MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes

Herein we describe a new test system to produce a standardized partial muscle-tendon junction (MTJ) stretch injury. In anesthetized rabbits the tibialis anterior (TA) muscle-tendon unit is unilaterally shortened using a custom designed clamp roller system. An angular displacement (average velocity of 450 degrees x s[-1]) is applied about the foot to plantarflex the ankle 90 degrees while the lower extremity is fixed. During ankle rotation the TA muscle is tetanically stimulated to generate an eccentric stretch injury at the MTJ. Forty-eight hours after injury, isometric torque deficit (injured/sham) was measured. Two groups of animals (N = 6 in each group) were tested with the only difference between the two groups being the initial tendon shortening. In Group 1 (tendon shortening = 1.2 cm. N = 6) the torque deficit was 36.7+/-5.9% (mean+/-SD). In Group 2 (tendon shortening = 1.5 cm. N = 6) the torque deficit was 58.7+/-7.4% (mean+/-SD). No order effect was suggested by the data (P = 0.6062), but the difference in torque deficit between the two groups was highly significant (P = 0.0001). For all tests in which the tendon was temporarily shortened before muscle stimulation and stretch (N = 12) there was a visible hematoma at the MTJ similar to the injury that is common in athletic injuries. Histological evaluation 48 h after injury revealed both fiber tearing and inflammation at the MTJ. In addition, there was focal fiber damage in the muscle belly for both groups. The damage and inflammatory process, however, were more severe in the group with greater initial tendon shortening.     

Surveillance for geographic and secular trends in congenital syphilis--United States, 1983-1991

PROBLEM/CONDITION: CDC monitors trends in the occurrence of congenital syphilis (CS) in the United States by using surveillance data sent from state and local health departments. Comparisons of data from this surveillance system with data from the Division of Sexually Transmitted Diseases/HIV Prevention and the Birth Defects Monitoring Program (BDMP) can be used to assess the potential effects of changes in case finding and reporting practices on these trends. REPORTING PERIOD COVERED: This report covers CS surveillance in the United States for the years 1983-1991. DESCRIPTION OF SYSTEM: Cases of CS among infants < 1 year of age and primary and secondary (P&S) syphilis among women are reported quarterly to CDC. The BDMP is a CDC national surveillance system that samples hospital discharge data on U.S. births. RESULTS: During the period 1983-1991, 12,151 CS cases were reported. Before 1988, regional CS incidence increased 35%-131% annually. Larger increases occurred in the Northeast (578%) in 1989 and in the South (178%), Midwest (244%), and West (777%) in 1990. Within regions, these larger increases were temporally related to increases in P&S syphilis in women and changes to a more sensitive CS case definition. INTERPRETATION: CS incidence has increased since 1983 in all regions of the United States. Increases since 1988 reflect both changes in surveillance reporting practices--the surveillance case definition for CS was changed in 1988 and further revised in 1989--and a true increase in incidence. ACTIONS TAKEN: These data indicate where CS prevention efforts need to be targeted. To facilitate reporting of CS cases, CDC has developed a) a shorter form for reporting cases of CS after 1991 and b) a software package for use by state and local health departments to enter and analyze CS data.     

Successful polymerase chain reaction-based diagnosis of fungal meningitis in a patient with chronic granulomatous disease

The structural and electronic properties of seventeen alkylxanthine derivatives were calculated using the MO program PM3 to elucidate the key features related to their inhibitory activity on phosphodiesterase (PDE) IV isoenzyme. Except for 7-alkylxanthine derivatives, a good correlation could be established between the distance between the tops of the two alkyl groups at the N1 and N3 positions of the xanthine skeleton (molecular length) and the PDE IV inhibitory activity (r=0.973, n=13). The same inhibitory activity could also be significantly correlated with the following electronic parameters of alkylxanthines: HOMO energy (r=0.850), absolute hardness (r=-0.806), and absolute electronegativity (r=-0.825). These results suggest that the electronic properties are partly responsible for PDE IV inhibition as far as the effects of structural properties associated with molecular length are concerned. Alkylxanthines may also act as electron donors in the charge-transfer interaction with the active sites on PDE IV isoenzyme.     

Sacral chordoma in early childhood: clinicopathological and immunohistochemical study

Two cases of sacral chordoma in a 7-year, 9-month-old boy and a 3-year, 4-month-old boy are presented. In addition to the typical histology of conventional chordoma, both tumors showed the less differentiated sarcomatoid appearance of atypical chordoma in the major portion. Immunohistochemically, in both cases neoplastic cells in areas of conventional as well as atypical chordoma were positive for keratins (CAM 5.2, AE1 and AE3), epithelial membrane antigen, vimentin, S-100 protein, carcinoembryonic antigen, and glial fibrillary acidic protein. Both patients underwent resection of the tumor and chemotherapy. In comparison with conventional chordomas in adults, however, these two tumors showed more aggressive clinical course and were less amenable to therapeutic control. The older boy died of multiple metastasis 1 year after initial diagnosis. At the last follow-up, 15 months after initial diagnosis, the younger boy was alive, but with recurrent and metastatic disease of the left parasacral area and chest wall. Our studies of these two cases and the reported cases suggest that sacral chordoma in children has distinctive clinicopathologic features denoting a highly aggressive tumor and that it should be treated as such.     

Effects of dopamine on N-terminus-deleted human tyrosine hydroxylase type 1 expressed in Escherichia coli

Hyaluronan is a major component of synovial fluid. It is synthesized in the joint and partly degraded in joint capsule and partly carried by lymph to lymph nodes and the general circulation. During various joint disorders, especially inflammatory ones, the amount of hyaluronan in the joint and its turnover rate are increased leading to pathologically high serum levels of the polysaccharide. These levels are a complex function of synovitis mass and the physical activity of the patient. Intra-articular injection of hyaluronan has been used in the treatment of osteoarthritis. Although it results in a relief of pain, controlled clinical trials have not yet convincingly shown any beneficiary effects of the treatment.     

Effect of l-asparaginase and asparagine deprivation on RNA metabolism in mouse leukemia L 5178Y cells in suspension culture

We analyzed the effect of asparagine starvation and L-asparaginase on RNA metabolism of mouse leukemia cell lines L5178Y, whose growth is dependent on the presence of asparagine, and L5178Y-R, whose growth is independent of the presence of asparagine. The deprivation of asparagine from the medium inhibited cellular protein synthesis by 30 to 40% of the control value in L5178Y cells, but not in L5178Y-R cells, whereas L-asparaginase inhibited synthesis by more than 80% in both L5178Y and L5178Y-R cells. The decrease in protein synthesis caused by asparagine starvation in L5178Y cells was accompanied by a decrease in ribosomal RNA synthesis. The synthesis of rRNA was also markedly blocked when L5178Y and L5178Y-R cells were exposed to L-asparaginase. The rate of synthesis of pulse-labeled RNA decreased significantly in the cells treated with L-asparaginase, and smaller pieces of polyadenylate containing pulse-labeled RNA (presumptive messenger RNA) appeared among monosomes and polysomes. However, the rate of messenger RNA synthesis was constant during asparagine starvation, and a marked accumulation of monosome was observed.     

Erythroenzymopathy-molecular abnormality of erythrocyte pyruvate kinase (PK) (author''s transl)

A case is described of cryptococcosis presenting as a large round intrathoracic lesion with superior vena caval obstruction and clubbing of the fingers. The patient was satisfactorily treated by lobectomy under cover of amphotericin B therapy.     

Clinical evaluation of postoperative adjuvant arterial infusion chemotherapy in resected hepatoma patients

Eighty surgically treated patients with advanced hepatocellular carcinoma (HCC) were divided into two groups. In group I, twenty patients whose mean diameter of tumors was 56 mm, prophylactically underwent hepatic arterial infusion chemotherapy after liver resection. Chemotherapeutic agents (5-FU, ADM, MMC, CDDP, Lipiodol) were administered 4 times a year via Infuse A port. The remaining 60 patients, whose mean diameter of tumors was 57 mm, served as the control without prophylactic infusion (group II). The 2-year cumulative survival rate was higher in the prophylactic group (71%) than the control (48%, p = 0.040). The two-year disease-free survival rate was improved in group I (38%) compared with that in group II (27%, p = 0.021). Intrahepatic multiple recurrence within 1 year after surgery was recognized in four out of 18 patients of group I (22%) and in thirty-three out of 60 patients of group II (55%, p = 0.029). In group I, two cases who died of hepatic failure with no recurrence, had lower functional reverse and a larger amount of Lipiodol than the remaining 18 patients. Adjuvant arterial infusion chemotherapy can thus be be efficacious in alleviating hepatoma recurrence after liver resection. For patients with poor liver function, a smaller volume of chemotherapeutic agents might be feasible.     

Differential display analysis of murine collagen-induced arthritis: cloning of the cDNA-encoding murine ATPase inhibitor

Perforin-deficient (-/-) mice were used as T-cell donors for infusion into irradiated major histocompatibility complex (MHC)-disparate recipients to investigate the requirement for perforin-mediated cytolysis during graft-versus-host disease (GVHD) generation. Administration of 5x10(6) C57BL/6 (H2b) perforin -/- splenocytes was significantly less effective in inducing GVHD lethality when given to MHC class I + II disparate B10.BR (H2k) recipients, as compared with wild-type (+/+) controls. Perforin expression by donor T cells was not required for GVHD induction because recipients given fivefold higher numbers of perforin -/- donor splenocytes uniformly succumbed to lethal GVHD. Because both CD4+ and CD8+ donor T cells are required for optimal GVHD lethality in this strain combination, to discern the relative contribution of perforin-mediated cytolysis by CD4+ and CD8+ T cells, additional studies were performed. For these latter studies, we used a sensitive assay involving the infusion of highly purified CD4+ or CD8+ T cells into sublethally irradiated MHC class II or I disparate recipients, respectively. As compared with recipients of perforin +/+ T cells, recipients of either CD4+ or CD8+ perforin -/- T-cell subsets had a significant reduction in GVHD-mediated lethality at T-cell doses that were uniformly lethal. T-cell dose titration studies established that GVHD lethality in recipients of perforin -/- CD4+ or CD8+ T cells was reduced by approximately threefold. These data are the first to indicate that approaches to limit perforin-mediated cytolysis should be similarly effective in situations in which CD4+ or CD8+ T cells dominate the GVHD response.     

Long-term results of preoperative hyperthermo-chemo-radiotherapy (HCR) for patients with esophageal carcinoma invading neighboring structures (T4)

PATIENTS: A total of 180 patients with esophageal carcinoma invading the neighboring structures (T4) were surgically treated by esophagectomy and reconstruction in the Department of Surgery II, Kyushu University from January 1965 to April 1997. Any of these cases with distant node metastasis and demonstrating organ metastasis or a combined resection of adjacent structures were excluded from this study. As a result, twenty-six patients treated with preoperative hyperthermo-chemo-radiotherapy (HCR Group), 39 treated either with preoperative radiotherapy or preoperative chemo-radiotherapy (R or CR Group) and 23 non-treated patients (Non-tx Group) were thus entered in this study. RESULTS: The 3-year survival rates after esophagectomy in HCR Group, R or CR Group and Non-tx Group were 26.5%, 0% and 9%, respectively, while the 5-year survival rate of the HCR group was 15.9%. The group with preoperative HCR thus showed a significantly more favorable outcome than R or CR Group and Non-tx Group. (p < 0.05). DISCUSSION: The significant difference observed in the prognosis was thought to be due to the reinforced effect of local regulation due to hyperthermia. Our data thus suggest that preoperative HCR contributes to the prolonged post-operative survival for carcinoma of the esophagus invading the neighboring structures.