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Biomedical subjects

A Perlmutter

Publications and source records attributed to A Perlmutter.

At least 19 recordsLinked to original sources

Bleomycin upregulates gene expression of angiotensin-converting enzyme via mitogen-activated protein kinase and early growth response 1 transcription factor.

Pulmonary fibrosis is a progressive disorder characterized by the loss of alveolar architecture through epithelial and endothelial cell apoptosis and fibroblast proliferation. Recent studies showed that angiotensin-converting enzyme (ACE) activity is increased in fibrotic tissues, and ACE inhibitors administered in vivo ameliorate fibrosis, suggesting that ACE may play a critical role. However, the regulation of ACE expression is not well understood. In the present study, we demonstrate that bleomycin, a chemotherapeutic agent which induces pulmonary fibrosis in animals and humans, increases gene expression of ACE. Treatment of primary bovine pulmonary artery endothelial cells with 0.1 to 1.0 microg/ml bleomycin increased ACE enzymatic activity and ACE mRNA, as monitored by hippuryl-L-histidyl-L-leucine assay and competitive quantitative reverse transcriptase polymerase chain reaction (RT-PCR), respectively. Luciferase reporter constructs showed that upregulation of ACE transcription by bleomycin is mediated through element(s) in the 97-bp ACE promoter. Bleomycin activated p42/p44 mitogen-activated protein kinase (MAPK) and induced nuclear translocation and activation of the early growth response (Egr)-1 transcription factor, a factor previously shown to positively regulate ACE expression. The MAPK kinase1/2 (MEK1/2) inhibitor U0126 blocked MAPK and Egr-1 activation by bleomycin, suggesting that Egr-1 activation is MAPK dependent. These data provide the first evidence that bleomycin activates ACE gene expression through the MAPK pathway and Egr-1.

Animals↗

Demographics, family histories, and psychological characteristics of prostate carcinoma screening participants.

BACKGROUND: The goals of this study were to 1) understand the reasons that men seek prostate carcinoma screening, in light of the ongoing medical controversy surrounding screening; and 2) assess the level of psychological distress and perceived risk among men seeking screening, and whether or not these variables were dependent on a man's family history of prostate carcinoma. METHODS: The subjects were 126 men (40% had a family history of prostate carcinoma) who participated in a free prostate carcinoma detection program. Questionnaires, which were completed prior to prostate carcinoma screening, included demographic and medical information, reasons for screening participation, general and cancer-related psychological distress, and perceived risk for prostate carcinoma. RESULTS: Among both family history groups, self-referral was the most common reason for attending the screening, compared with receiving a recommendation from a health professional or from a friend or family member. Men with a positive family history were not more distressed than those without a family history; but as the authors predicted, men with a positive family history of prostate carcinoma did report higher levels of perceived risk relative to those without a family history. In addition, an interaction revealed that psychological distress was greater among men with a family history only among those who also reported elevated perceived risk. CONCLUSIONS: Similar to other prostate carcinoma screening programs, men in the current sample largely elected to attend the screening on their own. Furthermore, although perceived risk was higher among men with a family history compared with those without a family history, psychological distress was greater among men with a family history only among those who also reported elevated perceived risk. Thus, among men with a family history of the disease, perceived risk may be a marker of elevated psychological distress. Screening programs should assess family history and perceived risk because of the potential psychological implications for screening participants.

Attitude to Health↗

Microwave thermotherapy for benign prostatic hyperplasia with the Dornier Urowave: results of a randomized, double-blind, multicenter, sham-controlled trial.

OBJECTIVES: To study the efficacy and safety of a new transurethral microwave thermotherapy device (the Urowave) in the treatment of men with clinical benign prostatic hyperplasia (BPH) in a randomized, double-blind, sham-controlled trial. METHODS: A total of 220 patients (mean age 66.2 years) with clinical BPH, an American Urological Association symptom index (AUA SI) of 13 points or more, and a peak flow rate of 12 mL/s or less were enrolled and randomized 2:1 for active versus sham treatment. All treatments were conducted as an outpatient procedure under local anesthesia, with oral sedation and analgesia only. Patients were followed up at 1 week and 1, 3, and 6 months after treatment. RESULTS: The treatments were well tolerated, and no patient received general or spinal anesthesia. The AUA SI dropped from 23.6 to 12.7 points at 6 months (P < 0.05) in the active group and from 23.9 to 18.0 points in the sham-treated group (P < 0.05, between-group difference). Statistically significant improvements were also noted for peak flow rate (7.7 to 10.7 mL/s at 6 months for active treatment, 8.1 to 9.8 mL/s for sham treatment, P < 0.05, between-group difference) and for average flow rate. A decrease in AUA SI of more than 30% was achieved in 72% versus 38% of patients (active versus sham treatment, respectively) and more than 50% in 50% versus 19% of patients. In general, active Urowave-treated patients perceived "a lot" of improvement, whereas sham-treated patients perceived "a little" to "some" improvement. More of the actively treated patients had dysuria and urgency after treatment, and ejaculatory dysfunction (e.g., hematospermia) was more common in actively treated patients as well. Secondary urinary retention after removal of the catheter occurred in 8 patients (5.4%). CONCLUSIONS: The Dornier Urowave transurethral microwave thermotherapy device for treatment of clinical BPH is effective in decreasing symptoms and bother and improving quality of life and flow rate and is superior to sham treatment. Patients perceive a great deal of improvement, independent of their baseline symptom severity. Adverse events are in general transient and mild in nature. Extended follow-up is necessary to document long-term durability of improvements.

Aged↗

Is there a best alternative to treating the obstructed upper pole?

PURPOSE: We addressed whether salvage of upper pole renal units in comparison to partial nephrectomy affects differential renal function in patients with a duplicated obstructed upper pole. MATERIALS AND METHODS: We retrospectively reviewed the records of all children who underwent surgery for a unilateral obstructed duplicated kidney at our institution from 1988 to 1995. Patients were evaluated with respect to postoperative complications, reoperation rate and percent change in differential renal function of the obstructed duplicated kidney, as determined by nuclear renography. RESULTS: We identified 46 patients with a unilateral obstructed upper pole of a duplicated kidney who were divided into 2 groups. Group 1 (12 patients) underwent an upper pole salvage procedure, that is ureteropyelostomy or ureteroureterostomy, and group 2 (31 patients) underwent partial nephrectomy. Three reoperations (25%) were performed in group 1 and 1 (4%) was done in group 2. Postoperative symptomatic urinary tract infections were diagnosed in 3 group 1 patients (25%) and in 2 (8%) in group 2. Average change in ipsilateral renal function in the 8 patients who underwent upper pole salvage procedures was 2.25 +/- 2.34% (range -6 to 12). In the 8 patients who underwent upper pole nephrectomy and who also had postoperative renal scans average change in function was -1.25 +/- 4.51% (range -23 to +16). CONCLUSIONS: There was no statistically significant loss of relative renal function in patients treated with partial nephrectomy and no significant gain in relative renal function in those treated with an upper pole salvage procedure. The reoperation rate was higher in the upper pole salvage than in the partial nephrectomy group (25 versus 4%). While not statistically significant, we believe that this rate is clinically important. We think that partial nephrectomy should remain the preferred treatment for most patients with obstructed duplicated kidneys.

Adolescent↗

Properties of human affect induced by static color slides (IAPS): dimensional, categorical and electromyographic analysis.

Human affect elicited by static color slides was evaluated quantitatively using dimensional (N = 60 subjects) and differential or categorical (N = 57) self report, and facial electromyography (N = 20). Mean dimensional self reports of affective responses were highly replicable across cohorts. Mean categorical response profiles over seven affective categories were monomodal for some slides, but multimodal for most, and nearly identical within the same cohort for slides of similar content. Mean categorical response profiles for individual slides were also similar across different cohorts and for different experimental conditions. Valence calculated from weighted categorical self report scores was highly correlated with the self reported valence (r = +0.98), demonstrating a simple, linear relationship between dimensional and categorical (differential) measures of affect. Categorical response strength was synergically patterned, i.e. invariably correlated positively for affect of the same dimensional valence and generally correlated negatively for affect of opposite valence. Facial electromyograms associated with affective responses to slides were correlated with valence, but smaller in magnitude than those associated with the weakest possible voluntary facial movements involving the same muscles. This study, therefore, demonstrates that self reported affective responses to color IAPS slides are replicable within and between cohorts, complex but synergically patterned, and relatively weak.

Affect↗

Toradol, an NSAID used for renal colic, decreases renal perfusion and ureteral pressure in a canine model of unilateral ureteral obstruction.

Toradol is a new parenteral, nonsteroidal anti-inflammatory drug which is efficacious in treating renal coli. In the present experiments, Toradol was administered to both control dogs and dogs with unilateral ureteral obstruction. In control dogs, Toradol had no effect on RBF or GFR, despite inhibition of renal prostaglandin synthesis (measured as urinary prostaglandin release). In contrast, RBF fell acutely by 35% (p < 0.001) within 15 minutes of Toradol administration in the setting of ureteral obstruction; contralateral RBF was unaffected. Ipsilateral ureteral pressure also fell. Changes in RBF and ureteral pressure, together with the known effects of NSAIDs on pain pathways, may contribute to the pain relief observed clinically with Toradol. However, the abrupt changes in renal hemodynamics brought on by Toradol to the obstructed kidney may compromise renal reserve, and Toradol should be used cautiously in treating renal colic.

Animals↗

Hyperthermic suppression of a genetically programmed melanoma in hybrids of fishes: genus Xiphophorus.

In fishes of the genus Xiphophorus, hybrid offspring of the spotted dorsal female platyfish, X. maculatus, and male swordtails, X. helleri, are genetically programmed to develop melanoma when raised at ambient laboratory temperatures. When these hybrid offspring were raised under hyperthermic conditions, there was no development of melanoma. Electron microscopy revealed degenerative changes in the melanocytes of heat-treated hybrids not seen in hybrids raised at ambient temperatures. The platyfish-swordtail melanoma system represents an appropriate model for the investigation of the relationship between hyperthermia and melanoma formation and treatment in poikilothermic vertebrates.

Adaptation, Physiological↗

Retrovirus-like particles in embryonic kidney tissue of the platyfish, Xiphophorus maculatus.

Ultrastructural studies were performed on embryos of an inbred strain (163A) of the platyfish Xiphophorus maculatus, and a pooled stock of the Rio Sarabia strain of the swordtail, X. helleri. Viral-like particles were found in the kidney tissue of platyfish embryos. Exposure of pregnant platyfish to 5-bromodeoxyuridine during the time of differentiation of embryonic melanocytes enhanced the production of viral-like particles in platyfish embryos. Viral-like particles were not found in untreated or drug-treated swordtail embryos. The morphology of these particles corresponds to type C retroviruses.

Animals↗

Urethral hemangioma.

Urethral hemangiomas are uncommon lesions that can cause significant hemorrhagic morbidity. Since the lesions tend to recur complete urethral excision and subsequent urethral reconstruction have been advocated in the past as the preferred method of treatment. We present an alternative method of management of urethral hemangioma.

Adolescent↗

A technique for assaying the activities of alpha-GPD, LDH, and MDH in the teleost, the goldfish, Carassius auratus.

1. A spectrophotometric assay using rho-iodo-nitro-triphenyl tetrazolium chloride as the indicator was developed for splenic tissue in the goldfish Carassius auratus. 2. This technique permits a rapid test for the activities of the enzymes lactic dehydrogenase, malic dehydrogenase, and alpha-glycerophosphate dehydrogenase which are indicative of the relative activities of various metabolic pathways.

Animals↗

Reversible stage-specific embryonic inhibition mediated by the presence of adults in the annual fish Nothobranchius guentheri.

Nothobranchius guentheri, an annual fish from East Africa, is found in temporary ponds, pools, and streams that dry seasonally. The populations survive the dry seasons in the form of thickly chorionated embryos encased in the muddy substrates. When N. guentheri adults are allowed to spawn in the laboratory at 24.0 +/- 1 degree C and the fertilized eggs are collected shortly afterwards, formation of the embryonic axis normally occurs within 5 to 11 days. However, examination of embryo populations obtained from unaerated aquaria after uninterrupted spawning periods of up to 2 or 3 months revealed only rare instances of embryogenesis. The overwhelming majority of embryos proceeded no further than the dispersed cell phase (diapause I, stage 20). Spawning was found to be continuous throughout these prolonged periods and the possibility of adult predation was eliminated. While low PO2 has been determined to be a factor contributing to the duration of diapause I, determinations of PO2, PCO2, pH, free ammonia and bacterial flora indicated that aquarium conditions could support embryogenesis. Only embryos at stages 20 and 32, both being stages of naturally occurring diapause, could be inhibited. The inhibitory effect was dependent on the adult density and was diminished with aeration. It is proposed that, in nature, the adult-produced inhibitory factor may be useful in the conservation and augmentation of the embryonic reserve which is the mainstay of annual fish populations in tropical areas of alternating rainy and dry seasons.

Ammonium Chloride↗

A sexual aggregating pheromone system in the zebrafish, Brachydanio rerio (Hamilton-Buchanan).

Zebrafish, Brachydanio rerio, when placed in a T-maze demonstrated preference for, or avoidance of, donor water produced when specified numbers of conspecifics of either sex were kept in holding systems for specific lengths of time. Inter- and intrasexual attractions were found to occur in different ranges of concentration of the attractant material(s). Insufficient or excessive concentrations of the attractant(s) failed to elicit the attractant response. The proposed pheromone attractant was shown to be removable from the aquatic environment. Its possible role in the behavioral aspects of schooling and spawning is discussed.

Animals↗

Inheritance and longevity of infectious pancreatic necrosis virus in the zebra fish, Brachydanio rerio (Hamilton-Buchanan).

Zebra fish (Brachydanio rerio) were injected with infectious pancreatic necrosis virus (IPNV) and then spawned to determine whether the virus was passed on to the eggs, and if it was, how long it remained in the free-swimming F1. The mating variations included parents receiving one or two injections of virus, and within these categories, matings in which both parents were treated or only one parent was treated. The results showed that transmission of IPNV to the egg did occur, and that this transmission was via the female alone. However, if the female was allowed to produce antibodies to the virus, as when she received two injections of IPNV, she transmitted the virus to the eggs for only a short period of time. In addition, when the virus was transmitted to the egg, it remained in the free-swimming F1 for a period of at least 5 months.

Animals↗