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Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 415 records · Page 23Linked to original sources

Cell detachment and metastasis.

Cancer cell detachment in three distinct and critical parts of the metastatic cascade is discussed. The detachment of cancer cells from their parent tumors is an initial early event in metastasis. The site of detachment with respect to proximity to blood vessels may determine the initial dissemination route. Many factors affect cell detachment; we specifically consider the effects of growth-rate, necrosis, enzyme activity, and stress on cell release in terms of metastasis-promoting mechanisms. Detachment is also discussed in relation to active cancer cell locomotion, where localized detachment from the substratum is a prerequisite for translatory movement. The importance of active cell movement in tissue invasion has only recently been assessed, and, in the case of at least some human malignant melanomas, a zone of actively moving cancer cells is believed to precede the growing body of the tumor. The secondary release of cancer cells from temporary arrest sites at the vascular endothelium consequent upon intravascular dissemination is also a major area of investigation. Circulating cancer cells arrest at vascular endothelium or are impacted in small vessels, however, most are released into the circulation and subsequently perish. The blood stream is a hostile environment, and it is probable that cancer cells are sufficiently damaged in translocation by hemodynamic trauma and humoral factors such that they easily detach or are 'sheared-off' the vascular endothelium by blood flow. Another possibility is that in some cases they are processed by 'first organ encounters' and perish before or shortly after arriving in a second organ. Animal studies have shown that, following intravenous injection, 60-100% of the injected dose of viable cancer cells are initially arrested in the lungs, but very few remain after 24 hr. As it is only those retained cells which produce tumors, the mechanisms involved in this secondary release, which occurs in all organs so far examined, are critical to any understanding of the metastatic cascade and metastatic inefficiency. The arrest of cancer cells at the vascular endothelium and their subsequent release have been associated with the presence of platelets, and the deposition of fibrin and manipulation of platelet-aggregating mechanisms and fibrinolysis are discussed in terms of their antimetastatic effects. The role of the reticuloendothelial system, natural killer cells, and polymorphs is discussed in relation to cancer cell clearance from blood vessels and also to inherent cancer cell properties which may act to inhibit their metastasis. Although detachment of cancer cells from a primary tumor may be regarded as metastasis promoting, secondary release of cancer cells may be associated with inhibition of metastasis.

Blood Vessels↗

The silent period in the stretch response of Ia-activated dorsal spino-cerebellar tract neurons to sinusoidal muscle stretch in cats.

By means of extracellular recordings of action potentials the stretch responses of single neurons of Clarke's column were analysed. The neurons were monosynaptically activated from Ia afferents of both ipsilateral gastrocnemius muscles. When stretch cycles of more than 0.2 mm amplitude and frequencies above 2 Hz were applied to the gastrocnemius muscles, the discharging was found to cease during the period of stretch release, whereas the average discharge rate was found to increase. In the frequency range between 0.1 and 10 Hz a sinewave of stretch frequency - the response sinewave - fitted to the non-zero bins of cycle histograms described the stretch response at small and large amplitudes equally well. The amount of increase in the average firing rate corresponded quite well to the portion of the response sinewave below the zero discharge rate. This indicates that the occurrance of discharge pauses and the relation of the average discharge rate to frequency and amplitude of stretch can be described successfully by a half-wave rectification of the response at zero discharge rate. If one regards the shape of cycle histograms to be a nearly sinusoidal modulation plus a non-linear clipping at zero the application of linear systems analysis is worthwhile in describing the response not only at very small amplitudes but in the whole range of muscle stretch.

Action Potentials↗

Hypothermic perfusion of human kidney carcinoma: effects on viability and perfusate distribution.

A more deteriorating effect on tumour tissue than on normal renal parenchyma by hypothermic perfusion has previously been observed. The purpose of this study was to further evaluate changes in the perfusate distribution and the viability of normal cortical tissue and of kidney carcinoma during hypothermic perfusion. Tumour-involved kidneys obtained by nephrectomy from 12 patients were studied either with regard to viability, as measured with the Na+-K+ pump function in incubated tissue slices, or with regard to perfusate flow, as analysed with an isotope labelled microsphere technique. Six days of hypothermic perfusion decreased the potassium content in the tumour tissue, while it was mainly unchanged in the cortical tissue. The steady-state level of potassium in incubated slices reflected that the transmembrane K+ influx was unchanged after 6 days of perfusion in normal cortical tissue, whereas a significant reduction was observed in the tumour tissue. The relative perfusate flow in the tumour, when compared to the normal kidney cortex flow, was reduced from 60% after 1 hr of perfusion to 30% after 6 days of perfusion.

Adult↗

Do metastases arise from pre-existing subpopulations of cancer cells?

The hypothesis that metastases arise from pre-existing metastatic sub-populations of cancer cells with heritable metastasis-related characteristics, was tested by comparing the metastatic behaviour of cancer cells derived from pulmonary metastases with those from corresponding primary tumours, after implanting them subcutaneously in mice. In the case of KHT osteosarcomas and B16 melanomas, injected minces of metastases gave rise to more pulmonary metastases than cells derived from minces of the primary cancers generating them. However, in the case of 3LL and T241 cancers, the primary tumour minces gave rise to more pulmonary metastases than those derived from minced metastases. It is therefore concluded that the subpopulation hypothesis cannot be accepted as a general rule. When fragments of solid tumours were implanted into animals, no differences were detected between the metastatic behaviour of implants taken randomly from pulmonary metastases and the volume/age matched primary tumours generating them. These experiments thus provide no support for the hypothesis that metastases arise exclusively or predominantly from pre-existing metastatic subpopulations of cancer cells. Finally, implants of matched fragments from 3LL tumours of different volume and age, essentially produced no statistically significant differences in numbers of metastases. These observations do not therefore support the concept of a progressive evolution of subpopulations of cancer cells with heritable metastatic phenotypes during tumour growth.

Animals↗

Influence of bilirubin on the determination of acid phosphatase in serum.

Bilirubin interferes greatly in the continuous measurement of acid phosphatase, using alpha-naphthyl phosphate as substrate and diazotized 2-amino-5-chlorotoluene (Fast Red TR) as the colorimetric reagent. Fast Red TR and the so-called "direct" (but not "indirect") bilirubin form a coloured azo-compound which absorbs light above 480 nm. Negative absorbance changes are observed at 405 nm, which is used in the determination of acid phosphatase. This leads to apparently negative activities.

Acid Phosphatase↗

Improved techniques using Giemsa stained glycol methacrylate tissue sections to quantitate basophils and other leukocytes in inflammatory skin lesions.

Improved techniques were developed for processing inflammatory skin lesions in glycol methacrylate (JB-4, Polysciences, Inc.) and for quantitating their leukocyte infiltrates by light microscopy: (1) fixation of entire pelts from rabbits, guinea pigs, rats and mice bearing multiple lesions eliminated artifacts due to biopsy and produced uniformly oriented skin sections; (2) adding dimethylsulfoxide and hydrogen peroxide to the Karnovsky-type fixative increased the rate and effectiveness of fixation; (3) the presence of glycerol in the infiltrating methacrylate and the polymerized plastic block improved the sectionability of skin and other tissues; (4) coating slides with JB-4 Solution A prevented detachment of specimens; (5) Giemsa staining at a carefully selected pH provided optimal differentiation of leukocytes from the several species examined, including man. These techniques, which allowed an accurate histologic assessment of inflammatory skin lesions, were especially valuable for quantitating basophils.

Animals↗

Suppression and elimination of BCL1 leukemia by allogeneic bone marrow transplantation.

Mice carrying the B cell leukemia (BCL1)+ were successfully treated by total lymphoid irradiation (TLI), cyclophosphamide, and allogeneic bone marrow (BM) transplantation. Long-term survivors were examined for residual BCL1 cells and for the ability to transfer adoptively graft vs. leukemia (GVL) activity. Residual BCL1 cells could not be detected in the allogeneic BM chimeras (greater than 14 to 16 months) with the use of indirect immunofluorescent staining with anti-idiotype antibody. However, residual tumor cells were present in 50% of the "cured" chimeric mice since adoptive transfer of 10(6) spleen cells from 50% of the treated chimeric mice caused leukemia in BALB/c recipients. In order to determine whether leukemia had been prevented in the "cured" chimeras by a persistent cell-mediated mechanism, BALB/c mice were injected with 10(6) spleen cells from the "cured" BM chimeras together with a dose of 10(2) or 5 x 10(5) BCL1 cells. Onset of leukemia was delayed or completely abolished in a significant proportion of recipients receiving the cell mixtures, suggesting the presence of anti-tumor immunity in the cured mice. The data suggest that a persistent active immune mechanism may be responsible, in part, for the significant antileukemic effects observed in mice tolerant to donor alloantigens.

Animals↗

Hematopoietic tissue in malaria: facilitation of erythrocytic recycling by bone marrow in Plasmodium berghei-infected mice.

In P. berghei murine malaria, parasitized erythrocytes and nonparasitized reticulocytes were concentrated in the lumen of venous sinuses of bone marrow, adherent to endothelium and to one another. Merozoites maturing in erythrocytes contained in venous sinuses are so positioned against adherent reticulocytes that when they break out they can penetrate adherent reticulocytes without significant extracellular exposure. Merozoites from cells not adjacent to reticulocytes would spill into the plasma and be opsonized and phagocytized. The vascular sinuses of bone marrow therefore appear to be sites where erythrocytic parasitization is secured and where the severity and chronicity of the erythrocytic phase of the disease is regulated in P. berghei and, perhaps, other reticulocyte-prone malarias. In P. chabaudi, where fully mature erythrocytes rather than reticulocytes are preferentially parasitized, parasitized erythrocytes show far less predilection for bone marrow.

Animals↗

Vascular reactivity and perfusion characteristics in 7,12-dimethylbenz(a)anthracene-induced rat mammary neoplasia.

Blood flow during "resting conditions" and during noradrenaline infusion were studied by the labeled microsphere technique in dimethylbenz(a)anthracene-induced mammary tumors, skin, muscle, and lung in the rat. Intratumoral distribution of flow was studied by autoradiography of spheres trapped in the vascular beds of the tumors. Histological examination was performed and correlated to the blood flow data. Mean blood flow to the tumors during "resting conditions" was relatively high (49 ml/min/100 g tissue) but was substantially decreased (5 ml/min/100 g tissue) during noradrenaline infusion which produced a pressure elevation of 35 mm Hg. Thus, vascular resistance of the tumor tissue increased dramatically. Cardiac output increased, but total systemic resistance was unchanged. Vascular resistance in muscle was unchanged in contrast to an increase seen in skin. Shunted systemic blood flow to the lungs and bronchial arterial flow decreased indicating reactivity of abnormally large arteriovenous passages in the tumors. Poorly differentiated tumors had a higher vascular resistance than did well-differentiated tumors. Autoradiography revealed a nodular flow distribution with a slight tendency of higher perfusion in the periphery of these tumors.

9,10-Dimethyl-1,2-benzanthracene↗

Opportunistic pulmonary aspergillosis with chest wall invasion. Plain film and computed tomographic findings.

A 37-year-old man with leukemia had the unusual complication of pulmonary aspergillosis eroding through adjacent bone. We were able to demonstrate this on computed tomography (CT) and even on the plain chest film. Bone invasion by an adjacent pulmonary lesion is most often attributed to other organisms or causes. This case demonstrates that aspergillosis must be added to the differential diagnosis of this finding. Recognizing this can be important for the prompt, appropriate treatment of opportunistic infections in the immunocompromised host.

Adult↗

Random and nonrandom processes in metastasis, and metastatic inefficiency.

Basically two hypotheses can be used to account for the metastatic inefficiency of cancer cells. The first is that the inefficiency is apparent, and reflects the small proportions of cells of a preexisting metastatic phenotype in primary tumors which are available for metastasis; thus, metastasis and metastatic inefficiency result from nonrandom processes. The opposed view is that most cancer cells have metastatic potential which is not realized unless they randomly enter a transient metastatic compartment which increases their chances of random survival in the metastatic cascade; thus, metastasis and metastatic inefficiency are basically random events. Discussion of this issue has been confused by the indisputable existence of cancer cell heterogeneity and cell lines with 'high' and 'low' metastatic or metastasis-related behavior. However, the relationship of these lines to naturally occurring metastasis is not at all clear. The evidence suggests that metastasis and metastatic inefficiency are determined by a series of random events, and although the presence of metastatic variants could alter the rate or efficiency with which metastasis occurs, they are not expected to determine whether they occur or not, or to produce major modifications in either.

Animals↗

Adult polycystic kidney disease: presymptomatic diagnosis for genetic counselling.

We evaluated 30 first degree relatives of 9 patients with end-stage renal disease secondary to adult polycystic kidney disease. The diagnostic accuracy of renal ultrasonography was compared with intravenous pyelogram with nephrotomography. In 27 patients the two tests were in agreement. In 3 patients both tests were abnormal but findings on IVP did not completely agree with ultrasonography. For early detection and genetic counselling, we recommend ultrasonography as the initial screening procedure for the evaluation of asymptomatic family members of a patient with APKD. IVP should only be considered if ultrasonogram is abnormal but not diagnostic of APKD.

Adolescent↗

Lauge-Hansen classification: a clockwork injury.

The purpose of this article is to present the Lauge-Hansen classification of ankle injuries, in a simplified system according to clockwork function. By familiarization with this classification system, one will gain an invaluable tool in evaluating and treating ankle injuries.

Ankle Injuries↗