Search PubMed⌕ Search

Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 379 records · Page 21Linked to original sources

Survival of L1210 and Ehrlich ascites cancer cells after mechanical trauma is a random event.

Mechanical trauma in the microcirculation is thought to contribute to the inefficiency of the metastatic process in terms of cancer cells. In order to study some aspects of the kinetics of cancer cell destruction in passing through narrow pores, we have developed a model system in which cancer cells are passed through polycarbonate filter membranes in vitro. Filtration through 5-micron pores causes immediate internal damage, reflected in the arrest of active cellular metabolism and reproduction, followed by loss of plasma membrane integrity and, ultimately, the death of the majority of the cells. In this communication, we address the question of whether survival from mechanically initiated filtration damage is a random event, or whether it is a manifestation of a subpopulation of cells, with hereditary resistance to mechanical trauma. Studies on the patterns of cell survival after repeated filtration, and comparisons of the filtration resistance of clonal derivatives developed from filtration survivors with original 'wild' populations, indicate that survival from mechanical trauma is a random event and that resistance to trauma is a nonhereditary property.

Animals↗

Gastrointestinal manifestations of the acquired immunodeficiency syndrome: a review of 22 cases.

Patients with acquired immunodeficiency syndrome (AIDS) frequently have diarrhea and weight loss. We prospectively examined the upper and lower gastrointestinal tracts in 22 AIDS patients, although severe medical problems often precluded full evaluation. Ninety-six percent (21 of 22) lost weight, and 55% (12 of 22) had diarrhea. The mean (+/- SD) weight loss was 34 +/- 19 lb. Steatorrhea was found in 4 of 14 patients, and D-xylose tests were abnormal in 8 of 14 patients. Mean serum albumin was 3.3 +/- 0.8 g/dl. A significantly diminished plasma selenium level, which can influence immune function, was noted in these AIDS patients. Gastrointestinal infections were identified in 45% of patients. Although diarrhea and malabsorption were more common in the infected group, weight loss and albumin were similar in those with and without demonstrated infections. Flexible sigmoidoscopy showed that of 15 patients, there were two with Kaposi's sarcoma, 10 normals, and three with nonspecific endoscopic changes of colitis. Infection was documented in all patients with colitis. Panendoscopy of the upper gastrointestinal tract was positive for AIDS-related pathology in five of 10 patients, including two with Kaposi's sarcoma, one with Candida esophagitis, one with herpetic esophagitis, and one with gastroduodenitis (biopsy positive for cryptosporidia); five patients had a normal-appearing tract. Small bowel or colonic biopsies frequently showed nonspecific inflammatory changes, although pathogens were identified in six patients (27% of all biopsies). We conclude that a wide variety of gastrointestinal pathology, which includes infectious agents, neoplasms, and inflammatory changes, may occur in AIDS patients. Therefore, AIDS patients, particularly those with diarrhea or weight loss, deserve an intensive evaluation for remediable lesions of their gastrointestinal tracts.

Acquired Immunodeficiency Syndrome↗

Five methods for measuring low-density lipoprotein cholesterol concentration in serum compared.

Five methods for the quantification of low-density-lipoprotein cholesterol were compared: ultracentrifugation, electrophoresis, precipitation with polyvinyl sulfate or heparin, and an indirect calculation procedure (Friedewald formula). Excellent agreement of results was obtained with all procedures for 49 of 51 sera. Discrepancies were as much as 1.69 g/L for the remaining two cases, which contained appreciable amounts of "floating" beta-cholesterol as detected with a combination of ultracentrifugation and electrophoresis.

Chemical Precipitation↗

[Reaction of unconjugated and conjugated bilirubin with Fast Red TR and related diazonium salts].

In the present study, the reaction of 15 different diazonium salts with serum bilirubin is examined. It is shown that the selectivity of the determination of non-conjugated and total bilirubin greatly depends on two conditions: the pH-value of the reaction mixture and the nature and position of substituents within the benzene ring. Introduction of "electron-pushing" groups such as the o-methyl group of Fast Red TR will change the reactivity of the diazonium cation towards bilirubin in such a way that the co-reaction of the conjugated fraction becomes negligible at pH-values between 2 and 5. After neutralization to pH 7 the total bilirubin can be determined.

Adult↗

Elimination of graft-versus-host disease by in-vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human lymphocyte antibody (CAMPATH-1).

A new monoclonal rat anti-human lymphocyte antibody (CAMPATH-1) which lyses cells with autologous human complement was used for depletion of T lymphocytes from human bone-marrow allografts in vitro before transplantation in 11 high-risk patients. HLA-matched siblings were used as marrow donors. T-cell depletion was substantial when measured by E-rosette formation (0-0.18% residual T cells) and immunofluorescence with a monoclonal anti-T-cell antibody (0-0.5%). No anti-graft-versus-host disease prophylaxis was given after transplantation. Rapid engraftment was reported in all patients, and the post-transplantation course was uneventful. No signs of graft-versus-host disease developed in any of the patients, who were observed for a maximum period of 12 months. The method might be suitable for larger-scale studies in high-risk patients. The late graft failure seen in 2 patients may reflect residual host resistance uncompromised by GvHD.

Adolescent↗

Target organ patterns of tumors in mice following the arterial dissemination of B16 melanoma cells.

The arrest of B16 melanoma cells and the subsequent development of tumors have been studied following left intraventricular injections (LVI) into mice of radiolabelled and unlabelled cells respectively; the proportions of cardiac output going to different target organs were also determined by LVI of radiolabelled microspheres. B16 cell arrest in the various target organs was as predicted by relative arterial blood supply, except in the lungs and liver where more radioactive counts were detected than could be accounted for in terms of initial arterial dissemination alone; and the numbers of counts remaining in all organs after 24 h were related to the numbers of counts initially obtained. When the incidence of tumor-bearing organs was related to the cell arrest patterns, the organs could be divided into two major distinct groups. Within both of these groups, the patterns of tumor incidence were correlated with cancer cell delivery. These results on a model system suggest that the two major hypotheses used to account for metastatic patterns are not mutually exclusive: the "soil" effect divides the target organs into the two major groups; however, within these groups the incidence of tumors is explicable in terms of the "mechanical" hypothesis.

Animals↗

The development of a technique for the morphometric analysis of invasion in cancer.

We describe tests of the feasibility of a reconstructive technique to discriminate between expansive growth and active cell movement in the invasion of tissues by cancer cells. The densities of cancer cells in 2210 microns2 (grid) squares of standard 6 microns fixed, stained histologic sections of a nodule and an invasive cutaneous melanoma were determined, and density maps of the tumors constructed. An abrupt transition from saturation density to zero cell density was observed at the advancing edge (towards the stratum corneum) of the tumor nodule which was consistent with a model for expansion by growth (vis a tergo). In contrast, at the advancing edge of the invasive tumor, the transition from saturation to zero density (towards the subcutaneous tissues) occurred more gradually, over approximately 400 mum, which was consistent with a model for invasion by active movement of melanoma cells. The occurrence of statistically significant "high density regions" near to the advancing edge of the invasive tumor is consistent with an invasive pattern of active movement followed by focal proliferation of the cancer cells, in a repetitious manner. It therefore appears feasible to make kinetic reconstructions of some of the events in invasion, from static quantitative observations.

Cell Count↗

The hematopoietic stroma.

The stroma of the hematopoietic tissues includes a number of diverse cell types, i.e., bone-lining cells and related capsular and trabecular structures, epithelial-reticular cells and other epithelial cells, reticular cells, macrophages, and antigen-presenting cells. These stromal cells possess a variety of mechanical and metabolic functions. They support and confine the hematopoietic tissues and their vasculature. They regulate the migrations of blood and hematopoietic cells. Stromal cells contribute to the microenvironment that induces the differentiation of stem cells into the several blood-cell lines. The nature of the interactions of stromal and hematopoietic cells depends upon long- and short-range humoral factors, and upon such cell-surface compounds as immunoglobulins and major histocompatability antigens. Blood cells themselves, as neutrophils and lymphocytes, play regulatory roles in hematopoiesis along with stromal cells. Moreover, certain stromal cells, such as macrophages, originate as blood cells and have migratory phases. Distinctions between blood cells, their derivatives, and stromal cells may therefore be difficult to draw.

Animals↗

Acute gastric hemorrhage secondary to wandering spleen.

A patient presenting with acute life-threatening upper gastrointestinal hemorrhage caused by a wandering spleen is reported. Emergency laparotomy revealed profuse gastric bleeding, large engorged varicose veins in the gastric wall, and a normal liver parenchyma. Gastroscopy after arrest of the hemorrhage showed varicose veins in the fundus without esophageal varices. Angiography revealed an ectopic spleen, occlusion of the splenic vein, and large venous collaterals in the gastric fundus. Elective splenectomy was performed. Wandering spleen as a cause of left-sided portal hypertension, also referred to as segmental splenic hypertension, is discussed.

Acute Disease↗

A fluid mechanical analysis of the velocity, adhesion, and destruction of cancer cells in capillaries during metastasis.

Metastasis, a multistep process by which cancer disseminates through the body, mainly by intravascular routes, constitutes a major problem in cancer. When cancer cells are injected directly into the veins of animals, they are apparently arrested in the vascular bed of the first organ encountered and gradually released over the next 24 h. These interactions with the microvasculature are often associated in some manner with the death of many cancer cells, and are thought to contribute to the inefficiency of the metastatic process. We have made a theoretical analysis of cancer cells deformed into capillaries with respect to their intravascular velocity, adhesion to the vascular endothelium and intravascular destruction, in terms of the dynamics of the thin liquid film separating the surfaces of the blood vessels and cancer cells. Our calculations, which are based on previously reported experimental observations, indicate that the transit of cancer cells through the microvasculature is discontinuous, being interrupted by adhesions between the two. In addition, in some cases cell membrane rupture (and cell death) will occur when the critical membrane tension of the cancer cells is exceeded by the sum of their initial equilibrium membrane tension and the increased tension in the cancer cell membranes caused by friction generated as they move over the intraluminal surfaces of the capillaries. Our calculations on membrane rupture are consistent with previously unexplained observations by Sato and Suzuki relating cancer cell deformability to death on transpulmonary passage, and constitute a novel mechanism for "metastatic inefficiency" in terms of intravascular cancer cell death.

Animals↗

Demonstration and characterization of virus released by murine B cell leukemia cells (BCL1).

LPS-stimulated leukemia cells derived from BALB/c mice bearing transplantable B-lymphocytic leukemia (BCL1) which arose spontaneously in a female BALB/c mouse, contained viral particles as suggested by electron microscopy as well as by tissue cultures using the XC assay. Some cell free extracts prepared from BCL1 cells were capable of transforming normal B-lymphocytes when inoculated into untreated syngeneic recipients. Cytogenetic analysis of spleen cells obtained from a splenomegalic male mouse neonatally inoculated with cell-free extract indicated that the tumor cells had a male karyotype with 42 chromosomes as compared to 37 chromosomes and a female karyotype in original BCL1 cells, thus excluding the possibility of tumor propagation by transplantation of intact BCL1 cells. These findings suggest viral involvement in the etiology of BCL1.

Animals↗

Blood flow and reactivity to noradrenaline in induced and autotransplanted DMBA rat mammary neoplasia.

Blood flow during the 'resting condition' and during noradrenaline infusion was compared by means of a microsphere tracer technique in induced DMBA-tumours along the mammary ridge and in autotransplanted tumours, as well as in abdominal skin, skeletal muscle, liver and kidneys. During 'resting conditions' the blood flow of tumours transplanted into skeletal muscle of the hindlimb, liver and kidney was similar to that of the non-transplanted tumours present along the mammary ridges. A pronounced decrease of blood flow upon moderate noradrenaline infusion was characteristic of autotransplanted as well as non-transplanted tumours, which contrasted to the insignificant reaction of skeletal muscle. The striking similarities in blood flow and reactivity of non-transplanted DMBA tumours and autotransplanted ones, and the dissimilarities of the transplanted tumours and the hosting tissues, favour the idea that these tumours regulate their blood supply irrespective of host tissue.

9,10-Dimethyl-1,2-benzanthracene↗

The neoplastic potential of gastric irradiation. IV. Risk estimates.

No significant tumor increase was found in the initial analysis of patients irradiated for peptic ulcer and followed through 1962. A preliminary study was undertaken 22 years later to estimate the risk of cancer due to gastric irradiation for peptic ulcer disease. A population of 2,049 irradiated patients and 763 medically managed patients has been identified. A relative risk of 3.7 was found for stomach cancer and an initial risk estimate of 5.5 X 10(-6) excess stomach cancers per person rad was calculated. A more complete follow-up is in progress to further elucidate this observation and decrease the ascertainment bias; however, preliminary data are in agreement with the Japanese atomic bomb reports.

Follow-Up Studies↗

Asymmetric skeletal anomalies in siblings.

We describe two siblings with asymmetric limb reduction malformations. Such anomalies are usually considered to result from sporadic events, but the recurrence in siblings without any identifiable teratogenic insult suggests a genetic etiology. This finding becomes important when parents are counseled about future pregnancies. The use of prenatal diagnostic techniques during subsequent pregnancies should be considered.

Abnormalities, Multiple↗

Transcapillary passage of albumin in mammary tumours and in normal lactating mammary glands of the rat.

A triple-isotope technique was used to obtain albumin clearances and blood flow in DMBA induced mammary tumours, normal lactating mammary glands and various other tissues of the rat. Albumin clearance was high both in tumours (0.0337 ml/min/100 g) and in lactating mammary glands (0.0414 ml/min/100 g). Albumin extraction (defined as the ratio of clearance over plasma flow) was exceptionally high in tumours (23 X 10(-4)) and lactating glands (18 X 10(-4)) as compared to all other tissues (1-7 X 10(-4)). This probably reflects an increased capillary permeability to macromolecules and/or a change in the relation between blood flow and available capillary surface area, both in the physiological, hormonally induced gland and in the abnormal neoplasia derived from the same tissue. Increased extravasation of albumin, together with other changes (e.g. impaired lymph formation) may be important factors behind the production of increased tumour interstitial pressure, which tend to reduce nutritional blood flow in tumours.

Albumins↗

Specific immunoglobulin A antibodies to a peptide subunit sequence of bacterial cell wall peptidoglycan.

Immunoglobulin A (IgA) antibodies in human sera with binding specificity for the C-terminal R-D-Ala-D-Ala sequence of the precursor peptide from bacterial cell wall peptidoglycan were detected by an enzyme-linked immunosorbent assay (ELISA). Specificity of the test system was proved by comparing the high binding of specific IgA to albumin-(D-Ala3) as an antigen with the failure to bind to albumin-(L-Ala3), by binding inhibition studies with L-Ala3, D-Ala3, or peptides with structural analogy to peptidoglycan peptide subunit peptides as inhibitors, and by excluding binding of peroxidase-labeled anti-human IgA to immunoglobulin classes others than IgA. Interference of rheumatoid factors of IgA class was excluded by an ELISA for assaying IgA-rheumatoid factor and by the fact that an IgA fraction essentially free of IgG and IgM was isolated from a serum reacting strongly positive in the ELISA for measuring specific IgA to the peptide subunit of peptidoglycan. This isolated IgA again exhibited binding specificity in the ELISA, thus corroborating the existence of specific IgA in human serum to the C-terminal R-D-Ala-D-Ala sequence of peptidoglycan precursor peptide. The existence of IgA antibodies with specificity for bacterial peptidoglycan was further proved by preadsorption of serum to peptidoglycans and subsequent measurement of specific IgA in the ELISA. Screening of human sera for IgA antibodies with specificity for R-D-Ala-D-Ala peptides revealed that specific antibodies directed against this sequence of bacterial cell wall peptidoglycan may be detected in several human sera.

Adult↗