Psoriatic epidermis is associated with upregulation of CDK2 and inhibition of CDK4 activity.

BACKGROUND: The cyclin-dependent kinases (CDKs) CDK2 and CDK4 are involved in regulation of cell-cycle progression, and psoriasis is characterized by hyperproliferation of basal epidermal cells. CDK inhibitory proteins (CKIs) such as p16INK 4A (p16) bind CDK4/6 kinases and prevent their interaction with D-type cyclins. CKIs such as p21Cip1 (p21) and p27Kip1 (p27) associate with CDK-cyclin complexes and prevent their activation. OBJECTIVES: To gain insight into the molecular implication of CDK2 and CDK4 kinases in psoriasis, we sought to characterize expression of these kinases and associated cyclins, as well as of CKIs, and addressed the status of CDK2 and CDK4 activity in human psoriatic epidermis. METHODS: A cohort of 24 patients with psoriasis participated in the study. Biopsies were removed from a chronic plaque and from nonlesional skin. CDK2, CDK4, cyclin D1, cyclin E and CKI protein expression was assessed by immunoblotting, immunohistochemistry and immunofluorescence. CDK4 and CDK2 mRNA expression was determined by real-time polymerase chain reaction. Specific kinase activities of CDK2 and CDK4 were evaluated using fluorescent peptide biosensors. RESULTS: CDK2-cyclin E expression and activity were significantly increased in psoriatic epidermis compared with uninvolved adjacent skin. In contrast, CDK4-cyclin D1 activity was inhibited, although its expression was increased in psoriatic epidermis and its transcription slightly inhibited. p27 expression was reduced, while p16 and p21 expression was induced in psoriatic epidermis. CONCLUSIONS: Epidermal CDK2 activity is increased in psoriatic epidermis while CDK4 activity is completely inhibited. These alterations are not associated with changes in CDK transcription and instead involve post-translational control mediated by decreased expression of p27 and p16 overexpression, respectively. What's already known about this topic? Cyclin-dependent kinases (CDKs) are involved in cell-cycle progression. The levels of cyclin partners and CDK inhibitors regulate their activity. Psoriasis is a chronic T-cell-driven inflammatory skin disease characterized by hyperproliferation of basal epidermal cells. What does this study add? Thanks to fluorescent peptide biosensors, this study demonstrates that epidermal CDK2 activity is increased in psoriatic epidermis while CDK4 activity is completely inhibited. These alterations involve post-translational control mediated by decreased expression of p27, and p16 overexpression, respectively. What is the translational message? CDK2 and CDK4 are involved in regulation of cell-cycle progression, and psoriasis is characterized by hyperproliferation of basal epidermal cells. Epidermal CDK2 activity is increased in psoriatic epidermis while CDK4 activity is completely inhibited. These alterations are not associated with changes in CDK transcription and instead involve post-translational control mediated by decreased expression of p27 and p16 overexpression, respectively. Pharmacological modulation of CDK2 and CDK4 may constitute a promising therapeutic strategy.

An improved method of closure for saphenous vein donor sites.

In the modern surgical era, the functional result and aesthetics of wound closure have become important parts of any surgical procedure. The saphenous vein donor site for coronary artery bypass is often the most troublesome portion of a patient's postoperative course. Presented herein is a method for closure of saphenous vein donor sites that is aesthetically and functionally pleasing.

Experimental assessment of small intestinal submucosa as a bladder wall substitute.

OBJECTIVES: This study determined the feasibility of promoting urinary bladder regeneration with porcine-derived small intestinal submucosa (SIS). METHODS: Twenty-two Sprague-Dawley rats underwent partial cystectomy with immediate bladder augmentation with SIS. Bladders were harvested for histologic evaluation at 2, 4, 8, 12, 24, and 48 weeks. RESULTS: Histologically at 2 weeks, there was infiltration of the graft material with viable host cells consisting of fibroblasts, macrophages, and blood vessels covered by complete mucosal urothelium comprised of transitional cells. During the next 10 weeks, collagen formation and maturation were noted, and by the end of 12 weeks, the SIS graft was comprised of a mature collagen matrix admixed with thinly scattered disorganized smooth muscle bundles and covered by normal urothelium. At 48 weeks, all three layers of the normal bladder (urothelium, smooth muscle, and serosa) were present and were grossly and microscopically indistinguishable from the normal rat urinary bladder. CONCLUSIONS: This study further supports the concept of bladder regeneration and suggests that SIS may be a viable material for bladder augmentations.

Fibro-osseous pseudotumor of the distal phalanx.

Recurrent soft-tissue digital masses with osseous components frequently result in diagnostic and treatment dilemmas. We discuss a case of a recurrent fibro-osseous pseudotumor of the digit, review specific diagnostic and histological features, and recommend treatment.

Nonmetallic fixation in traumatic midfacial fractures.

The possibility of resorbable plate and screw fixation devices that provide adequate strength to allow facial fracture healing and are completely degraded thereafter has long had significant appeal. Favorable clinical experiences, however, have been very limited, and their use in the traumatized facial skeleton has yet to be proven a useful technology in the actual patient. In this regard, we review our experience in the management of orbital, zygomatic, and maxillary skeletal injuries with resorbable fixation.

Endoscopic retrieval of severed flexor tendons: a study of technique using cadaveric hands.

Retrieval of retracted zone 1, 2, and 3 flexor tendons without a proximal incision can occasionally lead to excessive tendon trauma or injury to neurovascular structures. To determine if endoscopic flexor tendon retrieval is a reliable, reproducible technique, 34 zone 2 flexor tendon lacerations were created in four cadaveric hands (2 male; 2 female). The tendons were retracted proximally an average of 4.3 +/- 1.9 cm (range, 2-10 cm) through a separate transverse wrist incision. A 2.5-mm flexible endoscope was introduced into the distal tendon sheath, and all transected tendons (N = 34) were clearly visualized. Thirty-two tendons (94%) were retrieved endoscopically by using either a loop snare or grasping forceps. Two tendons (6%) in a small female hand could not be retrieved endoscopically. This minimally invasive technique may be an alternative to the blind grasping maneuvers, proximal incision extensions, and counter-incisions in the palm.

Acrocephalosyndactyly syndromes: a review.

Over the last quarter century, a revision has taken place in the classification of the acrocephalosyndactyly syndromes. This reflects the advances in molecular biology that have led to improved genetic mapping of these syndromes. In this review we provide an overview of these major acrocephalosyndactyly syndromes, including the current classification system. The craniofacial, neurological, cardiac, pulmonary, visceral, and extremity anomalies are discussed with special emphasis on hand anomalies. Hand reconstruction techniques, including specific surgical procedures, the timing of the surgical reconstruction, and postoperative therapy are discussed. The need for coordinated care of the multidisciplinary disorders of these patients cannot be overemphasized, especially in the perioperative period.

Histoplasma capsulatum necrotizing myofascitis of the upper extremity.

Necrotizing myofascial fungal infections of the upper extremity is a rare event even in immunocompromised hosts. We report the course of a renal transplant patient who developed extensive necrotizing myofascial infection of an upper extremity secondary to Histoplasma capsulatum. Initial, functional, upper limb salvage was achieved after aggressive surgical debridement and high doses of amphotericin B. The patient ultimately succumbed to systemic fungal sepsis. The etiology and treatment of these infections are discussed.

Poland's syndrome in one identical twin.

Female twins were evaluated at the Shriners Hospital in Lexington, Kentucky. One twin was normal, and the other twin had the classic findings of Poland's syndrome, manifested by absence of the pectoralis major and symbrachydactyly of the right upper extremity. Buccal smears from each child were submitted for DNA testing. The test confirmed monozygosity with 99.9% probability. Some previous reports have stated that Poland's syndrome is an autosomal dominant, genetically determined trait, whereas others have maintained that there is no genetic association. The original case described by Poland in 1841 was his cadaver, and no family history was reported. This twin study provides strong evidence that the condition is not determined by gene transmission.

Proprietes de nucleoles debarrasses de chromatine perinucleolaire, isoles en milieu MgCl(2) a haute force ionique a partir de cellules d'hepatome ascitique de rat.

A method is devised for isolation of pure nucleoli, devoid of perinucleolar chromatin, from rat hepatoma in a medium of high ionic strength (I = 1, MgCl(2) = 0.33 M).

Resorbable bone fixation: its potential role in cranio-maxillofacial trauma.

The concept of biodegradable bone fixation devices, which provide sufficient rigidity to allow fracture healing and resorption thereafter, has significant appeal in cranio-maxillofacial trauma treatment; however, biodegradable bone fixation devices have not yet become available for clinical use in the craniofacial skeleton. This article reviews the obstacles in developing a resorbable polymer bone fixation system and describes the initial use of such a system in the treatment of cranio-maxillofacial trauma patients. It also discusses the potential role of a resorbable polymer bone fixation system in conjunction with the use of metal fixation in the management of facial fracture.

Biomechanical testing of titanium self-tapping versus pretapped lag screw fixation of spiral metacarpal fractures.

Biomechanical tests of torsional loading and cantilevered bending were used to study the effects of varying screw size design of five different titanium miniscrews and microscrews in a metacarpal spiral oblique fracture model. Sixty-six fresh frozen human cadaveric metacarpal bones were subjected to torsional loading until failure, producing a spiral oblique fracture. The randomized fractured metacarpal bones were then repaired utilizing two 1.2-mm, 1.7-mm, or 2.3-mm self-tapping Leibinger lag screws; and 1.5-mm or 2.0-mm pretapped Synthes lag screws. Following repair, the specimens were then subjected to cantilevered bending or torsional loading. Failure torque and bending loads were then used to calculate failure stresses at the midshaft for torsional loading or at the proximal screw for cantilevered bending. Analysis of variance statistical analysis revealed that within the cortical thickness of bone studied, no significant difference in shear stress or axial stress was observed with increasing screw diameter and screw design.

A biomechanical analysis of the stability of titanium bone fixation systems in proximal phalangeal fractures.

Apex bending and torsional loading were utilized to study the effects of different plate design and thickness, and screw size and design on the rigidity and strength of seven different titanium mini- and microplates placed onto osteotomized proximal phalanges. One hundred forty-four fresh frozen human cadaveric proximal phalangeal bones underwent a mid shaft osteotomy followed by application of one of the following plates: (1) Synthes linear 1.5-mm five-hole plates, (2) Leibinger linear 1.2-mm five-hole or (3) 1.7-mm four-hole plates, or (4) Leibinger three-dimensional 1.2-mm four-hole, (5) 1.2-mm eight-hole, (6) 1.7-mm four-hole, or (7) 1.7-mm eight-hole plates. Three-point bending (apex dorsal or apex volar) and torsional loading were utilized for each plating configuration. Analysis of variance models of bone specimen width, depth, cortical thickness, and length revealed that increasing plate thickness was associated with increasing rigidity, but that the three-dimensional design yielded a higher relative rigidity except under apex volar loading.

The extrinsic blood supply of the ulnar nerve at the elbow: an anatomic study.

The extrinsic vasculature of the ulnar nerve as it relates to the treatment of cubital tunnel syndrome has not previously been described in detail. For a study of the anatomy, 18 fresh-frozen cadaver upper limbs were dissected after intra-arterial injection of latex. Two major pedicles were present in all 18 specimens--the superior ulnar collateral artery proximally and the posterior ulnar recurrent artery distally. A single minor pedicle, the inferior ulnar collateral artery, was present in 5 of 18 specimens. Total vessel length as well as distance to the medial epicondyle for the extrinsic arteries was measured. On the basis of these anatomic dissections, it is suggested that the extrinsic vascular supply can be preserved during anterior transposition of the ulnar nerve, even after extensive mobilization of the nerve.

Effects of a positively charged biomaterial for dermal and subcutaneous augmentation.

Based on previous experimental connective tissue work, the use of a positively charged dextran-based biomaterial in subcutaneous tissue sites was evaluated. After hydration with saline, the biomaterial was injected beneath the abdominal skin in rats. A robust macrophage response was initially seen at 30 days without acute inflammation. By one year postoperatively, extensive intermaterial fibroblast and collagen ingrowth had occurred. No evidence of a foreign-body or chronic inflammatory response was seen. These preliminary findings suggest good tissue compatibility of this biomaterial and suggests that when combined with a biocompatible liquid medium, the potential for development of a bioactive dermal and subcutaneous injectable substance exists.

Mechanical anastomosis of nerves: a histological and functional comparison to conventional suturing.

The use of a mechanical coupling device in microsurgery offers speed of application in addition to a secure vascular union. Despite its success in a vascular setting, mechanical coupling device nerve repair remains to be studied. Forty-five male rats were tested over 7- and 14-week study periods. One half of the animals underwent primary suture repairs for transected sciatic nerves, and the remainder of the animals had their nerves repaired using a mechanical coupling device. Postoperative analysis consisted of histological evaluation of pre- and postrepair site nerve morphology (axonal continuity and counts) as well as functional testing using walking track analysis. Mechanical coupling device coaptation of the nerves using the epineurium was done in approximately one half the time compared with conventional suturing. After both 7 and 14 weeks postoperatively, walking track analysis showed no difference in the amount of functional return between the two repair groups. No animal exhibited complete return of function. Axonal continuity occurred across both repairs without significant difference in their pre- and postrepair axonal counts. Although no clear advantage was seen in this study, the concept of mechanical nerve coupling merits further investigation based on its potential clinical utility.

Coverage of widely separate defects of the lower extremity: application of cluster analysis.

A patient with lower extremity reconstruction is presented with a radial forearm free flap designed using the cluster analysis method of cutaneous perforators. The cutaneous vascular anatomy of fasciocutaneous flaps is discussed as well as the application of the mathematical model of analysis of the vascular territories within specific flaps to assist in "custom" flap design. The ultimate goal of this technique is the creation of flaps that provide a more precise and anatomical reconstruction of the proposed defect.

Tire explosion injuries to the upper extremity.

Several articles have been published that bring attention to the destructive potential of tire explosions. Although the severity of tire explosion injuries to the head and neck region is well established, only one previous article has reported injuries to the upper extremity. Fourteen patients with upper extremity tire explosion injuries have been treated by us from 1980 to 1988. Each injury was caused by single-piece wheel assemblies, as opposed to multipiece wheel assemblies, which have traditionally been associated with the injury. Three representative patient reports are discussed. Prevention of this injury can be achieved by increased public awareness, formal industrial safety training, tire servicing with dedicated equipment including restraining devices or barriers, complete evaluation of wheel/tire serviceability before tire mounting, separation of servicing of single and multipiece wheels, and complete tire deflation before servicing.