Ahch, the mouse homologue of DAX1: cloning, characterization and synteny with GyK, the glycerol kinase locus

We cloned the murine full-length cDNA encoding Ahch, the mouse homologue of DAX1 (DSS-AHC Region on Human X Chromosome, Gene1) which is the gene responsible for human X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH). Sequence analysis revealed that the murine and human cDNAs have 65% aa identity and 75% aa similarity overall. The cysteine residues in the putative DNA binding domain, which may interact with Zn2+ ions to form zinc fingers, are 100% conserved between the two species, indicating that the novel zinc-finger structures in DAX1 may be functional. In addition, mouse interspecific backcrosses show that the Ahch gene is closely linked to the glycerol kinase locus, GyK, on the mouse X chromosome, indicating that the order of the loci is conserved in this syntenic region between mouse and human.     

Breast cancer screening of the medically underserved: results and implications

Socioeconomic status is the most significant factor influencing the decreased survival associated with breast cancer in minority groups in the United States. Barriers to the use of early detection programs by low-income women often result in the detection of breast cancer at stages too advanced to assure optimum outcomes. In an effort to increase accessibility of breast cancer screening among such individuals, the Early Detection Program (EDP) was initiated in 1987. The program provided breast cancer screening to women 40 years of age and older who attended eight primary healthcare centers located in low-income neighborhoods throughout Dade County, Florida. From its inception in October 1987 through December 1993, 23,866 medically underserved women had mammography examinations, with more than 17,000 of these women undergoing baseline mammograms. Since the program's inception, 126 cancers were diagnosed in 123 women. A dramatic shift from later to earlier stage breast cancers was observed. These results warrant a greater inclusion of medically underserved and lower socioeconomic status women in screening programs for the early detection of breast cancer.     

Nerve conduction velocity and H-reflex recovery in bipolar illness

Bipolar illness may be characterized by dysregulation and dysfunction of biologically active ions and ion pumps, respectively. In an effort to examine whether purported physiologic abnormalities may have functional counterparts, nerve conduction velocities (NCVs) and H-reflex recovery were examined in 7 acutely manic, 11 euthymic bipolar, 13 remitted schizophrenic, and 6 normal control individuals. All electrophysiologic tests were clinically normal. However, euthymic bipolar patients had significantly slower NCVs than either manic or normal individuals. Percent decrement of H-reflex recovery was nonsignificantly increased in manic versus euthymic bipolar subjects. Data analysis suggests lithium was not responsible for these changes. These data indicate that different mood states in bipolar illness are associated with alterations in electroneurophysiologic function.     

The life you save may be your own

Intravesical potassium sensitivity can readily elicit abnormal epithelial permeability responses in subjects with diseased bladder, primarily interstitial cystitis. The technique involves eliciting responses in each subject to 40 cc of plain water or 40 cc of potassium chloride solution (40 mEq per 100 cc water). The subjects are asked to rate their subjective responses 3-5 minutes after instillation of the test solution and told to compare the water and potassium. An abnormal provocation to potassium but not water is considered a positive response and a useful way to delineate people with epithelial dysfunction and loss of permeability control. On the other hand, normal subjects will not respond to either the water or potassium.     

Replication of O6-methylguanine-containing DNA by repair and replicative DNA polymerases

The biological consequences of O6-methylguanine (m6G) in DNA are well recognized. When template m6G is encountered by DNA polymerases, replication is hindered and trans-lesion replication results in the preferential incorporation of dTMP opposite template m6G. Thus, unrepaired m6G in DNA is both cytotoxic and mutagenic. Yet, cell lines tolerant to m6G in DNA have been isolated, which indicates that some cellular DNA polymerases may replicate m6G-containing DNA with reasonable efficiency. Previous reports suggested that mammalian pol beta could not replicate m6G-containing DNA, but we find that pol beta can catalyze trans-lesion replication; however, the lesion must reside in the optimal context for pol beta activity, single- or short nucleotide gapped substrates. Primed single-stranded DNA templates, with or without template m6G, were poor substrates for pol beta as reported in earlier studies. In contrast, trans-lesion replication by bacteriophage T4 DNA polymerase was observed for primed single-stranded DNA templates. Replication of m6G-containing DNA by T4 DNA polymerase required the gp45 accessory protein that clamps the polymerase to the DNA template. The rate-limiting step in replicating m6G-containing DNAs by both DNA polymerases tested was incorporation of dTMP across from the lesion.     

Tetrahydrobiopterin and biogenic amine metabolism in the hph-1 mouse

hph-1 mice, which have defective tetrahydrobiopterin biosynthesis due to decreased GTP cyclohydrolase I activity, have been used to investigate the effects of tetrahydrobiopterin deficiency on aromatic L-amino acid monooxygenases and brain monoamine metabolism. Liver tetrahydrobiopterin levels were decreased, and tetrahydrobiopterin deficiency and reduced levels of dopamine, norepinephrine, serotonin, and their metabolites in the brain occurred both pre- and postnatally. Chronic subcutaneous tetrahydrobiopterin elevated brain levels to values higher than those seen in controls but had no effect on monoamine metabolism. In vivo activities of tyrosine hydroxylase and tryptophan hydroxylase were significantly decreased. There was a 30% decrease in the in vitro activity of striatal tyrosine hydroxylase and 50% decrease in liver phenylalanine hydroxylase. Western blotting demonstrated that the lower monooxygenase activities resulted from a reduced absolute amount of tyrosine hydroxylase and phenylalanine hydroxylase protein. The findings suggest involvement of tetrahydrobiopterin in the control of the steady-state concentration of the aromatic L-amino acid monooxygenases. In addition, demonstration of central monoamine changes in the hph-1 mouse make it a possible model system for the investigation of the neuropathological mechanisms in Dopa-responsive dystonia, which has recently been linked with mutations in the gene for GTP cyclohydrolase I.     

Sociodemographic factors of Pap smear screening in Taiwan

We report the differences between using either EDTA plasma or serum in a turbidimetric assay for quantitation of C-reactive protein (CRP). A systematic discrepancy was found for these two sample materials. This was most pronounced in the low concentration range (below 20 mg1(-1)) at which lower values were found in serum than in EDTA plasma. Conversely, in the high concentration range, serum showed slightly higher values. Addition of K3-EDTA to the reaction buffer improved the kinetics for sera with low concentrations of CRP, thus increasing the sensitivity of the assay. We found an overall constant discrepancy of approximately 8% lower values in plasma than in serum (equally for low and high levels of CRP) after the addition of K3-EDTA. The most probable explanation for this effect seems to be the differing water content of serum and EDTA plasma. We discuss the role and function of EDTA in the CRP assay and suggest some hypothetical mechanisms.     

Relation between the level of E. coli gene expression and the structure of translation initiation region (TIR). III. Sites of complementary interaction of TIR with 16S rRNA

The addition of vertebral disc degeneration to the job-related disease register raises the question of vertebral disc degeneration patterns according to loading strain. The readings of the lumbar vertebra of construction workers and nurses were compared with those of a group without workload. In the groups examined, aged 35 to 50, monosegmental damage was found in only 17% of the patients with high workload, as opposed to 29% of those with no workload, mostly with monosegmental damage at level L5/S1. Damage to the upper segments of the lumbar spine with intact discs in between was found exclusively in patients with high workload. Multiple segment damage in the age range examined was found in subjects with activities that add to the load of the spinal column. The value of MRI in assessing and evaluating illness originating from the vertebral discs is currently being discussed.     

Subependymal astrocytic hamartomas in the Eker rat model of tuberous sclerosis

Tuberous sclerosis (TSC) is an autosomal dominant syndrome that is linked to two genetic loci: TSC1 (9q34) and TSC2 (16p13). Brain manifestations such as cortical tubers and subependymal hamartoma/giant cell astrocytomas are major causes of TSC-related morbidity. In this study, we describe the central nervous system involvement in a unique rodent model of tuberous sclerosis. The Eker rat carries a spontaneous germline mutation of the TSC2 gene and is predisposed to multiple neoplasia. In a series of 45 adult Eker carriers (TSC2 +/-), three types of focal intracranial lesions were found, of which the subependymal and subcortical hamartomas were most prevalent (65%). There exist remarkable phenotypic similarities between the Eker rat and human subependymal lesions. Our study indicates that the predominant cellular phenotype of the subependymal hamartomas is astroglial and suggests that the neuronal contribution within these lesions is, in part, the result of pre-existing myelinated axons. The hamartomas did not show evidence of loss of the wild-type TSC2 allele; it remains to be determined whether TSC2 inactivation is necessary for their pathogenesis. This genetically-defined rodent model may be useful in elucidating the molecular and developmental basis of the subependymal giant cell astrocytoma in humans.     

Isolation of a novel Helicobacter species, Helicobacter cholecystus sp. nov., from the gallbladders of Syrian hamsters with cholangiofibrosis and centrilobular pancreatitis

A filamentous, gram-negative, motile bacterium with a single polar sheathed flagellum was isolated from gallbladders of hamsters with cholangiofibrosis and centrilobular pancreatitis. Bacteria grew under microaerophilic conditions at 37 and 42 degrees C, were oxidase, catalase, arginine aminopeptidase, and L-arginine arylamidase positive, reduced nitrate to nitrite, were resistant to cephalothin, and exhibited intermediate susceptibility to nalidixic acid. Sequence analysis of the 16S rRNA gene indicated that the bacterium was a novel member of the Helicobacter genus, most closely related to Helicobacter pametensis. We propose to name this bacterium Helicobacter cholecystus. In epidemiologic studies, isolation of H. cholecystus correlated strongly with the presence of cholangiofibrosis and centrilobular pancreatitis; however, further studies are needed to define the role of this bacterium in pathogenesis.