The environmental health of Ocean County

Glycosaminoglycanes (GAG) were measured in 24-h urine of patients with chronic pyelonephritis (CP) and chronic glomerulonephritis (CGN) at different stages of nephrosclerosis. These patients developed hyperglycosaminoglycanuria at early stages of nephrosclerosis before establishment of chronic renal failure. There is a positive correlation between the severity of excretion of GAG and leukocyturia in CP patients (p < 0.05). Estimation of GAG 24-h urinary excretion can help evaluate metabolism of connective tissue of the kidneys in CP and CGN patients for early diagnosis of nephrosclerosis, control of the treatment efficacy and the disease prognosis. It can also serve as additional criterion for rating of inflammation. The method is non-invasive, informative, available for clinical diagnostic laboratories.     

Synergistic anticancer effects of ganciclovir/thymidine kinase and 5-fluorocytosine/cytosine deaminase gene therapies

BACKGROUND: A bacterial enzyme, Escherichia coli cytosine deaminase, which converts the prodrug 5-fluorocytosine into the toxic drug 5-fluorouracil, and a viral enzyme, herpes simplex virus thymidine kinase, which converts ganciclovir from an inactive prodrug to a cytotoxic agent by phosphorylation, are being actively investigated for use in gene therapy for cancer. The purpose of this study was to determine whether combining these prodrug-activating gene therapies might result in enhanced anticancer effects. METHODS: Rat 9L gliosarcoma cells were transfected with plasmids containing the E. coli cytosine deaminase gene (9L/CD cells), with plasmids containing the herpes simplex virus thymidine kinase gene (9L/TK cells), or with both expression plasmids (9L/CD-TK cells). The drug sensitivities of the cell lines were evaluated; in addition, the sensitivities of 9L and 9L/CD-TK cells mixed in varied proportions were measured. The effects of prodrug treatment on 9L/CD-TK tumor growth (i.e., size and volume) in nude mice were monitored. The isobologram method of Loewe and the multiple drug-effect analysis method of Chou-Talalay were used to measure the interaction between the two prodrug-activating gene therapies. To elucidate the mechanism of interaction, the phosphorylation of ganciclovir in 9L/CD-TK cells after varying prodrug treatments was studied. RESULTS AND CONCLUSIONS: The presence of transfected cytosine deaminase and thymidine kinase genes in 9L gliosarcoma cells reduced cell survival, both in vitro and in vivo, following treatment with the relevant prodrugs; the effects of the two components appeared to be synergistic and related mechanistically to the enhancement of ganciclovir phosphorylation by thymidine kinase following 5-fluorouracil treatment.     

In vitro activity of metronidazole alone and in combination with clotrimazole against clinical isolates of Trichomonas vaginalis

The impetus for shorter hospital stay of mother and newborn infant after delivery is based on economic constraints and parental preference. Earlier published studies did not demonstrate any increase in morbidity rate with shorter stay, but these studies were limited by methodologic flaws and biases that limited the validity and generalizability of the conclusions. More recent studies showed that readmission rates increased with shorter stay and that the severity of illness of readmitted infants may have increased. In addition, the interpretation of current newborn screening tests may not be applicable when performed prior to early discharge. In light of recent changes in neonatal hospital length of stay, a careful review and update of current guidelines and practices for newborn care are required.     

Glycogen levels in human term placental disks, umbilical cords, and membranes

Glycogen in the placenta and its appendages is important for fetal well-being. The precise location of the glycogen stores, however, is unknown. This study was initiated to quantitate glycogen levels at well-defined sampling sites in more than 641 samples from 10 uncomplicated pregnancies and to correlate these glycogen levels with clinical and morphological variables. By biochemical assay, glycogen levels were greatest in the midumbilical cord section (29.08 +/- 1.18 mg/g dry wt) and lowest in the amnionic membrane (2.31 +/- 0.08 mg/g dry wt). Within the placental disk, parenchymal glycogen levels were greatest near the cord insertion (9.31 +/- 2.68 mg/g dry wt) and lowest at the periphery (5.71 +/- 1.14 mg/g dry wt). The midumbilical cord glycogen level showed strong direct correlations (P < .001) with birth weight, umbilical cord weight, and total calculated umbilical cord glycogen and somewhat lower but significant (P < .037) direct correlations with the calculated mean umbilical cord glycogen level, total calculated placental glycogen content, and placental weight. The glycogen level in the middisk parenchymal section from the fetal surface correlated directly with gestational age. Periodic acid-Schiff stains showed that magenta glycogen granules were most abundant in the cytoplasm of the vascular smooth muscle cells. These data show significant variations in glycogen levels among sampling sites. Definition of the precise sampling site is important for clinicopathologic studies of placental glycogen and for interstudy correlations.     

Haemonchus contortus glycoproteins contain N-linked oligosaccharides with novel highly fucosylated core structures

Structural studies on the N-linked oligosaccharides of Haemonchus contortus, an economically important nematode that parasitizes domestic ruminants, have revealed core fucosylation of a type not previously observed in any eukaryotic glycoprotein. Mass spectrometric analyses were performed on detergent extracts of homogenized adult H. contortus and on purified H11, a glycoprotein isolated from intestinal brush borders which has been previously shown to be an effective vaccine antigen. The major N-linked glycans identified in the present study have up to three fucose residues attached to their chitobiose cores. The fucoses are found at the 3- and/or 6-positions of the proximal GlcNAc and at the 3-position of the distal GlcNAc. The latter substitution is unique in N-glycans. Most anti-H11 monoclonal antibodies are known to recognize carbohydrate epitopes, and it is possible that the newly discovered multifucosylated core structures are highly immunogenic in this glycoprotein.     

Escherichia coli O157:H7 requires intimin for enteropathogenicity in calves

Enterohemorrhagic Escherichia coli (EHEC) strains require intimin to induce attaching and effacing (A/E) lesions in newborn piglets. Infection of newborn calves with intimin-positive or intimin-negative EHEC O157:H7 demonstrated that intimin is needed for colonization, A/E lesions, and disease in cattle. These results suggest that experiments to determine if intimin-based vaccines reduce O157:H7 levels in cattle are warranted.     

Glycine conjugation of para-aminobenzoic acid (PABA): a quantitative test of liver function

N-Acetyl aspartate (NAA) is the second most abundant amino acid in the human brain. NAA is synthesized by L-aspartate N-acetyl transferase or by cleavage from N-acetyl aspartyl glutamate by N-acylated alpha-linked L-amino dipeptidase (NAALADase); and it is catabolized to acetate and aspartate by N-acetyl aspartate amino hydrolase (amino acylase II). NAA is localized primarily to neurons, where it is concentrated in the cytosol. Although NAA is devoid of neurophysiological effects, it serves as an acetyl donor, an initiator of protein synthesis or a carbon transfer source across the mitochondrial membrane. The concentration of NAA in human brain increases 3-fold between midgestation and adulthood. In Canavan's Disease, an autosomal recessive disorder due to a null mutation in amino acylase II, NAA levels in brain are markedly increased and disrupt myelination. NAA levels have been found to be reduced in neurodegenerative disorders, including Alzheimer's Disease and Huntington's Disease. Since endogenous NAA can be readily detected in human brain by magnetic resonance spectroscopy, it is increasingly being exploited as a marker for functional and structural integrity of neurons in an expanding number of disorders.