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Biomedical subjects

J Bass

Publications and source records attributed to J Bass.

At least 19 recordsLinked to original sources
PubMed2001

Combined posterior sagittal and three-flap anoplasty in the repair of anorectal anomalies.

PURPOSE: The aim of this study was to describe a new technique for the repair of high and intermediate imperforate anus. METHODS: From 1989 to 1999, 22 children with high and intermediate imperforate anus (17 boys, 5 girls) were operated on with a combination of a posterior sagittal and 3-flap perineal anoplasty. Long-term clinical follow up (to a maximum of 10 years) was done in all patients as well as a recent phone interview with a questionnaire regarding bowel function and degree of satisfaction with the result of the surgical correction. A continence ratio (CR, patient score/maximum possible score) was obtained by a blinded interviewer. RESULTS: A continence survey was obtained in 19 patients. The average CR was 0.68. The CR for high anomalies was 0.62 and for intermediate anomalies was 0.78 (0.84 for girls and 0.64 for boys). Patients with sacral anomalies had a CR of 0.58. Two patients with Trisomy 21 had associated Hirschsprung's disease and were excluded from analysis. CONCLUSIONS: Advantages of this combined surgical approach are excellent anatomic exposure, the ability to limit rectal mobilization to a minimum, reduction of the incidence of mucosal prolapse, the new skin-lined anal canal may assist attainment of continence by providing a "sensory warning zone," and, finally, the cosmetic appearance is satisfactory.

Abnormalities, Multiple↗
PubMed2000

Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation.

Myostatin, a member of the transforming growth factor-beta (TGF-beta) superfamily, has been shown to be a negative regulator of myogenesis. Here we show that myostatin functions by controlling the proliferation of muscle precursor cells. When C(2)C(12) myoblasts were incubated with myostatin, proliferation of myoblasts decreased with increasing levels of myostatin. Fluorescence-activated cell sorting analysis revealed that myostatin prevented the progression of myoblasts from the G(1)- to S-phase of the cell cycle. Western analysis indicated that myostatin specifically up-regulated p21(Waf1, Cip1), a cyclin-dependent kinase inhibitor, and decreased the levels and activity of Cdk2 protein in myoblasts. Furthermore, we also observed that in myoblasts treated with myostatin protein, Rb was predominately present in the hypophosphorylated form. These results suggests that, in response to myostatin signaling, there is an increase in p21 expression and a decrease in Cdk2 protein and activity thus resulting in an accumulation of hypophosphorylated Rb protein. This, in turn, leads to the arrest of myoblasts in G(1)-phase of cell cycle. Thus, we propose that the generalized muscular hyperplasia phenotype observed in animals that lack functional myostatin could be as a result of deregulated myoblast proliferation.

Animals↗
PubMed2000

Furin-mediated processing in the early secretory pathway: sequential cleavage and degradation of misfolded insulin receptors.

Improperly folded membrane proteins are retained in the endoplasmic reticulum and then diverted to a degradative pathway by a network of molecular chaperones and intracellular proteases. Here we report that mutant insulin proreceptors (Pro(62)) retained in the early secretory pathway undergo proteolytic cleavage at a tetrabasic concensus site for the subtilisin-like protease furin (SPC 1), generating two unstable proteolytic intermediates of 80/120 kDa corresponding to alpha (135 kDa) and beta (90 kDa) subunits. These are degraded more rapidly than the uncleaved proreceptor protein. Site-directed mutagenesis of the normal RKRR processing site prevented cleavage. Use of inhibitors and furin-deficient cell lines confirmed that furin is responsible for proreceptor cleavage; furin overexpression increased the degradation of mutant but not wild-type receptors. Together, these results suggest that processing and degradation occur sequentially for mutant proreceptors.

Base Sequence↗
PubMed2000

Generation and detection of phase-coherent current-driven magnons in magnetic multilayers

The magnetic state of a ferromagnet can affect the electrical transport properties of the material; for example, the relative orientation of the magnetic moments in magnetic multilayers underlies the phenomenon of giant magnetoresistance. The inverse effect--in which a large electrical current density can perturb the magnetic state of a multilayer--has been predicted and observed experimentally with point contacts and lithographically patterned samples. Some of these observations were taken as indirect evidence for current-induced excitation of spin waves, or 'magnons'. Here we probe directly the high-frequency behaviour and partial phase coherence of such current-induced excitations, by externally irradiating a point contact with microwaves. We determine the magnon spectrum and investigate how the magnon frequency and amplitude vary with the exciting current. Our observations support the feasibility of a spin-wave maser' or 'SWASER' (spin-wave amplification by stimulated emission of radiation).

Journal Article↗
PubMed2000

Myostatin regulation during skeletal muscle regeneration.

Myostatin, a member of the TGF-beta superfamily, is a key negative regulator of skeletal muscle growth. The role of myostatin during skeletal muscle regeneration has not previously been reported. In the present studies, normal Sprague-Dawley and growth hormone (GH)-deficient (dw/dw) rats were administered the myotoxin, notexin, in the right M. biceps femoris on day 0. The dw/dw rats then received either saline or human-N-methionyl GH (200microg/100g body weight/day) during the ensuing regeneration. Normal and dw/dw M. biceps femoris were dissected on days 1, 2, 3, 5, 9 and 13, formalin-fixed, then immunostained for myostatin protein. Immunostaining for myostatin revealed high levels of protein within necrotic fibres and connective tissue of normal and dw/dw damaged muscles. Regenerating myotubes contained no myostatin at the time of fusion (peak fusion on day 5), and only low levels of myostatin were observed during subsequent myotube enlargement. Fibres which survived assault by notexin (survivor fibres) contained moderate to high myostatin immunostaining initially. The levels in both normal and dw/dw rat survivor fibres decreased on days 2-3, then increased on days 9-13. In dw/dw rats, there was no observed effect of GH administration on the levels of myostatin protein in damaged muscle. The low level of myostatin observed in regenerating myotubes in these studies suggests a negative regulatory role for myostatin in muscle regeneration.

Animals↗
PubMed2000

An ovine model of chronic stable heart failure.

BACKGROUND: Chronic stable large animal models of heart failure are difficult to establish. We report an ovine model of chronic stable heart failure achieved by a technique of repetitive myocardial infarctions (one of the most common causes of cardiac failure) with catheter-based techniques. METHODS AND RESULTS: Ejection fraction (EF) was assessed by echocardiography. A perfusion catheter was positioned in either the left anterior descending or circumflex artery by using standard angioplasty techniques. Myocardial infarction was induced by a Gelfoam embolism via this catheter and was confirmed by electrocardiographic (ECG) changes and new segmental abnormalities. The procedure was repeated at 2 weekly intervals until the EF was less than 40%. Target EF was achieved in 15 animals, with a mean of 3.4 embolizations (range 2 to 8). Baseline EF was 68%, with a mean final EF of 33%. This resulted in a 54% reduction in EF (range 44% to 68%) from baseline values. Two animals developed late symptomatic heart failure and died, whereas EF was stable at 3-month follow-up echocardiography in the remaining animals with no significant spontaneous improvement. CONCLUSION: Chronic stable heart failure can be established in sheep with catheter-based skills and a microembolization technique that causes repetitive myocardial infarctions.

Animals↗
PubMed2000

Transcatheter closure of post-infarction ventricular septal defect with the Amplatzer Septal Occluder device.

There is an 80-90% mortality rate within the first 2 months of the occurrence of a post-infarction ventricular septal defect (VSD) with medical treatment alone. The muscular VSD presents a technical problem for the surgeon. Surgical treatment was unsuccessful in two patients. They were treated successfully using the Amplatzer Septal Occluder, with improvement in their condition.

Aged↗
PubMed2000

Familial British dementia: expression and metabolism of BRI.

Vidal et al. (1999. Nature 399: 776-778) discovered that the underlying genetic lesion in familial British dementia (FBD) is a T-A transversion at the termination codon of a membrane protein, termed BRI. The mutation creates an arginine codon; translational read-through generates a novel protein, termed BRI-L, that is extended by 11 amino acids at the carboxyl-terminus. BRI-L is the precursor of the ABri peptide, a component of amyloid deposits in FBD brain. We demonstrate that both BRI and its mutant counterpart are constitutively processed by furin, resulting in the secretion of carboxyl-terminal peptide derivatives that correspond to all, or part of, ABri. Notably, elevated levels of peptides are generated from the mutant BRI precursor, suggesting that subtle conformational alterations at the carboxyl-terminus may influence furin-mediated processing. We have examined BRI/BRI-L processing by other members of the prohormone convertase (PC) family (PACE4, LPC, PC 5/6) and found that these enzymes also process BRI, albeit inefficiently. Moreover, BRI-L processing by the other PC members is severely compromised. Finally, our electron microscopic studies reveal that synthetic ABri peptides assemble into insoluble beta-pleated fibrils. Collectively, our results support the view that enhanced furin-mediated processing of mutant BRI generates amyloidogenic peptides that initiate the pathogenesis of FBD.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Congenital insulin resistance associated with a conformational alteration in a conserved beta-sheet in the insulin receptor L1 domain.

The hormone binding site of members of the insulin receptor family is contained within a highly conserved extracellular region of the receptor. Recent crystallization of the N-terminal region of the binding site revealed two large domains (L1, L2), each organized as a single-stranded right-handed beta-helix, connected by a rod-shaped cysteine-rich domain. Here, we analyze two new naturally occurring mutations in a single beta-sheet within L1, D59G and L62P, that we previously identified in a young woman with classic congenital insulin resistance (type A). Substitution of D59G, a beta-sheet connecting loop residue, caused decreased hormone binding but did not disrupt overall folding, assembly, or movement to the cell surface. In contrast, replacement of the adjacent residue L62P, which is located within the beta-sheet, and positioned in a hormone binding surface, completely disrupted intracellular folding, oligomerization, and trafficking and resulted in aberrant proteolytic degradation. Immunohistochemistry in combination with biosynthetic studies showed that misfolded receptors were retained in an incorrect cellular location and that they colocalized with the resident endoplasmic reticulum chaperone calnexin. This study, together with other mutagenesis data, shows that formation of beta-sheet elements within the L1 beta-helix are critical for the folding of the entire extracellular domain of the receptor and that the hormone contact site is composed in part by residues in this domain.

Biotinylation↗
PubMed1999

Poor outcome of gastrointestinal perforations associated with childhood abdominal non-Hodgkin's lymphoma.

BACKGROUND/PURPOSE: With modern chemotherapeutic protocols and advances in medical care, the outcome of intraabdominal non-Hodgkin's lymphoma (NHL) in children can be excellent for limited disease. Advanced disease, however, is associated with increased tumor aggression and requires more rigorous adjuvant therapy. Hence, complications early in the course of the disease process or its management often lead to a poor outcome. Perforation of the gastrointestinal tract, either iatrogenic, tumor related or chemotherapeutically induced is one such complication and may result significant morbidity and mortality. METHODS: The authors reviewed their experience with this disease, and present two cases of children with abdominal NHL, which poignantly demonstrate these points. Results and a review of the literature are then discussed. RESULTS: Fifteen cases of abdominal NHL were examined with an overall mortality rate of 40%. This increased to 100% in the presence of perforation. In two cases, inadvertent entry into the bowel occurred at the time of laparotomy for tumor biopsy. In the first case, intestinal wall was included in the biopsy specimen; in the second, laparotomy unmasked an already sealed-off perforation secondary to tumor invasion. Sepsis ensued in both cases. In the first, this resulted in repeated delays in chemotherapy, and the child succumbed to the disease. In the second, chemotherapy was continued, and although the small bowel leak was controlled, the initial insult hampered marrow recovery and host defenses, resulting in fatal sepsis. CONCLUSIONS: These data and other reported cases in the literature indicate that intestinal perforation associated with abdominal lymphomas in children portends an extremely poor prognosis. All attempts to avoid this complication should be made, including avoiding direct tumor biopsy whenever possible.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Use of a state data bank to measure incidence and prevalence of a chronic disease: end-stage renal failure.

The Western Australian Health Services Research Linked Database was used to examine trends in the incidence rate and prevalence of end-stage renal failure and to describe treatment patterns in these patients. Linked hospital morbidity and mortality records from 1980 to 1994 were selected if a record had a principal diagnosis or procedure of chronic renal failure, dialysis, or renal transplantation. Patient records were grouped according to the stage of care (predialysis, dialysis, transplant, or death). A total of 1, 046 patients with a principal diagnosis or procedure that met our criteria for end-stage renal failure was admitted to the hospital from 1985 to 1994. Trends in the incidence rate and prevalence of end-stage renal failure by sex and race, patterns of care, indices of comorbidity, and waiting time to transplantation were calculated. Results showed that both the incidence rate and prevalence of end-stage renal failure increased from 1986 to 1994, most noticeably in the aboriginal population. Rates of renal failure in 1994 were 15 times greater in aborigines than in nonaborigines. Of the hospital patients, 73.5% received dialysis three times a week. Complications associated with dialysis treatment were the most common cause of comorbid hospitalization. The mean waiting time to transplantation was 503 days for those who had a transplant and 6.3 years for all patients. The escalating numbers of patients undergoing renal dialysis, the high cost of maintaining them on dialysis, and the additional use of hospital services for comorbid conditions highlight the need to develop programs to prevent the occurrence of renal failure, particularly in the aboriginal population.

Adult↗
PubMed1999

Growth factors controlling muscle development.

The enlarged muscles of certain breeds of cattle, such as the Belgian Blue, have been shown to result from a marked increase in the number of normal sized muscle fibers. Originally insulin-like growth factors (IGFs) were implicated in this myofiber hyperplasia, as IGFs have been shown to stimulate myoblast proliferation as well as maintain fiber differentiation. Recently it has been reported that mice lacking a myostatin gene, a member of the TGFbeta superfamily, have enhanced skeletal mass resulting from increased muscle fiber number and size. Mutations in this gene have been found in double-muscled cattle, indicating that myostatin is an inhibitor of muscle growth. Myostatin is expressed early in gestation and then maintained to adulthood in certain muscles. Myostatin expression in bovine muscle is highest during gestation when muscle fibers are forming and some of the myogenic regulatory factors have elevated expression over the same period as myostatin. Molecular expression of the IGF axis does not differ between Belgian Blue and normal muscled cattle, and IGF-II mRNA is increased throughout formation of secondary fibers in both breeds. However, myostatin and MyoD expression in muscle differ between normal and hypertrophied muscle cattle breeds. This evidence strongly suggests that lack of myostatin is associated with an increase in fiber number which then results in a marked increase in potential muscle mass in double-muscled cattle.

Amino Acid Sequence↗
PubMed1999

Violence prevention and young adolescents' participation in community youth service.

PURPOSE: To examine whether participation in a school-sponsored community youth service program reduces self-reported violent behaviors among young urban adolescents. METHODS: A total of 972 seventh- and eighth-grade students at two large, urban, public middle schools were surveyed at baseline and at 6-month follow-up. One school was assigned to interventions and the other served as a control. All students at the intervention school received the Reach for Health classroom curriculum that included a 10-lesson unit focusing on violence prevention. In addition, approximately half the students were randomly assigned by classroom to participate in the Reach for Health Community Youth Service program (CYS). Under the guidance of teachers and community nurses, these students spent several hours each week providing service in local health care agencies. Regression analyses were used to assess the influence of treatment condition on violent behavior outcomes. RESULTS: Comparing students in the curriculum-only and curriculum-plus-CYS interventions to the control group, there is a statistically significant interaction (p < .03) among grade, CYS participation, and violence at follow-up. Eighth-grade CYS students reported significantly less violence at follow-up than students in the control school, taking into account baseline level of risk behavior, gender, ethnicity, and social desirability (p < .04). There was no significant difference between controls and students in the curriculum-only condition. Comparing students in the CYS intervention to the curriculum-only condition within the intervention school, the grade by intervention interaction again is significant (p < .05). Eighth-grade CYS students-who received the broadest CYS experience-reported less violence at follow-up than their curriculum-only counterparts. CONCLUSION: When delivered with sufficient intensity, school programs which couple community service with classroom health instruction can have a measurable impact on violent behaviors of a population of young adolescents at high risk for being both the perpetrators and victims of peer violence. Community service programs may be an effective supplement to curricular interventions and a valuable part of multicomponent violence prevention programs.

Adolescent↗
PubMed1999

Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia.

The genetic lesion underlying familial British dementia (FBD), an autosomal dominant neurodegenerative disorder, is a T-A transversion at the termination codon of the BRI gene. The mutant gene encodes BRI-L, the precursor of ABri peptides that accumulate in amyloid deposits in FBD brain. We now report that both BRI-L and its wild-type counterpart, BRI, were constitutively processed by the proprotein convertase, furin, resulting in the secretion of carboxyl-terminal peptides that encompass all or part of ABri. Elevated levels of peptides were generated from the mutant BRI precursor. Electron microscopic studies revealed that synthetic ABri peptides assembled into irregular, short fibrils. Collectively, our results support the view that enhanced furin-mediated processing of mutant BRI generates fibrillogenic peptides that initiate the pathogenesis of FBD.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Retrograde esophageal balloon dilatation for caustic stricture in an outpatient clinic setting.

Caustic injury to the esophagus, with resultant esophageal stricture, is a challenge for the surgeon. These strictures require multiple esophageal dilatations, which are usually performed under general anesthesia and frequently under fluoroscopic control. Because of the risks of multiple general anesthetics and frequent radiation, a technique is described for retrograde esophageal balloon dilatation in an outpatient clinic setting without a general anesthetic or fluoroscopic control.

Ambulatory Care↗
PubMed1998

Folding of insulin receptor monomers is facilitated by the molecular chaperones calnexin and calreticulin and impaired by rapid dimerization.

Many complex membrane proteins undergo subunit folding and assembly in the ER before transport to the cell surface. Receptors for insulin and insulin-like growth factor I, both integral membrane proteins and members of the family of receptor tyrosine kinases (RTKs), are unusual in that they require homodimerization before export from the ER. To better understand chaperone mechanisms in endogenous membrane protein assembly in living cells, we have examined the folding, assembly, and transport of the human insulin receptor (HIR), a dimeric RTK. Using pulse-chase labeling and nonreducing SDS-PAGE analysis, we have explored the molecular basis of several sequential maturation steps during receptor biosynthesis. Under normal growth conditions, newly synthesized receptor monomers undergo disulfide bond formation while associated with the homologous chaperones calnexin (Cnx) and calreticulin (Crt). An inhibitor of glucose trimming, castanospermine (CST), abolished binding to Cnx/Crt but also unexpectedly accelerated receptor homodimerization resulting in misfolded oligomeric proreceptors whose processing was delayed and cell surface expression was also decreased by approximately 30%. Prematurely-dimerized receptors were retained in the ER and more avidly associated with the heat shock protein of 70 kD homologue binding protein. In CST-treated cells, receptor misfolding followed disordered oligomerization. Together, these studies demonstrate a chaperone function for Cnx/Crt in HIR folding in vivo and also provide evidence that folding efficiency and homodimerization are counterbalanced.

Animals↗