate (75 W: r = 0.93 +/- 0.07) and high (125 W: r = 0.97 +/- 0.02). The first-order exponential curve fitted only the moderate load response. Although the second-order exponential equation fitted the HR response for both the moderate and high loads, the equation did not fit the low-load response (r = 0.43 +/- 0.26). In low-load exercise, the sum of the power of the residuals for the exponential hyperbolic sine curve fitting was significantly smaller than that for the first- or second-order exponential curve fitting. In conclusion, the exponential hyperbolic sine function is useful for quantitative analyses of the HR response to exercise loads of various intensities.     

Two cases of limited cutaneous nodular amyloidosis with primary Sj?gren's syndrome]

We described two female patients with primary Sj?gren's syndrome associated with localized cutaneous nodular amyloidosis (LCNA), in which amyloid protein was derived from immunoglobulin light chain. Case 1; a 70-year-old female had complained with polyarthralgia, low-grade fever and parotid gland swelling. She was diagnosed as primary Sj?gren's syndrome. Three years later she noticed brown color small tumor on the thigh and yellow to brown nodules on the bilateral calves of legs. Skin biopsy from the left thigh revealed amyloid L protein deposition, which was positive for anti-lambda light chain staining, in almost entire dermis. Infiltration of lymphocytes and plasma cells around the amyloid deposit were prominent. Case 2; a 51-year-old female had noticed increasing eruption on the hip. Skin biopsy revealed amyloid L protein deposition in the dermis, which was negative for anti-lambda nor kappa light chain staining. When she was refereed to our hospital, she complained of xerostomia and xerophthalmia. She was diagnosed as primary Sj?gren's syndrome. In both cases, histological examination of a minor salivary gland biopsy revealed infiltration of lymphocytes and plasma cells but not amyloid deposit. Serum M protein and urine Bence-Jones protein were not detected. These cases represent localized amyloidosis without systemic involvement. It is widely recognized that Sj?gren's syndrome is frequently accompanied by B cell lymphoproliferative disorders. In LCNA, infiltration of plasma cells around the amyloid deposits was frequently prominent. The relation between these two disorders is discussed.     

CHEMOTACTIC ACTIVITY FOR POLYMORPHONUCLEAR AND MONONUCLEAR LEUKOCYTES IN RHEUMATOID SYNOVIAL FLUIDS

In order to why polymorphonuclear leukocytes (PMNs) are predominant and mononuclear leukocytes (MNLs) are few in rheumatoid synovial fluids, chemotactic factor(s) for PMNs and MNLs were studied in the synovial fluids of rheumatoid arthritis (RA-SF) and osteoarthritis (OA-SF) using both Boyden's and agarose methods. The RA-SF showed strong chemotactic activity for human peripheral blood PMNs compared with non-rheumatoid OA-SF. The chemotactic activity for PMNs was well correlated with the number of PMNs in RA-SF, suggesting that it was a natural mediator for PMN emigration into rheumatoid joint cavity. The major chemotactic factor for PMN in RA-SF was of apparent molecular weight of 14,000 and its activity was suppressed to less than 10 percent by anti-C5a antibody, but it failed to show any anaphylatoxin activity which was an attribute of C5a. It was, therefore, suggested to be C5a-like molecule but not C5a itself. The possibility that the factor may be a C5a des-Arg was discussed. On the contrary, the chemotactic activity for MNLs was not found neither in RA-SF nor OA-SF. These findings may explain the fact that PMNs are predominant in rheumatoid synovial fluids.     

Clinical studies on cefminox in pediatric field

Clinical studies on cefminox (CMNX, MT-141) were conducted and the following results were obtained. Twelve cases of bacterial infections were treated with CMNX with a satisfactory result of "excellent" in 9 and "good" in 3. Antibacterial activity was examined in 7 cases. Pathogenic organisms which were S. aureus, beta-Streptococcus, H. influenzae, S. pneumoniae and P. morganii were eradicated in all the cases. Mean maximum serum concentrations of CMNX after intravenous injection of 10, 20 and 40 mg/kg were 54.5 mcg/ml, 102.3 mcg/ml and 202.4 mcg/ml, respectively which were obtained 15 minutes after each injection. Mean half-lives of each dose group were 1.60, 1.13 and 1.51 hours, respectively. Mean urinary excretion rates of CMNX at 6 hours after intravenous injection in 10, 20, 30 and 40 mg/kg groups were 73.5%, 80.9%, 92.6% and 66.5%, respectively. Side effects were not observed clinically, but anemia in 1 case and eosinophilia in 2 cases were noted in laboratory examination.     

Amiodarone pharmacokinetics. I. Acute dose-dependent disposition studies in rats

Single intravenous bolus doses of amiodarone hydrochloride of 30, 60, 90 and 120 mg/kg were administered to male Sprague-Dawley rats to determine the effects of dose on amiodarone pharmacokinetics. Serial blood samples and total urine were collected over 48 hr and assayed for amiodarone and desethylamiodarone by HPLC. The blood amiodarone concentration-time curves for the four doses were best described by a triexponential equation with terminal half-lives (t _1/2 ) ranging from 17 to 20 hr. Over the dose range studied, no changes in , t _1/2 , or central compartment volume (Vc=1.2–1.4 L/kg) were observed. On the other hand, reductions in amiodarone clearance (CL and steady-state volume of distribution (V _ss of 44% (17.7 to 10.0 ml/min per kg) and 50% (16.4 to 8.2 L/kg), respectively, were noted as the dose of amiodarone increased. The conversion of amiodarone to desethylamiodarone (fm was dose-independent and amounted to approximately 10% of each amiodarone dose. No amiodarone or desethylamiodarone was detected in the urine of any of the treated animals. The blood-to-plasma concentration ratio of amiodarone was concentration-independent and therefore did not account for the dose-dependent changes in V_ss and CL observed. The data suggested that the dose-dependent changes noted were due to an alteration in the volume (s) of the peripheral tissue compartment(s).Supported by a Grant-in-Aid from the American Heart Association, Nebraska Affiliate.     

Effects of gelonin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma on antigen-producing tumor cells in vitro

Missile therapy, which destroys cancer cells specifically, has been considered to be an effective modality for treatment of carcinoma. We have developed a monoclonal antibody MSN-1 (immunoglobulin class: IgM), of which the immunogen is the endometrial adenocarcinoma cell line SNG-II, which strongly reacts with endometrial adenocarcinomas. We describe an immunoconjugate consisting of the MSN-1 and a plant hemitoxin named gelonin which has revealed to assume selective cytotoxicity against the SNG-II in a colony formation assay in vitro. The results of our study suggest that the 'inhibitory concentration' or IC50, of the MSN-1-gelonin immunoconjugate against the SNG-II was 188 fold that of gelonin alone. These results indicated that the MSN-1-gelonin immunoconjugate exhibited highly selective cytotoxicity to endometrial adenocarcinoma, which expressed an epitope against the MSN-1, and it is suggested that the MSN-1-gelonin immunoconjugate has possibility of clinical application to treatment of endometrial adenocarcinomas.