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Biomedical subjects

W A Anderson

Publications and source records attributed to W A Anderson.

At least 109 records · Page 6Linked to original sources

The preparation of stroma-free hemoglobin by selective DEAE-cellulose absorption.

The preparation of stroma-free hemoglobin by selective DEAE-cellulose absorption is reported. The stroma-free hemoglobin prepared by this method is compared to the product obtained by crystallization from sodium phosphate. Both show normal serum potassium, sodium, and pH values, and no coagulant activity or blood type activity by blood type test. PAA gradient gel electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and isoelectric focusing in polyacrylamide gel all show the same well-defined bands in both preparations. The DEAE procedure requires 11 h as compared to 4 days for the crystallization method. The recovery of hemoglobin is 77% (less than 1% methemoglobin) in the DEAE preparation compared to 34% (greater than 3% methemoglobin) by the crystallization method. In addition, far fewer expensive materials are required.

Absorption↗

Analogs of arachidonic acid methylated at C-7 and C-10 as inhibitors of leukotriene biosynthesis.

The syntheses and biological activity of (all Z)-7,7-dimethyl-5,8,11,14- eicosatetraenoic acid, (all Z)-7,7,-dimethyl-5,8,11-eicosatrienoic acid, (Z,Z)-7,7-dimethyl-5,8-eicosadienoic acid, (all Z)-10,10-dimethyl-5,8,11,14-eicosatetraenoic acid, (all Z)-10,10-dimethyl-5,8,11-eicosatrienoic acid, and rac.-(Z,Z)-15-hydroxy-7,7-dimethyl-5,8-eicosadienoic acid are described. These arachidonic acid analogs are all inhibitors of ionophore-induced SRS-A biosynthesis in rat peritoneal cells. Their mode of action may involve inhibition of phospholipase A2 rather than delta 5-lipoxygenase. These compounds failed to exhibit significant activity in an in vivo model designed to detect inhibitors of antigen-induced, leukotriene-mediated bronchoconstriction in sensitized guinea pigs.

Animals↗

Sensitivity of rat inferior olivary neurons to 3-acetylpyridine.

Climbing fiber deafferentation of the weanling rat was performed initially by means of intraperitoneal administration of 3-acetylpyridine (3-AP, 65 mg/kg). This dosage of 3-AP, which has been used routinely to achieve olivary ablations in the adult rat, is inappropriate for the total destruction of the inferior olivary complex in weanling rats (21-23 days). Examination of the inferior olivary complex at both the light and electron microscopic levels has revealed a consistent sparing of neurons within the nucleus beta, the genu of the principal nucleus and the caudal portion of the medial accessory olive following long-term (120 days) 3-AP treatment. Complete olivary ablations in weanling rats were obtained only after the injection of a higher dose of 3-AP (90 mg/kg). It would appear that immature inferior olivary neurons are less sensitive to the toxic effect of 3-AP but become increasingly susceptible to 3-AP with maturation. If the appropriate dosage of 3-AP is employed, however, it can be used reliably to produce a chemical ablation of the total climbing fiber input to the cerebellar cortex in weanling rats.

Animals↗

Cervical mucus peroxidase is a reliable indicator for ovulation in humans.

This study was designed to establish whether fluctuation in cervical mucus peroxidase concentration correlates with the cyclic pattern of the menstrual cycle hormones in the human female. Forty healthy, normal-cycling women between the ages of 19 and 29 years were chosen for the study. Blood samples and cervical mucus were collected on days 6, 9 through 15, and 17 through 19 of the menstrual cycle for three consecutive cycles in each volunteer. Blood estrogen, progesterone, follicle-stimulating hormone, and luteinizing hormone levels were quantitated by radioimmunoassay, and cervical mucus peroxidase concentrations were measured spectrophotometrically. The data showed that in the typical menstrual cycle the mucus peroxidase peak was reached immediately prior to the luteinizing hormone/follicle-stimulating hormone surge and coincided with the estrogen peak. Consistent data in three consecutive menstrual cycles in each volunteer led us to postulate that the mucus peroxidase peak during the menstrual cycle precedes the ovulatory period in the normal healthy woman.

Adult↗

Pediatric gastrointestinal foreign body ingestions.

One hundred twenty-five consecutive emergency department cases of pediatric gastrointestinal foreign body ingestions were analyzed retrospectively to tabulate data, identify high risk ingestions, and draw conclusions regarding the standard of care. Eleven patients (9%) were admitted for endoscopy or observation of high risk situations. Twenty patients (16%) were managed invasively, 19 with esophageal foreign bodies; 17 of 20 attempts at invasive management were successful. There was a 2% incidence of minor complications; no major complications (perforation, obstruction, bleeding, or mediastinal infection) or complications of invasive procedures were observed. High risk factors identified included the following: 1) the ingestion of rounded objects (esophageal impaction); 2) the presence of social, developmental, or psychiatric risk factors (29.6% incidence); and 3) esophageal disease (significantly associated with recurrent foreign bodies and frequent endoscopy or other surgical procedures). We conclude that, while asymptomatic gastric and intestinal foreign bodies can be managed with outpatient observation, hospitalization is indicated for endoscopic management and for symptom complexes suggestive of complication. Immediate endoscopy is recommended for removal of esophageal foreign bodies and for direct evaluation of the esophagus.

Adolescent↗

Similarities and differences in the ultrastructure of two hormone-dependent and one independent human breast carcinoma grown in athymic nude mice: comparison with the rat DMBA-induced tumor and normal secretory mammocytes.

The human breast cancer cell lines MCF-7 (ER positive), ZR 75-1 (ER positive) and MDA-MB 231 (ER negative) form solid tumors within one week following inoculation into athymic nude mice. Tumor formation by MCF-7 and ZR 75-1 cells was dependent upon estrogen, whereas MDA-MB 231 cells formed tumors in ovariectomized mice with or without supplemental estrogen. Ultrastructural comparison of tumors formed by the three human breast carcinoma lines in athymic nude mice indicated that lactoperoxidase activity, milk protein and fat globule formation were virtually absent from all three tumors. The estrogen-dependent tumors (MCF-7, ZR 75-1), however, had more desmosomes, intermediate-sized microfilaments and collagen than the estrogen-independent tumor (MDA-MB 231). When the ultrastructure of the three human tumors was compared to the hormone-dependent, DMBA-induced rat mammary carcinoma and to the normal lactating rat mammocytes, the following observations were evident: a) the estrogen-dependent human tumors closely resembled the normal rat tissue in the distribution of desmosomes and collagen, b) the rat mammary carcinoma differed from both the estrogen-dependent and -independent human tumors, in having milk protein, milk fat globules and intense lactoperoxidase activity. The results indicate that these hormone-dependent and -independent human mammary tumors maintained in athymic nude mice differ markedly in their ultrastructure from the lactating rat mammocytes and the rat DMBA-induced mammary carcinoma.

9,10-Dimethyl-1,2-benzanthracene↗

Analysis of the performance of pathologists in the grading of bladder tumors.

Fifty-seven transurethrally resected bladder tumors were analyzed to determine whether different pathologists, using the World Health Organization grading system, graded the same bladder tumor differently (interindividual consistency) and whether the same pathologist graded a bladder tumor differently at different times (intraindividual consistency). Disturbingly high inter- and intraindividual inconsistency in the grading of bladder tumors was found. All pathologists showed essentially the same degree of intraindividual inconsistency: In almost 50 per cent of cases the tumor was graded differently at different times by the same pathologist. The inconsistencies might invalidate the usefulness of bladder tumor grading in clinical decision-making.

Humans↗

Effect of high-dose estrogen on growth and steroid receptor activity in DMBA-induced mammary tumors and uteri of rats.

High doses of estrogen (5-500 micrograms) induce regression of hormone-dependent DMBA mammary tumors in rats at the same rate and degree as treatment with the antiestrogen C1628 (Parke-Davis). In contrast, high dose estrogen stimulated growth of uteri in tumor-bearing rats, while C1628 was antiuterotrophic. Within 72 h following treatment with estrogen, diethylstilbestrol (DES), or C1628, changes in the levels of estrogen receptor (ER) and progesterone receptor (PgR) were evident in both uterine and mammary tumor tissue. Both estrogen and antiestrogen induced depression of the total cytosolic ER and altered the 8S/4S receptor ratio. The tumor cytosolic ER levels of DES- and C1628-treated rats were 4.67 +/- 1.7 fmol/mg protein and 15.89 +/- 3.1 fmol/mg protein, respectively, compared to 48.89 +/- 13.6 fmol/mg protein in tumors of untreated rats. In spite of reduced levels of cytosolic ER, there was an apparent increase in the 8S/4S ratio (62% increase in 8S/4S ER ratio compared to control 8S/4S ratio; p less than 0.05). Total uterine cytosolic ER was low after treatments with DES (5.69 +/- 2.08 fmol/mg protein) or C1628 (94.76 fmol/mg +/- 30.3 fmol/mg protein), as compared to untreated controls (188.2 +/- 7.6 fmol/mg protein). The cytosolic PgR was consistently high in tumors of control rats (42.99 +/- 11.9 fmol/mg protein) and in castrated rats treated with high doses of DES or C1628 (DES, 55.15 +/- 27.0; C1628, 65.07 +/- 9.8 protein).

Animals↗

Quantitative cytochemistry of the diaminobenzidine cytochrome oxidase reaction product in mitochondria of cardiac muscle and pancreas.

The rate constant (k) of the cytochrome oxidase reaction under optimal conditions for cytochemical staining (i.e., 15 min fixation, incubation for 180 min for heart, 120 min for pancreas) can be used as a measure of the enzyme concentration within mitochondria. The rate constant derived from microdensitometric measurements of the mass thickness of the 3,3'-diaminobenzidine (DAB) cytochrome oxidase reaction in cristae times correlated data derived from morphometry on the surface density of cristae (SVcristae/Vmit micron-1) and the volume density of mitochondria per cell (Vmit/Vcell) has been used to determine the respiratory index (RI) of these tissues according to the following equation: RI = k(SVcristae/Vcell). Using this formula, the RI of cardiac muscle tissue was computed to be 33 times the RI of pancreas under the conditions of our experiments. The greater cristae surface density and the large mitochondrial volume density in cardiac muscle and high k value accounted for the higher RI of cardiac muscle.

3,3'-Diaminobenzidine↗

The significance of femoral fractures in children.

This study was undertaken to determine the clinical circumstances of femoral fractures in children. The study was a retrospective investigation of 117 consecutive patients with femoral fractures admitted to The Children's Mercy Hospital, Kansas City, Missouri, from December 1975 to September 1979. Of the 117 patients. 41 had associated injuries. No patient whose only injury consisted of a closed-single femur fracture had evidence of shock. Of 24 children under 2 years of age, 19 sustained injury in an abusive incident. Of 27 children 5 to 6 years of age, 18 sustained injury in an auto-pedestrian accident. Closed-single femur fractures in children do not produce shock. Children who are less than 2 years of age are likely to have sustained injury through abuse.

Accidents, Traffic↗

Some effects of glucagon on chick embryo development.

Glucagon concentrations ranging from 1.16 to 300-0 microgram/0.1 ml diluent were injected into the yolk of chick embryos on incubation days 8, 10, and 12. Studies of survival rates, embryo weights, blood sugars, liver and tibiotarsus glycogen histochemistry, and pancreatic alpha and beta tissue histogenesis were undertaken during the 9- to 16-day incubation period. Glucagon dosages of 37.5 and 150.0 microgram/0.1 ml diluent gave the best survival rates. Glucagon caused an increase in embryo weight, increased liver glycogen storage, a chondrocyte glycogen storage pattern which correlated with blood sugar levels, an increase in pancreatic beta tissue and a decrease in pancreatic alpha tissue. Studies of blood sugars following glucagon treatment showed that most concentrations caused an initial (first 16 h) hyperglycemia. Following this, two general patterns were exhibited: (1) the lower glucagon concentrations caused hypoglycemia after about 24 h, and (2) the higher concentrations caused amore prolonged hyperglycemia when administered on incubation day 10 but caused hypoglycemia when administered on incubation day 10 but caused hypoglycemia when administered on days 8 and 12. Interpretation of these results is based on the contribution of three factors to the expression and duration of the glucagon effect: (1) concentration of glucagon administered, (2) insulin secretion, and (3) levels of glycogen storage at the incubation stage of administration.

Animals↗

A light and electron microscopic study of the effects of 3-acetylpyridine intoxication on the inferior olivary complex and cerebellar cortex.

The effects of 3-acetylpyridine (3-AP) intoxication on the inferior olivary complex and cerebellar cortex of the rat were examined at both the light and electron microscopic level. Following intraperitoneal injection of 65 mg of 3-AP per kg body weight, the inferior olivary neurons were observed to undergo a rapid form of electron dense degeneration. A complete bilateral involvement of the nuclear complex was well advanced as early as 12 hours following injection. Marked astrocytic proliferation also occurred by 12 hours and appeared essential for neuronal fragmentation and disintegration. Microglial activity was prominent in the later stages, from 60 hours onwards, and participated in the phagocytic removal of degenerating neuronal fragments. By the end of the second week, all cytoplasmic and nuclear debri was removed. Concurrently, degenerative changes in the cerebellar cortex were evident from 12 hours onwards. All climbing fiber varicosities were observed to be degenerative as early as 24 hours following treatment. Electron microscopic observations revealed that these electron dense fragments were largely phagocytized and cleared by Bergmann glial cells around 7 days. The sensitivity of the olivocerebellar system to 3-AP thus provides a convenient and selective means of eliminating all of the inferior olivary neurons and their axons, the climbing fibers of the cerebellar cortex. In contrast to the more conventionally used electrolytic methods, 3-AP causes a complete bilateral ablation of all olivary neurons while avoiding the problems inherent to electrolytic procedures, such as incomplete destruction of the nucleus and involvement of fibers of passage.

Animals↗

Induction of prophage lambda by daunorubicin and derivatives correlation with antineoplastic activity.

The antineoplastic drug daunorubicin and 15 other anthracyclines were tested for their ability to induce prophage lambda in Escherichia coli K12. Prophage lambda induction by daunorubicin was obtained in excision-repair deficient uvr- bacteria at doses about 3-fold lower than in excision-repair proficient uvr+ cells; this suggests that some of the lesions produced in DNA by daunorubicin are subject to excision repair and may be adducts. Daunorubicin seems to be converted to active species capable of causing prophage inducing lesions in DNA by bacterial enzymes. The antineoplastic and prophage inducing potencies of the anthracyclines were compared in a blind test. These two parameters were correlated for two thirds of the compounds. Such a correlation supports the idea that the antineoplastic activity of the anthracyclines is a consequence of their capacity to damage DNA.

Antibiotics, Antineoplastic↗

Yeast, rye, and calf histones. Similarities and differences detected by electrophoretic and immunological methods.

Yeast histones H2A, H2B, and H3 were purified using the standard histone purification procedures of differential solubility and exclusion chromatography. Yeast histone H4 was isolated by the same methods in a fraction containing one other major protein component. The four yeast core histones were identified by their reactions with antisera against rye and (or) calf histone fractions as well as by their electrophoretic, chromatographic, and solubility properties. The immunological distances between yeast H2B and rye and calf H2B fractions are substantial, as is the rye-calf distance for H2B. The immunological distance between yeast H2A and rye H2A is also large and is similar to the rye H2A - calf H2A distance. On the other hand, the immunological distance between yeast H3 and rye and calf H3 is much greater than that between rye H3 and calf H3. These and other results indicate that yeast H3 differs appreciably from the H3 of higher eucaryotes.

Animals↗

Mammalian endogenous peroxidases as cellular markers and as biosynthetic endpoints of hormone-mediated activity: viewpoint from cytochemistry.

Aldehyde-resistant, diaminobenzidine-stained endogenous peroxidases form ideal markers for the biochemical endpoints of hormone stimulation and differentiation of certain mammalian cells and tissues. The lactoperoxidase (LPO)-type of endogenous peroxidases are synthesized by the acinar cells of the salivary, Harderian, lacrimal and mammary glands and are present in their secretions. These LPO-type enzymes, that are inhibited by cyanide and aminotriazole, appear to operate extracellularly as bactericidal agents in milk and in other biological fluids. In the mammary gland, lactoperoxidase is a consistent marker enzyme for differentiated acinar cells engaged in lactogenesis. Myeloperoxidase (MPO)-type endogenous peroxidases are prominent markers for the GERL endomembrane system and differentiated lysosomes in certain cells of the reticuloendothelial system and phagocytes. MPO is prominent within eosinophils, peritoneal macrophages and in Kupffer cells. The MPO-type endogenous peroxidases function primarily within lysosomes as bactericidal agents. Thyroid peroxidase (TPO) is relegated to the cisternae of the granular endoplasmic reticulum and Golgi apparatus, to apical cytoplasmic vesicles and to the luminar cell membrane surface of acinar cells. The enzyme is probably activated at release and functions both in the organification reaction (T leads to To) and in the biosynthesis of thyroxine. Thyroid stimulating hormone (TSH) appears to play a key role in the regulation of TPO levels and activity in the thyroid gland. Certain tissues displaying growth-dependency on estrogen (i.e., uterus, cervix, vagina and the DMBA-induced rat mammary tumor) synthesize and secrete endogenous peroxidase into their lumina. These enzymes serve as important marker proteins of estrogen action, in that they occur distal to the binding of estrogen to its receptor protein. Estrogen antagonists, particularly CI-628 (Parke-Davis) and Nafoxidine (Upjohn) that appear to function through the estrogen receptor mechanism, also induce synthesis of the reproductive tract endogenous peroxidase but inhibit growth of these tissues. Progesterone antagonizes the synthesis of the reproductive tract peroxidases and inhibits growth of the tissues as well, in part, through the reduction of the cytosol estrogen receptor protein. Endogenous peroxidase activity appears to represent a reliable marker for rodent breast cancer tissues displaying dependency for estrogen and is of potential interest as a diagnostic marker protein in human breast cancer. Rat uterine peroxidase (UP) has been investigated by microelectrophoretic techniques. The molecular weight of UP has been determined in the range of 100,000 by using polyacrylamide gradient gels in the absence and presence of nonionic and anionic detergents. The isoelectric point of UP is located between pH 4.5 and 5.9. Employing the two-dimensional combination of isoelectric focusing and gel gradient electrophoresis, UP was separated into two subunits, one having a molecular weight of 70,000, the other less than 20,000.

Animals↗

Reproductive tract peroxidases as endproducts of estrogen-specific gene expression.

Estrogen is an essential requirement for the postpubertal trophic development and maintenance of the differentiated state of the oviduct, uterus, cervix, vagina and mammary glands of mammals. Estrogen, apparently functioning through its specific cytoplasmic receptor protein via a multistep interaction pathway induces gene expression of specific biochemical events leading to growth and differentiation of target tissues (Jensen et al., Proc Natl Acad Sci, 59:632, 1968; Gorski et al., Recent Prog Horm Res 24:45, 1968). One biochemical expression of the estrogen gene is the synthesis of specific mRNA transcripts for certain specific marker proteins, including ovalbumin, lysozyme and ovomucoid in the chick oviduct (O'Malley and McGuire, Proc Natl Acad Sci 60:1527, 1968; Palmiter and Schimke, J Biol Chem 248:1502, 1973), tubulin in the mammalian oviduct (Brenner and Anderson, Handbook of Physiology 7(2):123, 1973; Brenner et al., Endocrinology 95:1094, 1974) and peroxidase (EC 1,11.1.7) in the rodent uterus (Brockelmann and Fawcett, Biol Reprod 1:59, 1969; Churg and Anderson, J Cell Biol 62:449, 1974; Anderson et al., J Cell Biol 64:668, 1975).

Animals↗