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Biomedical subjects

S Erdman

Publications and source records attributed to S Erdman.

At least 19 recordsLinked to original sources

Typhlocolitis in NF-kappa B-deficient mice.

Activation of inflammatory gene expression by the transcription factor NF-kappaB is a central pathway in many inflammatory disorders, including colitis. Increased NF-kappaB activity has been linked with development of colitis in humans and animal models, thus it was unexpected when NF-kappaB-deficient mice developed spontaneous typhlocolitis. To further characterize this finding, we induced typhlocolitis in rederived NF-kappaB-deficient mice using intragastric infection with Helicobacter hepaticus. At 6 wk postinfection (PI), severe colitis with increased type 1 cytokine expression was seen in infected mice that lacked the p50 subunit of NF-kappaB and were also heterozygous for the p65 subunit of NF-kappaB(p50(-/-)p65(+/-)). Mice lacking the p50 subunit alone (p50(-/-)) were less severely affected, and wild-type mice and p65(+/-) mice were unaffected. T cell development in NF-kappaB-deficient mice was normal. These data indicate that p50 and p65 subunits of NF-kappaB have an unexpected role in inhibiting the development of colitis.

Animals↗

A filamentous growth response mediated by the yeast mating pathway.

Haploid cells of the budding yeast Saccharomyces cerevisiae respond to mating pheromones by arresting their cell-division cycle in G1 and differentiating into a cell type capable of locating and fusing with mating partners. Yeast cells undergo chemotactic cell surface growth when pheromones are present above a threshold level for morphogenesis; however, the morphogenetic responses of cells to levels of pheromone below this threshold have not been systematically explored. Here we show that MATa haploid cells exposed to low levels of the alpha-factor mating pheromone undergo a novel cellular response: cells modulate their division patterns and cell shape, forming colonies composed of filamentous chains of cells. Time-lapse analysis of filament formation shows that its dynamics are distinct from that of pseudohyphal growth; during pheromone-induced filament formation, daughter cells are delayed relative to mother cells with respect to the timing of bud emergence. Filament formation requires the RSR1(BUD1), BUD8, SLK1/BCK1, and SPA2 genes and many elements of the STE11/STE7 MAP kinase pathway; this response is also independent of FAR1, a gene involved in orienting cell polarization during the mating response. We suggest that mating yeast cells undergo a complex response to low levels of pheromone that may enhance the ability of cells to search for mating partners through the modification of cell shape and alteration of cell-division patterns.

Cell Division↗

Gastric dilatation syndrome associated with chronic nephropathy, hypergastrinemia, and gastritis in mice exposed to high levels of environmental antigens.

Gastric dilatation (GD) has been observed in Tac:(SW)fBR surveillance mice, with mean age of 10 months, that are exposed to high levels of environmental antigens during routine exposure to dirty bedding. The aim of the study reported here was to determine whether GD was associated with other systemic conditions affecting mice. Three groups of nine animals including-surveillance mice not exposed to dirty bedding (control), surveillance mice with out GD (NGD), and surveillance mice with GD (group GD)-had mean stomach weight with ingesta of 0.5 +/- 0.02 g, 1.09 +/- 0.07 g (P < 0.0001), and 2.54 +/- 0.4 g (P < 0.0001), respectively. Mean serum creatinine concentration was significantly higher in GD (1.6 +/- 0.25 mg/dl), compared with NGD (0.17 +/- 0.22 mg/dl, P < 0.0001) and control (0.2 +/- 0.16 mg/ dl, P < 0.0001) mice. In addition, lesions consistent with severe chronic nephropathy and mild gastritis were common in GD, compared with NGD and control mice. Finally, serum amidated gastrin concentration was significantly high in GD (179.37 +/- 53.86 pM, P < 0.03) and NGD (264.89 +/- 115.89 pM, P < 0.009), compared with control (60.77 +/- 8.39 pM) mice. Gastric dilatation syndrome is associated with chronic nephropathy, hypergastrinemia, and gastritis in surveillance mice exposed to high levels of environmental antigens.

Animals↗

E2F4 is essential for normal erythrocyte maturation and neonatal viability.

The retinoblastoma protein (pRB) plays a key role in the control of normal development and proliferation through the regulation of the E2F transcription factors. We generated a mutant mouse model to assess the in vivo role of the predominant E2F family member, E2F4. Remarkably, loss of E2F4 had no detectable effect on either cell cycle arrest or proliferation. However, E2F4 was essential for normal development. E2f4-/- mice died of an increased susceptibility to opportunistic infections that appeared to result from craniofacial defects. They also displayed a variety of erythroid abnormalities that arose from a cell autonomous defect in late stage maturation. This suggests that E2F4 makes a major contribution to the control of erythrocyte development by the pRB tumor suppressor.

Animals↗

Pheromone-regulated genes required for yeast mating differentiation.

Yeast cells mate by an inducible pathway that involves agglutination, mating projection formation, cell fusion, and nuclear fusion. To obtain insight into the mating differentiation of Saccharomyces cerevisiae, we carried out a large-scale transposon tagging screen to identify genes whose expression is regulated by mating pheromone. 91,200 transformants containing random lacZ insertions were screened for beta-galactosidase (beta-gal) expression in the presence and absence of alpha factor, and 189 strains containing pheromone-regulated lacZ insertions were identified. Transposon insertion alleles corresponding to 20 genes that are novel or had not previously been known to be pheromone regulated were examined for effects on the mating process. Mutations in four novel genes, FIG1, FIG2, KAR5/ FIG3, and FIG4 were found to cause mating defects. Three of the proteins encoded by these genes, Fig1p, Fig2p, and Fig4p, are dispensible for cell polarization in uniform concentrations of mating pheromone, but are required for normal cell polarization in mating mixtures, conditions that involve cell-cell communication. Fig1p and Fig2p are also important for cell fusion and conjugation bridge shape, respectively. The fourth protein, Kar5p/Fig3p, is required for nuclear fusion. Fig1p and Fig2p are likely to act at the cell surface as Fig1:: beta-gal and Fig2::beta-gal fusion proteins localize to the periphery of mating cells. Fig4p is a member of a family of eukaryotic proteins that contain a domain homologous to the yeast Sac1p. Our results indicate that a variety of novel genes are expressed specifically during mating differentiation to mediate proper cell morphogenesis, cell fusion, and other steps of the mating process.

Amino Acid Sequence↗

Single pass lead VDD pacing in children and adolescents.

Implantation of permanent pacemakers in children and adolescents is possible but usually is limited to single chamber generators. The natural growth of these patients may require physiological pacing, but until recently two leads were required for this type of pacing. The single pass lead VDD pacing mode makes possible physiological pacing by using only one lead, for both atrial sensing and ventricular sensing and pacing. The feasibility of VDD pacing using endocardial lead was evaluated in 16 children and adolescents with congenital or postsurgical atrioventricular block. Their mean age was 7.9 +/- 4.9 years (range 1-16 years) and the smallest patient's weight was 8.2 kg. In all the patients, a single pass pacing lead with atrial sensing rings and bipolar ventricular pacing and sensing capability was implanted through the left or right subclavian vein. The pacemaker generator was implanted in a rectopectoral position. The mean atrial electrogram during the implantation was 4.2 +/- 2.1 mV and 2.6 +/- 1.9 mV after a mean of 1 week. The ventricular pacing threshold was 0.5 +/- 0.2 V; the ventricular pacing impedance was 560 +/- 95 omega; and the ventricular electrogram amplitude was 9.9 +/- 2.1 mV. This is a first report to demonstrate the feasibility of atrial synchronous ventricular endocardial pacing using a single pass lead in a relatively large group of children and adolescents.

Adolescent↗

Implantation of cardioverter defibrillator and pacemaker using the same pectoral quadrant.

We implanted a cardioverter defibrillator (ICD) together with a pacemaker system in three patients with ventricular tachycardia and bradyarrhythmias. Both systems (ICD and pacemaker) were implanted in the same left pectoral quadrant using a single skin incision and the subclavian and/or the cephalic vein. The ICD was implanted deep to the pectoralis major muscle, the pacemaker was placed subcutaneously in a more medial pocket. There were no technical difficulties during implantation or complications during follow-up.

Aged↗

Single lead VDD pacing: multicenter study.

Optimal treatment for patients with AV block and normal sinoatrial node (SA) function entails atrial sensing and ventricular pacing (VDD mode). Single-lead VDD pacing preserves AV synchrony, precludes the need to insert two leads, and makes the implanter's work simpler and quicker. Our objectives were to verify the performance of the Thera VDD pacing system (medtronic, Inc., Minneapolis, MN, USA), and evaluate the effectiveness of its atrial sensing and its ventricular sensing and pacing. In 165 patients, 150 adults (mean age 62 +/- 18 years) and 15 children (mean age 7 +/- 5 years) with 1 degree-3 degrees AV block and normal SA node function, a Thera VDD system (Models 8948 or 8968) was implanted. Intraoperative ventricular electrical measurements were not significantly different from those of VVI pacemakers. The mean amplitude of the atrial signal during implantation was 4.1 +/- 1.9 mV. Optimal atrial signals during implantation were usually obtained in the mid or lower part of the right atrium by using a special technique. Adequate atrial measurements remained stable throughout 24 months. There was no difference between serial measurements of atrial signal amplitudes at predischarge and during follow-up visits. Reposition of the lead was done in 2 patients (1.4%), and reprogramming to VVI in 7 patients: due to atrial fibrillation in 3 (1.8%) and due to atrial undersensing in 4 patients (2.4%). Thera VDD pacing is reliable and easy to manage with dependable atrial sensing and ventricular pacing. The survival rate of VDD pacing at 2 years was 96%.

Adolescent↗

Plasticity in spinal opioid control of lower urinary tract function in paraplegic cats.

Spinal cord injury disrupts micturition reflexes, which produces morbidity. The contribution of endogenous opioid systems to urinary retention were assessed in chronic spinal cats by administering the opioid receptor antagonist, naloxone (5-500 micrograms kg-1, i.p.), to unanesthetized paraplegic cats while monitoring lower urinary tract function and observing hind limb reflexes. While naloxone had no overt effect in acute spinal cats, in chronic spinal cats naloxone induced the release of large volumes of urine and produced marked hind limb hyper-reflexia. Prominent tachyphylaxis and tolerance to the effects of naloxone were evident. Immunohistochemical studies indicated a marked increase in leucine enkephalin and dynorphin in sacral spinal neurons. Together, these data indicate hyperactivity of the endogenous spinal opioid system following recovery from spinal cord injury and, furthermore, suggest that the spinal neural circuitry may become 'dependent' upon elevated levels of endogenous opioid peptides.

Animals↗

Cardiomyoplasty review: physiological principles and characteristics of electrically stimulated skeletal muscle. II. A therapeutic option.

Chronic heart failure continues unsolved as ever despite recent advances in cardiac surgery and pharmacological new armamentarium and remains a significant cause of death, regardless of etiology. Cardiomyoplasty (CMP), a new form of biomechanical ventricular support, has given new life to the field of mechanical circulatory support, providing a "bridge" to transplantation and serving as a possible alternative to surgical treatment. The geographic distribution of world experience in 401 patients shows that 80% were centralized in Europe (50%) and South America (30%). This review of the data analysis, documented improved changes in patients clinical status, further clarifies and appropriate patients population indications for DCMP as well as that more than 80% survival probability for NYHA class II & III and an early procedure related mortality of 8 to 10%.

Cardiomyopathy, Dilated↗

Geometric reconstruction in left ventricular aneurysm. Surgical aspects and early results.

The early results of 79 patients who underwent left ventricular aneurysmectomy with geometric and circular reconstruction in a seven-year experience are analyzed. The most common indication for operation was congestive heart failure (78.4%), either isolated (25.3%) or with angina (53.1%). Sixty patients (76%) were in NYHA class III and 10 (12.6%) in NYHA class IV at the time of surgery. Fifty-eight (73.4%) underwent coronary artery by-pass graft surgery. Hospital mortality was 5.1%, in patients older than 60 (12%), in NYHA class IV (20%), with poor left ventricular function (EF < 0.30-20% and LVED > 25) (14%), and with extensive coronary artery disease (10%) were under increased risk. Low cardiac output and use of intra-aortic balloon pump were also associated risk factors. Other risk factors mentioned in the literature are discussed. There were no deaths from isolated left ventricular aneurysmectomy. The early results of this study and the early and late results of others using the same technique are better than the results obtained in previous studies of different types of correction, suggesting that this is the procedure of choice for treating left ventricular aneurysm.

Adult↗

Localization of peripheral pulmonary nodules for thoracoscopic excision: value of CT-guided wire placement.

OBJECTIVE: One of the indications for the rapidly expanding use of thoracoscopic surgery as an alternative to thoracotomy is the excision of peripheral lung nodules. Nodules judged too small or too far from the pleural surface to be seen or palpated during thoracoscopy must be localized beforehand. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous placement of spring hookwires to localize such nodules before video-assisted thoracoscopy. SUBJECTS AND METHODS: Under CT guidance, 17 nodules in 14 patients were preoperatively localized with the Kopans breast lesion localization system. Three patients who had solitary nodules had thoracoscopic resections for diagnosis because a previous transthoracic needle or transbronchial biopsy had been unsuccessful. Four patients who had lesions less than 8 mm in diameter had thoracoscopic biopsies because transthoracic fine-needle aspiration biopsy was not likely to be diagnostic. Seven patients, who had a total of 10 nodules, had therapeutic wedge resections of either limited metastases or a second bronchogenic carcinoma. Mean nodule diameter was 10 mm (range, 3-20 mm). The mean distance from nodule to costal pleura was 9 mm (range, 0-25 mm). At the end of the procedure, wire placement was confirmed by CT scanning. After thoracoscopy, the surgeons were questioned about the stability and utility of each hookwire localization. RESULTS: In all 17 procedures, a hookwire was placed successfully. In one case, the wire dislodged before thoracoscopy (after a 6-hr preoperative delay and severe bending of the wire during induction of anesthesia). In 16 of the 17 resections, the surgeon thought that thoracoscopic identification of the lesion would not have been possible without hookwire localization. Only one localization, across a major fissure, required placement of a second wire to localize a nodule. Wire-related complications included two instances of serious pain, five cases of clinically insignificant pneumothorax, and one large pneumothorax requiring drainage before a second nodule in the same lung was localized. CT scanning showed presumed local pulmonary hemorrhage in six cases without hemoptysis or hemothorax. CONCLUSION: CT-guided hookwire localization is easily and safely performed and permits thoracoscopic resection of lung nodules, which might otherwise be impossible.

Adult↗

Seven years of left ventricular pacing due to malposition of pacing electrode.

The case report is presented of a patient in whom an uncomplicated left ventricular transvenous pacing produced right bundle branch block (RBBB). A diagnostic echocardiography, confirmed by cine cardiovascular computed tomography, showed that there was no rupture of the right ventricle and diagnosed a left ventricular pacing, due to malposition of the pacing electrode. The patient was treated with aspirin and dipyridamole during the last 6 years of follow-up, without any complications, including 1 year of pacing, prior to admission.

Bundle-Branch Block↗

Alterations in afferent pathways from the urinary bladder of the rat in response to partial urethral obstruction.

Afferent pathways from the urinary bladder were examined with axonal tracing techniques in normal female Wistar rats and in those with partial urethral ligation. Following injection of wheat germ agglutinin-horseradish peroxidase (HRP) into the bladder wall, HRP was detected in lumbosacral dorsal root ganglion cells and in afferent projections to the L6-S1 spinal cord at sites in laminae I, II, V-VII, and X known to receive visceral afferent input. Partial urethral ligation (6 weeks) produced a sixfold increase in bladder weight and altered the morphology of bladder afferent pathways. Changes included an increase in the average cross-sectional area of labelled neuronal profiles in L6 and S1 dorsal root ganglia in obstructed (766 +/- 378 microns 2, P less than 0.001) compared to control rats (528 +/- 189 mu 2). The cross-sectional area of the largest profiles also increased by approximately 40%. The mean number of labelled dorsal root ganglion cell profiles was similar in ligated (837 +/- 198) and control (883 +/- 352) groups. When compared to control animals the obstructed animals exhibited a 60% increase in the area of the labelled afferent terminal field in the intermediolateral region of the L6-S1 spinal cord. This increased labelling was even more remarkable given that the volume of tracer per bladder weight injected into the hypertrophied bladder was 87% less than controls. These results provide evidence that bladder afferents project to regions of the spinal cord known to regulate micturition and that these afferents can undergo morphological alterations and/or changes in axoplasmic transport in response to urethral ligation. Changes may occur in response to increased target organ mass, increased neural activity, or alterations in the levels or activity of neurotrophic factors.

Afferent Pathways↗

Neonatal hepatitis and extrahepatic biliary atresia associated with cytomegalovirus infection in twins.

Prenatally acquired cytomegalovirus infection in twins was temporally associated with a discordant development of neonatal hepatitis and extrahepatic biliary atresia. This case presents evidence suggesting an association between perinatal cytomegalovirus infection and selected extrahepatic biliary atresia and neonatal hepatitis. Congenital cytomegalovirus infections and cytomegalovirus hepatitis are also discussed.

Biliary Atresia↗

Postnatal development of opioid regulation of micturition in the kitten.

Endogenous opioids tonically regulate micturition in adult mammals. The present study sought to determine if opioids regulate micturition in neonatal kittens. Naloxone (up to 2 mg/kg given i.p. or i.v. to unanesthetized/ketamine-anesthetized or chloralose-anesthetized kittens, respectively), an opioid receptor antagonist, produced no effects in unanesthetized, ketamine-anesthetized, or chloralose-anesthetized kittens that had been prepared for bladder pressure recording, until 3 weeks of age. This indicates that endogenous opioids are not tonically regulating micturition in neonatal kittens. From 3 weeks up to at least 6 weeks of age, naloxone (100 micrograms/kg i.p. or i.v.) weakly facilitated bladder activity by transiently increasing the amplitude and/or duration of bladder contractions, but no effects on frequency of contractions was recorded. Morphine (up to 2 mg/kg given i.p. or i.v. to unanesthetized/ketamine-anesthetized or chloralose-anesthetized kittens, respectively), an opioid agonist, did not inhibit bladder contractions in unanesthetized or ketamine-anesthetized neonatal kittens, but it did inhibit (at a threshold dose of 100 micrograms/kg) and completely abolished (at a dose of 300 micrograms/kg) bladder activity in chloralose-anesthetized kittens in a dose-dependent, naloxone-reversible manner. Surprisingly, following morphine administration to unanesthetized or ketamine-anesthetized neonatal kittens, naloxone now produced an adult-like enhancement of bladder activity. These latter results indicate that opioid receptors, whose inhibitory effects are anesthetic-dependent, are present along the micturition reflex pathway in neonates. Immunohistochemical studies of the sacral spinal cord revealed that opioid peptides are distributed similarly in neonatal and adult cats.

Animals↗