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Biomedical subjects

A Aszodi

Publications and source records attributed to A Aszodi.

At least 19 recordsLinked to original sources

Type IX collagen is crucial for normal hearing.

cDNA microarray analysis indicated that COL9A1 and COL9A3 are highly expressed in the human inner ear, suggesting that type IX collagen has a crucial functional role in the inner ear. This study further confirmed, by means of real-time PCR, the presence of collagen type IX genes in the mouse inner ear. Immunocytochemical analysis also revealed that type IX collagen is distributed in the tectorial membrane, where it co-localizes with type II collagen, indicating that type IX collagen may contribute to the three-dimensional integrated structure of type II collagen molecules. Mice with targeted disruption of the col9a1 gene were shown through assessment by auditory brain stem response to have hearing loss, suggesting an important role of type IX collagen in maintaining normal hearing. At the light microscopic level, the tectorial membrane of knock-out mice was found to be abnormal in shape, and electron microscopy confirmed disturbance of organization of the collagen fibrils. An antibody against type II collagen failed to detect type II collagen in the tectorial membrane of type IX collagen knock-out mice, suggesting that a lack of type IX collagen may affect the three-dimensional structure of type II collagen molecules. These findings indicate that genes encoding each chain of type IX collagen may fulfill an important function associated with the tectorial membrane in the auditory system.

Animals↗

Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice.

The generation of nitric oxide (NO) in penile erectile tissue and the subsequent elevation of cyclic GMP (cGMP) levels are important for normal penile erection. Current treatments of erectile dysfunction elevate either cGMP levels by blocking cGMP degrading phosphodiesterase 5 or cyclic AMP (cAMP) levels by intrapenile injection of prostaglandin E1. The molecular target or targets of cGMP in erectile tissue and the role of cAMP for normal penile erection are not known. Herein, we report that mice lacking cGMP-dependent kinase I (cGKI) have a very low ability to reproduce and that their corpora cavernosa fail to relax on activation of the NO/cGMP signaling cascade. Elevation of cAMP by forskolin, however, induces similar relaxation in normal and cGKI-null corpus cavernosum. In addition, sperm derived from cGKI-null mice is normal, can undergo acrosomal reactions, and can efficiently fertilize eggs. Altogether, these data identify cGKI as the downstream target of cGMP in erectile tissue and provide evidence that cAMP signaling cannot compensate for the absence of the cGMP/cGKI signaling cascade in vivo.

Animals↗

Profilin II is alternatively spliced, resulting in profilin isoforms that are differentially expressed and have distinct biochemical properties.

We deduced the structure of the mouse profilin II gene. It contains five exons that can generate four different transcripts by alternative splicing. Two transcripts encode different profilin II isoforms (designated IIa and IIb) that have similar affinities for actin but different affinities for polyphosphoinositides and proline-rich sequences. Profilins IIa and IIb are also present in humans, suggesting that all mammals have three profilin isoforms. Profilin I is the major form in all tissues, except in the brain, where profilin IIa is most abundant. Profilin IIb appears to be a minor form, and its expression is restricted to a limited number of tissues, indicating that the alternative splicing is tightly regulated. Western blotting and whole-mount in situ hybridization show that, in contrast to the expression of profilin I, the expression level of profilin IIa is developmentally regulated. In situ hybridization of adult brain sections reveals overlapping expression patterns of profilins I and IIa.

Alternative Splicing↗

Ischemia detection after myocardial infarction: diagnostic value of exercise-induced QRS duration changes evaluated by a new computerized method.

A new computerized optical scanner was used to measure QRS complex duration during exercise stress testing, both pre- and postdischarge, as a means of ischemia detection after acute myocardial infarction. Thallium stress testing was used as a standard of comparison. Each patient underwent predischarge exercise testing (while receiving anti-ischemic drug therapy) and a postdischarge test 1 month later (without anti-ischemic drug therapy), as well as thallium stress testing within 4 months of infarction. In the population of 68 patients, 42 of the predischarge tests and 43 of the postdischarge tests showed an ischemic response of QRS prolongation. When compared with thallium testing for QRS prolongation criteria, the sensitivity was 95% with a specificity of 77% predischarge and 89% with a specificity of 65% postdischarge. According to ST-T criteria, only 12 of 68 patients were positive for ischemia predischarge; this number increased to 29 postdischarge (predischarge sensitivity 24% and specificity 90%, with postdischarge sensitivity 68% and specificity 87%), when compared with thallium testing. Measuring QRS duration during exercise increased the sensitivity of detection of ischemic patients over that of ST-T criteria by 71% predischarge and 21% postdischarge, with a 22-23% loss of specificity, and was apparently not influenced by anti-ischemic drug therapy.

Adult↗

Structure of the rabbit kappa-casein encoding gene: expression of the cloned gene in the mammary gland of transgenic mice.

The rabbit kappa-casein (kappa-Cas) encoding gene has been isolated as a series of overlapping DNA fragments cloned from a rabbit genomic library constructed in bacteriophage lambda EMBL3. The clones harboured the 7.5-kb gene flanked by about 2.1 kb upstream and 9 kb downstream sequences. The cloned gene is the most frequently occurring of two kappa-Cas alleles identified in New Zealand rabbits. Comparison of the corresponding domains in rabbit and bovine kappa-Cas shows that both genes comprise 5 exons and that the exon/intron boundary positions are conserved whereas the introns have diverged considerably. The first three introns are shorter in the rabbit, the second intron showing the greatest difference between the two species: 1.35 kb instead of 5.8 kb in the bovine gene. Repetitive sequence motives reminiscent of the rabbit C type repeat and the complementary inverted C type repeat were identified in the fourth and first introns, respectively. Transgenic mice were produced by microinjecting into mouse oocytes an isolated genomic DNA fragment which contained the entire kappa-Cas coding region, together with 2.1-kb 5' and 4.0-kb 3' flanking region. Expression of transgene rabbit kappa-Cas mRNA could be detected in the mammary gland of lactating transgenic mice and the production of rabbit kappa-Cas was detected in milk using species-specific antibodies. The cloned gene is thus functional.

Amino Acid Sequence↗

Skin wounds and severed nerves heal normally in mice lacking tenascin-C.

A large number of functions have been demonstrated for tenascin-C by antibody perturbation assays and in vitro cell culture experiments. However, these results contrast sharply with the lack of any apparent phenotype in mice with a genetic deletion of tenascin-C. A possible explanation for the lack of phenotype would be expression of some altered but functional tenascin-C in the mutant. We report the generation of an independent tenascin-C null mouse and conclude that the original tenascin-C knockout, which is genetically very similar to ours, is also a true null. As found previously, the absence of tenascin-C has no influence on development, adulthood, life span, and fecundity. We have studied in detail two models of wound healing. After axotomy, the regeneration of the sciatic nerve is not altered without tenascin-C. During healing of cutaneous wounds, deposition of collagen I, fibulin-2, and nidogen is identical in mutant and wild-type mice. In contrast. fibronectin appears diminished in wounds of tenascin-C-deficient mice. However, the lack of tenascin-C together with the reduced amount of fibronectin has no influence on the quality of the healing process.

Animals↗

Laparoscopic repair of a diaphragmatic laceration.

The role of laparoscopy in the management of trauma patients has yet to be determined. In the stable patient, laparoscopy can be used to verify peritoneal penetration and intra-abdominal organ injuries. This report describes a diaphragmatic laceration in a 17-year-old boy secondary to a single stab wound. This injury of the left hemidiaphragm was identified and repaired using laparoscopic techniques. This case demonstrates the value of laparoscopy as both a diagnostic and a therapeutic tool in the management of trauma patients.

Adolescent↗

Giant nonfunctioning islet cell tumor requiring pancreaticoduodenectomy and complete liver revascularization.

Pancreaticoduodenectomy with revascularization of the hepatic artery and portal vein was performed on a 17-year-old girl with giant nonfunctioning islet cell tumor of the pancreas. She had a remote history of neonatal hypoglycemia leading to mental retardation and a right Wilms' tumor resected at 8 months. Serum pancreatic polypeptide levels were elevated. Her postoperative course was complicated by an ischemic perforation of the colon, which did not infect her prosthetic vascular grafts. The relationship between her neonatal hypoglycemia, Wilms' tumor, and subsequent islet cell neoplasm is unclear.

Adenoma, Islet Cell↗

Detecting changes in neuronal activities induced by N-methyl-D-aspartate receptor blockade using non-linear dynamics techniques.

The dynamics of N-methyl-D-aspartate receptor blockade-induced transitions between two types of intracellularly recorded spontaneous membrane potential oscillation from cat thalamic neurons have been studied using non-linear dynamics techniques. We report that, as previously predicted by theoretical studies, the number of degrees of freedom of these oscillations (the minimal number of independent variables governing the activity) is small, i.e. they are low dimensional. The N-methyl-D-aspartate receptor antagonists DL-2-amino-5-phosphono-valeric acid and ketamine, which transformed one type of oscillation into another, decreased the calculated dimension. DL-2-Amino-5-phosphono-valeric acid had no effect on the dimension when Mg2+ was present in the perfusion medium. The decrease in dimension was gradual and its time-course had a sigmoidal shape. It is suggested that the application of the machinery of dynamical systems theory might help to detect and monitor drug-induced membrane potential state transitions and to identify the factors underlying membrane potential oscillations.

2-Amino-5-phosphonovalerate↗

Simple modification of the Gavriliu-Heimlich gastric tube.

A modification of the Gavriliu-Heimlich reversed gastric tube technique is described. We successfully used this method on eight patients. This procedure is more technically simple than the Gavriliu-Heimlich technique, and it avoids the necessity of splenectomy.

Esophagus↗

Effects of transient ischemia on the healing small bowel anastomosis.

The small bowel may be subjected to transient, yet reversible ischemia in situations such as volvulus, thromboembolism, and low flow states. The surgeon is frequently faced with the necessity of intestinal resection in treating such cases. The remaining bowel, while judged viable may have been exposed to significant ischemic injury. The surgeon must decide whether such bowel will heal satisfactorily if used in an anastomosis. This study was undertaken to determine the effect of transient ischemia on intestinal anastomotic healing in the rat. Male albino rats were subjected to superior mesenteric artery occlusion for periods of 30 minutes or 45 minutes. The circulation was then re-established. The small bowel was the transected and anastomosed. Animals in each group were sacrificed at 7 and 10 days and bursting pressures performed to test the healing of the anastomosis. Results were compared with a control group having an anastomosis without precedent ischemia. There were no significant differences among the groups. The data clearly indicate that if the bowel remains viable following an ischemic insult its healing is unimpaired.

Animals↗

Percutaneous approaches to enteral alimentation.

Feeding gastrostomy and jejunostomy provide effective access for long-term enteral nutrition. Traditional operative techniques for the performance of these procedures requires laparotomy and often, general anesthesia. This report describes our experience with two relatively new methods, percutaneous endoscopic gastrostomy and percutaneous endoscopic jejunostomy. Results of percutaneous gastrostomy and jejunostomy to date in 323 cases include a morbidity of 5.9 percent and a 0.3 percent operative mortality. Percutaneous endoscopic gastrostomy and jejunostomy should become the procedures of choice for the establishment of enteral access in patients requiring long-term enteral alimentation.

Adolescent↗

Effects of 5-fluorouracil on the healing of bowel anastomosis in rats.

This study looks at the effects of 5-Fluorouracil (5-FU) on surgical wound healing. A small bowel anastomosis was done 10 cm distal to the duodenum in rats. 5-FU was given by intramural infiltration on both sides of the suture line. Five, 10, and 20 mg of 5-FU were given in single doses. The control groups were given normal saline in the same manner. All groups were examined on days 4, 7, 8, and 12 postoperatively. The following methods were used to evaluate the anastomotic site: 1) bursting pressure measurements for tensile strength, 2) microangiography (micropaque), and 3) histopathologic sections. During the first 3 days postoperatively, the bowel had not healed sufficiently to permit significant bursting pressure measurements. Analysis of bursting pressure data and examination of the histopathologic sections showed no significant difference between the control groups and the 5-FU groups. Microangiography showed impaired dye distribution in the 5-FU groups during the first 4 to 6 days postoperatively. The control groups exhibited normal dye distribution. From day 7 on, the distribution in all groups became normal. Impaired dye distribution was the only measurable macroscopic change caused by intramural 5-FU administration. 5-FU injections had no apparent effect on anastomotic strength.

Animals↗

Surgical treatment of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a serious problem in nurseries for premature infants and neonatal intensive care units, with a high incidence of morbidity and mortality. During the 5-year period 1973-77, 86 infants with NEC were treated at the University of Iowa Hospitals and Clinics; 43 of them underwent surgery and 43 were treated medically. The surgical candidates were more seriously ill, and their survival rate was 42% compared with 63% for those treated conventionally. Early diagnosis and aggressive surgical treatment of NEC may decrease or even prevent the severity of life-threatening complications.

Abdomen↗

Effects of corticosteroid on the healing bowel anastomosis.

Conflicting results have been reported as to whether or not wound healing is retarded following treatment with corticosteroids. The surgical literature is lacking information on the effects of steroids on the healing bowel anastomosis. It has seemed reasonable to evaluate the bursting pressure, blood supply, and histologic changes of the bowel anastomosis in rats systemically pretreated with various doses of steroids. Male albino rats were pretreated with corticosteroids for 14 days in 20, 10, and 5 mg/kg of hydrocortisone acetate (intramuscular injection). A small bowel loop was divided and reanastomosed in each group (10 test and 5 control animals). The anastomosis was subsequently tested after 4, 5, 7, and 10 days. Three different methods of testing were used: 1) bursting pressure; 2) microangiography; and 3) histologic study. Large doses of 20 and 10 mg/kg of steroid deteriorated the test rats, significantly reducing the healing process within these 10 days as compared with the control rats. The 5 mg/kg group showed differences in bursting pressure only between the 4th and 7th postoperative days (statistical significance). Microangiography and histologic changes were not significant between the test and control rats. These results demonstrate decreased bursting pressure in steroid pretreated rats between the 4th and 7th postoperative days. These results may have implications regarding the care of steroid treated patients undergoing intestinal surgery.

Animals↗