Wnt signaling from the dorsal neural tube is required for the formation of the medial dermomyotome

Signals originating from tissues surrounding somites are involved in mediolateral and dorsoventral patterning of somites and in the differentiation of the myotome. Wnt-1 and Wnt-3a, which encode members of the Wnt family of cystein-rich secreted signaling molecules, are coexpressed at the dorsal midline of the developing neural tube, an area adjacent to the dorsomedial portion of the somite. Several lines of evidence indicate that Wnt-1 and Wnt-3a have the ability to induce the development of the medial and dorsal portion of somites, as well as to induce myogenesis. To address whether these Wnt signalings are really essential for the development of somites during normal embryogenesis, we investigated the development of somites in mouse embryos lacking both Wnt-1 and Wnt-3a. Here we demonstrate that the medial compartment of the dermomyotome is not formed and the expression of a lateral dermomyotome marker gene, Sim-1, is expanded more medially in the absence of these Wnt signalings. In addition, the expression of a myogenic gene, Myf-5, is decreased at 9.5 days post coitum whereas the level of expression of a number of myogenic genes in the later stage appeared normal. These results indicate that Wnt-1 and Wnt-3a signalings actually regulate the formation of the medial compartment of the dermomyotome and the early part of myogenesis.     

The role of intraoperative transesophageal echocardiography during ventricular septation

PURPOSE: To determine whether teaching medical students has concurrent economic effects on physicians and their practices. METHOD: The authors reviewed 869 patient-encounter forms completed in April 1994 and July 1995 by four family medicine physicians who were clinical faculty at the State University of New York Health Science Center at Syracuse. The authors compared those forms that were completed when a third-year medical student was present for the patient encounter with those completed when a student was not present. The authors looked for differences in the distributions of billing codes and in the frequencies of in-office procedures performed and diagnostic tests ordered. RESULTS: The presence or absence of a third-year medical student had no significant effect on the variables studied. CONCLUSION: In the clinical settings studied, concurrent medical student teaching did not appear to affect the distribution of billing codes or the frequency of in-office procedures performed or diagnostic tests ordered.     

Diagnostic cytology for detection of early cancer

Cytologic methods for detection of early cancers of the uterine cervix, lung and various other organs are discussed. The scraping smear method using a spatula is more effective than the cotton swab or vaginal pool smear method for detection of preinvasive intraepithelial lesions, such as, carcinoma in situ and dysplasias of various degrees of the uterine cervix. The use of sputum specimens pooled for three to five days is recommended for cytologic examination in population screening of lung cancer. Good cytopreparatory techniques, suitable screening and cytodiagnostic classifications of malignancy are also described and emphasized, especially, the importance of properly fixed cytologic material for correct cytopathological diagnosis.     

Epstein-Barr virus contributes to the malignant phenotype and to apoptosis resistance in Burkitt's lymphoma cell line Akata

In the present study, we established an in vitro system representing the Burkitt's lymphoma (BL)-type Epstein-Barr virus (EBV) infection which is characterized by expression of EBV-determined nuclear antigen 1 (EBNA-1) and absence of EBNA-2 and latent membrane protein 1 (LMP1) expression. EBV-negative cell clones isolated from the EBV-positive BL line Akata were infected with an EBV recombinant carrying a selectable marker, and the following selection culture easily yielded EBV-infected clones. EBV-reinfected clones showed BL-type EBV expression and restored the capacity for growth on soft agar and tumorigenicity in SCID mice that were originally retained in parental EBV-positive Akata cells and lost in EBV-negative subclones. Moreover, it was found that EBV-positive cells were more resistant to apoptosis than were EBV-negative cells. EBV-infected cells expressed the bcl-2 protein, through which cells might become resistant to apoptosis, at a higher level than did uninfected cells. This is the first report that BL-type EBV infection confers apoptosis resistance even in the absence of expression of LMP1 and BHRF1, both of which are known to have an antiapoptotic function. Surprisingly, transfection of the EBNA-1 gene into EBV-negative Akata clones could not restore malignant phenotypes and apoptosis resistance, thus suggesting that EBNA-1 alone was not sufficient for conferring them. Our results suggest that the persistence of EBV in BL cells is required for the cells to be more malignant and apoptosis resistant, which underlines the oncogenic role of EBV in BL genesis.     

Clonidine reduces dopamine and increases GABA in the nucleus accumbens: an in vivo microdialysis study

The spectrum of infectious disease (ID) emergencies in hospitalized patients was assessed in a prospective study of 3,626 inpatient ID consultations in a 1,350-bed teaching hospital. ID emergencies, defined by a need or anticipated need for advanced life support or by irreversible organ damage leading to permanent functional loss, were encountered in 175 patients. Infections of the central nervous system (26.3%), cardiovascular system (14.9%), alimentary system (13.1%), and lower respiratory tract (7.4%) and adverse reactions to antimicrobial agents (7.4%) were most common. In 18.9% of the cases, the referring clinicians were unaware of the emergency at the time of referral. Drug reactions (46.1%), severe alimentary and peritoneal infections (32.0%), upper respiratory tract infections (28.6%), and skin and soft-tissue infections (27.3%) were most frequently missed. The emergency ID conditions were not recognized because they had an atypical presentation (51.5%), were not commonly seen in the referring specialty (24.2%), were due to rare organisms (15.2%), or had unusual anatomical sites of involvement (9.1%). A close liaison between clinicians and the ID team is crucial for recognition of ID emergencies at their early stages so that appropriate investigations and management can be instituted expediently, before the occurrence of irreversible damage.     

Anti-atherosclerotic effect of E5324, an inhibitor of acyl-CoA:cholesterol acyltransferase, in Watanabe heritable hyperlipidemic rabbits

E5324, n-butyl-N'-[2-[3-(5-ethyl-4-phenyl-1H-imidazol-1-yl)propoxy]-6- methylphenyl]urea, a novel and potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), was evaluated for its anti-atherosclerotic and lipid-lowering effects in Watanabe heritable hyperlipidemic (WHHL) rabbits. At 3 months of age, 40 male WHHL rabbits were divided into 4 groups. The rabbits were fed a standard rabbit chow (control group), or standard rabbit chow containing E5324 (0.1% or 0.02%) or 1% probucol for 16 weeks. Even the high dose of E5324 did not lower the plasma total cholesterol levels throughout the experiment. Probucol slightly reduced the plasma cholesterol levels, and showed anti-atherosclerotic activity, i.e., reductions of atherosclerotic plaque formation and cholesterol content in the aorta. Although E5324 did not lower plasma cholesterol, atherosclerotic plaque formation in the aortic arch and thoracic aorta was reduced (by about 34% and 41%, respectively, at the high dose; P < 0.05). Cholesterol content in the aortic arch and thoracic aorta was also reduced (by about 59% and 62% at the high dose, respectively) compared with the control. These results suggest that E5324 acts directly on the arterial wall through ACAT inhibition, and prevents the progression of atherosclerosis in WHHL rabbits.     

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.     

The Chlamydomonas reinhardtii ODA3 gene encodes a protein of the outer dynein arm docking complex

We have used an insertional mutagenesis/ gene tagging technique to generate new Chlamydomonas reinhardtii mutants that are defective in assembly of the uter ynein rm. Among 39 insertional oda mutants characterized, two are alleles of the previously uncloned ODA3 gene, one is an allele of the uncloned ODA10 gene, and one represents a novel ODA gene (termed ODA12). ODA3 is of particular interest because it is essential for assembly of both the outer dynein arm and the outer dynein arm docking complex (ODA-DC) onto flagellar doublet microtubules (Takada, S., and R. Kamiya. 1994. J. Cell Biol. 126:737- 745). Beginning with the inserted DNA as a tag, the ODA3 gene and a full-length cDNA were cloned. The cloned gene rescues the phenotype of oda3 mutants. The cDNA sequence predicts a novel 83. 4-kD protein with extensive coiled-coil domains. The ODA-DC contains three polypeptides; direct amino acid sequencing indicates that the largest of these polypeptides corresponds to ODA3. This protein is likely to have an important role in the precise positioning of the outer dynein arms on the flagellar axoneme.     

Supermode selection of a subterahertz-harmonic colliding-pulse mode-locked semiconductor laser using continuous-wave light injection

The supermode of a 192-GHz sixth-harmonic colliding-pulse mode-locked semiconductor laser can be selected by continuous-wave (CW) light injection adjusted to the unlocked fundamental cavity modes. This selection scheme offers a technique for wide-range simultaneous multiwavelength allocation at each fundamental mode spacing and will be useful for providing standard light sources for wavelength-division multiplexed (WDM) systems.     

Diurnal variation in serum remnant-like lipoproteins, platelet aggregation and fibrinolysis in healthy volunteers

The linkage of cobalamin and folate deficiency to psychiatric illness has been studied and debated since these vitamins were first discovered in the 1940s. The clinical relevance of these deficiencies remains the subject of investigation and scholarly discussion. This article reviews case reports and studies derived from a MEDLINE search for English-language articles related to folate, cobalamin, and psychiatric illness. Emphasis is given to clinical research and recent developments. Preclinical evidence for direct effects of folate and cobalamin on brain functioning is compelling, and numerous associations of their deficiencies to psychiatric illness are evident. These vitamin deficiencies may typically present initially with psychiatric symptoms, but any direct causal relationship to specific neuropsychiatric illnesses are not well defined. The relationship of these vitamins in dementia is significant, but they may only rarely be a cause of truly reversible dementia. Folate deficiency appears most tightly connected with depressive disorders, and cobalamin deficiency with psychosis. Contrary to intuition, vitamin deficiencies appear to occur infrequently with eating disorders. Other diagnoses have been investigated much less extensively. The diagnosis and management of these deficiencies in the context of neuropsychiatric illness is still a matter of discussion. The quality of clinical research in this area is improving, but there are many unanswered questions that affect clinical practice. Clinicians should remain vigilant to the possibility of deficiencies of folate and cobalamin in diverse psychiatric populations. Normal hematological indices do not rule out the deficiencies. Further study is needed to refine the detection and clinical management of these vitamin deficiencies in psychiatric populations.