Serum levels of P-selectin in men with high-functioning autism.

Immune dysfunction has been proposed as a mechanism for the pathophysiology of autistic-spectrum disorders. The selectin family of adhesion molecules plays a prominent role in immune/inflammatory responses. We determined the serum levels of three types of soluble-form selectin (sP, sL and sE) in 15 men with high-functioning autism and 22 age-matched healthy controls by enzyme-linked immunosorbent assay. Levels of sP-selectin and sL-selectin were significantly lower in patients than in controls. Furthermore, sP-selectin levels were negatively correlated with impaired social development during early childhood.

Caldesmon suppresses cancer cell invasion by regulating podosome/invadopodium formation.

The podosome and invadopodium are dynamic cell-adhesion structures that degrade the extracellular matrix (ECM) and promote cell invasion. We recently reported that the actin-binding protein caldesmon is a pivotal regulator of podosome formation. Here, we analyzed the caldesmon's involvement in podosome/invadopodium-mediated invasion by transformed and cancer cells. The ectopic expression of caldesmon reduced the number of podosomes/invadopodia and decreased the ECM degradation activity, resulting in the suppression of cell invasion. Conversely, the depletion of caldesmon facilitated the formation of podosomes/invadopodia and cell invasion. Taken together, our results indicate that caldesmon acts as a potent repressor of cancer cell invasion.

Host cyclooxygenase-2 modulates carcinoma growth.

Cyclooxygenase-2 (COX-2; Ptgs2) acts as a tumor promoter in rodent models for colorectal cancer, but its precise role in carcinogenesis remains unclear. We evaluated the contribution of host-derived COX-1 and COX-2 in tumor growth using both genetic and pharmacological approaches. Lewis lung carcinoma (LLC) cells grow rapidly as solid tumors when implanted in C57BL/6 mice. We found that tumor growth was markedly attenuated in COX-2(-/-), but not COX-1(-/-) or wild-type mice. Treatment of wild-type C57BL/6 mice bearing LLC tumors with a selective COX-2 inhibitor also reduced tumor growth. A decrease in vascular density was observed in tumors grown in COX-2(-/-) mice when compared with those in wild-type mice. Because COX-2 is expressed in stromal fibroblasts of human and rodent colorectal carcinomas, we evaluated COX-2(-/-) mouse fibroblasts and found a 94% reduction in their ability to produce the proangiogenic factor, VEGF. Additionally, treatment of wild-type mouse fibroblasts with a selective COX-2 inhibitor reduced VEGF production by 92%.

Intra-osseous ganglion of the proximal humerus: a case report.

We report a 72-year-old woman with a type-1 intra-osseous ganglion in the proximal humerus, extending to the bone surface. We conducted a systemic review of intra-osseous ganglion cases in Japan to identify clinical features and pathogenesis of this condition. The anatomical distribution between intra-osseous ganglia without a communicating soft tissue ganglion (type 1) and those with (type 2) is different. The origins of intra-osseous ganglia vary and depend on their anatomical location. They can arise from within the bone or in the adjacent soft tissue, and can progress to a type-2 lesion in either an outside-in or inside-out fashion.

Locking of the metacarpophalangeal joint of the thumb caused by a fracture fragment of the radial condyle of the metacarpal head after dorsal dislocation.

We report a case of a locked thumb metacarpophalangeal joint secondary to metacarpal head fracture. As fractures of the radial condyle are not readily seen in routine X-rays, other imaging modalities, including CT, should be considered if the patient complains of limited extension after hyperextension injury of the thumb.

G1 delay in cells overexpressing prostaglandin endoperoxide synthase-2.

Colorectal cancer is the second leading cause of death from cancer in the United States. Continuous use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the risk of colorectal cancer in humans by 40-50%. Patients with familial adenomatous polyposis who take NSAIDs, such as sulindac, undergo a regression of intestinal adenomas. Rodents exposed to carcinogens that cause colon cancer have a 50-60% reduction in the size and number of colonic tumors when treated continuously with NSAIDs. One common target for these drugs is prostaglandin endoperoxide synthase, also referred to as cyclooxygenase (COX). We and others have shown recently that COX-2 levels are increased dramatically in 85-90% of human colorectal adenocarcinomas and in 40-50% of colonic adenomas. We prepared intestinal epithelial cells that express the COX-2 gene permanently and found that they have altered adhesion properties and resist undergoing apoptosis. We report here that these cells also have a 3-fold increase in the duration of G1, lower levels of cyclin D1 protein, and a marked decrease in retinoblastoma kinase activity associated with cyclin-dependent kinase 4. The delay in G1 transit may relate to the resistance of these cells to undergo programmed cell death, which could affect their tumorigenic potential.

Injuries in elite motorcycle racing in Japan.

OBJECTIVES: To investigate the incidence and pattern of injuries, relative risks, and factors affecting incidence among elite motorcycle competitors in Japan. METHODS: A total of 117 elite motorcycle competitors including 36 road racers, 60 motocross racers, and 21 trial bike riders completed a questionnaire about injuries. RESULTS: Sixty major injuries (25 in road racing, 32 in motocross, and three in trial bike riding) were reported. The most common injuries were fractures (45), followed by ligament injuries (8), dislocations (5), and soft tissue injuries (2). The overall injury rate was 22.4 per 1000 hours, and the death rate was zero. There was no significant correlation between risk of injury and age, experience, or accumulated competition points. CONCLUSIONS: Injury rates in competitions such as road racing and motocross are high, and therefore additional safety measures are needed to protect competitors from injury.

Usefulness and complications associated with thenar and standard portals during arthroscopic surgery of thumb carpometacarpal joint.

PURPOSE: Advances in small arthroscopy have enabled a minimally invasive surgery for thumb carpometacarpal joints. However, surgery is often difficult using standard CM-radial (CM-R) and CM-ulnar portals (CM-U). Here, we describe the clinical applications and complications associated with using thenar portal (TP) and standard portals. METHODS: Arthroscopic surgeries of thumb carpometacarpal joint were performed in 21 patients including 15 patients with osteoarthritis and six Bennett's fracture-dislocations. Complications and the frequency of use associated with each portal were evaluated. RESULTS: Complications associated with the CM-R portal comprised paresthesia due to damage of the radial nerve branches in two patients. No nerves were damaged but the operation scar became tender at the TP in three patients. The CM-R was used at a lower frequency when the TP was utilized. CONCLUSION: The clinical use of TP may decrease the risk of radial sensory nerve damage through decreasing frequency of use of the CM-R that is located near the nerve. LEVEL OF STUDY: IV.

Ammonia: a possible promotor in Helicobacter pylori-related gastric carcinogenesis.

Helicobacter pylori (HP) has been shown to possibly be a pathogen of gastric carcinoma. HP has urease activity and produces ammonia in the stomach. In this study, the role of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in rats. After 24 weeks pretreatment with MNNG (83 mg/l), 0.01% ammonia or tap water as a drinking water was administered for 24 weeks. The ammonia-treated rats showed a significantly higher incidence of gastric cancer (percent of animals with tumors and number of tumors per rat). Ammonia would thus appear to have an important role in HP-related human gastric carcinogenesis.

Helicobacter pylori extract stimulates inflammatory nitric oxide production.

This study examined whether an extract of Helicobacter pylori had the ability to stimulate an inflammatory synthesis of nitric oxide, a mutagen and precursor of nitrosocompounds. Macrophages and neutrophils were prepared from rat and incubated with the Helicobacter pylori extract. L-Arginine-dependent nitric oxide production in these cells was significantly stimulated by the co-incubation with the Helicobacter pylori extract. This ability of the extract was strongly attenuated by protease digestion or heating. These results indicate that Helicobacter pylori induces production of nitric oxide and participates in development of gastritis and gastric carcinogenesis.

Review article: inflammation-related promotion of gastrointestinal carcinogenesis--a perigenetic pathway.

Chronic inflammation has been reported to accelerate neoplasmas in gastrointestinal tract. Certain bacteria including Helicobacter pylori directly interact with host cells, induce proinflammatory cytokines and stimulate production of free radicals. Free radicals cause mutations in target cells so that neoplastic clones are established. Accumulation of such genetic alterations may cause malignant transformation of some established clones. In addition, inflammatory alterations may promote growth, expansion and invasion of gastrointestinal epithelial cells. The latter changes caused by inflammation may occur even without further genetic mutations or epigenetic alterations, and therefore may be categorized as 'perigenetic alterations' of neoplastic cells. For an example, tumour necrosis factor alpha (TNF-alpha) plays pivotal roles not only in the reduction but also in the growth, invasion and metastases of certain neoplasmas. Our studies show that TNF-alpha increases intracellular radical production, degradates E-cadherin / beta-catenin complex and promotes dispersion and migration in epithelial cells transformed with an activated src oncogene (v-src). These data indicate that an inflammatory cytokine induces the malignant potential of src-activated neoplastic cells. Interestingly, TNF-alpha also induced these phenotypic changes in nonmutated cells whose c-Src was activated by TGF-alpha, suggesting that the invasive properties of the cell were not necessarily related to gene mutation. Furthermore, certain radical scavengers suppressed the invasive phenotype of the cells. These results indicate that perigenetic alterations are an important target of pharmacological intervention of carcinogenesis.

Helicobacter bilis infection in biliary tract cancer.

BACKGROUND: Biliary tract cancer is a highly fatal disease with poor prognosis, but the aetiology is poorly understood. AIM: We aimed to identify Helicobacter bilis infection in the gallbladder in patients with biliary tract disease. METHODS: Archival gallbladder specimens from 34 patients (14 males and 20 females) with an average age of 61.4 +/- 12.2 years (mean +/- SE) were retrieved, consisting of 11 cases of gallbladder cancer, three of bile duct cancer, 16 of cholecystolithiasis and four of pancreatic cancer. DNA was extracted and nested PCR using primers specific for 16S rRNA of H. bilis was performed. RESULTS: Amplification was observed in 3 of 11 gallbladder cancer cases (27.2%) and one of three cases with biliary duct cancer (33.3%). In total, four of 14 cases with biliary tract cancer were positive for H. bilis (28.6%). In addition, the presence of H. bilis was shown in two of 16 cases (12.5%) with cholecystolithiasis. Notably, although the number of cases examined was small, none of the four cases with pancreatic cancer showed the presence of H. bilis infection in the gallbladder without apparent abnormalities. CONCLUSION: H. bilis infection may play a role in biliary tract disease, particularly in biliary tract cancer.

Cyclooxygenase-2 alters transforming growth factor-beta 1 response during intestinal tumorigenesis.

BACKGROUND: Recent investigation suggests that cyclooxygenase-2 plays an important role in colorectal carcinogenesis. Transforming growth factor-beta1 (TGF-beta 1) is one of the most potent stimulators of cyclooxygenase-2 expression. A key step in intestinal tumorigenesis involves alteration of the normal cellular response to TGF-beta 1. We have hypothesized that overexpression of cyclooxygenase-2 alters intestinal epithelial response to TGF-beta 1. METHODS: RIE-1 cells were stably transfected with rat cyclooxygenase-2 complementary DNA in either the sense (RIE-S) or antisense (RIE-AS) orientation. Tumor cell invasion was assessed with a modified Boyden collagen type I invasion assay in the presence of TGF-beta 1, antibody to urokinase plasminogen activator (uPA), or the selective cyclooxygenase-2 inhibitor SC-58125. Expression of uPA, uPA receptor, and plasminogen activator inhibitor-1 were determined by Western blot and enzyme-linked immunosorbent assay. RESULTS: RIE-1 and RIE-AS did not invade although RIE-S cells were minimally invasive at baseline. TGF-beta 1 had no effect on RIE-1 or RIE-AS invasion; however, TGF-beta 1 significantly upregulated RIE-S cell invasion. All 3 RIE cell lines produce minimal uPA under basal conditions. TGF-beta 1 upregulated uPA production only in the RIE-S cells. Both antibody to uPA and SC-58125 reversed TGF-beta-mediated RIE-S cell invasion. SC-58125 inhibited TGF-beta-mediated RIE-S uPA production. CONCLUSIONS: These results demonstrate that overexpression of cyclooxygenase-2 alters intestinal epithelial response to TGF-beta 1, which may be a mechanism by which cyclooxygenase-2 promotes colon carcinogenesis.

Involvement of cyclooxygenase-2 in proliferation and morphogenesis induced by transforming growth factor alpha in gastric epithelial cells.

Transforming growth factor alpha is one of the most potent growth factors for gastrointestinal epithelium. In this study, we examined the roles of cyclooxygenase-2 on proliferation and morphogenesis of RGM1 rat gastric epithelial cells after stimulation with transforming growth factor alpha in vitro, RGM1 cells increased expression of cyclooxygenase-2 messenger RNA 20-60 min after stimulation with transforming growth factor alpha. Transforming growth factor alpha stimulated [3H]thymidine incorporation and tubulogenesis of RGM1 cells in collagen matrix, both of which were significantly suppressed by treatment with a cyclooxygenase-2 specific inhibitor, NS-398 or cyclooxygenase-2 antisense oligonucleotide. Both of the treatment lowered prostanoid production by enzyme immunoassay. The transforming growth factor alpha-induced expression of cyclooxygenase-2 is followed by cell proliferation and development of tubular morphology of RGM1 gastric epithelial cells. Treatment with cyclooxygenase-2 inhibitor and cyclooxygenase-2 antisense oligonucleotide suppressed these responses induced by transforming growth factor alpha suggesting the involvement of cyclooxygenase-2 in proliferation and morphogenesis in gastric mucosal epithelium.

Expression of cyclooxygenase-2 and nitrotyrosine in human gastric mucosa before and after Helicobacter pylori eradication.

To determine whether cure of Helicobacter pylori infection influences the expression of COX-2 and nitrotyrosine in the distal stomach of humans, biopsy specimens were examined immunohistochemically. H. pylori infection was determined using a rapid urease test, culture and histology. Positive staining of COX-2/nitrotyrosine in the epithelium was expressed as the percentage of stained cells to the total epithelial cells. There was a significant increase in COX-2/nitrotyrosine staining in H. pylori -positive subjects compared with H. pylori -negative subjects. Cure of the infection resulted in a significant decrease in both COX-2/nitrotyrosine staining in all patients (52.1+/-12.1% vs 15. 4+/-7.2%, P<0.001; and 57.3+/-13.6% vs 36.1+/-18.0%, P<0.01, respectively). However, immunoreactivity of COX-2/nitrotyrosine was observed in all cases with intestinal metaplasia even after the cure of H. pylori infection.Thus, cure of H. pylori infection may decrease the risk of gastric carcinogenesis due to COX-2 and NO-related compounds in gastric mucosa but not in those patients with intestinal metaplasia.