Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase

SHPS-1 is an approximately 120 kDa glycosylated receptor like protein that contains three immunoglobulin-like domains in its extracellular region as well as four potential tyrosine phosphorylation and SRC homology 2 (SH2) domain binding sites in its cytoplasmic region. Lysophosphatidic acid (LPA) stimulated the rapid tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2, a protein tyrosine phosphatase containing SH2 domains in Rat-1 fibroblasts. LAP-induced tyrosine phosphorylation of SHPS-1 was inhibited by Clostridium botulinum C3 exoenzyme (which inactivates RHO) but not by pertussis toxin. The protein kinase C activator phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) also stimulated tyrosine phosphorylation of SHPS-1; however, down-regulation of protein kinase C by prolonged exposure of cells to TPA did not affect LAP-induced tyrosine phosphorylation of SHPS-1. LPA-induced tyrosine phosphorylation of SHPS-1 was markedly reduced in either focal adhesion kinase (FAK)-deficient mouse cells or CHO cells overexpressing the tyrosine kinase CSK. Overexpression of a catalytically inactivate SHP-2 markedly inhibited MAP kinase activation in response to low concentrations of LPA in CHO cells, whereas overexpression of a wild-type SHPS-1 did enhance this effect of LPA. Furthermore, MAP kinase activation in response to a low concentration of LPA was inhibited by botulinum C3 exoenzyme. These results indicate that LPA-induced tyrosine phosphorylation of SHPS-1 and its association with SHP-2 may be mediated by a RHO-dependent pathway that includes FAK and a SRC family kinase. Thus, in addition to its role in receptor tyrosine kinase-mediated MAP kinase activation, the formation of a complex between SHPS-1 and SHP-2 may, in part, play an important role in the activation of MAP kinase in response to low concentrations of LPA.     

Comparison of surgically attached and non-attached repair of the rat Achilles tendon-bone interface. Cellular organization and type X collagen expression

The effects of surgical repair versus non-repair on cell morphology and type X collagen expression were investigated using a rat model of Achilles tendon avulsion. The animals were divided into four groups. In Group 1, tendon was reattached to the original attachment site by suturing through a drill hole in the calcaneus; in Group II, tendon was not reattached and a drill hole was not made; in Group III, tendon was not reattached but a drill hole was made; and the animals in Group IV were sham operated. In Group I (tendon reattached), at 2 weeks postoperatively, many hypertrophic chondrocytes appeared at the reattachment site adjacent to bone and type X collagen was detected immunologically both in the cells and in the extracellular matrix. After 4 weeks, the cells at the original site of attachment were arranged in rows along the newly formed tendon fibers and were stained with type X collagen antibody. By contrast, when tendon was not reattached (Groups II and III), a gap between the original attachment site and the tendon stump was observed through the entire postoperative period. At 8 weeks, the original attachment site was covered by fibrocartilaginous tissue and tendon became attached to the calcaneal fibrocartilage area, which is proximal to the original attachment site. Type X collagen was detected in the cells which were adjacent to bone. In Group IV (sham operation), there were no changes in histology or type X collagen distribution, either at the attachment site or in tendon and bone, compared with the non-operated control rats. These results suggest that surgical reattachment of tendon to the original site is important to help reorganize cells during the repair process. Type X collagen was identified immunohistochemically in the cells adjacent to bone in all the groups, suggesting that it may play a role in maintaining distinct areas of calcified and non-calcified fibrocartilage.     

Familial occurrence of congenital bile duct cysts

Congenital bile duct cysts are now a well-documented anomaly of the biliary tree, and have become more common in Japan. Familial occurrence of congenital bile duct cysts, however, is extremely rare, with only six reported cases in the literature. We report a familial pattern of congenital bile duct cysts in a mother and her daughter. A 33-year-old female was admitted for evaluation of right upper quadrant abdominal pain and fever 6 days after an uneventful delivery of her second child. A computed tomography (CT) and ultrasound scan (US) revealed an obstructed biliary tract. Percutaneous transhepatic biliary drainage was then performed, and a cholangiogram revealed a Scholtz type B choledochocele without an anomalous connection of the pancreaticobiliary ducts. Endoscopic US demonstrated that the choledochocele was associated with a stone in the cyst. A pylorus-preserving pancreatoduodenal resection was performed, and a histological study revealed that the choledochocele was lined by biliary mucosa without evidence of malignancy. The newborn infant had an abdominal tumour. An US and CT revealed a congenital bile duct cyst. An operation was performed and the intraoperative cholangiogram showed an Alonso-Lej type I congenital bile duct cyst with an anomalous connection of the pancreaticobiliary ducts. Whether congenital bile duct cysts are hereditary remains to be elucidated.     

Cyclin D1 gene amplification and p16 gene deletion in patients with esophageal carcinosarcoma

BACKGROUND: Interventional magnetic resonance (MR) imaging allows neurosurgeons to interactively perform surgery using MR guidance. High-field (1.5-Tesla) strength imaging provides exceptional visualization of intracranial and spinal pathology. The full capabilities of this technology for pediatric neurosurgery have not been defined or determined. MATERIALS AND METHODS: From January 1997 through June 1998, 10 of 85 cases performed in the interventional MR unit were in the pediatric population (mean age 8.3, median 8, range 2-15 years). Procedures included 2 brain biopsies, 5 craniotomies for tumor, 2 thoracic laminectomies for syringomyelia, and placement of a reservoir into a cystic brainstem tumor. The biopsies and reservoir placement were performed using MR-compatible equipment. Craniotomies and spinal surgery were performed with conventional instrumentation outside the 5-Gauss magnetic footprint. Interactive and intraoperative imaging was performed to assess the goals of surgery. RESULTS: Both brain biopsies were diagnostic for cerebral infarct and anaplastic astrocytoma and the reservoir was optimally placed within the tumor cyst. Of the 5 tumor resections, all were considered radiographically complete. One biopsy patient and 1 tumor resection patient experienced transient neurological deficits after surgery. The patient with the thoracic syrinx required reoperation when the syringosubarachnoid shunt migrated into the syrinx 3 months after initial placement. No patient sustained a postoperative hemorrhage. Tumor histologies found at craniotomy were craniopharyngioma, ganglioglioma, and 3 low-grade gliomas. No evidence of tumor progression has been seen in any of these patients at a mean follow-up of 5.3 (range 4-8) months. The goals of the procedure were achieved in all 10 cases. There were no untoward events experienced related to MR-compatible instrumentation or intraoperative patient monitoring, despite the present inability to monitor core body temperature. CONCLUSIONS: 1.5-Tesla interventional MR is a safe and effective technology for assisting neurosurgeons to achieve the goals of pediatric neurosurgery. Preliminary results suggest that surgical resection of histologically benign tumors is enhanced in the interventional MR unit. The incidence of surgically related morbidity is low.     

Analysis on temperature-dependent deployment behavior of bi-stable composite rods

Bi-stable composite rods attract many researchers to investigate the mechanical and deployment behaviors for possible application to space deployable structures. Operation requires the bi-stable composites to be in a compact form prior to deployment. The deployment behavior is influenced by the storage conditions and the environmental temperature, of which, the latter is focused on in the present study. This study utilizes plain woven carbon fabrics composites to make bi-stable composites. Temperature-dependent mechanical properties of bi-stable composites are measured, and temperature-dependent deployment forces of bi-stable rods are evaluated using analytical formulations and finite element simulations with the measured properties.     

Proposal of an alternating bending technique for evaluating low‐to‐high cycle fatigue of structural steels

This paper proposes an alternating bending technique for evaluating fatigue life in the low‐to‐high cycle fatigue regime. A method was developed for estimating the stress, elastic strain, and plastic strain ranges of a plastically deformed specimen subjected to alternating bending with consideration of stress and strain distributions. To evaluate its effectiveness, fatigue testing was conducted using a specimen made of a steel used for pressure vessels. The stress, elastic strain, and plastic strain ranges could be obtained during cyclic bending. The elastic strain amplitude life and plastic strain amplitude life curves were linear in a log–log plot in the low‐to‐high cycle fatigue regime. Hence, the fatigue life under alternating bending could be evaluated using the proposed strain‐based approach. However, these curves could not be predicted using equations with parameters obtained from tensile testing, such as the universal slope method, due to the strain gradient in the specimen.     

Morphological analysis of germ cell apoptosis during postnatal testis development in normal and Hsp 70-2 knockout mice

Ideomotor apraxia, disordered movement execution to command, commonly follows left-hemisphere damage, implying left-hemisphere dominance for certain kinds of movements. To delineate this dominance we used different command modalities to elicit meaningful movements and tested imitation of nonsense movements. Twenty-seven patients with unilateral hemispheric stroke and 10 age-matched controls were evaluated. Patients with left-hemisphere damage performed both meaningful and nonsense movements poorer than the other study groups; thus, the meaningfulness of the movements is irrelevant for the left-hemisphere motor dominance. The performance varied, however, with the command modality and movement type. Based on this and earlier studies we posit that the left-hemisphere motor dominance is determined by the artificiality of the test situation (it concerns movements performed to command and out of the natural context) and increased spatial and temporal complexity of the demanded movements. No association between the lesion locus within the left hemisphere and the severity of the ideomotor apraxia was found.     

A mesenchymal malignant mesothelioma that changed from mixed type to purely sarcomatous type]

STUDY OBJECTIVE: To evaluate the long-term efficacy of laparoscopic Burch urethropexy. DESIGN: Pilot study. SETTING: Private practice. PATIENTS: Thirty-five consecutive women (average age 45.5 yrs, average parity 2.3, average weight 67.7 kg) treated for genuine stress incontinence between May 1992 and July 1994. INTERVENTIONS: Urethropexy was performed with curved needle suturing in 7 women, straight needle suturing in 5, and Stamey needle suturing in 23. Twenty-five (71.4%) patients had concomitant pelvic surgery. MEASUREMENTS AND MAIN RESULTS: Wilcoxon two-sample, chi2, and Fisher's exact tests were performed to determine which variables were significantly associated with surgical success. Average operating time was 190 minutes, hospitalization 24 hours, and catheterization 5 days. The cure rate of stress incontinence was 89% 3 months and 86% 1 year after surgery. At average follow-up of 34 months, only 68.6% of patients reported complete or almost complete cure, 11.4% were improved, and 20% were complete failures. The only operative variable approaching statistical significance for predicting surgical success was type of suture needle (p = 0.07), with the Stamey needle group having the highest cure rate. Women who were cured or almost cured had a significantly shorter follow-up than those who were improved or failures (p = 0.001). CONCLUSION: The success rate of laparoscopic Burch urethropexy compares with that of open Burch procedure at 1 year, but drops considerably thereafter.     

Lichenoid skin lesions as a sign of beta 2-microglobulin-induced amyloidosis in a long-term haemodialysis patient

We report a case of beta 2-microglobulin-induced amyloidosis. The patient was a 40-year-old man suffering from non-amyloid nephropathy, who had been treated by haemodialysis for 20 years. Lichenoid skin lesions, consisting of groups of pin-head-sized shiny papules, were present on the arms and trunk. On histological examination, amyloid deposits were present, principally in the dermal papillae, but also around the sweat ducts and hair follicles. The amyloid displayed potassium-permanganate-resistant Congo red affinity, and green birefringence under polarized light. Immunohistochemically, beta 2-microglobulin was demonstrated in the lesions, confirming that they were a manifestation of beta 2-microglobulin-associated amyloidosis. Skin lesions of this type have not been reported previously in beta 2-microglobulin-associated amyloidosis.