Vascular endothelial growth factor, placenta growth factor and their receptors in isolated human trophoblast

The expression of the angiogenic growth factors, vascular endothelial cell growth factor (VEGF) and placenta growth factor (PIGF) was demonstrated in isolated human term cytotrophoblast and in vitro differentiated syncytiotrophoblast. RNase protection assays demonstrated VEGF expression in both cytotrophoblast and syncytiotrophoblast while prominent PIGF expression was detected in both types of trophoblast by Northern blot analyses. VEGF expression increased approximately eightfold in trophoblast cultured under hypoxic conditions (1 per cent O2) yet PIGF expression decreased 73 +/- 5.5 per cent in the same trophoblast. These results suggest distinct regulatory mechanisms govern expression of VEGF and PIGF in trophoblast. Characterization of the VEGF/PIGF receptors, KDR and flt-1, revealed the presence of flt-1 mRNA in isolated cytotrophoblast and in vitro differentiated syncytiotrophoblast. KDR was not detected in the isolated trophoblast. Exogenous rhVEGF induced c-Jun N-terminal kinase (JNK) activity in the normal trophoblast indicating that the flt-1 receptors on trophoblast are functional. Trophoblast-derived VEGF/PIGF could act in a paracrine fashion to promote uterine angiogenesis and vascular permeability within the placental bed. In addition, presence of function flt-1 on normal trophoblast suggests that VEGF/PIGF functions in an autocrine manner to perform an as yet undefined role in trophoblast invasion, differentiation, and/or metabolic activity during placentation.     

Evaluation of staging conformity CTNM and PTNM for lung cancer

A series of 225 consecutive lung cancer patients were prospectively randomized into study group (75 patients) and control group (150 patients), and the conformity of CTNM and PTNM staging was was evaluated. Radical mediastinal lymph node dissection was performed and in average 11.5 nodes were dissected in the study group. Only suspected metastatic lymph nodes, 3.4 in average, were dissected in the control group. CTNM classification was made according to clinical examination, chest image examination and bronchoscopy in every patient and PTNM staging was made after thoracotomy. Then the conformity of CTNM and PTNM staging was examined by Kappa value. The results showed that the Kappa value in the two groups was lower than the effective standard value of 0.4. The study group (Kappa = 0.097) was poorer than the control group (Kappa = 0.371). The principal influencing cause was that N was not well evaluated by CTNM. The principal manifestation of the staging inconsistency was that the stage of PTNM was advanced than that of CTNM. In the study group 43% of patients showed an increased stage and this occurred in 33% of the control group (P < 0.05). The results of the study show that at present the CTNM staging has not fully satisfied the needs of practice and requires to be further improved. The operative procedure which only dissects suspected involved mediastinal lymph nodes can not meet the needs of PTNM staging. In order to make PTNM staging accurately and evaluate the results of treatment for lung cancer, radical mediastinal lymph node dissection should be performed in every operable patient.     

Mitochondrial DNA depletion in a patient with long survival

We studied a 29-year-old woman with myopathy since childhood with evidence of mitochondrial DNA (mtDNA) depletion. Muscle biopsy sample showed cytochrome c oxidase (COX)-negative fibers. Biochemistry showed COX deficiency. Southern blot analysis showed 76% depletion of mtDNA as compared with controls. This patient's clinical course suggests that long survival is possible in some patients with mtDNA depletion.     

Aminopeptidase N purified from gypsy moth brush border membrane vesicles is a specific receptor for Bacillus thuringiensis CryIAc toxin

We have evaluated the binding of Bacillus thuringiensis Cry toxins to aminopeptidase N (APN) purified from Lymantria dispar (gypsy moth) brush border membrane vesicle (BBMV). CryIAc toxin bound strongly to APN, while either the structurally related CryIAa and CryIAb toxins or CryIC, CryIIA, and CryIIIA toxins showed weak binding to APN. An in vitro competition binding study demonstrated that the binding of CryIAc to L. dispar BBMV was inhibited by APN. Inhibition of short circuit current for CryIAc, measured by voltage clamping of whole L. dispar midgut, was substantially reduced by addition of phosphatidylinositol-specific phospholipase C, which is known to release APN from the midgut membrane. In contrast, addition of phosphatidylinositol-specific phospholipase C had only a marginal effect on the inhibition of short circuit current for CryIAa. These data suggest that APN is the major functional receptor for CryIAc in L. dispar BBMV. A ligand blotting experiment demonstrated that CryIAc recognized a 120-kDa peptide (APN), while CryIAa and CryIAb recognized a 210-kDa molecule in L. dispar BBMV. In contrast, CryIAa and CryIAb bound to both the 120- and 210-kDa molecules in Manduca sexta BBMV, while CryIAc recognized only the 120-kDa peptide. The 120-kDa peptide (APN) in L. dispar BBMV reacted with soybean agglutinin, indicating that N-acetylgalactosamine is a component of this glycoprotein.     

Which bacteria are found in Belgian women with uncomplicated urinary tract infections in primary health care, and what is their susceptibility pattern anno 95-96?

OBJECTIVE: The purpose of a curfew is to decrease the amount of crime inflicted on minors during the late hours of the night. On June 1, 1994, a city curfew was instituted in New Orleans, requiring all persons 17 years of age or younger to be off the streets from 9 PM to 6 AM Sunday through Thursday, and from 11 PM to 6 AM on Friday and Saturday. This study evaluated the effect of the curfew on emergency medical services (EMS) transports for patients who were 17 years old or younger (pediatric). METHODS: Data from all pediatric transports were included from the months before (5/94) and after (6/94) the institution of the curfew, and from the same two months one year earlier (5/93 and 6/93). A chi-square test was used to evaluate comparisons. RESULTS: The city EMS transports 48,000 patients per year in a one-tiered system (paramedic only) that acts as the sole provider of emergency EMS transport in the city. Approximately 10% of all transports are pediatric, and 40% of the pediatric transports are for trauma. A total of 1,642 transports were found that fit the inclusion criteria. In May 1993, there were 415 total pediatric transports; 234 were pediatric trauma. In June 1993, there were 406 total pediatric transports; 250 were pediatric trauma. In May 1994, there were 447 total pediatric runs; 243 were pediatric trauma. During the postcurfew month, June 1994, there were a significant decrease in pediatric transports to 370 (p < 0.01) and a significant decrease in pediatric trauma transport to 189 (p < 0.01). CONCLUSION: The institution of a curfew may lead to a drop in pediatric EMS runs during curfew hours. Another value of the curfew may be in the secondary effects of the curfew in preventing childhood injury during noncurfew hours.     

Pore stoichiometry of a voltage-gated chloride channel

Ion channels allow ions to pass through cell membranes by forming aqueous permeation pathways (pores). In contrast to most known ion channels, which have single pores, a chloride channel belonging to the CIC family (Torpedo CIC-0) has functional features that suggest that it has a unique 'double-barrelled' architecture in which each of two subunits forms an independent pore. This model is based on single-channel recordings of CIC-0 that has two equally spaced and independently gated conductance states. Other CIC isoforms do not behave in this way, raising doubts about the applicability of the model to all CIC channels. Here we determine the pore stoichiometry of another CIC isoform, human CIC-1, by chemically modifying cysteines that have been substituted for other amino acids located within the CIC ion-selectivity filter. The CIC-1 channel can be rendered completely susceptible to block by methanethiosulphonate reagents when only one of the two subunits contains substituted cysteines. Thiol side chains placed at corresponding positions in both subunits can form intersubunit disulphide bridges and coordinate Cd2+, indicating that the pore-forming regions from each subunit line the same conduction pathway. We conclude that human CIC-1 has a single functional pore.     

Periurethral fat injection in the treatment of recurrent genuine stress incontinence

A benign, transient proliferation of atypical lymphocytes and a monoclonal rearrangement of the T-cell receptor beta (TRB) locus was found in a 60-year-old woman who presented with low-grade fever, anorexia and fatigue. A marked and transient atypical lymphocytosis (white blood cell count 90.5 x 10(9)/l) with CD8 surface antigen improved without specific treatment. Although tests for IgM antibodies to hepatitis A, varicella zoster, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all negative, a monoclonal gene rearrangement of TRB locus was observed in the DNA of the proliferated atypical lymphocytes by Southern blotting. The clonal rearrangement and the atypical lymphocytes disappeared after 14 d, and the patient has remained well for 7 years. These results suggest that monoclonal proliferation of CD8 lymphocytes can occur based on a non-neoplastic aetiology.     

Estradiol inhibits LDL oxidation: do the progestins medroxyprogesterone acetate and norethisterone acetate influence this effect?

Estrogen replacement therapy in postmenopausal women must be combined with progestin to avoid endometrial cancer. However, progestin addition could antagonize cardioprotective effects of estradiol. Therefore we investigated the effect of the two most commonly used progestins--medroxyprogesterone acetate (progesterone-derivative) and norethisterone acetate (nortestosterone-derivate)--alone and in combination with 17 beta-estradiol on copper-mediated oxidation of low density lipoprotein (LDL). Whereas 17 beta-estradiol alone inhibited the onset of LDL oxidation at the concentrations 0.5, 1.0, 5 and 10 microM, the progestins alone did not demonstrate any significant effect. In the estrogen-progestin combinations of 0.5 microM 17 beta-estradiol with 0.5, 1.0, 5 and 10 microM progestin, respectively, the estradiol effect was not changed. These results suggest that medroxyprogesterone acetate as well as norethisterone acetate do not counteract the beneficial effect of 17 beta-estradiol on LDL oxidation when used in hormone replacement therapy.