Mitogen-activated Xenopus laevis lymphocytes produce a T-cell growth factor.

Mitogen-free and serum-free supernatants (SNs) from cultures of phytohaemagglutinin (PHA)-stimulated Xenopus splenocytes, co-stimulated thymocytes, induced proliferation of splenic and thymic lymphoblast and supported growth of alloreactive T-cell lines. These SNs had no effect on 'resting' splenocytes, as measured by uptake of tritiated thymidine ([3H]TdR). Growth-promoting activity was also detected in SNs of cultures containing alloreactive T-cell lines and either PHA or irradiated stimulator cells that expressed the original priming alloantigens. Thus, T lymphocytes appear to be involved in producing, as well as responding to, a Xenopus T-cell growth factor (TCGF). TCGF activity could be absorbed from these active SNs with PHA-activated splenic blasts. No functional cross-reactivity among different mammalian interleukin-2 (IL-2) and Xenopus TCGF preparations was detected.     

Reciprocal translocation mosaicism in man

We report on an8-month-old girl with a de novo 5q/6q autosomal translocation with loss of the distal part of the long arm of chromosome 6 (6q23.3→6qter); clinical manifestations are peculiar craniofacial stigmata, truncal obesity and persisting hypotonia. The similarity with a previously reported patient with 6q interstitial deletion is discussed.     

Legionella gormanii sp. nov

A new species of Legionella was isolated from soil collected from a creek bank. The name Legionella gormanii sp. nov. is proposed.     

The initial vestibulo-ocular reflex and its visual enhancement and cancellation in humans

The gain (ratio of eye velocity to head velocity) of the initial horizontal vestibulo-ocular reflex (VOR) was calculated in 12 normal subjects over 350 ms during impulsive, unpredictable whole body rotation under three conditions: (1) darkness; (2) visual enhancement of the VOR, while the subjects fixated a stationary target; and (3) visual cancellation of the reflex, while subjects fixated a target that rotated with the head. The gain of the initial 80 ms of compensatory eye movement increased significantly during visual fixation in 5 subjects and decreased during attempted VOR cancellation in 3 subjects, when compared with VOR gain in darkness. Compensatory vestibular smooth eye movements were slowed, becoming curved at the onset of VOR cancellation, at mean latencies ranging from 78 to 149 ms in individual subjects (group mean 128 ms). At about 190 ms, quick phases moved the eyes in the same direction as head and target motion. The subsequent vestibular eye movements were about 50% slower than the initial smooth eye movements, indicating more effective cancellation. Visual enhancement of the VOR can occur prior to the onset of pursuit, providing evidence that fixation and smooth pursuit are distinct ocular motor systems. Visual cancellation of the VOR also begins prior to smooth pursuit initiation and becomes more effective after the latency of smooth pursuit.     

Expression of a calpastatin transgene slows muscle wasting and obviates changes in myosin isoform expression during murine muscle disuse

Muscle wasting is a prominent feature of several systemic diseases, neurological damage and muscle disuse. The contribution of calpain proteases to muscle wasting in any instance of muscle injury or disease has remained unknown because of the inability to specifically perturb calpain activity in vivo . We have generated a transgenic mouse with muscle-specific overexpression of calpastatin, which is the endogenous inhibitor of calpains, and induced muscle atrophy by unloading hindlimb musculature for 10 days. Expression of the transgene resulted in increases in calpastatin concentration in muscle by 30- to 50-fold, and eliminated all calpain activity that was detectable on zymograms. Muscle fibres in ambulatory, transgenic mice were smaller in diameter, but more numerous, so that muscle mass did not differ between transgenic and non-transgenic mice. This is consistent with the role of the calpain-calpastatin system in muscle cell fusion that has been observed in vitro . Overexpression of calpastatin reduced muscle atrophy by 30 % during the 10 day unloading period. In addition, calpastatin overexpression completely prevented the shift in myofibrillar myosin content from slow to fast isoforms, which normally occurs in muscle unloading. These findings indicate that therapeutics directed toward regulating the calpain-calpastatin system may be beneficial in preventing muscle mass loss in muscle injury and disease.     

Advection and Diffusion of Substances in Biological Tissues With Complex Vascular Networks

For highly diffusive solutes the kinetics of blood–tissue exchange is only poorly represented by a model consisting of sets of independent parallel capillary–tissue units. We constructed a more realistic multicapillary network model conforming statistically to morphometric data. Flows through the tortuous paths in the network were calculated based on constant resistance per unit length throughout the network and the resulting advective intracapillary velocity field was used as a framework for describing the extravascular diffusion of a substance for which there is no barrier or permeability limitation. Simulated impulse responses from the system, analogous to tracer water outflow dilution curves, showed flow-limited behavior over a range of flows from about 2 to 5 ml min^–1 g^–1, as is observed for water in the heart in vivo. The present model serves as a reference standard against which to evaluate computationally simpler, less physically realistic models. The simulated outflow curves from the network model, like experimental water curves, were matched to outflow curves from the commonly used axially distributed models only by setting the capillary wall permeability–surface area (PS) to a value so artifactually low that it is incompatible with the experimental observations that transport is flow limited. However, simple axially distributed models with appropriately high PSs will fit water outflow dilution curves if axial diffusion coefficients are set at high enough values to account for enhanced dispersion due to the complex geometry of the capillary network. Without incorporating this enhanced dispersion, when applied to experimental curves over a range of flows, the simpler models give a false inference that there is recruitment of capillary surface area with increasing flow. Thus distributed models must account for diffusional as well as permeation processes to provide physiologically appropriate parameter estimates. © 2000 Biomedical Engineering Society. PAC00: 8719-j, 8710+e     

Association study of dopamine D3 receptor gene and schizophrenia

Several groups have reported an association between schizophrenia and the MscI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3). We studied this polymorphism using a North American sample (117 patients plus 188 controls) and an Italian sample (97 patients plus 64 controls). In the first part of the study, we compared allele frequencies of schizophrenia patients and unmatched controls and observed a significant difference in the total sample (P = 0.01). The second part of the study involved a case control approach in which each schizophrenia patient was matched to a control of the same sex, and of similar age and ethnic background. The DRD3 allele frequencies of patients and controls revealed no significant difference between the two groups in the Italian (N = 53) or the North American (N = 54) matched populations; however, when these two matched samples were combined, a significant difference was observed (P = 0.026). Our results suggest that the MscI polymorphism may be associated with schizophrenia in the populations studied. © 1995 Wiley-Liss, Inc.     

Cytotoxic effects of ingested Staphylococcus aureus on bovine endothelial cells: Role of S. aureus α-hemolysin

Previously we observed that Staphylococcus aureus phagocytized by cultured bovine endothelial cells do not proliferate intracellularly, but are cytotoxic to bovine endothelial cells. To investigate S. aureus virulence factors which may be produced intracellularly and cause lysis of endothelial cells, we tested S. aureus mutants defective in production of one or more potential virulence factors and corresponding parent strains for cytotoxicity to endothelial cell monolayers subsequent to being ingested. Following incubation of endothelial cell monolayers with S. aureus for 3.5 h, cultures were supplemented with lysostaphin to destroy extracellular but not intracellular S. aureus. At subsequent times, viability of endothelial cells was assayed by retention of ³H-adenine and the number of intracellular S. aureus was measured. The cytotoxic activity of S. aureus culture supernatants was also characterized. The results indicate that S. aureus α-hemolysin is cytotoxic to bovine endothelial cells and plays an important role in the damage suffered by bovine endothelial cell monolayers following ingestion of S. aureus. Ingestion of α-hemolysin-producing S. aureus by endothelial cells in vivo might be expected to result in destruction of endothelium followed by development of platelet-fibrin vegetations. This possible sequence of events is compatible with the frequently fulminant course of S. aureus endocarditis.