Neuropathology of bovine herpesvirus type 5 (BHV-5) meningo-encephalitis in a rabbit seizure model

CI-994 (acetyldinaline) is an orally active anticancer drug currently in Phase 1 clinical trials. To assess its preclinical toxicity, CI-994 was administered orally as suspensions to Wistar rats (10/sex/dose) and in capsules to beagle dogs (3/sex/dose) once daily for two weeks. Doses were 1.5, 5, and 15 mg/kg for rats (9, 30, and 90 mg/m2, respectively), and 0.5, 2, and 5 mg/kg for dogs (10, 40, and 100 mg/m2, respectively). Systemic exposure was dose-proportional based on toxicokinetic analysis in dogs. Severe clinical signs and mortality occurred at the highest dose in both species beginning on Day 10. Neutropenia, lymphocytopenia, thrombocytopenia, lymphoid depletion, bone marrow hypocellularity, and testicular degeneration were observed in both species, primarily at the mid- and high-doses. Despite continued treatment, neutrophil counts in dogs returned to control levels in Week 2. Other microscopic findings in rats included splenic hematopoietic depletion at all doses and epithelial cell necrosis in various tissues at 15 mg/kg. Additional bone marrow changes in dogs involved myeloid and megakaryocyte hyperplasia at 2 mg/kg and abnormal myeloid and megakaryocyte maturation at 2 and 5 mg/kg. Except for the testicular effects in both species, all changes were reversible within a 4-week (rat) or 9-week (dog) recovery period. The results of these studies show that target organ effects of CI-994 principally involve tissues with rapidly dividing cell populations and that bone marrow suppression is the dose-limiting toxicity. CI-994 also seems to interfere with the release and/or maturation of cells in the bone marrow.     

Murine cytomegalovirus-inhibitory effects of ImuVert

ImuVert, a sterile preparation composed primarily of Serratia marcescens membrane vesicles and ribosomes, was significantly inhibitory to murine cytomegalovirus (MCMV) infections in BALB/c mice. Antiviral activity was manifested as increased survivor number and decreased recoverable virus titers in spleens, lungs and salivary glands. Treatments were intraperitoneal (i.p.) beginning 24 h pre, 4 h post- or 24 h post-virus inoculation and then repeated 4 days later. Doses of 5, 16 or 50 micrograms/mouse were effective; 160 micrograms/mouse, which caused host weight loss in toxicity controls, was not inhibitory to the infection. A single i.p. treatment of mice substantially augmented natural killer (NK) cell activity and increased total B-cells, while reducing total T- and T-helper cells. A late (48 h) decline in T-cell function and transient increases in B-cell function were observed in the treated animals. Serum interferon was not induced. Mice pretreated with anti-asialo GM1 antibody to reduce their NK cell populations, then infected with MCMV and treated with ImuVert were protected to the same degree as normal animals. Severe combined immunodeficient mice infected with MCMV and treated with ImuVert were not protected from the infection. These data suggest ImuVert to act by a mechanism other than NK cell activation in preventing MCMV infections.     

Taking enzyme kinetics out of control; putting control into regulation

The matrix formulation of metabolic control analysis, which states that multiplying the elasticity matrix for any system by the corresponding control matrix yields an identity matrix, can be transformed into a statement that multiplying a matrix expressing internal regulatory properties by a matrix expressing external regulatory properties also yields an identity matrix. This transformation supplies the formal basis for metabolic regulation analysis, and provides the key to determining the control structure of a system without the need to know the exact changes in enzyme activities that are made to measure control coefficients.     

A PET study of the neural systems of stuttering

The cause of stuttering is unknown. Failure to develop left-hemispheric dominance for speech is a long-standing theory although others implicated the motor system more broadly, often postulating hyperactivity of the right (language nondominant) cerebral hemisphere. As knowledge of motor circuitry has advanced, theories of stuttering have become more anatomically specific, postulating hyperactivity of premotor cortex, either directly or through connectivity with the thalamus and basal ganglia. Alternative theories target the auditory and speech production systems. By contrasting stuttering with fluent speech using positron emission tomography combined with chorus reading to induce fluency, we found support for each of these hypotheses. Stuttering induced widespread overactivations of the motor system in both cerebrum and cerebellum, with right cerebral dominance. Stuttered reading lacked left-lateralized activations of the auditory system, which are thought to support the self-monitoring of speech, and selectively deactivated a frontal-temporal system implicated in speech production. Induced fluency decreased or eliminated the overactivity in most motor areas, and largely reversed the auditory-system underactivations and the deactivation of the speech production system. Thus stuttering is a disorder affecting the multiple neural systems used for speaking.     

Comparative fate of 1,1-diphenylethylene (DPE), 1,1-dichloro-2,2-bis(4-Chlorophenyl)-ethylene (DDE), and pentachlorophenol (PCP) under alternating aerobic and anaerobic conditions

First, annual cost of electronic filing of medical images were calculated and compared with that of film storage in two hospitals under different conditions. Storage of medical images using a pixel size of 100 microns x 100 microns and 2-byte depth on the 130 mm, 650 MB magneto-optical disks costs with four times as much as the cost for film storage. However, 175 microns x 175 microns 12 bits combined with implementation of lossless compression would reduce the cost to a level equal to that for films storage. Doubled or tripled densities of MOD will improve the cost ever further. Second, the effectiveness of Hospital Information System/Radiological Information System (HIS/RIS) was evaluated. Examination time, film delivery time and the total turn-around time was markedly shortened by more than 23 hours on average. Our measurement method employing IC cards in pre-post HIS/RIS/PACS procedures is generally applicable to other hospitals. Third, to determine the optimal method of maximizing the efficacy of diagnostic imaging, 260 questionnaires were sent to the staff of 13 university hospitals. Every situation was described by both a radiologist and the physician who ordered the examination and received the reports and images. The level of technical efficacy and diagnostic accuracy of radiology strongly influenced the diagnostic thought processes of the physician.     

High level expression of the homeobox gene HB24 in a human T-cell line confers the ability to form tumors in nude mice

Epidermal growth factor (EGF)-induced c-fos and c-jun expression is strongly suppressed in microgravity. We investigate here whether this is due to inhibition of processes occurring during the initiation of EGF-induced signal transduction. For this purpose, EGF-induced receptor clustering is used as a marker. The lateral distribution of EGF receptors is directly visualized at an ultrastructural level by the label-fracture method. Quantification of the receptor distributions shows that EGF-induced receptor redistribution is similar under normal and microgravity conditions. This suggests that microgravity influences EGF-induced signal transduction downstream of EGF binding and EGF receptor redistribution, but upstream of early gene expression in human A431 cells.