Lack of ETV6 (TEL) gene rearrangements or p16INK4A/p15INK4B homozygous gene deletions in infant acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) occurring in infants less than 1 year of age differs clinically and biologically from that observed in older children. Cytogenetically, 11q23 translocations are detected in approximately 50% of infant ALLs and fuse the 11q23 gene HRX with a variety of partner chromosomal loci. Overall, HRX rearrangements are detected molecularly in 70-80% of infant ALLs as compared to 5-7% of ALLs arising in older children. Two recently described molecular abnormalities in childhood ALL are ETV6 gene rearrangements and homozygous deletions of p16(INK4A) and/or p15(INK4B). Each of these abnormalities occurs in 15-20% of all childhood ALLs, and neither can be accurately identified by routine cytogenetic analyses. The incidence of these genetic abnormalities and their potential relationship to HRX gene status in infant ALL is unknown. Using Southern blot analyses, we determined ETV6 and p16(INK4A)/p15(INK4B) gene status in a cohort of infant ALLs. No ETV6 rearrangements or homozygous deletions (n=69) or homozygous p16(INK4A) and/or p15(INK4B) gene deletions (n=54) were detected in any of the infant ALLs. Therefore, ETV6 and p16(INK4A)/p15(INK4B) do not play a significant role in the pathogenesis of infant ALL, further emphasizing the distinctive biology of this subset of leukemias.     

Rapid spread of HIV among injecting drug users in north-eastern states of India

Manipur, a north-eastern state of India bordering Myanmar, has experienced very rapid transmission of the human immunodeficiency virus (HIV) among its vast drug-injecting population. Seroprevalence among intravenous drug users increased from 0 per cent in September 1989 to 50 per cent within six months. With a minimum injecting population of 15,000 and seropositivity of over 50 per cent, the infection quickly spread to the population at large. One per cent of antenatal mothers tested seropositive by 1991. Forming part of the area of South-East Asia known as the Golden Triangle, and producing opium and its derivatives, Myanmar shares a long international border with four States of the region, and populations with a common language and culture move freely across borders. Two other north-eastern states of India bordering Myanmar have faced a similar epidemic within a short period of time. As a result of serosurveillance for HIV since 1986, the epidemic could be detected at an early stage. The present paper provides an account of the results of ongoing comprehensive studies conducted in the north-eastern states of India on drug-related HIV infection, already a serious problem, but possibly still restricted to that region of the country. The prevalence of intravenous drug users, their HIV serological status, the demographic profile, risk behaviour, the spread of the infection to other groups and the problems of harm minimization are also covered.     

Maternal dietary protein deficiency decreases nitric oxide synthase and ornithine decarboxylase activities in placenta and endometrium of pigs during early gestation

Little is known about the mechanism responsible for retarded placental and fetal growth induced by maternal dietary protein malnutrition. On the basis of the recent finding that nitric oxide (NO) and polyamines (products of L-arginine) play an important role in embryonic and placental development, the present study was designed to determine whether protein deficiency decreases placental and endometrial activities of NO synthase (NOS) and ornithine decarboxylase (ODC) (the first and key regulatory enzyme in polyamine synthesis). Primiparous gilts selected genetically for low or high plasma total cholesterol concentrations (low line and high line, respectively) were mated and then fed 1.8 kg/d of isocaloric diets containing 13% or 0.5% crude protein. At d 40 or 60 of gestation, they were hysterectomized, and placenta and endometrium were obtained for incubations, NOS and ODC assays, and measurements of free amino acids and polyamines. Maternal dietary protein restriction decreased arginine and ornithine concentrations, constitutive and inducible NOS activities and NO production, as well as ODC activity and polyamine concentrations in placenta and endometrium of both lines of gilts. Placental NO synthase activity and NO generation were lower in high line gilts than in low line gilts. ODC activities and polyamine concentrations in placenta and endometrium were decreased at d 60 compared with d 40 of gestation. These changes in placental and endometrial synthesis of NO and polyamines during early gestation may be a mechanism responsible for reduced placental and fetal growth in protein-deficient gilts and for altered conceptus development in high line gilts.     

Experiences of ethnic minority faculty employed in predominantly white schools of nursing

This qualitative study describes the bicultural experience of ten ethnic minority faculty employed in predominately white baccalaureate and higher degree nursing programs in the Southeastern section of the United States. Seven themes emerged from the data: (a) appraising, (b) proving, (c) fitting-in, (d) defending, (e) distancing, (f) being invisible, and (g) mentoring to describe their experience. Results also provided support for the authors' generated Bicultural Systems Model which evaluates why and to what extent a particular transaction or series of transactions between the person and the environment is perceived as stressful. The general perception among participants was that they were not fully accepted in the academic setting of predominately white nursing programs. As a result, some faculty were expending energy trying to convince others of their legitimacy; while others were choosing to distance themselves from the academic setting and white colleagues. This study indicates a need for dialogue between white and ethnic minority faculty to facilitate adoption of strategies that reduce the negative effects of the bicultural phenomenon.     

Breaking strength retention and histologic effects around 1.3-mm. ORTHOSORB polydioxanone absorbable pins at various sites in the rabbit

Absorbable 1.3-mm polydioxanone (ORTHOSORB) pins were implanted in 75 New Zealand White rabbits in three sites: within the lateral subcutaneous tissue parallel to the femur, down the femoral intramedullary canal, and mediolaterally across the femoral condyles (transcondylar). Pins were harvested at periodic intervals up to 56 and 365 days for mechanical and histologic analyses, respectively. Mechanical analyses were performed by loading the pin in double shear. Histologic analyses were performed on the pin and surrounding tissue. Histologic observations revealed a typical nonspecific foreign-body reaction at all implant sites that resolved at 1 year after resorption of the pin. On histologic examination, there was complete resorption of the pin material in the subcutaneous site by day 182, and there was complete resolution of all response to the pin in six of nine rabbits by day 365. In the intramedullary site, pin material was completely resorbed, based on histologic examination, in five of six rabbits by day 182, and there was complete resolution of the response to the pin in eight of nine rabbits by day 365. The pin material was completely resorbed based on histologic examination of the transcondylar site by day 210, and there was complete resolution of the response to the pin in four of six rabbits by day 270 and in four of nine rabbits by day 365. No enlarged pin tracks or sinus formations were observed in or near the implants sites. The average initial shear strength as 171.4+/ 5.1 MPa, and the breaking strength retention decreased with increasing implantation time. Pins from the subcutaneous regions maintained above 97% of their initial strengths at 28 days, and those from the intramedullary canals maintained above 92%. At later times the strength of the pins implanted in the intramedullary canal decreased more rapidly than those from the subcutaneous region. Overall, the average breaking strength of the subcutaneous pins was significantly greater than that of the intramedullary pins at all time points beyond 14 days. These data indicate that the pins exhibited a strength retention profile sufficient to allow normal healing of bone without enlarged pin tracts, allergic reactions, or sinus formations.     

Characterization of the active site of a hydrogen sensor from Alcaligenes eutrophus

BACKGROUND: The Maastricht Consensus Report advises that, in Helicobacter pylori-positive patients after surgery for peptic ulcer disease, H. pylori should be eradicated. The aim of the present study was to investigate the symptomatic response of H. pylori eradication in previously vagotomized peptic ulcer patients with persistent dyspeptic complaints. METHODS: The study was performed as a randomized, double-blind, placebo-controlled study. Pretreatment diagnostic upper endoscopy was omitted. All the results were submitted to intention-to-treat and efficacy analyses. RESULTS: We could not find any differences between the two groups with regard to intensity or frequency of upper abdominal pain, nausea, heartburn, or other abdominal symptoms during the 12-month follow-up. The triple therapy eradication rate was 88% at both 3- and 12-month controls. CONCLUSION: Vagotomized peptic ulcer patients with persistent dyspeptic complaints should undergo a diagnostic upper endoscopy to detect ulcer recurrence before H. pylori eradication treatment is considered.     

Development of AIDS in a chimpanzee infected with human immunodeficiency virus type 1

The condition of a chimpanzee (C499) infected with three different isolates of human immunodeficiency virus type 1 (HIV-1) for over 10 years progressed to AIDS. Disease development in this animal was characterized by (i) a decline in CD4+ cells over the last 3 years; (ii) an increase in viral loads in plasma; (iii) the presence of a virus, termed HIV-1JC, which is cytopathic for chimpanzee peripheral blood mononuclear cells; and (iv) the presence of an opportunistic infection and blood dyscrasias. Genetic analysis of the V1-V2 region of the envelope gene of HIV-1JC showed that the virus present in C499 was significantly divergent from all inoculating viruses (> or = 16% divergent at the amino acid level) and was suggestive of a large quasispecies. Blood from C499 transfused into an uninfected chimpanzee (C455) induced a rapid and sustained CD4+-cell decline in the latter animal, concomitant with high plasma viral loads. These results show that HIV-1 can induce AIDS in chimpanzees and suggest that long-term passage of HIV-1 in chimpanzees can result in the development of a more pathogenic virus.     

Staging of carcinoma of the gallbladder--an ultrasonographic evaluation

BACKGROUND/AIMS: Preoperative staging of carcinoma of the gallbladder is important in choosing the most appropriate treatment modality. Ultrasonography is commonly used for the diagnosis of carcinoma of the gallbladder, but its role in staging of the disease has not been adequately evaluated. The aim of this study was to prospectively evaluate the role of ultrasonography performed by a single operator in the staging of carcinoma of the gallbladder. METHODOLOGY: Twenty-six patients with carcinoma of the gallbladder were evaluated in this study. Ultrasonographic staging was done by a single senior radiologist and compared with surgical staging using the AJCC TNM staging system. A retrospective evaluation was done of 122 operated patients with carcinoma of the gallbladder, and the findings were compared to the results of the prospective study. RESULTS: In the prospective study, the overall accuracy of ultrasonogaphy in correctly staging the disease was 38% (10/26). Only 1 patient was overstaged, while the majority of patients were understaged (15) due to missed distant metastasis (10) and missed advanced local infiltration (5). The sensitivity in detecting liver infiltration was 50%; lymph node metastasis, 50%; and liver metastasis, 8%. In the retrospective study, the similar detection rates were 27%, 25% and 10%, respectively. CONCLUSION: Real time ultrasonography has been found to have inherent limitations in staging carcinoma of the gallbladder. Its accuracy, though improved in a prospective study, is inadequate in staging the disease accurately. More accurate imaging modalities are therefore required to accurately stage the disease preoperatively, so as to avoid unnecessary laparotomies.     

Tissue factor pathway inhibitor: potential therapeutic applications

Tissue factor pathway of coagulation plays a dominant role during normal haemostasis. Tissue factor pathway inhibitor (TFPI), expressed primarily by the microvascular endothelium, appears to be the major physiologic inhibitor of TF-induced coagulation. TF-initiated coagulation also plays an important role in the pathophysiology of many diseases including coronary thrombosis, sepsis, disseminated intravascular coagulation, stroke, cancer, acute respiratory distress syndrome, and ischemia-reperfusion injury. Several animal studies have found a beneficial effect of anti-TF monoclonal antibodies and, recombinant TFPI in some of the above clinical conditions. rTFPI is presently being used in clinical trials in patients with sepsis and in those following microvascular surgery. This article discusses many of the animal studies addressing inhibition of TF-induced coagulation, as well as potential therapeutic uses of rTFPI in humans.     

Inhibition effect of shengma-gegen-tang on measles virus in Vero cells and human peripheral blood mononuclear cells

The nucleotide sequence of gene 6 encoding the rotavirus major capsid protein VP6 of EDIM strain (EW) was determined and compared to that of 20 previously reported strains with known subgroup specificities. Multiple alignments of amino acid sequences exhibited a high level of sequence conservation (87 to 99.2%). Site-specific mutagenesis experiments were undertaken to localize regions involved in subgroup specificity. Amino acid positions 305, 315, and a region 296-299 (or 301 for equine strain H-2) were identified as contributing to subgroup epitopes. A single amino acid mutation at position 305 or 315 was sufficient to change the subgroup specificity of EW VP6 protein from non I/II to subgroup I- or subgroup II-like, respectively. Mutation at these sites may be another important mechanism for subgroup variation, along with gene reassortment.