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Biomedical subjects

T Brand

Publications and source records attributed to T Brand.

53 records · Page 3Linked to original sources

Proto-oncogene expression in porcine myocardium subjected to ischemia and reperfusion.

The molecular basis of myocardial adaptation to ischemia and reperfusion is poorly understood. It is thought that nuclear proto-oncogenes act as third messengers, converting cytoplasmic signal transduction into long-term changes of gene expression. We studied the expression of six nuclear proto-oncogenes (Egr-1, c-fos, fosB, c-jun, junB, and c-myc) in myocardium subjected to ischemia and reperfusion in anesthetized pigs. Stunning was achieved by two 10-minute left anterior descending coronary artery occlusions separated by 30 minutes of reperfusion. Hearts were excised after the first occlusion, after the first reperfusion, and at 30, 120, 150, and 210 minutes of reperfusion after the second occlusion. Total RNA was prepared from stunned as well as normally perfused myocardial tissue and subjected to Northern blotting. The response of the six nuclear proto-oncogenes varied.fosB gene expression was never detected. The c-myc gene was expressed, but its level was unchanged by ischemia. c-jun expression was slightly increased by ischemia (3.1 +/- 0.6-fold). The c-fos, Egr-1, and junB genes were highly induced, being fivefold to sevenfold higher in experimental than in control tissue. In three animals pretreated with the beta 1-antagonist metoprolol and then subjected to the above experimental protocol, the induction of proto-oncogenes was similar to that in nonblocked controls. Our results show that the myocardial adaptive response to ischemic stress includes the induction of at least four transcription factors that may be further operative in repair processes and angiogenesis.

Animals↗

Molecular biology of the coronary vascular and myocardial responses to ischemia.

To understand the complex mechanism(s) involved in molecular responses to ischemia, we developed two experimental models in pigs. In a "stunning" model of repetitive ischemia and reperfusion, we studied the mRNA expression of immediate early genes like c-fos, c-myc and heat shock protein-70 (HSP-70). Myocardial stunning was achieved by two cycles of 10-min left anterior descending coronary artery (LAD) occlusion and 30 min reperfusion. We observed several-fold enhanced expression of c-fos and HSP-70 mRNA in the stunned myocardium as compared with the control, whereas c-myc mRNA levels remained almost unchanged. In the second model, we examined the expression of the peptide mitogens heparin-binding growth factor 1 (HBGF-1) and transforming growth factor beta 1 (TGF-beta 1) after a chronic coronary artery occlusion leading to myocardial collateralization. Progredient stenosis of the circumflex coronary artery was induced by implanting a hygroscopic ameroid constrictor ring around it and occlusion was verified by in vivo angiography. Using polymerase chain reaction (PCR) and Northern hybridization techniques, we observed significantly enhanced expression of HBGF-1 and TGF-beta 1 in collateralized myocardium as compared with normal. In situ techniques revealed the localization of HBGF-1 transcripts in the blood vessel wall, and TGF-beta 1 in cardiac myocytes and Purkinje cells. Our results clearly indicate that myocardial stunning stimulates the expression of transcription factors which might be involved in regulation of certain growth factors like HBGF-1 and TGF-beta 1 which may play a significant role in the development of a collateral circulation.

Animals↗

Perinatal flutamide and mounting and lordosis behavior in adult female Wistar and Sprague-Dawley rats.

The present study was designed to investigate the possible role of perinatal androgens acting via the androgen receptor, as opposed to the estrogen receptor, for the differentiation of adult mounting and lordosis behavior in female rats. Female Wistar (W) and Sprague-Dawley (SD) rats were exposed to the anti-androgen flutamide prenatally (days 11-22 of pregnancy) and/or neonatally (days 1-10). The females were ovariectomized in adulthood and repeatedly tested for mounting and lordosis behavior. Flutamide, given both pre- and neonatally to SD rats, reduced adult T-induced female mounting. Flutamide administered only prenatally or only neonatally did not lower adult mounting behavior of SD rats. Mounting behavior of female W rats, following pre- and/or neonatal flutamide treatment was not affected. Lordosis behavior was also not altered by perinatal flutamide treatment of either strain. The results of the present study, no effect of prenatal flutamide, do not support the hypothesis that female rats require prenatal androgen receptor-mediated actions of testosterone in the organization of neural tissues for the occurrence of adult mounting and lordosis behavior. Only in SD rats androgenic organization of adult mounting behavior via the androgen receptor seems to occur both pre- and neonatally. Since clear behavioral effects of prenatal flutamide treatment have been published earlier in Long-Evans females, we suggest strain differences in sensitivity for perinatal androgenization in female rats. Future research into that possibility is needed.

Animals↗

Differential synthesis by cultured atrial and ventricular rat cardiac myocytes of myosin light chain isoforms.

Dissociated cells from neonatal rat atria and ventricles were cultured in monolayers for 3 days. Newly synthesized 35S-methionine labeled myosin light chain isoforms ALC-1, ALC-2 (atrial) and VLC-1, VLC-2 (ventricular) were identified on 2D gels, and their pattern of synthesis was compared to that of myocard fragments immediately after explanation. ALCs were synthesized in 5- to 10-fold excess over VLCs by atrial cultures, whereas the converse was true for ventricular cultures, with two exceptions: one third of the LC-1 synthesized by ventricular fragments was ALC-1, and dissociated atrial cells synthesized very little LC-2 of either isoform. The former finding corresponds to the relatively high proportion of ALC-1 in neonatal ventricular tissue. We conclude that the regional programme of LC isoform expression is basically retained after tissue explantation and even after dissociation and culturing of cardiac myocytes.

Animals↗

Adult partner preference and sexual behavior of male rats affected by perinatal endocrine manipulations.

Intact adult male rats, in which aromatization of testosterone to estradiol was prevented pre- and/or neonatally by ATD (1,4,6-androstatriene-3,17-dione), were repeatedly tested for partner preference behavior (choice: estrous female vs active male). In consecutive tests increasing preference scores for the female were found. Neonatal ATD males showed significantly lower preference scores for an estrous female than controls or prenatal ATD males. Prenatal ATD caused preference scores only slightly lower than those of controls. Ejaculation frequencies were markedly reduced or even absent in neonatal ATD males. Prenatal ATD treatment only had no or a moderately lowering effect on ejaculation frequency. Lordosis behavior of adult intact males was more facilitated following neonatal ATD treatment than following prenatal ATD treatment. In a number of tests the serotonergic drug 8-OH-DPAT was injected prior to testing for sexual partner preference and copulatory behavior. DPAT significantly increased preference for an estrous female in all groups of males when interaction was possible, but had no effect when sexual interaction was prevented by wire mesh. DPAT was able to increase the number of ejaculators in nonejaculating groups (i.e., perinatally ATD-treated males). "Premature ejaculations," i.e., ejaculations with the first intromission, were frequently observed with DPAT treatment in all groups of males. In conclusion, the availability of neonatal estrogen (derived from testosterone) organizes, at least partially, the preference for an estrous female normally shown by adult male rats. The lack of neonatal estrogen causes males to be less masculinized, both in partner preference behavior and ejaculatory behavior, and less defeminized in lordosis behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neonatal organization of adult partner preference behavior in male rats.

Male rats were castrated or sham castrated shortly after birth. Castrated males were then injected every other day on days 0-10 with testosterone propionate (TP, 0.5 mg), dihydrotestosterone propionate (DHTP, 0.5 mg) or the oil vehicle (0.05 ml); sham-castrated males received oil injections. In adulthood, when substituted with DHT, DHT + E2, or T (silastic implants), sexual partner preference was measured in an automated open field (AOF), in which wire mesh prevented sexual interaction with incentives, and in a 3-compartment box (3-CB), in which sexual interaction with tethered incentives was possible. Choices were an estrous female and a nonestrous female or an estrous female and a sexually active male. In adulthood, following long-term treatment with DHT or DHT + E2, the males did not show any partner preference when sexual interaction with incentives was prevented. Following sexual experience with an estrous female these males preferred the estrous over the nonestrous female, although this change could also be due to long-term hormone treatment. In the 3-CB, a clearcut preference emerged for the estrous female over the nonestrous conspecific, although the neonatally DHTP- or oil-treated males scored lower than the neonatally TP-treated or control males. Six weeks after removal of the hormone implants, when tested in the 3-CB (estrous female vs. active male), the males showed no partner preference. Unexpectedly the control males showed a low preference for the active male. Three weeks T-treatment made all males show a preference for the estrous female (in 3-CB).(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

On the organization of partner preference behavior in female Wistar rats.

The possible prenatal organizing effects of testosterone (T) on adult sexual partner preference, i.e., sexual orientation in female rats, were studied through prenatal exposure (days 11-22) of female fetuses to the antiandrogens flutamide (Sch 13521; 4'-nitro-3'-trifluoromethylisobutyranilide; 5 or 10 mg/day; Experiment 1) or anandron [RU 23908; 5,5-dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)- 2,4-imidazolidinedione; 35 mg/kg/day; Experiment 2]. The neonatal organizing effects of T were further studied by giving T, dihydrotestosterone (DHT) or oil within 9 h after birth to female pups (Experiment 3). In adulthood sexual orientation was ascertained, after ovariectomy followed by hormone treatment, in an automated open field (AOF), with stimulus animals behind wire mesh, and in a 3-compartment box (3-CB), with stimulus animals tethered. When given the choice between an estrous female and a sexually active male in the AOF, flutamide females, as well as controls, preferred the male partner. After long-term T treatment and 3 weekly pair-tests with an estrous female, flutamide females as well as controls switched their preference to the estrous female partner. In anadron females similar results were obtained. Thus the prenatal antiandrogens had no significant effect on sexual orientation in female rats. This suggests that adult sexual orientation in female rats is not organized prenatally through endogenous T. The change in preference after sexual experience corroborates earlier findings from our laboratory. When given the choice between an estrous female and a sexually active male in the 3-CB (sexual interaction with incentives possible), neonatally DHTP-treated females preferred the male; neonatally TP- or oil-treated females showed no preference.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen Antagonists↗

Peripubertal castration of male rats, adult open field ambulation and partner preference behavior.

The validity of the hypothesis put forward earlier, that testicular secretions during puberty have an organizing effect on open field ambulation was examined. Male rats were castrated or sham-operated at days 21, 43 or 70. At the age of 17 weeks the males were tested in an automated, octagonal open field (3 consecutive days, 3 min/day) for locomotor activity. Male rats castrated at day 21 or day 43 ambulated more than sham-castrated controls. Males castrated at day 70 did not differ from sham-castrated controls. It thus appears that pubertal testicular secretion(s) organize adult open field locomotor activity in male rats. From 18 weeks of age partner preference behavior was tested in the same open field apparatus with one adjacent cage containing an ovariectomized female and an opposite one containing an ovariectomized female brought into heat. The females in the adjacent cages were separated from the experimental males in the octagonal cage by wire mesh. Peripubertally castrated males did not show a clear-cut partner preference, whereas the intact males preferred the vicinity of the estrous female. There were no differences among the males castrated either before, during or after puberty. Testosterone treatment (crystalline T in silastic capsules) caused peripubertally castrated males to prefer the estrous female. Thus, adult partner preference behavior does not seem to be organized by peripubertal testicular androgens.

Animals↗

Immediate postnatal rise in whole body androgen content in male rats: correlation with increased testicular content and reduced body clearance of testosterone.

Whole body content of androgen (testosterone + 5 alpha-dihydrotestosterone) was invariably higher in male than in female rat pups killed 1 or 3 h after natural delivery, whereas androgen content was equivalent in males and females killed immediately or 6, 12, and 24 h after birth. Testicular content of androgen was significantly elevated in males killed 1 and 24 h after birth, compared with levels in males killed immediately, or 3, 6, and 12 h after birth. Thus, heightened testicular androgen content was only initially associated with increased systemic levels of androgen in males during the immediate postpartum period. A second study assessed the possibility that the body's clearance (i.e., metabolism plus excretion) of testosterone is lower in newborn rats upon separation from the placental circulation than in slightly older pups. Rats of both sexes killed 1 and 3 h after s.c. injection of [3H] testosterone had significantly higher plasma concentrations of [3H] testosterone as well as several 5 alpha-reduced androgens (5 alpha-dihydrotestosterone, 3 alpha-androstanediol, and androsterone) when injections were given within minutes as opposed to 24 h after birth. This suggests that in both sexes the clearance of testosterone is slower immediately after birth than at later ages. This phenomenon together with a brief postnatal elevation in the testicular synthesis and secretion of testosterone may explain the temporary rise in circulating androgen concentrations that occurs in the newborn male rat.

Age Factors↗

Early diagnosis and management of renovascular hypertension.

Renovascular hypertension is more common in hypertensive children than in hypertensive adults, and renal artery stenosis is second only to coarctation of the thoracic aorta as a cause of surgically correctable hypertension. Three infants presented with uncontrollable hypertension secondary to renal artery thrombosis due to umbilical artery catheterization for respiratory distress in the neonatal period. They all responded to nephrectomy. A fourth infant had stenosis of a polar vessel secondary to umbilical artery catheterization and was cured by partial nephrectomy. Two infants with renal artery stenosis secondary to fibromuscular dysplasia benefited from revascularization and, at last follow-up, were normotensive and off all blood pressure medication. Ultrasonography, isotope scanning, angiography and selective renal vein renin assays should be used to identify patients with surgically correctable lesions. The use of fine suture material and microvascular surgical techniques, including ex vivo revascularization and autotransplantation, can salvage renal parenchyma and relieve hypertension. Infants with less than 10 percent renal function on the involved side should have a nephrectomy. The infant with an umbilical arterial catheterization line needs blood pressure monitoring and aggressive evaluation and treatment of persistent hypertension.

Fibromuscular Dysplasia↗

Homosexual and heterosexual partner preference in ovariectomized female rats: effects of testosterone, estradiol and mating experience.

Ovariectomized female rats, longterm treated with estradiol benzoate (EB, 20 micrograms, 3 x/week) or testosterone propionate (TP, 0.4 mg, 3 X/week), were tested for homo- or heterosexual partner preference behavior with either tethered animals (sexually active male vs. estrous female) or animals behind a wire mesh. A preference score was calculated by subtracting the time spent in the vicinity of the stimulus female from the time spent in the vicinity of the stimulus male. Thus, a positive score indicates preference for the male (heterosexual preference), a negative score preference for the female (homosexual preference). Two weeks of EB treatment caused a clearcut preference for the male incentive. This heterosexual preference was significantly different from the indistinct preference of the TP-treated females. Sexual interaction with a freely moving active male (with or without a vaginal mask which prevented intromissions) did not alter the preference for the male of the EB-treated females. It did affect, however, the preference behavior of the TP-treated females significantly: it changed in the direction of the sexually active estrous incentive female, i.e., a homosexual preference. This change in preference could not be attributed to the experience of penile intromissions, it occurred despite the presence of a vaginal mask. Apparently, being mounted by a sexually active male had a negative reinforcing value in the TP-treated female rats and provoked a homosexual partner preference.

Animals↗

Technical consideration in management of renovascular hypertension in an infant with double renal arteries.

Renovascular hypertension is a curable disease that has recently been recognized with increasing frequency. A renal scan in a 1-month-old hypertensive white male showed diminished function of the right kidney, and his peripheral vein renin was elevated. Multiple antihypertensive medications failed to control his hypertension, and right kidney function deteriorated. An arteriogram showed two stenotic renal arteries supplying the right kidney. The smaller inferior artery supplied 35% of the kidney. Selective vein renin levels were greater than 15,000 ng/dL on the right side. Technical considerations in the repair of this lesion included midline transabdominal incision to expose the abdominal aorta and the inferior vena cava; dissection of inferior vena cava (IVC) with division of selected lumbar veins; full mobilization of right kidney and transsection of both renal arteries and the renal vein; perfusion of kidney via each renal artery with cold Sach's solution after resection of arterial stenoses; end-to-side microvascular anastomosis of the smaller (2 mm) renal artery to the main renal artery at the hilum with 10-0 nylon over in situ perfusion cannula; renal artery passed under the IVC to the aorta; and right kidney autotransplanted to a new site on the abdominal aorta with an end-to-side (5.0 mm) renal artery to the aorta and an end-to-side renal vein to IVC anastomosis. Following revascularization, perfusion was excellent and the blood pressure returned to normal. At 6 months follow-up, selective renal vein renins were normal and an arteriogram showed no stenosis. Meticulous dissection, cold perfusion, microvascular anastomosis, and autotransplantation salvaged this kidney and resolved the hypertension.

Humans↗

Brucellosis: a study of five calves from reactor dams.

Five calves from Brucella abortus reactor cows bought after they had been on infected farms for two to six weeks, were reared in isolation and examined serologically for approximately six months prior to cultural and biological examination post mertem. One calf which had been serologically negative to the Rose-Bengal, serum agglutination and complement fixation tests for the last eight weeks of its life yielded a culture of Br abortus biotype 1. This serotype had also been isolated from its dam at parturition.

Agglutination Tests↗

Effect of hearing loss, centre frequency, and bandwidth on the shape of loudness functions in categorical loudness scaling.

Loudness functions of narrow-band and broad-band stimuli were measured with eight normally-hearing and eight hearing-impaired listeners using a categorical loudness scaling method. In the normally-hearing listeners, narrow-band stimuli, generally generated loudness functions whose slope increased with increasing level, whereas broad-band stimuli generated more linear loudness functions. These differences can be explained by the level dependence of spectral loudness summation, which is known to be most prominent at moderate levels. In the hearing-impaired listeners, the narrow-band loudness functions generally showed a more linear shape than in the normally-hearing listeners. A consequence of these findings might be that the optimal shape of the input/output curve of a hearing aid is affected not only by the signal power in the respective frequency channels but also by the bandwidth of the input signal. However, there were considerable differences between listeners in both groups regarding the individual shape and absolute position of the loudness functions. Therefore, no normative reference could be extracted that would allow for a quantification of the bandwidth effect on an individual basis.

Adult↗