Lamb-type waves generated by a cylindrical bubble oscillating between two planar elastic walls.

The volume oscillation of a cylindrical bubble in a microfluidic channel with planar elastic walls is studied. Analytical solutions are found for the bulk scattered wave propagating in the fluid gap and the surface waves of Lamb-type propagating at the fluid-solid interfaces. This type of surface wave has not yet been described theoretically. A dispersion equation for the Lamb-type waves is derived, which allows one to evaluate the wave speed for different values of the channel height h. It is shown that for h<λt, where λt is the wavelength of the transverse wave in the walls, the speed of the Lamb-type waves decreases with decreasing h, while for h on the order of or greater than λt, their speed tends to the Scholte wave speed. The solutions for the wave fields in the elastic walls and in the fluid are derived using the Hankel transforms. Numerical simulations are carried out to study the effect of the surface waves on the dynamics of a bubble confined between two elastic walls. It is shown that its resonance frequency can be up to 50% higher than the resonance frequency of a similar bubble confined between two rigid walls.

Neuropathology of NFHgp160 transgenic mice expressing HIV-1 env protein in neurons.

The physiopathology of HIV-1 dementia remains largely hypothetical. Although several sets of evidence point towards an indirect multicellular inflammatory pathway, gp120, one of the HIV-1 env products, was shown to be very cytotoxic for neurons in vitro. To explore a direct pathway in the physiopathology of dementia in AIDS, we developed transgenic mouse models carrying the HIV-1 env proteins gp 120 and gp 41 (gp 160) under the control of the human light neurofilament and murine heavy neurofilament promoters. To date, this is the first mouse model in which the HIV-1 env protein can be detected in neurons by immunohistochemistry. The expression is found in several brainstem and spinal cord gray structures and in the cerebellum in one of the mouse lines bearing the NFHgp160 transgene. The morphological findings at 3 months are subtle and are dominated by a watery, dendritic degeneration and a reactive gliosis. At 12 months, the evidence of neuronal degeneration and loss is present along with various degenerative phenomena involving synapses, dendrites and axons, including axonal swellings. Cytoskeletal abnormalities were found by immunohistochemistry. Chronic inflammation was also observed in the leptomeninges of the spinal cord and brainstem and in the cerebellar white matter. These models thus offer an exciting sequence of morphological findings initiated by the neuronal expression of the HIV-1 env proteins and offer a different tool to explore the neuronal dysfunction in AIDS.

Immunolocalization of NAIP in the human brain and spinal cord.

The neuronal apoptosis inhibitory protein (NAIP) is known to have anti-apoptotic functions, and its gene is often mutated in severe cases of spinal muscular atrophy (SMA), a disease characterized by motor neuron degeneration. In this study, we examined the distribution of the endogenous NAIP protein in normal human spinal cord and brain tissue by using a polyclonal antibody against NAIP. Immunohistochemical staining demonstrated that NAIP is strongly expressed in anterior horn and motor cortex neurons of normal brains, and it is not altered in the remaining motor neurons of patients with amyotrophic lateral sclerosis (ALS). NAIP is also located in human fetal neurons and in adult choroid plexus cells. These results suggest that the anti apoptotic molecule NAIP may be important in motor neurons, but it specifically does not appear to be altered in ALS.

The neurobiology of apolipoproteins and their receptors in the CNS and Alzheimer's disease.

The importance of apolipoproteins in the central nervous system became increasingly clear with the association in 1993 of the epsilon4 allele of apolipoprotein E with familial and sporadic late-onset Alzheimer's disease. Apolipoprotein E is a ligand for several receptors, most of which are found to some extent in the brain. This review summarizes the various apolipoproteins and lipoprotein receptors found in the brain. A growing body of evidence now implicates irregular lipoprotein metabolism in several neurodegenerative disorders. We then focus on research linking apolipoprotein E and Alzheimer's disease, from clinical studies to biochemical models, which may explain some of the complex neurobiology of this disorder.

Neuronal expression of human immunodeficiency virus type 1 env proteins in transgenic mice: distribution in the central nervous system and pathological alterations.

It is now well documented that human immunodeficiency virus type 1 (HIV-1) induces encephalopathy in patients with AIDS. In vitro studies have implicated the envelope protein (gp120) as a factor which causes neuronal death. To better evaluate the role and elucidate the mechanisms of gp120 neurotoxicity, we have developed transgenic mice carrying a segment of the HIV-1 genome that expresses the viral gp160 protein under the control of the human neurofilament light gene promoter. In two separate lines of transgenic mice, the Env protein was found to be expressed in several nuclei of the brain stem and in the anterior horns of the spinal cord. The two lines showed identical patterns of Env expression. Neuropathological evaluation revealed numerous abnormal dendritic swellings in the immunostained motor neuron structures. Large and numerous neuritic swellings were also prominent in the nucleus gracilis and in the gracilis and cuneate fascicles. In addition, reactive astrocytosis was observed in several immunoreactive areas of the central nervous system. These transgenic mice offer a unique model to further investigate the role of HIV-1 Env protein in neuronal toxicity and to help elucidate the mechanisms that are involved.

Evaluation of infection with human immunodeficiency virus type 1 by using nonisotopic solution hybridization for detection of polymerase chain reaction-amplified proviral DNA.

A convenient assay combining solution hybridization and enzyme immunoassay for DNA-RNA hybrids (polymerase chain reaction-enzyme immunoassay [PCR-EIA]) was developed to detect human immunodeficiency virus type 1 (HIV-1) provirus amplified by the PCR and was compared with oligomer hybridization with 32P-labeled SK19. In PCR-EIA, a fragment of the HIV-1 gag gene from peripheral blood mononuclear cells was first amplified with primer pair SK38/SK39 or O1/O2. PCR-amplified material was reacted in solution with a biotinylated RNA probe. Biotinylated hybrids were measured in a microtiter-plate EIA with antibiotin antibody and a beta-D-galactosidase-conjugated monoclonal antibody to DNA-RNA hybrids. Ten copies of HIV-1 DNA could be detected by PCR-EIA by using two different sets of primers. HIV-1 DNA was detected in 104 of 108 peripheral blood mononuclear cell samples by using SK38/39 and oligomer hybridization, in 104 of 108 samples by using SK38/SK39 and PCR-EIA, and in 104 of 108 samples by using O1/O2 and PCR-EIA. HIV-1 provirus was detected in 107 of 108 samples by using a combination of two sets of primers. One sample from a seropositive patient was negative in all three PCR assays, and six samples gave discordant results between primer pairs. Six of the latter samples scored negative in a PCR for beta-globin but became positive when the sample was diluted before amplification. When applied to clinical samples, PCR-EIA generated results similar to those of an isotopic assay for detection of amplified DNA.

An in vitro model for cancer invasion: 1. Grading and quantitation of aggressiveness.

Invasion, destruction and replacement of normal tissues by cancer cells is the first critical step in the metastatic cascade and is the result of complex interactions between tumor and host factors. In an attempt to understand the complex mechanism of local invasion, we have developed a simple, reliable and generally applicable in vitro system using the confrontation of precultured heart fragments (PHF) with a constant known number of potentially invading (10(5)) cells. This grading system is based essentially on quantitative data standardized both for the portion of the explant invaded by the neoplastic cells and the type of invasion demonstrated. Using this system we could measure the ability of an aggressor cell to (a) adhere or attach to PHF (Grade 1), (b) invade the outer fibroblastic layers (Grade II) and/or the cardiac muscle cells (Grade III) and (c) destroy and completely replace the PHF (Grade IV). It was at once apparent from these experiments that, irrespective of their invasive capacity and/or their neoplastic state, both malignant (SKBR-2 III, BT-20, MCF-7, ZR-75-30 LoVo and YAC-1) and non-malignant (HBL-100) cells attach to the PHF. Only malignant cells, however, showed substantial local invasion of both the outer fibroblastic layers and/or the cardiac muscle cells. Most important for the actual problems of invasion in vivo, is the fact that malignant cells from different cell lines demonstrate a wide range in their invasion capacity: three different patterns of invasion were thus established; a highly invasive, a slowly invasive and a poorly invasive pattern. We also show that invasion and proliferation, as defined for the purposes of this study, are two different and independent properties of a given cell line. SKBR-2 III and YAC-1 are here shown to possess the most aggressive potential; they both invade the PHF very early and completely. The rapid proliferation of these aggressive cells and the destruction of the host tissue lead to the rapid disappearance of the myoblasts and their complete replacement by the invading cells. Non-malignant epithelial cells attached to but could not invade even the outer fibroblastic layers of the PHF.

[Prognosis of venous and lymphatic invasion in cancers of the renal parenchyma treated with enlarged nephrectomy]. / Le pronostic des envahissements veineux et lymphatiques dans les cancers du parenchyme rénal traités par néphrectomie élargie.

Fifty-three (22 p. 100) of 247 cases of renal parenchyma cancer seen between 1963 and 1978 were Robson's stage III cancers. Of the 211 patients treated by enlarged nephrectomy 18 (8.5 p. 100) had lymph node invasion, 35 venous extension without lymph node involvement, and 8 simultaneous spread into the large renal vessels or inferior vena cava and lymph nodes. Of the 10 patients N+ V0 operated upon, one died postoperatively and 7 from cancer, including 6 with a less than 5-year survival. There are only two survivors. Only one of the 8 patients with both lymph node and vein involvement operated upon is still alive. Ten (58.8 p. 100) of the 17 patients undergoing surgery with renal vein extension but no invasion of the inferior vena cava or lymph nodes, and truly exposed to a 5-year postoperative follow-up period, lived for 5 years and 9 of these are still alive. Invasion of the inferior vena cava in the absence of lymph node involvement (11 cases operated) produced no recurrence of the tumor in 5 patients after a prolonged follow-up period. These findings, together with those published in the literature, suggest the need for modifying Robson's classification.