Hydrogen peroxide-induced phospholipase D activation in rat pheochromocytoma PC12 cells: possible involvement of Ca2+-dependent protein tyrosine kinase

The mechanism for hydrogen peroxide (H2O2)-induced phospholipase D (PLD) activation was investigated in [3H]palmitic acid-labeled PC12 cells. In the presence of butanol, H2O2 caused a great accumulation of [3H]phosphatidylbutanol in a concentration- or time-dependent manner. However, treatment with H2O2 of cell lysates exerted no effect on PLD activity. Treatment with H2O2 had only a marginal effect on phospholipase C (PLC) activation. A protein kinase C (PKC) inhibitor, Ro 31-8220, did not inhibit but rather slightly enhanced H2O2-induced PLD activity. Thus, H2O2-induced PLD activation is considered to be independent of the PLC-PKC pathway in PC12 cells. In contrast, pretreatment with tyrosine kinase inhibitor herbimycin A, genistein, or ST638 resulted in a concentration-dependent inhibition of H2O2-induced PLD activation. Western blot analysis revealed several apparent tyrosine-phosphorylated protein bands after the H2O2 treatment and tyrosine phosphorylation of these proteins was inhibited by these tyrosine kinase inhibitors. Moreover, depletion of extracellular Ca2+ abolished H2O2-induced PLD activation and protein tyrosine phosphorylation. Extracellular Ca2+ potentiated H2O2-induced PLD activation in a concentration-dependent manner. Taken together, these results suggest that a certain Ca2+-dependent protein tyrosine kinase(s) somehow participates in H2O2-induced PLD activation in PC12 cells.     

Concentration of cadmium in rice and urinary indicators of renal dysfunction

OBJECTIVES: (1) To examine the relation between concentrations of cadmium (Cd) in rice and urinary concentrations of indicators of renal dysfunction and the prevalence of abnormalities in urine in areas polluted by Cd. (2) To establish the maximum allowable concentration of Cd in rice from these findings. METHODS: The target population consisted of 1703 inhabitants (832 men and 871 women) aged over 50 years who consumed home grown rice and had lived in the same hamlet in areas polluted by Cd in the Kakehashi River basin in Ishikawa Prefecture, Japan for at least 30 years. The correlation coefficients between concentrations of Cd in rice and several urinary substances, the prevalence of abnormalities in urine and sex in hamlets polluted by Cd were calculated. Finally, regression analysis was performed for significant indicators to calculate the maximum allowable concentration of Cd in rice based on values in a control group. CONCLUSIONS: Significant correlations between concentration of Cd in rice and concentrations of urinary beta 2-microglobulin, metallothionein, glucose, and aminonitrogen were established. Similarly, there were significant correlations between concentration of Cd in rice and the prevalence of beta 2-microglobulinuria, metallothioneinuria, glucosuria, proteinuria, proteinuria with glucosuria, and aminonitrogenuria. The highest maximum allowable concentration of Cd in rice calculated for these indicators was 0.34 ppm/l and 0.29 ppm/g creatinine. Both values are lower than 0.4 ppm, the tentative limit prescribed by the Japanese government.     

Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan

Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.     

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.