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Biomedical subjects

W J Miller

Publications and source records attributed to W J Miller.

At least 145 records · Page 8Linked to original sources
PubMed1984

In vitro tumoricidal activity of immunoadsorbed leukemic serum.

We studied the ability of untreated or immunoadsorbed acute myelogenous leukemia (AML) sera to kill AML blasts. Culture of blasts with sera adsorbed to protein A-bearing Staphylococcus aureus Cowan I (SAC), resulted in a marked loss of blast viability (42.7% of control). Immunoadsorption against non-protein A-bearing Wood 46 strain of S. aureus did not induce serum cytotoxic activity (94.8% viable cells). Sera adsorbed to Sepharose-bound protein A also killed blasts in vitro (64.3% viable cells). The addition of untreated sera to SAC-treated cultures partly abrogated the effect, suggesting a blocking substance in untreated serum. Cytotoxicity was not complement-dependent nor did it appear to be cell mediated. It was, however, eliminated by trypsin treatment of SAC-treated sera. These studies suggest that SAC-treated AML serum contains a protein that is cytotoxic to AML blasts, and that this protein is partly inactivated by untreated AML serum, possibly through interaction with immunoglobulins. The mechanism described here may be one of several mechanisms leading to tumor necrosis in tumor-bearing hosts treated with SAC-immunoadsorbed plasma.

Cells, Cultured↗
PubMed1984

Effect of strength training on glucose tolerance and post-glucose insulin response.

The effect of muscle strength training on glucose tolerance and the insulin response after glucose feeding was investigated in eight healthy male subjects. Glucose tolerance and the associated insulin response was assessed using a standard 100-g oral glucose load before and after a supervised 10-wk high-resistance, isotonic weight-lifting program. Blood samples were drawn before and at 30, 60, 90, 120, and 150 min after ingestion of glucose. Areas under the glucose and insulin curves were used to determine differences between treatments. Muscle strength training increased body weight 3.7% and lean body mass by 3.5%, but had no effect on fat mass as determined by hydrostatic weighing. Glucose tolerance was not changed by the training program. However, a significant reduction in the basal plasma insulin concentration (37.5%) and the area under the insulin response curve (18.0%) was found (P less than 0.05). This reduction in the insulin response was significantly correlated (r = 0.89; P less than 0.05) with the increase in lean body mass. These results suggest that the increased muscle mass resulting from strength training was responsible for the attenuated insulin response to a standard 100-g oral glucose challenge.

Blood Glucose↗
PubMed1984

Phagocytosis of sickle erythrocytes: immunologic and oxidative determinants of hemolytic anemia.

Hemolytic anemia in sickle disease involves both intravascular and extravascular destruction of erythrocytes. Since the latter presumably involves the reticuloendothelial system, we have examined interactions between sickle erythrocytes and macrophages. In erythrophagocytosis assays, 18.9 +/- 7.2% of human marrow macrophages ingest sickle RBCs, while only 3.1 +/- 2.1% ingest normal RBCs. This abnormality is not explained by reticulocytosis, and it is strongly dependent upon RBC density. The interaction between sickle RBCs and macrophages appears to be partly immunologic, since it is partially blocked by Fc receptor blockade. Also, admixture of sickle RBCs (pretreated with rabbit anti-human-Ig) and Fc-receptor-bearing K562 cells results in 15.6 +/- 10.6% K562-RBC rosette formation compared with only 0.5 +/- 1.2% for normal RBCs. Regarding other factors that might promote erythrophagocytosis, sickle RBCs are found to spontaneously generate twice-normal amounts of dialdehyde byproducts of lipid peroxidation ("malondialdehyde" or MDA). Peroxide or reagent-MDA treatment of normal RBCs significantly enhances their phagocytosis, and MDA is at least 50 times more potent than other aldehydes studied here. Oxidative and immunologic effects may be related, since exposure of MDA-treated RBCs to immunoglobulin-containing human sera results in a further significant enhancement of erythrophagocytosis. For comparison of different sickle patients, an adherence assay demonstrates that sickle RBCs are 1.03 to 6.85 times more adherent to macrophages than are normal RBCs, and degree of adherence correlates significantly with irreversibly sickled cell (ISC) counts and hematologic variables reflecting hemolytic rate. We conclude that propensity for RBC interaction with macrophages is likely to be a determinant of hemolytic rate in sickle disease. Pertinent mechanisms appear to involve modification of RBC membranes by dialdehyde byproducts of excessive autoxidation and the abnormal acquisition of surface immunoglobulin on sickle RBCs, although participation of other membrane defects has not been excluded. Interestingly, the data further suggest the possibility that appearance of the "senescence antigen" in old normal RBCs represents modification of the membrane by "MDA."

Anemia, Sickle Cell↗
PubMed1984

Clinical aspects of experimentally induced chloride deficiency in Holstein calves.

A severe total body chloride deficit was induced in Holstein calves by feeding a low-chloride ration (0.063% Cl) and removing digesta daily from the abomasum through a surgically implanted cannula. Clinical signs of the deficit observed included polydipsia, polyuria, dehydration, anorexia, scleral injection, decreased respiratory rate, and blood and mucus in the feces. Necropsy findings included dehydration, blood in the lumen of the small intestine, and renal lesions. The most extensive histopathologic changes occurred in the renal tubular epithelium of the outer medulla where mineralization of the tubular epithelium and basement membranes was frequently seen.

Animals↗
PubMed1983

Production of purified hepatitis B surface antigen from Alexander hepatoma cells grown in artificial capillary units.

An artificial capillary system was devised for growth of hepatoma cells that yields very high titers of hepatitis B surface antigen (HBsAg). High yield of antigen was facilitated by slowing cellular metabolism through reduction of incubation temperature and addition of 0.1 mM caffeine. Deletion of serum from the medium did not reduce the yield of antigen. HBsAg prepared from the culture fluid by affinity chromatography and additional chemical and enzymatic steps was essentially pure and was indistinguishable from HBsAg prepared from infected human plasma. Preparation of HBsAg from the cell culture source presents advantages over that of human plasma and might be a source of HBsAg for vaccine preparation.

Caffeine↗
PubMed1983

Automated cytopathic effect (CPE) assays.

An automated CPE procedure has been developed that increases the precision and ease of performing titrations of measles, mumps and rubella viruses in vaccine materials. By this procedure, additions of cell suspensions and reagents and the dilution of samples are performed automatically by a modified Dynatiter instrument, using 96-well microtitre plates. Cell monolayers are stained with carbolfuchsin dye to eliminate the need for microscopic examination. Finally, the trays are read in an optical scanner and the end points calculated automatically by a programmable calculator. The increased accuracy and precision attained by performing greater numbers of replicate assays at reasonable cost will be of particular value to vaccine manufacturers.

Automation↗
PubMed1983

Antithymocyte globulin treatment of severe aplastic anaemia.

Nineteen patients with severe aplastic anaemia were treated with antithymocyte globulin. Ten patients obtained remissions (transfusion independent, at least 45000 platelets and 2000 PMN/mm3) within 2-3 months and continue in remission 5-35 months after antithymocyte globulin. Ages of responders ranged from 17 to 71. Complications of antithymocyte globulin included arthralgias, rash, serum sickness, angioedema and fever. Two patients died during, two shortly after, and one 10 months after therapy. One patient with a previous remission following antithymocyte globulin relapsed and achieved a second remission with retreatment. Previous androgen therapy did not affect outcome since two of four patients with and eight of 15 patients without previous androgen therapy achieved remission with ATG. Treatment with antithymocyte globulin is a promising alternative to bone marrow transplantation in the treatment of severe aplastic anaemia.

Adolescent↗
PubMed1983

Primary adenocarcinoma of the middle ear.

Adenocarcinoma arising from the mucosa of the middle ear is a rare tumor. This report adds four new cases to the 13 cases that have been previously reported in the literature. These neoplasms tend to have a rather slow growth pattern and have an infrequent incidence of distant metastases. The observations that local recurrence is the major problem with adenocarcinoma of the middle ear suggest that aggressive locoregional treatment should be strongly considered.

Adenocarcinoma↗
PubMed1983

Retinoic acid treatment of acute promyelocytic leukemia: in vitro and in vivo observations.

We describe in vitro studies and a therapeutic trial of retinoic acid (RA) in a patient with acute promyelocytic leukemia (APL) refractory to chemotherapy. Bone marrow promyelocytes from the patient, prior to RA, matured morphologically in liquid culture with RA (97% maturing myeloid cells compared with 26% in control cultures at 7 days). RA-cultured cells displayed leukocyte alkaline phosphatase activity and cytoplasmic maturation (by electron microscopy). Retinoic-acid-treated cells, compared to controls, demonstrated increased functional maturation, with phagocytosis of opsonized zymosan (90% versus 10%) and production of superoxide (measured by nitroblue tetrazolium reduction) in response to phorbol ester, opsonized zymosan, or the chemotaxin F-met-leu-phe. There was no evidence of active proliferation in the cultures. RA-treated cells continued to show 15;17 chromosomal translocation after 7 days in culture. The patient was treated with oral 13-cis-retinoic acid (100 mg/sq m/day) for 13 days. During that time, the peripheral white blood count rose from 300 cu mm to 6,700 cu mm, and the maturing myeloid cell count rose from 54 cu mm to 3,800 cu mm. Bone marrow maturing cells increased from 1.8% to 8.0%. Despite the increasing number of maturing myeloid cells, the patient died on day 13 from disseminated candidiasis. These data confirm that RA induces maturation of leukemic promyelocytes in vitro and suggest that similar maturation is achievable in vivo. We suggest that oral retinoic acid may be a useful adjunct in the treatment of APL.

Adult↗
PubMed1982

Protein A adsorption of acute myelogenous leukemia serum induces in vitro blast lysis.

We studied cytotoxic activity of acute myelogenous leukemia (AML) sera for AML blasts before and after immunoadsorption with Staphylococcus aureus, Cowan I (SAC), which contains protein A. We found in vitro that incubation with treated AML sera reduced viability to 42.7% of control (p less than 0.01) for autologous and 21.0% of control (p less than 0.01) for allogeneic blasts. Normal peripheral blood cells were not killed by treated AML sera. Wood 46 strain of Staphylococcus aureus, which does not contain protein A, did not significantly reduce AML blast viability (94.8%, p greater than 0.4), while Sepharose-bound protein A reduced viability to 63.8% (p less than 0.01). Cytotoxicity does not appear to be complement-mediated, byt cytotoxic activity is trypsin-sensitive and is contained in the immunoglobulin fraction. This model for study of the tumoricidal action of protein A adsorption should be useful for predicting utility of plasma adsorption as a therapeutic adjunct in the future.

Cytotoxicity, Immunologic↗
PubMed1982

Rising lung cancer death rates among black men: the importance of occupation and social class.

From 1950 to 1977 the age-adjusted cancer death rates for nonwhite men in the United States rose an astonishing 63.2 percent, while rates for white men increased 22.2 percent and fell slightly for women of both races. The bulk of this increase can be accounted for by cancer of the lung. As a serious health problem that is increasing in severity, cancer in black men deserves close attention and definitive action. This discussion focuses on basic epidemiological relationships in the origins of this epidemic, particularly in regard to the relative importance of occupation, cigarette smoking, and social class.

Black or African American↗
PubMed1981

Transfer of selenium from blood to milk in goats and noninterference of copper with selenium metabolism.

The mechanism of selenium secretion by the mammary gland and effects of dietary copper and selenium metabolism on selenium in milk were investigated. Radioactive sodium selective selenite was injected into the jugular vein of lactating goats fed concentrates containing 15 or 115 ppm copper. Blood and milk samples were collected hourly for 8 h and daily for 1 wk. Whole blood, plasma, whole milk, and casein, whey, and cream fractions of milk were counted for selenium-75. No significant differences due to dietary copper were seen. The selenium-75 was primarily associated with the casein in milk. The association of selenium with the whey fraction was greater for early periods than later and varied between animals. The specific activity based on protein content was greater in casein than in whey. Peak selenium-75 in whole milk occurred 2 h after the peak in plasma. On day 7 following selenium-75 dosing, kidney had the highest specific activity, and liver was slightly higher than mammary tissue. All subcellular organelle fractions of liver, kidney, and mammary tissue by homogenization and differential centrifugation contained significant selenium-75. Selenium normally is secreted from the mammary secretory cell in combination with protein through the secretory vesicles, metabolism of selenite prior to milk secretion is important, and copper does not interfere with normal metabolism of selenium.

Animals↗
PubMed1981

Effect of high but nontoxic dietary intake of copper and selenium on metabolism in calves.

Sixteen male Holstein calves in a 2 X 2 factorial design with four animals per treatment were fed 0 and 100 ppm supplemental copper from copper carbonate and 0 and 1 ppm added selenium from sodium selenite for 15 days in a practical diet containing .1 ppm selenium and 15 ppm copper. On day 13, calves received an oral dose of selenium-75 and were sacrificed 48 h later. Feed consumption, serum glutamic oxaloacetic transaminase, creatine phosphokinase, and stable copper in blood and urine were unaffected by diets. Stable copper in pancreas, spleen, kidney, muscle, and spinal cord along with selenium-75 in lung, pancreas, liver, heart, and muscle also were unaffected. In calves fed high selenium, selenium-75 was lower in blood, kidney, and spinal cord, and more was excreted in the urine, indicating less retention. Urine was the major excretory pathway of excess selenium-75. Liverstable copper was greater for high copper diets. Stable copper in the lung was higher in calves fed high selenium-high copper than in either control or calves fed high copper. Stable copper was greater in heart tissue in both groups fed high selenium than in controls and slightly higher than the group fed high copper.

Animal Feed↗
PubMed1981

Chloride deficiency in Holstein calves from a low chloride diet and removal of abomasal contents.

Chloride deficiency signs were produced in young Holstein calves by a low chloride diet (.063% chlorine) and daily removal of chloride in abomasal contents. General clinical signs included anorexia, weights loss, lethargy, mild polydipsia, and mild polyuria. In latter stages of the deficiency, severe eye defects (scleral injection, sunken eyes, scaliness around eyes) and reduced respiration rate became evident. Feces contained varying amounts of blood and mucus. The chloride imbalance resulted in severe alkalosis and hypochloremia leading to secondary hypokalemia, hyponatremia, and azotemia. All deficient calves died after 24, 28, 38, and 46 days of treatment. Chloride concentrations of plasma in each of the calves just prior to death were similar at 31 to 35 meq/liter, which compares with normal 96 meq/liter. One additional calf made chloride deficient was recovered to normal health in 9 days following a single treatment with salt water and feeding of control diet containing .48% chlorine. Control calves fed a diet with .48% chlorine and which also had their abomasal contents removed daily grew normally and exhibited no deficiency signs. When dietary chloride was adequate, removal of abomasal contents (and chlorine) had no adverse effects on the animals.

Abomasum↗
PubMed1981

Cytogenetic conversion following allogeneic bone marrow transplantation for advanced chronic myelogenous leukemia.

We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allogeneic bone marrow transplantation after preparation with busulfan, vincristine, cyclophosphamide, and fractionated total body irradiation. Engraftment and conversion to normal chromosome patterns after transplantation occurred in all five patients. None of the patients reverted to an abnormal chromosome pattern of demonstrated clinical or hematologic evidence of recurrent disease during the course of this study; however, longest survival from transplant was 248 days. Allogeneic bone marrow transplantation can eradicate the abnormal clone even in far advanced chronic myelogenous leukemia and can provide normal hematopoiesis. We suggest that clinical complications of chemotherapeutic toxicity and infection were responsible for the short survival in this group of patients, and that these complications could be decreased by performing transplantation in the chronic phase or early accelerated phase of the disease.

Adult↗
PubMed1980

Effect of lactose, copper and iron on manganese retention and tissue distribution in rats fed dextrose-casein diets.

The effect of iron, lactose and copper on manganese retention was studied in rats fed two diets. Thirty-six male albino rats (75 to 100 g) were allotted to six groups of six rats each. Three groups received a purified manganese-free dextrose-casein diet, and three groups received the same purified diet with 17% lactose added at the expense of dextrose. One group fed each of the above diets received either a manganese-free mineral mixture, the mineral mixture with 5 ppm supplemental Cu or the same mineral mixture with Fe removed. After 7 days on the diets, each rat was given, by gavage, 10 muCi of 54Mn activity as 54MnCl2 in a sodium acetate buffer. On the third day after dosing, the rats were sacrificed and samples of liver, kidneys, semitendinosus muscle, spleen and tibia were taken for stable and radioactive manganese analysis. Lactose added to the purified diet depressed 54Mn retention in all tissues studied. Lactose addition also decreased specific activities of the livers and kidneys but tended to increase stable manganese values. Copper apparently had little direct effect on 54Mn retention but tended to reduce the effect of lactose on 54Mn retention. Omission of Fe greatly increased 54Mn retention values in all tissues studied with or without added lactose. Fe omission also significantly increased the specific activities and stable Mn values of livers and the specific activity of kidneys. The results indicate that low dietary Fe may be a contributing factor to the increased manganese retention observed in this study and a previous study.

Animals↗