Unilateral breast hyperplasia in pregnancy simulating neoplasm.
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Biomedical subjects
Publications and source records attributed to L A Solberg.
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We compared the extent of lesions in the coronary arteries of autopsied middle-aged men from Oslo, Norway, with lesions in autopsied men of similar ages in Tokyo, Japan. Certain risk factors for coronary heart disease as serum cholesterol, triglycerides, and blood pressure were also available from these men in the two locations. Our comparisons reveal large differences in the extent of atherosclerosis between Oslo and Tokyo, which are reflected in the levels of the risk factors, particularly serum cholesterol levels. Our findings suggest that preventive strategies could retard the development of atherosclerosis and coronary heart disease without the economic and nutritional problems that affect technically underdeveloped societies where atherosclerosis and coronary heart disease are not prevalent.
The isolation and characterization of human megakaryocyte growth factors has been hampered because evaluation of megakaryocyte growth in semisolid medium requires both lengthy incubation and visual quantitation. In addition, colony formation requires cell division, while most regulation of platelet production may involve individual, nonproliferating differentiating megakaryocytes. We have developed a radioimmunoassay (RIA) that makes use of an iodinated murine monoclonal antibody (MoAb) specific for platelet/megakaryocyte glycoprotein IIb/IIIa (GPIIb/IIIa) to measure megakaryocyte production in liquid marrow culture. This assay is sensitive to 3 X 10(3) platelets (roughly 30 megakaryocytes) and linear up to 1 X 10(6) platelets, and thus it provides a useful range for quantitating megakaryocyte production in in vitro marrow culture. Significant differences (threefold to fivefold) in megakaryocyte/platelet-specific GPIIb/IIIa complex are detected between stimulated and unstimulated marrow cultures by day 7, although antigen accrual in stimulated cultures continues through at least day 16. Conditions that promote megakaryocyte growth in semisolid medium (ie, aplastic plasma and PHA-LCM) have also been facilitory in liquid culture. This rapid and sensitive assay for cell-bound GPIIb/IIIa should facilitate recognition and isolation of megakaryocyte and platelet growth factors.
Bone marrow from a normal male pig was transplanted into a related female pig with severe homozygous von Willebrand's disease (vWd). After engraftment the circulating leukocytes were of the male karyotype, and the platelets were strongly positive for von Willebrand factor (vWF) by indirect immunofluorescence. The average level of vWF was 1.96 U/dl and of ristocetin cofactor was 2.8 U/dl. The ear immersion bleeding time before transplantation was consistently more than 15 min and afterwards varied between 5 min and more than 15 min. Transfused vWF corrected the bleeding time at a level of 10 U/dl, which is lower than that required for a von Willebrand pig. We concluded that: the plasmatic compartment is only minimally replenished by the vWF from platelets and megakaryocytes; and the platelet vWF alone only partially corrects the abnormal tests of the hemostatic mechanism in severe vWd.
Human megakaryocytes have been shown by immunofluorescent techniques to express platelet glycoprotein IIb/IIIa antigen. We report evidence that megakaryocytes derived from human committed megakaryocytic progenitor cells in vitro (CFU-M) synthesize glycoproteins IIb and IIIa. Nonadherent light-density human bone marrow cells were cultured in human plasma and methylcellulose using conditions that promote large megakaryocytic colonies. On day 13 the megakaryocytic colonies were picked, pooled, and pulsed with 35S-methionine in methionine-free media. Populations of approximately 100,000 cells with greater than or equal to 95% viability and containing 70% to 90% megakaryocytes were obtained reliably for study. After the radioactive pulse, the cell suspension was solubilized with nonionic detergent. To reduce nonspecific binding of 35S-labeled proteins to agarose, the lysate was chromatographed sequentially on glycine-quenched Affi-gel and antihuman factor X-Sepharose. The unbound material from these resins was then chromatographed on an antiglycoprotein IIb/IIIa monoclonal antibody resin (HP1-1D-Sepharose) or on a control monoclonal antibody resin. Bound fractions were eluted and analyzed by polyacrylamide gel electrophoresis and autoradiography. Autoradiograms of diethylamine eluates from HP1-1D-Sepharose revealed two labeled proteins with electrophoretic mobilities identical with those of human platelet membrane glycoproteins IIb and IIIa, isolated using similar conditions. Autoradiograms of material synthesized by control macrophages from the same donors revealed no significant labeling of proteins in the glycoprotein IIb/IIIa molecular weight range, nor were such proteins bound by HP1-1D-Sepharose. Our observations show that protein synthesis by CFU-M-derived human megakaryocytes can be readily studied using a small amount of bone marrow aspirate as starting material. This approach will allow the study of protein synthesis by megakaryocytes from normal subjects or from subjects with clinical disorders, and it will circumvent the need to obtain large amounts of bone marrow to prepare enriched populations of megakaryocytes.
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From 1972 to 1973, 16,202 Oslo men, aged 40 to 49 years, were examined for cardiovascular disease and coronary heart disease (CHD) risk factors. This report describes the results of autopsy examinations from 204 of 471 men who died in this cohort with regard to associations between selected risk factors and (1) raised coronary atherosclerotic lesions (RL), (2) coronary artery stenosis, and (3) CHD death. Total serum cholesterol and blood pressure levels were positively associated with all 3 measures of coronary atherosclerosis and its complications, both in univariate and multivariate analyses, whereas high-density lipoprotein (HDL) cholesterol was highly and inversely related. Triglyceride levels, cigarette smoking, social class and physical activity at work and at leisure were not significantly associated with either of the 3 measures. When RL was added to the model with stenosis as the dependent variable, the risk factors no longer appeared as independent; this is consistent with the hypothesis that these factors, when significant, work through the development of RL to produce stenosis. HDL cholesterol was the only risk factor independently and significantly associated with CHD death when RL or stenosis or both were put into the model for CHD. This points to the possibility of HDL cholesterol also working through mechanisms other than the prevention of RL and stenosis toward CHD death.
We have analysed the contribution to megakaryocyte colony formation in methylcellulose made by human plasma, serum, media conditioned by phytohemagglutinin (PHA) stimulated leukocytes (PHA-LCM), erythropoietin (EPO) preparations, and platelets. The culture system was used as a bioassay for megakaryocyte colony stimulating activity (Meg-CSA) in plasma samples of patients with perturbed megakaryocytopoiesis. Preparations of heparinized platelet-poor plasma yielded the most consistent results. Platelet-poor plasma of normal subjects will at best facilitate the occasional growth of small megakaryocyte colonies. Colony frequency and size are reproducibly enhanced in the presence of PHA-LCM as a source of exogenous Meg-CSA. Commercially available EPO preparations may vary in their content of activities that influence megakaryocyte colony formation. Addition of these preparations to cultures that contain plasma and PHA-LCM usually does not enhance colony formation. In contrast to platelet-poor plasma, platelet rich plasma and serum are less supportive of megakaryocyte colony growth. It is suggested that this loss of activity may be related to the release of inhibitors by activated platelets or alternatively caused by absorption of activities by platelets. Plasma samples from patients with megakaryocytopoietic dysfunction may contain components that promote colony formation without addition of PHA-LCM or EPO. This phenomenon is consistently observed for patients with severe aplastic anemia and bone marrow transplant recipients after completion of their ablative preparative regimen.
Specific monoclonal and polyclonal antibody reagents and a double antigen indirect immunofluorescence microscopy technique were used to visualize coagulation factor V in human bone marrow. Marrow aspirates were smeared directly on glass slides, or washed and cytospun onto glass slides, or processed and plated into a plasma/methylcellulose cell culture system. Morphologically identifiable colonies of megakaryocytes, erythrocytes, granulocytes, or monocytes/macrophages were removed from 14- to 18-day marrow culture dishes by micropipette and streaked onto glass slides. Smears of marrow cell preparations were air-dried, fixed, washed, and incubated sequentially with primary IgG antibody reagents and with secondary anti-IgG antibody reagents conjugated with either fluorescein or rhodamine. Preparations were examined and photographed through a microscope suitably equipped for two-color fluorescence and phase contrast analysis. Cells of megakaryocytic lineage were identified by their immunofluorescent reactivity with murine monoclonal antibody HP1-1D, specific for human platelet plasma membrane glycoprotein IIb/IIIa (GP IIb/IIIa), or by their immunofluorescent reactivity with monoclonal or polyclonal antibodies specific for von Willebrand factor (vWF) or for platelet factor 4 (PF4). Coagulation factor V in bone marrow was detected by simultaneous immunofluorescent staining with polyclonal burro anti-human factor V antibody or with a panel of murine monoclonal anti-human factor V antibodies. The double antigen immunofluorescence staining technique, incorporating appropriate controls, revealed that coagulation factor V was principally located in marrow cells simultaneously identified as megakaryocytes by antibodies to GP IIb/IIIa, vWF, or PF4. The specific immunofluorescence of factor V in megakaryocytes and platelets was eliminated when excess purified factor V antigen was preincubated with anti-factor V antibody. Our observations establish the presence of human megakaryocyte coagulation factor V, confirm the presence of human platelet factor V, and indicate that human megakaryocyte/platelet coagulation factor V is a lineage-associated protein.
In conclusion, a culture system is now available that reproducibly facilitates the development of megakaryocyte colonies and the emergence of megakaryocytes within multilineage colonies. The assay is dependent upon the use of human plasma and a source of exogeneous MEG-CSA. Patients with perturbed hemopoiesis plasma may contain activities able to replace exogeneous MEG-CSA. This system can therefore be used to evaluate MEG-CSA activities. In addition it is now feasible to study blast populations of patients with leukemia characterized by a megakaryocyte phenotype.
We compared mean extent of atherosclerotic lesions in carotid and intracranial arteries at autopsy among age, sex, and race subgroups in New Orleans. Most comparisons were made within similar broad cause-to-death categories after excluding deaths due to diseases associated with increased amount of atherosclerosis. Use of this basal group of cases reduces the effect of selection bias due to cause of death in this autopsy population. Fatty streaks were present in the carotid arteries of almost all cases even in the youngest age group (10 to 14 years) and were more extensive in blacks than in whites. Raised atherosclerotic lesions increased with age in the carotid arteries of blacks from age group 15 to 24 years and in whites from age group 25 to 34 years; black men and white men had about the same amount of raised lesions, whereas black women consistently had more than white women. In the intracranial arteries, fatty streaks and fibrous plaques began from age 15 to 24 years; blacks had more raised lesions than whites, particularly in the oldest age group, 65 to 69 years. These findings and mortality data suggest that in the 1960s and early 1970s black men and women were more susceptible to cerebral atherosclerosis and cerebrovascular diseases than white men and women.
Chronic ethanol consumption reduces the liver retinoid store in man and rat. We have studied the effect of ethanol on some aspects of retinoid metabolism in parenchymal and nonparenchymal liver cells. Rats fed 36% of total energy intake as ethanol for 5-6 weeks had the liver retinoid concentration reduced to about one-third, as compared to pair-fed controls. The reduction in liver retinoid affected both the parenchymal and the nonparenchymal cell fractions. Plasma retinol level was normal. Liver uptake of injected chylomicron [3H]retinyl ester was similar in the experimental and control group. The transport of retinoid from the parenchymal to the nonparenchymal cells was not found to be significantly retarded in the ethanol-fed rats. Despite the reduction in total retinoid level in liver, the concentrations of unesterified retinol and retinyl oleate were increased in the ethanol fed rats. Hepatic retinol esterification was not significantly affected in the ethanol-fed rats. Since our study has demonstrated that liver uptake of chylomicron retinyl ester is not impaired in the ethanol-fed rat, we suggest that liver retinoid metabolism may be increased.
Coronary heart disease is strongly associated with the presence of stenosis in the epicardial coronary arteries. This prospective autopsy study shows that the relationship between risk factors for coronary heart disease and the occurrence of stenosis is the same as between risk factors and coronary atherosclerotic lesions: serum cholesterol, systolic and diastolic blood pressure contribute to formation of coronary stenosis; high density lipoprotein cholesterol is inversely related to stenosis. None of the other risk factors for coronary heart disease, such as fasting triglycerides, smoking habits, social class, and physical activity at work and at leisure, was statistically associated with the occurrence of coronary stenosis. Additional statistical analyses show that these selected risk factors do not seem to have any independent influence on the development of coronary stenosis over and above that of the extent of raised atherosclerotic lesions.
The acute tumor lysis syndrome occurs rarely in nonhematologic malignancies. This patient, a 34-year-old woman with metastatic medulloblastoma, was receiving palliative radiotherapy for a rapidly expanding abdominopelvic mass. After a total of 300 rad, the patient developed the biochemical hallmarks of the acute tumor lysis syndrome, hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. This was complicated by oliguria from hyperuricemic acute renal failure. The patient responded well to hydration, alkaline diuresis, phosphate and potassium binders, and allopurinol. The potential for acute tumor lysis syndrome should be anticipated when treating metastatic medulloblastoma.
The influence of prazosin and propranolol on serum lipids and atherosclerosis was evaluated in standard fed pigs during a nine months experimental period. The incidence and severity of atherosclerotic lesions was very low, and no difference could be observed neither between the two drugs nor between the drug groups and the placebo group. Prazosin and propranolol induced no marked change in the serum lipid profile. The results could be explained by the very low fat content, 3.6 per cent, in the present standard diet.
Morphologic features may sometimes be interpreted differently by different pathologists. By introducing objective methods in the histological evaluation the subjectivity of the judgement is reduced and a higher degree of consistency achieved. In the present study three linear parameters of nasal epithelial basal cells: the largest transversal nuclear diameter, the sum of the longitudinal and transversal nucleolar axes and the basal cell width, i.e. the width of the attachment face to the basement membrane, were classified by means of three-class rulers. From this classification weighted indices were made which were then given equal weight and transformed, so that when added up their sum, the joint index (Q) to the largest possible extent was consistent with pseudostratified/stratified cuboidal, stratified squamous and dysplastic epithelium when Q less than or equal to 1, 1 less than Q less than or equal to 2 and Q greater than 2 respectively. Tested prospectively we found 91% agreement between the morphometric and histological classification. The method presented is extremely simple and rapid to perform, and appears to have diagnostic potential in distinguishing various types of epithelial alterations of the nasal mucosa. The method may also be useful in approaching similar problems in other epithelia.
Ten patients with thrombocytopenia (TTP) were treated recently in our institution with plasma exchange (PE), steroids, and antiplatelet drugs. Additionally, fresh frozen plasma (FFP) was administered to nine patients, with folic acid given to eight patients. After 13 to 25 months of follow-up, we found that four patients achieved and remained in remission after initial treatment. Three patients had four relapses, which developed while they were taking antiplatelet therapy, and which were treated successfully with FFP alone, or with PE in addition to FFP. Four patients suffered major neurological or renal damage during their presentation or initial treatment. One of these patients died during his initial hospitalization. Another patient died 7 months after initial treatment. After analyzing this experience, we have concluded that antiplatelet drugs or corticosteroid should be used as the sole initial treatment most cautiously. The relative importance of the exchange process, per se, versus plasma infusion cannot be inferred from our observations, but plasma exchange with FFP appears to have had a real impact on recovery.
Nasal histology and nickel concentration in the plasma and urine of nickel workers were reexamined after 4 a for an evaluation of the effect of improvements in the refining process and work conditions. Ninety-eight (31%) nickel workers who were part of a previous study were reexamined. In addition, 33 of the original 38 workers with nasal epithelial dysplasia were studied for possible regression of the histological changes. Reduction in the atmospheric content of nickel and improved hygienic conditions lowered the concentration of nickel in plasma and urine by approximately 50%. The mean histological score and frequency of dysplasia was virtually the same in the two investigations, 12 and 13%, respectively. Nasal biopsies are of limited diagnostic value in the examination of individual cases. However, the method seems to be of value in identifying and monitoring groups of persons with increased risk of developing nasal carcinoma.