Murine thymic lymphoma is associated with a species-specific hematopoietic progenitor cell subpopulation

Many strains of laboratory mouse are uniquely susceptible to the development of T cell lymphoma/leukemia, either spontaneously or as a result of chemical or radiation exposure. In contrast, T cell leukemias or lymphomas which are relatively uncommon in human populations, are not easily induced by radiation, and are not generally associated with chemotherapy or chemical exposure. Evidence is presented to suggest that differences in the susceptibility to the development of these malignancies is related to subtle but important variations in the regulation of hematopoietic stem cell differentiation between these two species.     

Health research in the developing world: a gastroenterological view from Bangladesh

OBJECTIVES: To identify knowledge levels of academic surgeons about Food and Drug Administration (FDA) and Institutional Review Board (IRB) regulations for clinical research and to determine whether being a member in an IRB, conducting or participating in clinical trials, or being a member in surgical societies affected knowledge levels. DESIGN: Survey of surgical department faculty members in 20 universities. RESULTS: Sixty-five responses were received from 14 sites. Overall mean (+/- SEM) correct score was 6.7 +/- 0.2 of a possible 20 points. The best predictor of overall score was being a primary investigator of a clinical trial (P < .001), followed by being or having been a member of an IRB (P < or = .02). The total mean score of members of the Surgical Infection Society (8.2 +/- 0.5) was significantly higher (P < .001) than that of nonmembers (6.1 +/- 0.2), a phenomenon not observed with other surgical societies. In certain hypothetical clinical scenarios, all respondents were mistakenly willing to conduct clinical trials without obtaining appropriate approval from the FDA. Four (22%) of 18 IRB member respondents and 16 (25%) of the 65 respondents were willing to conduct human research without appropriate approval from patients, the IRB, or both. CONCLUSIONS: Knowledge deficits exist in the academic surgical community about the role and requirements of the FDA and local IRBs for conducting clinical research. Further study is required to determine the reasons for this deficit and to identify appropriate interventions.     

Cloning and disruption of the antigenic catalase gene of Aspergillus fumigatus

Aspergillus fumigatus possesses two catalases (described as fast and slow on the basis of their electrophoretic mobility). The slow catalase has been recognized as a diagnostic antigen for aspergillosis in immunocompetent patients. The antigenic catalase has been purified. The enzyme is a tetrameric protein composed of 90-kDa subunits. The corresponding cat1 gene was cloned, and sequencing data show that the cat1 gene codes for a 728-amino-acid polypeptide. A recombinant protein expressed in Pichia pastoris is enzymatically active and has biochemical and antigenic properties that are similar to those of the wild-type catalase. Molecular experiments reveal that CAT1 contains a signal peptide and a propeptide of 15 and 12 amino acid residues, respectively. cat1-disrupted mutants that were unable to produce the slow catalase were as sensitive to H2O2 and polymorphonuclear cells as the wild-type strain. In addition, there was no difference in pathogenicity between the cat1 mutant and its parental cat1+ strain in a murine model of aspergillosis.     

Treatment of hypertension in nondiabetic renal disease

To clarify whether long-term impaired glucose tolerance (IGT) is associated with dysfunction of peripheral and autonomic nerves, age-matched men with IGT and diabetes mellitus were followed prospectively for 12-15 years, when peripheral and autonomic nerve function was assessed. The patients comprised four subgroups: (1) 51 IGT subjects (duration of IGT at least 12-15 years); (2) 35 diabetic patients, with IGT 12-15 years ago, who later developed diabetes; (3) 34 diabetic patients, duration of diabetes at least 12-15 years; and (4) 62 age-matched non-diabetic control subjects. Mean age of the whole study population was 61 +/- 2 years (mean +/- SD), not different in the four groups. Peripheral nerve function tests included nerve conduction velocities, amplitudes, distal latencies, F-reflexes, and sensory perception thresholds for heat, cold, and vibration. Autonomic nerve function tests included the heart rate reaction during deep breathing (expiration to inspiration ratio) and to tilt (acceleration and brake indices). Despite 12-15 years of IGT, peripheral nerve function did not differ between IGT and control subjects, whereas autonomic nerve function deviated; an abnormal expiration to inspiration ratio (a sign of vagal nerve dysfunction) was significantly more common (15/51 versus 5/62; p < 0.01) in IGT than in control subjects. Diabetic patients (groups 2 and 3) showed lower conduction velocities (in general 2-4 m s-1 lower) than IGT and control subjects in all tested nerves. In conclusion, diabetes but not IGT, is associated with peripheral nerve dysfunction.     

Driver detection and recognition of lineside signals and signs at different approach speeds

A study was carried out using simulation to investigate driver responses to lineside signals and signs at various approach speeds. The objectives of the study were: (1) to find out whether train speed would significantly affect signal/sign reading; (2) to examine at which point certain types of signs or signals could be detected or recognised, and (3) to determine a speed cut-off level above which certain types of signs or signals are no longer recognisable or detectable. Fifty-seven train drivers from 12 Train Operating Companies in the UK participated in the trials. Twenty different types of lineside signs and ten types of signals were tested under six different approach speeds ranging from 100 to 350 km/h (62–218 mph). Driver performance measures were ‘time remaining to the signal/sign’ at the point of detection or recognition, and reading error rate. The results showed a significant influence of train speed on driver responses to lineside signals/signs and demonstrated a non-linear relationship between driver responses to signals/signs and approach speed. This has been used to estimate a maximum approach speed limit within which a specific signal or sign can be correctly detected or recognised. The findings and implications of the study are discussed in the paper.     

Mantle cell lymphoma: a clinicopathologic study of 80 cases

Mantle cell lymphoma (MCL) is a relatively uncommon yet distinct type of malignant lymphoma whose clinical and pathological characterization has been limited by the small numbers of cases published to date. We studied 80 cases of MCL seen at a single institution over 7 years to determine both clinical and pathological prognostic factors. The patients in this study were predominantly male (70%) and older (mean age, 63 years) and presented with advanced-stage disease (88%). Extranodal involvement was common. Median overall survival (OS) was 43 months. Except for performance status, prognosis was not significantly influenced by clinical prognostic factors. Histologically, MCL architecture was classified as diffuse (78%), nodular (16%), or mantle zone (6%); the OS among these groups was identical. Increased mitotic activity (>20 mitotic figures per 10 high power fields), blastic transformation, and peripheral blood involvement at diagnosis also predicted for a worse outcome, but bone marrow involvement did not. The presence or absence of a translocation t(11; 14) by cytogenetic analysis or a bcl-1 rearrangement by Southern analysis did not significantly predict outcome. In summary, this study of 80 cases of MCL highlights its distinctive clinicopathologic features and shows that increased mitotic activity, blastic morphology, and peripheral blood involvement at diagnosis are prognostically important factors.