Common region of ALL-1 gene disrupted in epipodophyllotoxin-related secondary acute myeloid leukemia

Translocations at chromosomal band 11q23 characterize most de novo acute lymphoblastic leukemias (ALL) of infants, acute myeloid leukemias (AML) of infants and young children, and secondary AMLs following epipodophyllotoxin exposure. The chromosomal breakpoints at 11q23 have been cloned from isolated cases of de novo ALL and AML. Using an 859-base pair BamHI fragment of human ALL-1 complementary DNA that recognizes the genomic breakpoint region for de novo ALL and AML, we investigated two cases of secondary AML that followed etoposide-treated primary B-lineage ALL. In the first case, the translocation occurred between chromosomes 9 and 11 and the breakpoint at 11q23 localized to the same 9-kilobase region of the ALL-1 gene that is disrupted in most of the de novo leukemias. In the second case the translocation was between chromosomes 11 and 19. The breakpoint occurred outside of the ALL-1 breakpoint cluster region.     

Bulimia: From syncope to obsession.

The syndrome now known as bulimia is entirely different from the syndrome first described in its earliest use in the literature of classical Greece. Xenophon used the term bulimia in 399 B.C. to describe fainting in the cold with disturbed appetite. This use persisted across thousands of years of vivid debates in which bulimia was repeatedly differentiated from fames canina, an eating disorder characterized by excessive eating and vomiting. The centrality of syncope in bulimia disappeared during the 18th century, and the peripheral feature of hunger became the defining symptom. In very recent times, bulimia has been adopted as a formal name for a psychogenic eating disorder. The syndrome of syncope to which the diagnostic term bulimia was originally applied is identified as "hypoglycemia." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The importance of axial misalignment on the long term strength of polyethylene pipe butt fusion joints

The importance of axial misalignment at polyethylene pipe butt fusion joints has been assessed by undertaking elevated temperature lifetime tests. Both medium and high density polyethylene pipes were fusion joined to give aligned and controlled misaligned butt joints. These were tested under either a constant or fluctuating internal pressure loading using conditions that induced failure by slow, stable crck growth. It was observed that the lifetime of a butt joined system depends upon both the internal pressure or pressure range applied and the level of misalignment at the butt fusion joint. Increasing either the internal pressure (range) or the misalignment reduced system performance. These two variables of misalignment and internal pressure (range) may be incorporated into a single parameter, the amplified axial stress (or stress range) at the butt joint. This amplified or butt joint axial stress (or stress range) may be derived by considering the additional bending stresses introduced at the butt joint by virtue of misalignment combined with the axial stress loading.     

Molecular characterization of Vibrio cholerae O1 strains isolated during cholera outbreaks in Guinea-Bissau

In the present study, 19 strains of Vibrio cholerae O1 biotype El Tor isolated during outbreaks of cholera in Guinea-Bissau in 1987, 1994, and 1995 were characterized to investigate a possible epidemiological relationship among the isolates. On the basis of ribotyping with the restriction enzyme BglI, 5 strains isolated in 1987 showed two closely related ribotypes, while 14 strains isolated in 1994 and 1995 showed the same ribotype that was distinct from the ribotypes of strains isolated in 1987. Southern blot hybridization of BglI-digested genomic DNA with a cholera toxin probe demonstrated that the strains isolated in 1987 showed an identical cholera toxin genotype, whereas O1 strains isolated in 1994 and 1995 showed the same genotype that was distinct from the genotype of strains isolated in 1987. These results were supported by the results of antibiotic susceptibility testing, in which strains isolated in 1987 showed resistance to polymyxin B only, while each of the strains from 1994 and 1995 showed resistance to polymyxin B, trimethoprim-sulfamethoxazole, and the vibriostatic agent O/129. Although our results are based on a limited number of V. cholerae O1 strains, they suggest that the epidemic in Guinea-Bissau in 1994 and 1995 was due to the introduction of a new strain to the country.     

131I dose-dependent thyroid autoimmune disorders in children living around Chernobyl

The nucleotide sequence of 35,400 bp at approximately 10 kb from the right telomere of chromosome VII was determined. The segment contains the MAL1 locus, one of the five unlinked loci sufficient for maltose utilization. Until now, each of these loci was considered to contain three genes (for regulator, permease and alpha-glucosidase), but a fourth gene, presumably an extra alpha-glucosidase gene, was found at MAL1 adjacent to the usual cluster of three genes. The two glucosidase genes are present in opposite orientation, forming an inverted repeat structure. In addition to the four genes at MAL1, there are 11 complete, non-overlapping open reading frames (ORFs) longer than 300 bp in the sequence presented here. A new ABC transporter gene (YGR281w), required for oligomycin resistance was found (YOR1; Katzman et al., 1995), and the previously sequenced BGL2 (YGR282c), ZUO1 (YGR285c) and BIO2 (YGR286c) genes were located. The sequence of BIO2, a biotin synthetase gene, required substantial correction and the size of Bio2p is 375, rather than 356, amino acids. Two ORFs show rather weak similarities to animal genes: YGR278w to an unknown ORF of Caenorhabditis elegans and YGR284c to the murine Surf-4, a member of a cluster of at least four housekeeping genes. The remaining five ORFs do not encode known functions, but three of these show weak to high similarities to other ORFs in the Saccharomyces cerevisiae genome and one (YGR280c) codes for a particularly lysine-rich protein.     

Immunohistochemical detection and gene amplification of cyclin D1 in mammary infiltrating ductal carcinoma

The deregulation of cyclin D1 (BCL-1, PRAD1, CCND1) protein, normally synthesized in the G1 phase of the cell cycle, has been implicated in the pathogenesis of some malignant neoplasms, including invasive mammary carcinomas. We used rabbit polyclonal antibody 19 to detect cyclin D1 in 55 infiltrating ductal carcinomas and compared the findings to six important clinicopathologic parameters and cyclin D1 gene amplification. Nuclear immunoreactivity of variable intensity for cyclin D1 was present in 35% of the neoplasms, whereas immunoreactivity of normal mammary epithelial nuclei was absent. No significant correlations were observed between immunoreactivity and patient age, axillary lymph node status, estrogen receptors, progesterone receptors, histologic grade, or any of its three components. There was a correlation between cyclin D1 immunostaining and tumor size (P = 0.013). Fourteen of 15 tumors 2 cm or less were negative, whereas 7 of 12 neoplasms larger than 4 cm were immunopositive. Fifteen percent of the invasive carcinomas had cyclin D1 gene amplification. Of these eight tumors, six showed cyclin D1 immunoreactivity (P = 0.017). In this study, cyclin D1 was detected immunohistochemically in approximately one-third of infiltrating ductal carcinomas; approximately one-third of these had detectable cyclin D1 gene amplification. These results further implicate cyclin D1 in breast tumorigenesis and are additional evidence for the role of cell cycle regulatory proteins in invasive mammary carcinoma.     

Effects of retinoic acid (all-trans and 9-cis) on tumor progression in small-cell lung carcinoma

ON direction-selective (DS) ganglion cells were identified by electrophysiological recordings in DAPI labeled, isolated rabbit retinas. Their responses to a flashing spot were sustained. Their responses to moving stimuli were strong in the preferred direction and weak in the null direction. Injection of the recorded cells with Lucifer yellow revealed that the cells had a distinct dendritic morphology, consistent with that described previously (Buhl & Peichl, 1986; Amthor et al., 1989; Famiglietti, 1992a). When neighboring cells were injected, an extensive dendritic co-fasciculation was observed. The pattern of fasciculation restricts the possible synaptic connections of the ON DS cell.     

Activity of amoxicillin/clavulanate in patients with tuberculosis

Some beta-lactam antibiotics are active in vitro against Mycobacterium tuberculosis. There are anecdotal reports of successful treatment of tuberculosis caused by multiple-drug-resistant strains of M. tuberculosis with regimens that included amoxicillin/clavulanate. Reduction of M. tuberculosis in the sputum of patients with pulmonary tuberculosis during administration of amoxicillin/clavulanate was measured by a quantitative culture method to determine the activity in vivo. Patients were randomized to receive isoniazid, ofloxacin, or amoxicillin/clavulanate for 7 days. Isoniazid was the most effective agent, reducing M. tuberculosis after 2 days at a mean rate (+/- standard deviation) of 0.60 +/- 0.30 log10 cfu/mL per day, compared with 0.32 +/- 0.05 and 0.34 +/- 0.03 for ofloxacin and amoxicillin/clavulanate, respectively. The early bactericidal activity of amoxicillin/clavulanate was comparable to that reported for antituberculous agents other than isoniazid. Further studies of beta-lactam antibiotics with in vitro activity against M. tuberculosis are warranted to define their role in treatment of tuberculosis.     

Role of the actin cytoskeleton in the regulation of the cystic fibrosis transmembrane conductance regulator

The anion-selective channel CFTR (cystic fibrosis transmembrane conductance regulator), whose dysfunction is responsible for the onset of cystic fibrosis, is regulated by cAMP through the activation of protein kinase A (PKA). The nature of this activation process is unknown. In the present study, patch-clamp techniques were applied to both mouse mammary adenocarcinoma cells expressing human epithelial CFTR (CFTR cells) and cultured neonatal rat ventricular myocytes (NRVM), to determine whether CFTR is modulated by the actin cytoskeleton, and whether the actin cytoskeleton may be implicated in the cAMP-stimulated activation of the channel protein. Acute changes in the actin cytoskeleton by addition of cytochalasin D (CD) activated whole-cell currents in CFTR cells and NRVM. Addition of actin to excised, inside-out patches also activated CFTR. A functional characterization of CFTR in either cell type included cAMP-induced, linear whole-cell and single-channel currents in symmetrical Cl-, permeability to ATP, and inhibition by either diphenylamine-carboxylate (DPC) or a monoclonal antibody raised against CFTR. Incubation of CFTR cells and NRVM with CD for over 6 h prevented CFTR activation either by the cAMP pathway under whole-cell conditions or by PKA under excised inside-out conditions. Thus a complete derangement of the actin cytoskeleton prevents the cAMP-dependent activation of CFTR. CFTR activation, however, was restored by subsequent addition of actin. In summary, changes in actin filament organization modulate CFTR channel activity by a mechanism entailing a direct interaction between actin filaments and CFTR.     

Fibrolytic enzymes and parity effects on feeding behavior,salivation, and ruminal pH of lactating dairy cows

Four multiparous and four primiparous lactating dairy cows fitted with ruminal cannulas were used in a duplicated 4 x 4 Latin square design to study the effects of parity and inclusion of a fibrolytic enzyme product (Agribrands International, St. Louis, MO) on feeding and chewing behavior, salivation, and ruminal pH. Diets consisting of rolled barley, barley silage, and alfalfa haylage (55% forage, DM basis) differed in enzyme application: 1) control, 2) enzyme applied to concentrate (45% of TMR), 3) enzyme applied to supplement (4% of TMR), and enzyme applied to a premix (0.2% of TMR). Enzyme supplementation did not alter daily time spent eating or ruminating, but when enzymes were added to the ration daily, saliva production increased, with no difference among enzyme application treatments. Multiparous cows consumed a greater amount of feed, but spent a similar amount of time eating, compared to primiparous cows. Primiparous cows had shorter ruminating episodes, resulting in lower daily ruminating time compared with multiparous cows. Primiparous cows had lower daily saliva output compared with multiparous cows. These results indicate that application of this fibrolytic enzyme product did not alter the physical structure of the feed, as measured by feeding and chewing variables. The increase in total saliva production observed in cows fed enzyme-supplemented diets may be attributed to a physiological response to compensate for the increase in fermentation products during digestion. The increased intake for multiparous cows is attributed to increased eating rate and not to increased time spent eating. The higher DMI of multiparous cows resulted in increased rumination time needed to process the additional feed and increased salivation to buffer the greater production of VFA.