Group treatment for female sexual dysfunction.
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Behavior Therapy↗
Biomedical subjects
L Weiss
Publications and source records attributed to L Weiss.
The frequency and mutation rate of balanced autosomal rearrangements in man estimated from prenatal genetic studies for advanced maternal age.
The frequencies of balanced chromosome rearrangements were estimated from three series of advanced maternal-age prenatal genetic studies, and were compared to the frequencies that had been estimated from consecutive newborn surveys. In the maternal-age prenatal studies, the frequencies were: Robertsonian translocations, 0.11%; reciprocal translocations, 0.17%; and inversions, 0.12%. The total frequency of balanced rearrangements in the prenatal genetic studies performed with banding (0.40%, or 1 in 250) was twice that in the consecutive newborn surveys performed without banding (0.19%, or 1 in 526). The difference was limited to inversions and reciprocal translocations; the frequency of Robertsonian translocations was similar in the prenatal series and the newborn surveys. Both familial and de novo rearrangements were more common than anticipated. The de novo cases provided a mutation rate estimate of 4.3 per 10,000 gametes per generation (compared with 1.78 to 2.2 per 10,000 gametes in other surveys). These higher estimates may more reliably approximate the true mutation rate and frequencies of balanced rearrangements in the newborn population than do the newborn surveys.
Chromosome Aberrations↗
Intercellular junctions in the hematopoietic compartments of embryonic chick bone marrow.
Avian embryonic marrow is segregated into distinct erythropoietic and granulopoietic compartments. Within each compartment presumptive stem cells and immature blood cells establish intimate contact with their respective stromal cell. In this study we have examined one aspect of potential hematopoietic cell-stromal cell interaction by looking for the presence of intercellular junctions between these two elements. In previous studies, after aldehyde fixation, junctions were not observed, but after perfusion fixation with tannic acid-glutaraldehyde, pentilaminar junctions became evident. These junctions were most characteristically located in the intravascular erythropoietic compartment, but were also found in the extravascular granulopoietic compartment. Junctions frequently joined presumptive stem cells with sinusoidal endothelial cells as well as joining immature erythroblasts with sinusoidal endothelial cells; and less frequently, junctions connected adjacent erythroid cells. However, reticulocytes and erythrocytes were never seen to have formed junctions with any other type of cell. Similar junctions within the extravascular compartment connected contiguous reticular cells and also, on occasion, reticular cells with sinusoidal endothelial cells. Hematopoietic cell-reticular cell junctions were restricted to two classes of blood cells--extravascular presumptive stem cells and mast cells. There was no evidence of junctions connecting mature or maturing granuloid cells and any other cell type. The presence of intercellular junctions between immature blood cells and their respective stromal cells suggests that such interactions might play an important role in avian hematopoiesis. However, further work will be needed to determine if these junctions are merely adherence sites or whether they represent sites of intercellular communication. In either event, these junctions appear to reflect a mechanism whereby the marrow stroma could regulate erythroid maturation.
Animals↗
Genetic counseling in adult polycystic kidney disease.
We evaluated 22 patients with end-stage renal disease (ESRD) due to adult polycystic kidney disease (APKD) to assess their knowledge of the hereditary nature of the condition and to determine whether they received adequate genetic counseling. Patients were evaluated by means of a questionnaire and a review of their medical records. Only 5 of 22 (23%) knew their disorder was hereditary at the time of diagnosis, and in only 4 (18%) was genetic counseling suggested. In no instance had proband and spouse received genetic counseling together. Diagnostic studies of children at risk were rarely suggested. We also evaluated the children of 9 probands for APKD. Of 26 children evaluated, 17 had APKD (65%). Sixteen had no children at the time of testing. All but two of the 26 were less than 25 years old. Of the probands' children over 15 years of age, 55% knew the name of the condition in the family but only 9% knew they should be tested. Our study demonstrated inadequacy of genetic counseling and follow-up in this group of patients; we suggest that referral for counseling become a routine part of their management. Early diagnosis and effective counseling has the potential benefit for the individuals of making rational reproductive decisions appropriate for their situation. Counseling may have to be repeated during the course of the patients' disease, as their perception of risk may change with time. With advances in dialysis and transplantation, ESRD may not be as devastating in years to come as it is now.
Adolescent↗
The cellular organization of fibroblastic cells and macrophages at regions of uncalcified cartilage resorption in the embryonic chick femur as revealed by alkaline and acid phosphatase histochemistry.
Resorption of uncalcified cartilage in the embryonic chick femur appears to be mediated by two types of mononuclear cells. One cell type lies flattened and adherent along the surface of the cartilage matrix into which it extends cellular processes. Cytological characteristics of a large, euchromatic nucleus containing a nucleolus, and cytoplasm containing moderate to extensive amounts of rough endoplasmic reticulum indicate that these are protein synthetic cells. Macrophages, characterized by a pleomorphic shape and cytoplasm containing numerous mitochondria and vesicles, comprise the second cell type. These may be seen lying in contact with cartilage matrix, but are more likely located in the nonhematopoietic marrow adjacent to resorbing cartilage, where they establish close cellular associations with protein synthetic cells. Alkaline and acid phosphatase histochemical studies differentiate these two cellular types. Marrow alkaline phosphatase activity is restricted to the cartilage-marrow interface from which it diffuses a short distance into cartilage matrix, but does not diffuse into nearby marrow. Intracellular alkaline phosphatase is present only in protein synthetic cells that line the surface of cartilage, and thus appears to be produced by these cells. Acid phosphatase positive macrophages are scattered throughout the marrow, but are found in greatest concentrations in the region of cartilage resorption. They are rarely in direct contact with cartilage, and there is no evidence that acid phosphatase is released from these cells. The relative localizations and the presence of cellular interactions of these two cell types suggests that protein synthetic cells may be of fibroblastic origin, and may play a primary role in cartilage degradation, while macrophages, in keeping with biochemical evidence, play an adjunct or possibly a regulative role.
Acid Phosphatase↗
Development of the embryonic chick phagocytic system: intraembryonic erythrophagocytosis induced by phenylhydrazine.
The intraembryonic reticuloendothelial response to phenylhydrazine-induced hemolytic anemia was studied embryonic chicks (days 13-16) by light and electron microscopy and histochemical and biochemical assays for acid phosphatase. Phenylhydrazine was given on day 13 and tissue taken at 2, 5, and 10 h and at 1, 2, and 3 days after injections. The response varied in the three major reticuloendothelial organs. The spleen first demonstrated an increase in erythrophagocytosis that was accompanied by increased acid phosphatase levels. Erythrophagocytosis occurred primarily in the red pulp resulting in increased numbers of macrophages, increased to enlarge the spleens. By 2 days after phenylhydrazine injection, greatly enlarged macrophages began to migrate into the venous system, where some erythrophagocytosis continued to occur. The liver was also a major erythroclastic organ in which Kupffer cells became increasingly erythrophagocytic. However, erythrophagocytosis began later than in the spleen, and as measured by acid phosphatase levels, the liver was not as effective in removing damaged erythroid cells. Marrow erythrophagocytosis was only slightly enhanced; however, the marrow responded by increasing its production of red blood cells. Thus, the intraembryonic reticuloendothelial organs of the embryonic chick responded to phenylhydrazine-induced hemolytic anemia in much the same manner as might be expected of the adult bird.
Acid Phosphatase↗
Natural cell-mediated cytotoxicity in mice treated with total lymphoid irradiation (TL1).
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Animals↗
Effects of condylar immobilization.
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Cartilage, Articular↗
Metastatic inefficiency in mice bearing B16 melanomas.
When injected i.v. into mice, the F10 subline of B16 melanoma cells produced significantly more lung tumours over a 3-week period than cells of the F101.r-6 subline. However, in animals bearing intramuscular tumours produced by these sublines, the high pulmonary-colonization potential of the F10 cells was not realized, and no significant differences in natural pulmonary metastasis formation were observed in animals with untreated primary cancers, even when they progressed to the moribund state. Massage of i.m. tumours derived from the two sublines produced no change in metastasis and no changes in the numbers of cancer cells in the blood detectable by bioassay. In contrast, massage increased metastasis from tumours derived from an invasive BL6 subline and B16 wild-type cells and, in the case of the wild-type, the numbers of circulating cancer cells. In vitro experiments show that blood cells from non-tumour-bearing animals are toxic to both sublines; but less to F10 than to F101.r-6. In addition, after i.v. injection of radiolabelled cells, more of the F10 subline were retained in the lungs of recipients than the F101.r-6. In spite of these apparent metastatic advantages of the F10 subline following intravasation, the incidence of natural metastases from i.m. F10 and F101.r-6 tumours was similar, suggesting that substantially fewer F10 than F101.r-6 cells gained access to the circulation. Thus, the higher colonization potential of the F10 cells was not matched by its intravasation potential, since metastatic efficiency is determined by the least efficient step in the metastatic process.
Animals↗
Comparison of two methods for very low density and low density lipoprotein cholesterol determination.
It is shown that VLDL-cholesterol cannot be calculated from serum triacylglycerol at elevated triacylglycerol concentrations (above 2 g/l). Using the method of Friedewald et al. ((1972) Clin. Chem. 18,499-502), VLDL-cholesterol is usually overestimated in these sera and, consequently, LDL-cholesterol underestimated. Quantitative lipoprotein electrophoresis according to Wieland & Seidel ((1979) Innere Medizin 5,290-300), on the other hand, yields VLDL-cholesterol values which correspond to ultracentrifugation data within narrow limits, even in sera with high triacylglycerol contents. A nomogram has been developed for the evaluation of electropherogram.
Chemical Precipitation↗
Interstitial fluid pressure in DMBA-induced rat mammary tumours.
Interstitial fluid pressure (IFP) in DMBA-induced rat mammary tumours was measured by micropuncture with sharpened glass capillaries (diameter 1-3 micron) and by the 'wick-in-needle' technique (WIN). IFP in the superficial layers of the tumours (depth less than 800 micron) was measured with micropuncture, while WIN was used for measurements in deeper areas. IFP in the superficial layers of the tumours was 2.4 mmHg (SD 2.4, n=19), while IFP in deeper layers increased with increasing tumour weight. Thus central IFP in tumours weighing more than 5.5 g was 16.0 mmHg (SD 4.8, n=10), with a maximum value of 23.3 mmHg. When related to tumour histopathology a significant correlation was found between high cellular differentiation (i.e. low degree of malignancy) and high interstitial fluid pressure only. The high IFP may be secondary to a high capillary protein premeability and/or a relatively insufficient lymphatic drainage. A further rise in IFP might result from ischaemic cell swelling and/or a continuous cell proliferation within a tissue of rather low compliance. Together or alone one or more of these factors could facilitate the development of a compartment syndrome with concomitant cell death and tissue necrosis.
9,10-Dimethyl-1,2-benzanthracene↗
Long-term enzyme replacement therapy in beta-glucuronidase--deficient mice by allogeneic bone marrow transplantation.
Enzyme replacement therapy was successfully accomplished in beta-Glu-deficient C3H/HeJ mice after transplantation of BM cells obtained from normal BALB/c donors. Marrow recipients were prepared for transplantation by fractionated TLI. Enzyme activity increased from 20.5 +/- 7.0 nmol/mg of protein per hour to 180 +/- 30.2 in the liver (p less than 0.001) and from 8.2 +/- 2.0 to 17.5 +/- 5.0 nmol/ml/hr in the plasma (p less than 0.05) at 50 days after marrow infusion. Normal enzyme activity was maintained in treated mice for at least 100 days after marrow transplantation, as documented by repeated liver biopsies and examination of plasma samples. The marrow donors and the recipients were fully histoincompatible. Both immunologic rejection of the marrow allograft and GVHD were prevented by the prior conditioning of the recipients with TLI, resulting in bilateral transplantation tolerance of host vs. graft and graft vs. host. The data suggest that allogeneic BM transplantation may provide a possible therapeutic approach for certain enzyme deficiency syndromes.
Animals↗
Erythropoiesis in ha/ha and sph/sph mice, mutants which produce spectrin-deficient erythrocytes.
In order to characterize chronically accelerated erythropoiesis, we studied the ultrastructure of bone marrow and spleen of ha/ha and sph/sph mice, two mutants with profound hemolytic anemia secondary to deficiency of the erythrocyte membrane protein spectrin. The marrows and spleens of both varieties were extremely erythropoietic and were without histological abnormalities directly related to spectrin deficiency. Erythropoiesis was consistently associated with distinctive, dark branched cells which constituted large proportions of the stroma of the mutant spleens and marrow. These dark cells were not present in untreated and acutely bled controls. Plasma clot assays for erythroid progenitors revealed that CFU-E concentrations in the mutant marrows were significantly increased over those in untreated controls while BFU-E concentrations were approximately half. In addition, mutant CFU-E often gave rise to abnormal appearing colonies. Spectrin, though crucial to erythrocyte function is probably not important to the process of erythroid differentiation and maturation. The status of erythroid precursors in the marrows of the spectrin deficient mice is similar to that of mice subjected to an acute bleed. The divergent changes in CFU-E and BFU-E may indicate that these two cells play different roles in accelerated erythropoiesis. The dark cells that we describe are similar to stromal cells observed in models of the early stages of erythropoiesis.
Anemia, Hemolytic↗
Arrest and retention of circulating cancer cells in the lungs of animals with defined metastatic status.
The arrest and retention patterns in lung tissues of [125I]-5-iododeoxyuridine-labeled Lewis lung carcinoma cells injected into the systemic circulation of tumor-bearing (TB) mice with defined metastatic status and non-tumor-bearing mice were determined. The presence of overt lung metastases did not significantly alter the arrest or subsequent rates of release of cancer cells compared with non-tumor-bearing controls. However, the percentage of cancer cells retained in the 3-week TB animals was significantly greater than that in the 1-week TB mice. In 3-week TB animals, 4 times as many cancer cells were arrested in the "noninvolved" lung tissues than in the metastases. The relative vascularities of the metastases and lung tissues were assessed following injection of 51Cr-labeled erythrocytes, and from these and published data it is suggested that major factors determining the differential distribution of cancer cells are the relative areas of microvascular endothelium and blood flow per g in the lungs and metastases.
Animals↗
Enzymic reaction-rate assay for urinary creatinine.
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Amidohydrolases↗
Adipocyte development and the loss of erythropoietic capacity in the bone marrow of mice after sustained hypertransfusion.
In this electron microscopic study, erythropoiesis in mice was completely suppressed by repeated hypertransfusion for up to 6 wk. We describe a sequence of ultrastructural changes in the marrow's stromal cells that accompany the resulting shift from erythropoietic to granulopoietic tissue. These include the destruction of medullary macrophages, the accelerated development of marrow adipocytes and reticular cells, and a reduction in the amount of vascular space in the marrow. The absence of macrophages was highlighted by the complete lack of erythrophagocytosis in the marrows of hypertransfused mice that were injected with the hemolysing agent, phenylhydrazine. The changes in the marrow stroma probably underlie the shift in the marrow's hematopoietic microenvironment. Repeated phlebotomy of mice that had been hypertransfused for 2 wk evoked the appearance of unique stromal cells in the marrow, similar to cells that have been associated with accelerated erythropoiesis. The newly anemic mice were otherwise unable to mount an erythropoietic response to repeated bleeding, showing that the decline in the erythropoietic microenvironment brought on by sustained hypertransfusion was a lasting one.
Adipose Tissue↗
Haemopoiesis in mammalian bone marrow.
The bone marrow supports haemopoiesis of all blood cell types and delivers mature cells to the blood. Haemopoiesis is characterized not only by the differentiation and proliferation of haemopoietic stem cells but by a number of physically associated cell types. These include macrophages, lymphocytes and, when haemopoiesis is intense, a multinucleate branched stromal cell. The venous vasculature of the bone marrow is associated with both haemopoiesis and the delivery of blood cells to the circulation. The wall of the vascular sinus consists of an endothelium lying upon a basement membrane. On the outside surface of the basement membrane lie adventitial cells or pericytes which branch out into the haemopoietic space forming a scaffolding upon which haemopoietic clusters are arranged. These cells move away from the wall of the vascular sinus to permit maturing blood cells to penetrate the endothelium and enter the circulation. Under other circumstances, adventitial cells accumulate fat, becoming the adipocytes of marrow.
Animals↗
Bone marrow cells associated with heightened eosinophilopoiesis: an electron microscope study of murine bone marrow stimulated by Ascaris suum.
An acute eosinophilopoiesis occurs in mice secondarily exposed to Ascaris suum, the marrow eosinophils increasing from approximately 5% to 45%, and blood levels from 50/ml3 to more than 1000/ml3, within 14 days. Eosinophilopoiesis occurs in hematopoietic compartments of the bone marrow and is associated with four other cell types: branched stromal cells, macrophages, lymphocytes, and reticular cells adventitial to venous sinuses. Branched stromal cells, a newly recognized cell type, are presented in intensified hematopoiesis of at least several blood-cell types. They are characterized by extensive branches surrounding contiguous hematopoietic cells, dense cytoplasm, and multiple communications between nuclear cisternae and an extensive, dilated endoplasmic reticulum. These cells, moreover, have a capacity to coalesce to form an extensive, branching, multinucleate giant-cell system. They are neither phagocytic nor fibroblastic, and attend every phase of eosinophilic hematopoiesis. Macrophages lie among eosinophils, and they possess many processes which extend among eosinophils. The may constitute, with the eosinophils, islets similar to erythroblastic islets; or they may lie among eosinophils in sheets. Macrophages also lie against the outside surfaces of vascular sinuses and extend transmural processes into the lumina. Lymphocytes of a type not yet known are regularly present among developing eosinophils. Adventitial cells of vascular sinuses, fibroblastic cells, extend processes deep into perivascular hematopoietic spaces, and thereby envelop eosinophils and other maturing blood cells. While adventitial cells can be dense, they were typically quite lucent and had microfilaments clustered beneath their plasmalemmae. With the large-scale blood-cell delivery characteristic of this model, marked changes occurred in the walls of the vascular sinuses. Adventitial cells moved away from the vascular wall, permitting blood cells direct access to the basal surface and reducing their cover from more than 65% to less than 20%. Both adventitial and endothelial cells may be compact and dark, or expanded and quite lucent. Heterolysomes occur in moderate-to-large numbers in both adventitial and endothelial cells, and large gaps filled with blood cells in transit occur in endothelium. The hematopoietic-associated cells and the vasculature described here would appear to provide the cellular microenvironment which regulates hematopoiesis.
Animals↗