Metallothionein-I-transgenic mice are not protected from acute cadmium-metallothionein-induced nephrotoxicity

Mice pretreated with Zn have increased renal metallothionein (MT) levels and are protected from CdMT nephrotoxicity. To determine whether MT is important in this Zn-induced protection against CdMT-induced nephrotoxicity, MT-transgenic mice that have high levels of MT in their kidneys (10-fold over control mice) have been studied to determine whether they are resistant to CdMT-induced nephrotoxicity. Mice were injected with CdMT (0.1-0.6 mg Cd/kg, iv) and kidney injury was evaluated 24 hr later. CdMT produced renal toxicity in a dose-dependent manner. At a nephrotoxic dose of CdMT (0.4 mg Cd/kg), urinary protein and glucose excretion were increased 30- and 60-fold, respectively, in control mice. However, similar increases in protein and glucose excretion were also observed in MT-transgenic mice. CdMT also induced a similar dose-dependent proximal tubular cell necrosis in both control and MT-transgenic mice in a dose-dependent manner. Treatment of control mice with Zn (100 micromol/kg, sc x 2 days) increased renal MT to levels similar to those of untreated MT-transgenic mice and protected against CdMT-induced renal injury. Furthermore, when Zn (25-100 micromol/kg, sc) was given immediately before CdMT injection (i.e., without preinduction of MT), it was still effective in preventing CdMT nephrotoxicity. We conclude that Zn-induced protection against CdMT nephrotoxicity does not appear to be due to induction of renal MT.     

A flexible PC-based physiological monitor for animal experiments

We have developed a flexible physiological monitoring and analysis system for physiological studies in which data are obtained over extended periods. Our system uses low-cost personal computer hardware to concentrate data from existing multiple monitoring devices. All monitored parameters are displayed on a single screen and recorded in a single file. The system automates the process of physiological record keeping by providing continuous displays of vital signs. In addition, audible and visual alarms are produced when vital signs are outside of acceptable ranges, prompting the experimenter to take corrective actions. The central element of the system is a program running in a dedicated manner on an IBM PC-compatible computer. The program is written in the C language and makes use of a graphics library to display traces and analysis results in real time on any standard display for the PC. This program assigns the analog channels of an A/D board to particular physiological parameters by initially reading a configuration file, which also describes the alarm conditions and analysis routine for each parameter. All hardware specific code is isolated into well-defined modules. The program is both highly flexible with regard to different sets of parameters and highly portable for different experimental and computer environments.     

Agonist-induced phosphorylation of the angiotensin AT1a receptor is localized to a serine/threonine-rich region of its cytoplasmic tail

Autosomal recessive juvenile parkinsonism (AR-JP) is a distinct clinical and genetic entity characterized by selective degeneration of nigral dopaminergic neurons and young-onset parkinsonism with remarkable response to levodopa. Recently, we mapped the gene locus for AR-JP to chromosome 6q25.2-q27 by linkage analysis and we identified a novel large gene, Parkin, consisting of 12 exons from this region; mutations of this gene were found to be the cause of AR-JP in two families. Now we report results of extensive molecular analysis on 34 affected individuals from 18 unrelated families with AR-JP. We found four different homozygous intragenic deletional mutations, involving exons 3 to 4, exon 3, exon 4, and exon 5 in 10 families (17 affected individuals). In addition to the exonic deletions, we identified a novel one-base deletion involving exon 5 in two families (2 affected individuals). All mutations so far found were deletional types in which large exonic deletion accounted for 50% (17 of 34) and the one-base deletion accounted for 6% (2/34); in the remaining, no homozygous mutations were found in the coding regions. Our findings indicate that loss of function of the Parkin protein results in the clinical phenotype of AR-JP and that subregions between introns 2 and 5 of the Parkin gene are mutational hot spots.     

Correlates and consequences of workplace violence

A random telephone survey was used to interview 598 employees about instances, if any, when they had been physically attacked or threatened in the workplace. Demographic and workplace characteristics are analyzed as correlates of these forms of violence. The only characteristic consistently associated with higher risk is a work schedule that included nighttime hours. However, although few strong or consistent correlates of workplace violence were found, there were clear negative consequences associated with being victimized at work: lower job satisfaction, greater job stress, increased considerations of job change, and an increased likelihood of bringing mace, a gun, or another weapon to work.     

Mate choice and mate competition influence male body size in Japanese medaka

A sexual size dimorphism usually occurs when size-dependent reproductive advantages exist in only one sex. Studies on Japanese medaka, Oryzias latipes, have demonstrated reproductive size advantages in females but not in males, even though males and females are similar in body size. We conducted mate-choice and mate-copying tests in which a female could first associate with, then mate with, either a large (>/=1 sd+X standard length) or a small male (相似文献   

Cytokine priming reduces dependence on TNF-R2 for TNF-alpha-mediated induction of macrophage nitric oxide generation

In the presence of interferon-gamma (IFN-gamma), human tumor necrosis factor-alpha (Hu-TNF-alpha), which binds to murine TNF-alpha receptor type 1 (TNF-R1) but not to murine TNF-R2, was effective in inducing nitric oxide (NO) production in spleen-derived macrophages (M phi), albeit at concentrations 12.5-fold greater than those required by murine TNF-alpha (Mu-TNF-alpha), to achieve the same result. Addition of anti-TNF-R1 completely inhibited the Mu-TNF-alpha-mediated induction of NO, demonstrating that TNF-R1 is critical to the IFN-gamma-dependent TNF-alpha-mediated induction of M phi effector function. However, treatment with anti-TNF-R2 resulted in a partial inhibition of M phi activation. Spleen-derived M phi were more dependent on TNF-R2 than RAW 264.7 or peritoneal M phi based on their responsiveness to Hu-TNF-alpha. Priming of spleen-derived M phi with either IFN-gamma or granulocyte-macrophage colony-stimulating factor (GM-CSF) heightened the maximal responses to both TNF-alpha species and increased the overall effectiveness of Hu-TNF-alpha without increasing expression of either TNF-alpha receptor. The dependence of spleen-derived M phi on both TNF-alpha receptors for signaling the induction of effector function supports an active signaling role for TNF-R2 in its synergy with TNF-R1 rather than a passive ligand passing role.     

Heat tolerance in Tuli-, Senepol-, and Brahman-sired F1 Angus heifers in Florida

We investigated heat tolerance and growth rate in two trials under ambient conditions in central Florida. Trial 1 (1994) involved 38 Brahman (B), 21 Senepol (S), 19 B x Angus (A), 20 S x A, and 20 Tuli (T) x A heifers. Trial 2 (1995) involved 13 A, 35 B, 30 S, 23 B x A, 17 S x A, and 28 T x A heifers. Measurements were made on three consecutive weeks during the hotter and cooler seasons of each year and included rectal temperature (RT, degrees C), respiration rate (RR, bpm), temperament score (TS; 1 = very docile, 5 = very aggressive), blood packed-cell volume (PCV), and plasma cortisol concentration (CORT). Data for RT were transformed (log10 [RT - 37]) before analysis. On the hottest date in Trial 1, log10 RT was not different between B (.39 +/- .011) and B x A (.37 +/- .016) or between T x A (.35 +/- .015) and B x A, but log10 RT was lower (P < .05) in S x A (.30 +/- .015) than in either S (.35 +/- .015) or T x A. On all dates in Trial 1, RR was lower (P < .05 to .001) and PCV was higher (P < .05 to .001) in B than in B x A. There were few differences in TS except on two dates when B scored higher (P < .01 to .001) than B x A, and these differences were associated with higher (P < .05) CORT in B than in B x A. Using initial BW as a covariate, adjusted ADG (kg) of T x A (.52 +/- .023) was not different from adjusted ADG of B x A (.57 +/- .024) or S x A (.54 +/- .023). On the hottest date in Trial 2, log10 RT and RR were higher (P < .001) in A (.59 +/- .017, 74 +/- 2.7) than in B (.47 +/- .010, 39 +/- 1.6), S (.42 +/- .011, 50 +/- 1.8), and crossbred heifers (.47 +/- .011, 60 +/- 1.8; .43 +/- .014, 55 +/- 2.4; and .50 +/- .012, 48 +/- 2.0 for T x A, S x A and B x A, respectively), and RR was higher (P < .001) in B x A than in B. On the coolest date in Trial 2, RR was slightly lower in B (32 +/- .5) than in A(34 +/- .7, P < .01) and B x A (36 +/- .6, P < .001) and was associated with higher PCV in B than in A. On both dates, TS and CORT were higher (P < .01) in B than in A. In Trial 2, adjusted ADG (kg) was higher (P < .01) in B (.43 +/- .017) than in A (.32 +/- .033), higher (P < .001) in S (.45 +/- .018) than in A, and higher (P < .001) in crossbreds (B x A [.53 +/- .023] + S x A [.44 +/- .025] + T x A [.46 +/- .019]) than in A. These data indicate that heat tolerance in F1 crosses of tropically adapted breeds (Tuli, Senepol, Brahman) with a temperate breed (Angus) is similar to heat tolerance displayed by purebred tropical breeds (Senepol, Brahman).     

Success of surgery for primary aldosteronism judged by residual autonomous aldosterone production

Since February 1996 we have prospectively assessed residual adrenal autonomy by the fludrocortisone suppression test (FST) in 23 patients 3 months after unilateral adrenalectomy for Conn syndrome and in 45 patients after a longer interval. In regard to blood pressure, 36 (53%) patients were cured of hypertension and the remaining 32 (47%) patients had improved hypertension control at the time of their latest postoperative clinical assessment. In regard to the outcome of surgery, patients who achieved normal suppressibility of aldosterone were regarded as cured, and those who had greater suppressibility after surgery were considered improved. Time since surgery for the whole group averaged 26 months. By these biochemical criteria, 42 patients (62%) were cured by surgery, and the rest improved; 16 (76%) of 21 women were cured, and 26 (55%) of 47 men. The women (mean +/- SD age 47 +/- 11 years) were significantly (p < 0.05) younger than the men (52 +/- 9 years). Preoperative aldosterone levels before and after FST were similar in the cured and improved groups and fell significantly (p < 0.01) in both groups following surgery. After surgical reduction of autonomous aldosterone production, mean plasma renin activity levels increased sixfold in the cured group and threefold in the improved group. Surgical mortality in this group of 68 patients with Conn syndrome was zero.     

Clinical comparison of radiolocalization of two monoclonal antibodies (mAbs) against the TAG-72 antigen

Ten patients with colorectal cancer metastases received 125I-B72.3 and 131I-CC49 prior to laparotomy (five patients received 1 mg, and five 20 mg of each mAb). Tumor:serum ratios of 131I-CC49 were better than those of 125I-B72.3 (P < 0.01 at 1 mg; P = 0.05 at 20 mg; P < 0.01 at both doses). All known lesions > or = 1 cm in diameter were visualized at the 20 mg dose. There was no difference in absolute tumor uptake of 125I-B72.3 or 131I-CC49. We conclude that mAb CC49 has better relative uptake in colorectal cancers than mAb B72.3.