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Biomedical subjects

L Baskin

Publications and source records attributed to L Baskin.

At least 19 recordsLinked to original sources
PubMed2001

Hypospadias: a critical analysis of cosmetic outcomes using photography.

OBJECTIVE: To analyse the cosmetic outcome of hypospadias surgery using photography, rather than the classical assessment by reoperation rate secondary to fistula, diverticulum, stenosis and residual penile curvature. PATIENTS AND METHODS: The study included 181 consecutive patients with hypospadias who underwent surgery between 1997 and 1999. Distal hypospadias (47) was repaired using either the 'meatal advancement and glanuloplasty' or the glans approximation procedure. Proximal hypospadias (68) was repaired using the onlay island-flap technique with preservation of the urethral plate. Penile curvature when present was corrected by dorsal plication ( approximately 20%). Two patients with perineal hypospadias required a two-stage repair. Complex repeat repairs (36) were defined as those patients who had undergone previous surgery 1-7 times and required a new urethroplasty by a secondary onlay island-flap technique. The follow-up ranged from 6 months to 3 years. Photographs of the penis were taken before, immediately and 3-12 months after surgery; these were assessed to document objectively the cosmetic outcome. The final photographs were evaluated for overall appearance, a mucosal collar, the location and configuration of the meatus. The standard was to create a penis that would pass cosmetically as a normal circumcised penis. RESULTS: The patients who had chordee without hypospadias (15) and fistula repair (13) did not undergo glanuloplasty and therefore were not included in the final photographic analysis; this left 153 patients with follow-up photographs. There were five cases of urethral fistula (7%) and one of meatal stenosis (1%) in the proximal group, and three of fistula (8%) and two meatal stenosis (6%) in the complex group. The distal group had one complication (haematoma) and the two-stage group had no complications. Analysis of the photographs showed that most patients had the appearance of a normal circumcised penis. Not unexpectedly, the patients who had undergone previous surgery had the least satisfactory results (60% appearing normal) compared with the proximal and distal groups (76% and 82% appearing normal, respectively). CONCLUSIONS: Hypospadias can be repaired safely with few complications in a single stage in most patients. Classical complications such as fistula and stenosis occur in < 10% of patients, including those undergoing complex revisions. Cosmetic outcomes are generally good and photography is an objective means to document the appearance.

Follow-Up Studies↗
PubMed2001

Mesenchymal-epithelial interactions in bladder smooth muscle development: effects of the local tissue environment.

PURPOSE: We have previously shown that mesenchymal-epithelial interactions are necessary for the development of bladder smooth muscle. Specifically without fetal or adult urothelium embryonic rat bladder mesenchyma does not differentiate into smooth muscle. The mechanism responsible for this interaction is not known, although it is postulated that diffusable growth factors have a role. Our hypothesis is that diffusable factors within adult rat bladders influence smooth muscle differentiation. MATERIALS AND METHODS: Chimeric bladders were created by surgically implanting 14-day embryonic rat bladder mesenchyma before smooth muscle differentiation into the detrusor space of adult syngeneic hosts to test whether the host urothelium would induce smooth muscle differentiation without being in direct contact with fetal bladder mesenchymal tissue. Sub-detrusor pockets were created between the serosa and smooth muscle layer, between the smooth muscle layer and lamina propria, and between the lamina propria and urothelium in direct contact with urothelium. Controls consisted of intact 14-day embryonic rat bladders with the urothelium not removed, and 14-day embryonic bladder mesenchyma recombined with urothelium (direct contact) placed within the sub-detrusor space of the bladder and under the renal capsule. RESULTS: Immunohistochemical staining with antibodies directed against smooth muscle alpha-actin and urothelium (cytokeratin 7) revealed smooth muscle differentiation in intact embryonic bladders and bladder mesenchyma plus urothelium recombinants in contrast to bladder mesenchyma alone, which had no alpha-actin staining (morphometric smooth muscle analysis p = 0). There was no alpha-actin staining in chimeric bladders even when bladder mesenchymal grafts were placed directly in contact with host urothelium. In addition, bladder mesenchyma plus urothelial recombinants within the host bladder had less alpha-actin staining than their counterparts placed under the renal capsule (p = 0.001). CONCLUSIONS: A diffusable factor most likely exists within adult rat bladders that inhibits smooth muscle differentiation.

Animals↗
PubMed1998

Protein kinase C delta (PKCdelta) inhibits the expression of glutamine synthetase in glial cells via the PKCdelta regulatory domain and its tyrosine phosphorylation.

Protein kinase C (PKC) plays an important role in the proliferation and differentiation of glial cells. In a recent study we found that overexpression of PKCdelta reduced the expression of the astrocytic marker glutamine synthetase (GS). In this study we explored the mechanisms involved in the inhibitory effect of PKCdelta on the expression of glutamine synthetase. Using PKC chimeras we first examined the role of the catalytic and regulatory domains of PKCdelta on the expression of glutamine synthetase. We found that cells stably transfected with chimeras between the regulatory domain of PKCdelta and the catalytic domains of PKCalpha or epsilon inhibited the expression of GS, similar to the inhibition exerted by overexpression of PKCdelta itself. In contrast, no significant effects were observed in cells transfected with the reciprocal PKC chimeras between the regulatory domains of PKCalpha or epsilon and the catalytic domain of PKCdelta. PKCdelta has been shown to undergo tyrosine phosphorylation in response to various activators. Tyrosine phosphorylation of PKCdelta in response to phorbol 12-myristate 13-acetate and platelet-derived growth factor occurred only in chimeras which contained the PKCdelta regulatory domain. Cells transfected with a PKCdelta mutant (PKCdelta5), in which the five putative tyrosine phosphorylation sites were mutated to phenylalanine, showed markedly diminished tyrosine phosphorylation in response to phorbol 12-myristate 13-acetate and platelet-derived growth factor and normal levels of GS. Our results indicate that the regulatory domain of PKCdelta mediates the inhibitory effect of this isoform on the expression of GS. Phosphorylation of PKCdelta on tyrosine residues in the regulatory domain is implicated in this inhibitory effect.

Bryostatins↗
PubMed1998

Detection of oligoclonal bands in cerebrospinal fluid by immunofixation electrophoresis.

Multiple sclerosis is a severe demyelinating disease, the diagnosis of which is aided by biochemical tests, such as detection of oligoclonal immunoglobulin bands in the cerebrospinal fluid (CSF). Because interpretation of agarose gel electrophoresis (AGE) of CSF for oligoclonal bands is often equivocal, we compared immunofixation electrophoresis (IFE) with AGE for 124 consecutive CSF specimens submitted to the Parkland Memorial Hospital Clinical Chemistry Laboratory (Dallas, Tex) for detection of oligoclonal bands. Both methods used the Paragon Electrophoresis Systems (Beckman Instruments, Brea, Calif). Anti-IgG antisera was used exclusively on all specimens. Oligoclonal bands were identified in 23 specimens (18.5%), while the other 101 (81.5%) were interpreted as negative by both methods. Of the positive specimens, 17 (74%) were positive by both methods, 5 (22%) by IFE alone, and 1 (4%) by AGE alone. Of the 23 patients with positive specimens represented, 17 (74%) had been given a diagnosis of multiple sclerosis. The patient whose specimen was positive by AGE alone had a diagnosis of HIV infection with Guillain-Barré syndrome. The sensitivities (with 95% confidence intervals) of IFE and AGE were 73.9% (51.3-88.9) and 56.5% (34.9-76.1), respectively. The specificities of both methods were identical at 95.0% (88.3-98.2). Subjective assessment of the gels demonstrated that the IFE method is consistently easier to interpret than AGE. The IFE method seems to be superior in identifying oligoclonal bands and thus aiding in diagnosis of demyelinating disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Multicenter experience with the Mitchell technique for epispadias repair.

PURPOSE: We present a multicenter experience using the Mitchell epispadias technique to determine if satisfactory results could be obtained by various pediatric urologists at multiple centers using the same technique to repair epispadias. This particular technique involves complete disassembly of the penis into 2 separate hemicorporeal glandular bodies and a separate urethral plate, and relies on the unique blood supply to the epispadiac phallus. MATERIALS AND METHODS: A total of 17 boys 11 months to 21 years old underwent the Mitchell procedure for epispadias at 4 institutions by 6 different surgeons between 1994 and 1996. One patient in this group had undergone prior epispadias repair, which had failed. RESULTS: At followup (mean 13.5 months) 3 boys had pinpoint penopubic fistulas, which resolved spontaneously in 2. The 21-year-old patient had a complete wound dehiscence. All boys with intact repairs have straight erections, orthotopic meatus and satisfactory appearances. There were 15 boys with a conical glans appearance and 1 exhibiting glandular disproportion. There was 1 episode of postoperative pyelonephritis. CONCLUSIONS: The Mitchell technique for repair of epispadias is reproducible and successful in the hands of pediatric urologists from different centers. Chordee is reliably corrected, erectile function preserved, the urethra ventrally situated in an anatomically precise fashion and satisfactory cosmesis achieved.

Adolescent↗
PubMed1997

Prevalence of elevated anticardiolipin antibodies in pregnant women with unexplained elevations of alpha-fetoprotein.

The goal was to determine what proportion of pregnant women with unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) have increased levels of anticardiolipin antibodies (ACA), and if this might explain the increased prevalence of adverse pregnancy outcomes. Maternal serum alpha-fetoprotein levels of 12,295 pregnant women were evaluated at 15-19.5 gestational weeks. Elevated readings (> 2.5 MOM) were identified in 190 women (1.5%) and 86 (0.7%) of these had unexplained causes. Specimens (80) were recovered and ACA levels for cardiolipin were determined using enzyme-linked immunosorbant assay. Positive IgG ACA were identified in 10 out of 80 cases (12.5%) of elevated MSAFP; 3 out of 80 cases (3.8%) had positive IgM ACA. The control women with normal MSAFP levels had positive IgG ACA in 3 of 86 cases (3.5%) and 1 of 86 cases (1.2%) for IgM. Women with increased MSAFP and positive ACA had infants with an average birth weight of 2684 +/- 889 g compared to 2793 +/- 847 g in women with increased MSAFP and normal ACA. No significant differences in IgG ACA were found in pregnant women with unexplained elevated MSAFP (10/80, 12.5%) compared to women with normal MSAFP (3/86, 3.5%). As expected, lower birth weight was identified in women who had elevated MSAFP (2738 +/- 868 g) vs. women with normal MSAFP 3181 +/- 1082 g (P = 0.004), independent of ACA positivity.

Adolescent↗
PubMed1996

Prenatal diagnosis of hypospadias.

Despite the fact that hypospadias is one of the most common congenital abnormalities of the genitalia, it is often missed on prenatal sonograms. In this paper, sonographic findings of six fetuses who were prospectively suspected to have hypospadias are presented. Of the six patients, isolated hypospadias was found in three, hypospadias with chordee in two, and isolated chordee in one. Additional malformations were present in four of the six fetuses. Sonographic findings of fetal hypospadias are described, and the embryology, anatomy, and associated abnormalities are discussed.

Congenital Abnormalities↗
PubMed1994

Bovine bladder compliance increases with normal fetal development.

In this study we characterized the elastic properties of the normal bovine bladder throughout fetal life, the newborn period and into adulthood. The elasticity of the bladder was measured with a novel circularly clamped bladder testing system. Pressurization of a circularly clamped bladder tissue sample caused the tissue to deflect upward repetitively in the shape of a spherical cap. If the centerline deflection is much larger than the tissue thickness, the elastic modulus, considered the inverse of compliance, can be determined using linear regression techniques. The results of our analyses showed that the elastic modulus decreases in direct proportion with increasing gestational age. These data suggest that during normal development of the bovine fetal bladder there is a progressive change from a rather stiff noncompliant bladder characterized by a high elastic modulus to a compliant bladder with a lower elastic modulus. Moreover, the increase in compliance appears in the developmental period when urine production first occurs. These observations suggest that volume work may be a significant event in the normal development process of the bovine bladder and results in an increase in bladder compliance. Conversely, the poorly compliant fetal bladder may explain some of the transient dilatations of the upper urinary tract which have been documented in utero. Finally, from the newborn period to the mature adult bovine we documented a relatively modest increase in the elastic modulus or decrease in bladder compliance which may reflect the normal aging process.

Animals↗
PubMed1993

Genomic sequences capable of committing mouse and rat fibroblasts to adipogenesis.

The mouse Swiss 3T3-F442A/3T3-C2 cell system is well suited for the isolation of genes involved in commitment to adipogenesis. 3T3-F442A cells convert to adipocytes with high efficiency in response to confluence and insulin. The sister clonal line 3T3-C2 does not respond to these signals, but can convert to adipocytes when transfected with DNA from 3T3-F442A preadipocytes or from human fat. Human fat-tissue biopsy FO46 DNA transfected into 3T3-C2 gave rise to fat foci after two rounds of transfection and selection. A cosmid library of a subclone of secondary transfectant 3T3-C2/FO46-1 was screened for the human repetitive Alu sequence. Five out of eight Alu+ recombinant clones committed 3T3-C2 cells to adipogenesis. The adipose commitment (AC) activity of one cosmid, p18A4, was found to reside in two small, non-identical, subcloned sequences 1.2kb and 2.0kb in length, each separately able to commit 3T3-C2, precrisis mouse and rat fibroblasts and the multipotential C3H10T1/2 cell line to adipogenesis. We conclude that commitment to adipogenesis can be effected in vitro with high efficiency by transfection of specific sequences into a variety of host cells.

3T3 Cells↗
PubMed1993

Congenital penile curvature (chordee without hypospadias).

We treated 30 patients aged six months to nine years with congenital penile curvature from 1988 to 1993. Twenty-four patients appeared to have a primary curvature with normal corpus spongiosum. In 12 of these 24 patients dissecting skin and dartos fascia were adequate to straighten the penis. In the other 12 patients, artificial erection demonstrated a varied degree of convexity of the penis after the skin and dartos fascia release, implying a disproportion of the corpora cavernosa bodies. We corrected this deformity using dorsal tumica albuginea plications (TAP). The remaining 6 patients presented with a primary curvature and hypoplastic urethra. In 5 of these patients we divided the hypoplastic midportion of the urethra leaving the meatus naturally on the glans and replaced the midurethral segment using a tubularized island flap. Of these 5 patients 2 required TAP for penile straightening. The final patient with a hypoplastic urethra was managed by preserving the urethral plate and applying an only island flap urethroplasty. Complications were one fistula and two mild ventral penile curvatures, presently not severe enough for reoperation (mean follow-up 2.6 years). We present a systematic approach for the repair of congenital penile curvature using intraoperative artificial erection, TAP, and the island flap urethroplasty when needed.

Algorithms↗
PubMed1993

Effect of physical forces on bladder smooth muscle and urothelium.

Abnormalities in bladder physiology may be due to obstruction (pressure) and/or neurological impairment. Clinically they can result in an increase in connective tissue and a decrease in bladder compliance. To study the effects of physical forces on the bladder without the influence of the nerves we developed a cellular model system by isolating the 2 major cell types in the bladder: smooth muscle and urothelial cells. Extracellular matrix protein biosynthesis by these 2 cell types in vitro has been characterized by metabolic labeling of proteins with [14C] radiolabeled proline and analysis by gel electrophoresis. These studies demonstrate that fetal bovine bladder smooth muscle and urothelial cells synthesize fibronectin and types I and III interstitial collagen. Since bladder cells exist in an active physical environment, we have attempted to simulate this at the cellular level. Using a device developed in our laboratory, we applied a precise and reproducible mechanical strain (physical force) to these 2 cell types. By enzyme linked immunosorbent assay we quantitated collagen types I and III and fibronectin synthesized by fetal bovine bladder smooth muscle and urothelial cells undergoing mechanical strain (4.9%). These cells were compared to unstrained control cells that were exposed to the same experimental conditions. For bladder smooth muscle cells we found a significant increase in collagen type III and fibronectin synthesis when compared to unstrained cells. In contrast, collagen type I synthesis decreased with mechanical strain. For bladder urothelial cells we found an increase in collagen type I and fibronectin while collagen type III remained unchanged. These studies demonstrate that extracellular matrix synthesis by urothelial and smooth muscle cells can be modulated by stretch (strain) in the absence of neurological input. It is likely that bladder function may be impaired as a result of abnormal synthesis of connective tissue.

Animals↗
PubMed1993

Effect of mechanical forces on extracellular matrix synthesis by bovine urethral fibroblasts in vitro.

The role of mechanical forces in normal physiological processes is just beginning to be elucidated. Using a system developed in our laboratory, we can apply precise and reproducible mechanical deformations (biaxial strain) to cells. These deformations alter cell activities in a reproducible fashion and may mimic the physical environment found in portions of the urinary tract. At a low strain of 1.8% no change in the synthesis of types I and III collagen by urethral fibroblasts was found. However, at a high strain (4.9%) types I and III collagen showed a significant increase in synthesis compared to controls (type I, 1.4 +/- 0.25 microgram. versus 0.9 +/- 0.27 microgram., p = 0.053; type III, 110 +/- 7 ng. versus 88 +/- 10 ng., p = 0.036). In addition, fibronectin synthesis was increased at low and high strains when compared to controls (low strain 3.20 +/- 1.03 micrograms. versus 1.46 +/- 0.15 microgram., p = 0.042; high strain 8.90 +/- 1.09 micrograms. versus 3.12 +/- 0.69 microgram., p = 0.001). We have shown at the cellular level that mechanical force applied to fetal bovine urethral fibroblasts results in an increase in the amount of collagen synthesis and fibronectin synthesis. These findings suggest that alterations in the physical environment of cells found in the urethral wall can affect biochemical processes including those that govern the synthesis of structural macromolecules such as collagen.

Animals↗
PubMed1992

Evidence that oocyte maturation induced by an oncogenic ras-p21 protein and insulin is mediated by overlapping yet distinct mechanisms.

We have recently shown that a peptide (residues 35-47) from a functional region of the ras p21 protein, thought to be involved in the binding of p21 to GTPase activating protein, the antibiotic azatyrosine, known to induce the ras-recision gene, and the selective protein kinase C inhibitor, CGP 41,251, all inhibit oncogenic p21 protein-induced maturation of oocytes in a dose-dependent manner. We now show that these three agents only partially inhibit insulin-induced oocyte maturation, known to be dependent on activation of cellular p21 protein. On the other hand, the anti-p21 protein antibody Y13-259 completely inhibits both insulin- and oncogenic p21 protein-induced maturation as does a tetrapeptide, CVIM, known to block the enzyme farnesyl transferase which covalently attaches the farnesyl moiety to the p21 protein allowing it to attach to the cell membrane. Our results suggest that while the oncogenic and insulin-activated normal p21 proteins share certain elements of their signal transduction pathways in common, these pathways diverge and allow for selective inhibition of the oncogenic pathway.

Alanine↗
PubMed1992

Denial and the discrepancy between heart rate and reported negative affect: a study of convergent and discriminant validity.

This study examined the convergent and divergent validity of heart-rate (HR)-based response discrepancy scores as measures of denial. After standardizing measures of stressor-related anxiety, hostility, and HR, response discrepancy scores were calculated by subtracting each measure of negative affect from the HR value. Analyses revealed the response discrepancy scores to correlate positively with measures of denial, negatively with a measure of trait anger, and to not correlate with measures of the nondefensive need for approval and the positive trait of curiosity. These findings support the construct validity of response discrepancy scores as markers of denial.

Adolescent↗
PubMed1989

Ureteral obstruction caused by vasculitis.

We report 2 cases of ureteral obstruction caused by vasculitis (polyarteritis nodosa and systemic lupus erythematosus). Case 1, in which the diagnosis was unknown preoperatively, was managed surgically with ureteral resection and reimplantation. Case 2 was managed medically with chlorambucil and corticosteroids, which resulted in resolution of ureteral obstruction.

Adolescent↗