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A Ndoye

Publications and source records attributed to A Ndoye.

34 records · Page 2Linked to original sources

The pathophysiological significance of nondesmoglein targets of pemphigus autoimmunity. Development of antibodies against keratinocyte cholinergic receptors in patients with pemphigus vulgaris and pemphigus foliaceus.

OBJECTIVES: To determine whether nondesmoglein (non-Dsg) autoantibodies are pathogenic and whether they recognize keratinocyte cholinergic receptors that control cell adhesion because antikeratinocyte autoimmunity in patients with pemphigus vulgaris is not limited to the development of autoantibodies to Dsg. DESIGN: To determine whether non-DSg autoantibodies are pathogenic, we sought to induce pemphigus in genetically engineered neonatal mice lacking Dsg 3 using pemphigus vulgaris IgGs that did not cross-react with Dsg 1. To determine whether pemphigus autoimmunity involves keratinocyte cholinergic receptors, the latter were separated from cell membranes of human keratinocytes, tagged with the covalent label [3H]propylbenzilylcholine mustard, and used as an antigen in a radioimmunoprecipitation assay of 34 pemphigus vulgaris and 6 pemphigus foliaceus serum samples. SETTING: The dermatologic clinics of the University of Minnesota, Minneapolis; the Mayo Clinic, Rochester, Minn; and the University of California-Davis Medical Center, Sacramento. PATIENTS: Serum samples were collected from 34 patients with pemphigus vulgaris and 6 patients with pemphigus foliaceus (aged 31-89 years) and from 7 age-similar patients of both sexes with nonpemphigus blistering or the following immune-mediated conditions: pemphigoid gestation, bullous drug eruption, lupus erythematosus, erythema nodosum, urticaria, acute contact dermatitis, and skin ulcers. MAIN OUTCOME MEASURES: Clinical, laboratory, and histopathologic findings. RESULTS: Extensive skin blistering accompanied by the Nikolsky sign and suprabasilar acantholysis was induced in the Dsg3null mice that received pemphigus, but not normal human IgGs. In the radioimmunoprecipitation assays for reactivity with cholinergic receptors, the mean radioactivity precipitated by pemphigus serum samples significantly exceeded both normal- and disease-control levels (P = .001-.02). The mean individual levels of radioactivity precipitated by 34 pemphigus vulgaris and pemphigus foliaceus serum samples (85%) exceeded control values by a mean of approximately 2.6 times. CONCLUSIONS: Autoantibodies to keratinocyte cell-surface molecules other than Dsg 1 and Dsg 3 can induce clinical features of pemphigus vulgaris. Patients with pemphigus vulgaris and those with pemphigus foliaceus develop IgG antibodies that precipitate radiolabeled cholinergic receptors. Because these receptors control keratinocyte adhesion and motility, their inactivation by autoantibodies may elicit intracellular signals that cause disassembly of desmosomes, leading to acantholysis and blistering.

Acantholysis↗

Regulation of new blood vessel growth into ischemic skeletal muscle.

PURPOSE: In a rabbit model, transposition of a muscle pedicle flap to an ischemic hind limb has been shown to result in the development of new blood vessels that connect the arterial circulation of the flap to the circulation of the limb. The hypothesis that exogenous recombinant basic fibroblast growth factor (bFGF) would enhance the development of this new blood supply was examined and the regulation of bFGF in this process was investigated. METHODS: The right common iliac artery was ligated in 12 male New Zealand white rabbits. An abdominal wall muscle flap based on the left inferior epigastric artery was transposed to the right thigh. bFGF in phosphate-buffered saline (PBS) at 3 ng/h (n = 6), or PBS alone (n = 6), was infused for 7 days via mini-osmotic pumps with an infusion catheter positioned at the flap-muscle interface. The flap-muscle interface was immunostained with anti-alpha-actin antibody to determine blood vessel density (number of vessels/mm) and with anti-bFGF antibody to evaluate bFGF distribution. RNA was isolated from these sections, and polymerase chain reaction (PCR) was used to examine endogenous bFGF messenger RNA (mRNA) expression. RESULTS: Blood vessel density was significantly increased in animals receiving exogenous bFGF (22. 0 +/- 10.6 vessels/mm vs. 10.7 +/- 8.8 vessels/mm, P =.009). In the controls, neovessels were arranged in clusters with endogenous bFGF concentrated around these clusters. In bFGF-treated animals, vessels were diffusely scattered throughout the flap-limb interface, corresponding to the distribution pattern of infused bFGF. There was no difference in bFGF mRNA expression between the control and the bFGF-treated groups. CONCLUSION: Exogenous bFGF infusion significantly augmented new blood vessel development at the flap-limb interface. Endogenous bFGF was up-regulated around the newly developed microvessels in control animals, and vessel growth correlated with the diffuse distribution of exogenous bFGF, implicating bFGF as an important factor in angiogenesis. Exogenous bFGF did not affect bFGF mRNA expression, suggesting that the regulation of bFGF is not under autocrine control.

Animals↗

Identification and mapping of keratinocyte muscarinic acetylcholine receptor subtypes in human epidermis.

Acetylcholine mediates cell-to-cell communications in the skin. Human epidermal keratinocytes respond to acetylcholine via two classes of cell-surface receptors, the nicotinic and the muscarinic cholinergic receptors. High affinity muscarinic acetylcholine receptors (mAChR) have been found on keratinocyte cell surfaces at high density. These receptors mediate effects of muscarinic drugs on keratinocyte viability, proliferation, adhesion, lateral migration, and differentiation. In this study, we investigated the molecular structure of keratinocyte mAChR and their location in human epidermis. Polymerase chain reaction amplification of cDNA sequences uniquely present within the third cytoplasmic loop of each subtype demonstrated the expression of the m1, m3, m4, and m5 mAChR subtypes. To visualize these mAChR, we raised rabbit anti-sera to synthetic peptide analogs of the carboxyl terminal regions of each subtype. The antibodies selectively bound to keratinocyte mAChR subtypes in immunoblotting membranes and epidermis, both of which could be abolished by preincubating the anti-serum with the peptide used for immunization. The immunofluorescent staining patterns produced by each antibody in the epidermis suggested that the profile of keratinocyte mAChR changes during epidermal turnover. The semiquantitative analysis of fluorescence revealed that basal cells predominantly expressed m3, prickle cells had equally high levels of m4 and m5, and granular cells mostly possessed m1. Thus, the results of this study demonstrate for the first time the presence of m1, m3, m4, and m5 mAChR in epidermal keratinocytes. Because keratinocytes express a unique combination of mAChR subtypes at each stage of their development in the epidermis, each receptor may regulate a specific cell function. Hence, a single cytotransmitter, acetylcholine, and muscarinic drugs may exert different biologic effects on keratinocytes at different stages of their maturation.

Antibody Specificity↗

[Hazards of lumbar ureteroscopy: apropos of 4 cases of avulsion of the ureter].

Ureteroscopy is frequently indicated in the treatment of stones of the pelvic ureter. Access to the lumbar ureter is associated with a higher complication rate: wounds, ureteric rupture, haemorrhage, or more serious lesions such as avulsions of the ureter. We present 4 cases of avulsion of the ureter seen in our department, corresponding to 4 men with stones of the lumbar ureter treated by ureteroscopy, 2 of them after failure of in situ extracorporeal lithotripsy (ESWL) and an attempt to "flush" the stone and the other two because ESWL was not available. The ureteric lesion was related to a Dormia catheter in 2 cases and the ureteroscope in 2 cases. The lesion was diagnosed and treated immediately in 2 patients and after a delay in the other 2 cases. Repair consisted of ureteric reimplantation on a Boari flap (1 case), implantation onto a psoas bladder (1 case), ureteroileoplasty (1 case) and autologous transplantation (1 case). Ureteric lesions prevented uretero-ureterostomy. Ureteric reimplantation on psoas bladder and/or Boari flap appears to be the simplest method, but it cannot always be performed. In the case of avulsion of the ureteropelvic junction with a large defect, autologous transplantation is a method of choice in young subjects. Ureteroileoplasty appears to be reserved for elderly patients.

Adult↗

Nicotine enhances expression of the alpha 3, alpha 4, alpha 5, and alpha 7 nicotinic receptors modulating calcium metabolism and regulating adhesion and motility of respiratory epithelial cells.

The purpose of this study was to investigate the possibility of direct toxic effects of nicotine (Nic) on human bronchial epithelial cells (BEC) suggested by our previous findings of functional nicotinic acetylcholine receptors (nAChRs) in the epithelial cells lining mucocutaneous membranes. We now demonstrate for the first time that human and murine BEC both in vivo and in vitro express functional nAChRs, and that classic alpha 3, alpha 4, alpha 5 and alpha 7 subunits can contribute to formation of these acetylcholine-gated ion channels. In human bronchial and mouse lung tissues, and in cultures of human BEC, the nAChRs were visualized by subunit-specific antibodies on the cell membranes, particularly at the sites of cell-to-cell contacts. The epithelial cells of submucosal glands abundantly expressed alpha 7 nAChRs. Smoking significantly (p < 0.05) increased the relative numbers of nAChRs, and this effects could be reproduced in cultures of BEC exposed to 10 microM Nic. At a higher dose, Nic decreased the relative numbers of alpha 5-containing nAChRs, suggesting a role for receptor desensitization. The function of the nAChR channels expressed by BEC was demonstrated by biphasic increase in the concentrations of intracellular calcium ([Ca++]i) in response to activation of the channel by Nic and fluctuations of [Ca++]i due to channel blockade by mecamylamine (Mec). Long-term exposure to milimolar concentrations of Nic resulted in a steady increase of [Ca++]i, which may lead to cell damage. The biological roles of epithelial nAChRs apparently involve regulation of cell-to-cell communications, adhesion and motility, because Mec caused rapid and profound changes in these cell functions which were reversible by Nic. An over exposure of BEC to Nic, however, produced an antagonist-like effect, suggesting that the pathobiological effects of Nic toxicity might result from both activation of nAChR channels and nAChR desensitization. We conclude that medical consequences of smoking can be mediated by direct toxic effects of inhaled Nic on the respiratory tissues wherein Nic specifically binds to and activates the nicotinic ion channels present on the cell surfaces of BEC. We believe that outside the neural system Nic interferes with functioning of non-neuronal cholinergic networks by displacing from nAChR its natural ligand acetylcholine which acts as a local hormone or cytokine in a variety of non-neuronal locations.

Adolescent↗

[Legal restitution of bodily harm in the traumatic rupture of the posterior urethra].

Medical experts are responsible for evaluation of the urinary and sexual sequelae following traumatic rupture of the posterior urethra. Only definite and direct damage is compensated by the courts, which demands a methodical and meticulous examination by the expert. Sexual damage can be evaluated by certain criteria including the results of intracavernous injections.

Disability Evaluation↗

New blood vessels can be induced to invade ischemic skeletal muscle.

PURPOSE: Despite intense investigation of angiogenesis, little effort has been made to exploit this phenomenon in ischemic tissue. The few studies on this topic have focused primarily on the development of collateral arteries in existing arterial beds. A previous study showed that a perfused muscle flap transposed to an ischemic limb formed vascular connections, which were demonstrated with angiography, between the arteries of the flap and the limb vasculature. Microsphere studies suggested that these vascular connections increased the resting perfusion of the ischemic limb. This study is designed to confirm histologically that such connections develop and to quantitate the number and dimensions of these new vessels. METHODS: Through a midline laparotomy, the right common iliac artery was ligated and divided in 18 male New Zealand white rabbits. An abdominal-wall muscle flap based on the left inferior epigastric artery was transposed to the right thigh. On the seventh day, contrast dye was injected into the flap artery of eight rabbits and an arteriogram was obtained. The tissue of the remaining rabbits was perfusion-fixed at 3 days (n = 2), 7 days (n = 4), and 14 days (n = 4). Thin sections of the flap-thigh muscle interface were stained with hematoxylin and eosin and for alpha-actin and proliferating cell nuclear antigen and were examined microscopically. RESULTS: An arteriogram confirmed vascular connections between the flap and the native limb circulation in seven of the eight rabbits. Histologic evaluation of the flap-thigh muscle interface showed no new vessels on the third day. On the seventh day, 6.8 +/- 4.8 new vessels (positive alpha-actin staining, red blood cells in lumen) were seen per 40 x field; the vessels averaged 10.2 +/- 5.2 microns in diameter. On the fourteenth day, there were 7.3 +/- 3.8 vessels per 40 x field (p = 0.46), but the vessel diameter increased to 20.7 +/- 10.6 microns (p = 0.013). Proliferating cell nuclear antigen staining confirmed that these were proliferating vessels. CONCLUSION: Within seven days, new vessels that were more mature than capillaries (stained for alpha-actin, a smooth muscle cell protein) formed between the flap and the thigh muscle. These new connecting vessels continue to enlarge in diameter between 7 and 14 days, but the stimulus to form new vessels appeared to decline or disappear before the fourteenth day. Attempts to sustain this phenomenon with angiogenic factors are underway.

Angiography↗

[Epididymal manifestations of urogenital tuberculosis].

The morbidity of tuberculous epididymitis is due to the risk of male infertility secondary to vasal or epididymal obstruction or testicular necrosis. The aim of this study was to emphasize the epidemiological, clinical and therapeutical aspects of tuberculous epididymitis in adult. About eleven cases of epididymal localisation of urogenital tuberculosis, it appears that the diagnosis of the condition is rather difficult and often necessitate pathological exam of a specimen of epididymectomy. In other aspects, if antituberculous drugs are always effective in initial stages, surgery is usually radical, and rarely conservative. The latter procedures are vasovasostomy or vasoepididymostomy whose results are very hazardous.

Adult↗

[A new case of tibial stress fracture as a complication of knee osteoarthritis].

PURPOSE OF STUDY: Transverse stress fractures of the proximal tibia are associated with osteoarthritis of the knee. This uncommon complication is presented in this case report as a non-union form along with a literature review. CASE REPORT: A fifty nine year old black African woman who had a thirteen-year history of osteoarthritis in both knees, was seen for increasing pain in the proximal part of the left leg without demonstrative traumatism. This homemaker measured 155 cm for 85 kgs. Clinical and radiological examination revealed a non-united stress fracture of the proximal part of the tibia and bilateral osteoarthritis of the knee with varus deformity (40 degrees on the left). A compression plate with bone grafting was used for treatment of the tibial non-union. DISCUSSION: Eleven other cases have been published on the rheumatological and orthopaedical literature. All the twelve patients were female, elderly, overweight, had marked varus deformities and a long history of osteoarthritis of the knee. A non-united stress fracture was a complication of osteoarthritis in four cases and treated with a compression plate. CONCLUSION: Stress fractures of the proximal tibia are an unusual mechanical and an uncommon complication of osteoarthritis of the knee. Biomechanic is perhaps one of the possible explication of these tibial stress fractures.

Female↗

[Delayed emergency repair of traumatic ruptures of the posterior urethra].

The management of posterior urethral injuries is still a matter of controversies. Some authors recommend a primary or delayed emergency repair procedure, while others prefer late repair. The analysis of our series of fifteen cases showed that when patients are treated by delayed emergency operation, the results are usually good. However, when repair is performed later, results are less satisfactory, and the rate of impotence is higher. We conclude that delayed emergency repair operation is the procedure of choice in the management of ruptured posterior urethra.

Adolescent↗

In vitro effects of substance P and somatostatin on lymphoproliferation in rainbow trout (Salmo gairdneri).

Lymphocytes from peripheral blood of rainbow trout are put in the presence of increasing concentrations of substance P (SP) and somatostatin (SOM). We have shown that SP stimulates and SOM inhibits lymphoproliferation and that the effects are dose dependent. These results suggest that SP and SOM receptors may exist on fish peripheral blood lymphocytes. When cells are stimulated by PHA or LPS, the presence of SP enhances the response to PHA whereas it only modifies the response to LPS to a slight extent. The presence of SOM inhibits PHA- or LPS-induced stimulation. The inhibition of the proliferation is higher in the case of LPS-stimulated cells. These results suggest that there is an unequal distribution of neuropeptide receptors among the various lymphocyte subpopulations.

Animals↗

[Acute periurethritis: 155 cases].

Severe complications of urethral stricture, acute peri-urethral phlegmon can be localized or diffuse. They are characterized by polymicrobial infections. The mortality rates about 7% is the privilege of diffuses forms. The treatment associates medical and surgical procedures, and consists in polyantibiotherapy and excision of suppurative lesions. From a series of 155 cases we analyse the pathogenical, clinical and therapeutical aspects.

Adolescent↗

[Mortality caused by traffic accidents at the Traumatology and Orthopedics Center of Grand-Yoff. A 2-year study. Apropos of 156 cases].

Most of road accident casualties are directed to the "Centre de Traumatologie et d'Orthopedie" between March 1989 and March 1991, the emergency Department received 8250 casualties treated by a team core comprising anesthetist-intensive care doctors and orthopaedic surgeons supplemented when necessary by other specialists. Out of those 8250 casualties aged 30 in average, 156 died at the hospital in varying time limits. The authors of present study intend to assess the efficiency of the medical and surgical care provided to identify the most frequent death causes and to suggest ways means of reducing the death toll. Forensic autopsies revealed the following lesions by order of prevalence: brain traumas 68, polytraumatisms 58, cervical vertebral traumas 13, abdomen traumas 7, polyfractures 3. In despite of the working conditions improvement at this specialized center (intensive care, technical facilities and staff) the mortality rate remains high, specially in polytraumatisms and brain traumas. The authors insist upon the need for a medically assisted transport unit which would take care of casualties before their arrival at hospital and for the acquisition of modern diagnosis means (tomodensitometry).

Abdominal Injuries↗