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Biomedical subjects

D C Anderson

Publications and source records attributed to D C Anderson.

At least 379 records · Page 21Linked to original sources
PubMed1986

Effects of physiological concentrations of parathyroid hormone on acid phosphatase activity in cultured rat bone cells.

The mechanism by which parathyroid hormone (PTH) induces osteoclastic bone resorption is still incompletely understood. Recent evidence suggests that the hormone exerts its effects indirectly, via the osteoblasts. Bone cells isolated from fetal rat calvaria by enzymatic digestion were used. Two heterogeneous cell populations were isolated by equilibrium density centrifugation on Percoll gradients and maintained by differential culture conditions. These two populations, which are morphologically distinguishable from one another by light and electron microscopy, have been characterized previously both biochemically and with regard to their hormonal (PTH and calcitonin) responses. We have called them type C cells (containing cells with some of the properties of osteoclasts) and type B cells (containing osteoblast-like cells, as well as fibroblasts, chondrocytes and other stromal cells). In the present study, we have further characterized the functional relationship between the two cell populations, with particular regard to the hormonal responses of type C cultures. Acid phosphatase, measured cytochemically in individual cells, was used as a marker for C cell responses. C cells had significantly higher levels of acid phosphatase activity than either B cells or spleen macrophages. Calcitonin (0-10 pg/ml) decreased C cell acid phosphatase activity but was without effect on B cells or spleen macrophages. Co-culture of C cells with B cells produced increased enzyme activity only in the former; this effect could be mimicked if fibroblasts replaced B cells and cell contact was essential for this response. PTH (0-10 pg/ml) raised enzyme activity further in C cells only when they were cultured with B cells. When C cells were cultured so that they shared medium, but were not in contact, with B cells, PTH (2 pg/ml) still increased enzyme activity in the former. Fibroblasts were ineffective in this system. Spleen macrophages were also unresponsive to PTH when substituted for C cells. Calcitonin (10 pg/ml) blocked the effects of PTH on C cells. These results indicate that macrophages are probably not a significant proportion of the C cell population, and that PTH may produce increased acid phosphatase activity in C cells via a humoral factor produced by cells present in B cell cultures.

Acid Phosphatase↗
PubMed1986

Heterosis among closed lines of Hereford cattle. III. Postweaning growth and carcass traits in steers.

Feedlot and carcass characteristics of 276 steers from five closed lines of Hereford cattle and reciprocal crosses among these lines were studied. The traits studied were initial weight, final weight, 224-d gain, days on test, hot carcass weight, marbling score, longissimus muscle area, fat thickness, yield grade, dressing percentage and shear force. Year of record was a significant source of variation for most traits. Age of dam was a significant source of variation for growth traits but not carcass traits. Line of sire affected initial weight, final weight, 224-d gain, days on test, marbling score and dressing percentage. Significant heterosis was observed only for hot carcass weight. Heterosis estimates were 1.9% for initial weight, 2.2% for final weight, 2.5% for 224-d gain, -2.1% for days on test, .6% for hot carcass weight, -.6% for marbling score, 0 for carcass grade, .6% for longissimus muscle area, 2.3% for backfat thickness, .9% for yield grade, -.9% for dressing percent and -10.9% for shear force. Initial age on test affected only hot carcass weight. Hot carcass weight, dressing percentage, marbling score, longissimus muscle area and fat thickness were affected by slaughter weight. Slaughter age affected dressing percent and marbling score.

Animals↗
PubMed1986

Leukocyte complement receptors and adhesion proteins in the inflammatory response: insights from an experiment of nature.

The complement receptor type 3 (CR3) mediates phagocytosis and degradation of iC3b-opsonized particles by macrophages and granulocytes. The CR3 is identical to the Mac-1 molecule, which is composed of two non-covalently associated glycoprotein subunits, alpha M of Mr 170,000 and beta of Mr 95,000. Patients with recurring, life-threatening bacterial infections have been identified who have moderate (95%) or severe (greater than 99%) deficiency of Mac-1 and of the related LFA-1 and p150,95 molecules. The primary defect is in the shared beta subunit of these molecules. Patient leukocytes are not only deficient in CR3 but in a wide variety of adhesion-dependent functions, including granulocyte chemotaxis, adherence to surfaces, and aggregation. Monoclonal antibodies to the Mac-1 alpha subunit and to the beta subunit block these functions. The hypothesis will be advanced that Mac-1 functions dually as the CR3 and in 'nonspecific' adherence reactions. Adherence functions are stimulated in normal granulocytes by chemoattractants, which also induce a rapid 5-fold increase in Mac-1 and p150,95 on the cell surface. It is proposed that absence of Mac-1 and p150,95 expression and upregulation by patient granulocytes is causally related to their inability to extravasate and migrate into inflammatory sites.

Adult↗
PubMed1986

p150,95, the third member of the Mac-1, LFA-1 human leukocyte adhesion glycoprotein family.

Monoclonal antibodies specific for p150,95, a third member of the Mac-1 and lymphocyte function-associated antigen-1 (LFA-1) leukocyte adhesion protein family, have been identified and used to study the biochemistry and cellular expression of p150,95. p150,95 is a noncovalently associated heterodimer containing alpha X and beta subunits of Mr = 150,000 and 95,000 respectively. Findings suggest that the p150,95 alpha X beta complex shares a common beta subunit with the alpha L beta LFA-1 and alpha M beta Mac-1 complexes. Co-precipitation experiments demonstrated identity between the p150,95 molecule precipitated by anti-beta MAb and by p150,95-specific MAb. Patients with a previously demonstrated genetic deficiency in Mac-1 and LFA-1 fail to express p150,95. Deficiency of the Mac-1, LFA-1, and p150,95 alpha beta complexes on the surface of patient cells appears due to a defect in the common beta subunit. The lack of cross-reaction of p150,95-specific MAb with LFA-1 and Mac-1, which appear to utilize identical beta subunits, suggests that the determinant is specified by the alpha X rather than the beta subunit of p150,95. The data suggest that alpha X is yet a third member of a family of alpha subunit proteins that associate with a common beta subunit, are differentially regulated in leukocyte differentiation, and function in adhesion reactions. p150,95 is normally expressed on blood monocytes and granulocytes. Chemoattractants such as f-Met-Leu-Phe stimulate a rapid, fivefold increase in surface expression that is not dependent on protein synthesis and appears to reflect mobilization of an intracellular latent pool. The intimate relation between the lack of chemoattractant-stimulated upregulation of p150,95 and Mac-1 by patient granulocytes and their failure to upregulate adhesiveness to these same stimuli in vitro, or to diapedese and migrate into inflammatory sites in vivo, is discussed.

Antibodies, Monoclonal↗
PubMed1985

Past pets and Paget's disease.

There is strong morphological evidence that Paget's disease is caused by a chronic focal paramyxovirus infection of osteoclasts, but the source of this virus and the reason for the wide variation in the incidence of the disease are unknown. The infection may be a zoonosis, with a domestic animal as the usual host. Past exposure to pets was studied in 50 patients with Paget's disease and 50 age and sex matched control subjects with diabetes mellitus. Dog ownership was significantly more common in the patients than in the control subjects (odds ratios at different ages varied between 4 and 8). 44 of the Paget's patients and 30 of the control subjects had had dogs before diagnosis of Paget's disease (or the equivalent age in the control subjects). Exposure to domestic cats was identical in both groups (26 each), and there was no significant difference in exposure to budgerigars. This suggests that a canine virus (possibly canine distemper) might be the primary infective agent, although other factors probably contribute to the particularly high incidence in the North West of England.

Aged↗
PubMed1985

Prediction of carotid disease by ultrasound and digital subtraction angiography.

Ultrasound (US) technology (B-mode real-time imaging and Doppler signal analysis) and digital subtraction angiography (DSAV) were prospectively compared in 90 consecutive patients. Twenty-four endarterectomy specimens became available. The DSAV was uninterpretable in 9.4% of vessels and US, in 8.3%. Estimation of degree of stenosis by both modalities agreed well with endarterectomy specimens. Neither predicted the presence or absence of ulceration accurately. Not considering occlusions (where DSAV is probably more accurate), no clear superiority as a screening test compared against a common standard was demonstrated for either. In all 148 vessels with adequate studies by both, the technologies agreed in categorizing stenosis (less than or equal to 50% v greater than 50% diameter stenosis) in 89%. Correlation was poor for occlusions and ulceration. If DSAV were definitive, US would be an effective screen for surgically relevant stenosis with a negative predictive value of 95%.

Aged↗
PubMed1985

Study of the effect of estradiol on gonadotrophin levels in untreated male-to-female transsexuals.

This project was an attempt to test Dörner's theory that aspects of gender identity and sexual behavior depend on a defect in a normal imprinting mechanism of testicular testosterone (T) on the male hypothalamus. It has been suggested that such an action by T is incomplete in male-to-female transsexuals and that in this disorder the hypothalamus retains a cyclic pattern of gonadotrophin secretion and a positive feedback response to estrogens, such as is seen in the normal female. Five untreated male-to-female transsexuals and five normal male controls were each given 2 mg IM of estradiol, and T, estradiol, LH, and FSH globulin was measured serially over the following five days. No significant differences were found in the gonadotrophin or any of the other hormone responses in the transsexuals compared to normal controls. If there is a defect in imprinting of the hypothalamus in transsexual men, it does not seem to affect the basal levels of gonadotrophins or the pattern of their response to estrogen, at least in the intact male.

Adult↗
PubMed1985

Some characteristics of human adrenal microsomal 21-hydroxylase activity.

The following general characteristics of 21-hydroxylase activity were determined using pooled microsomes obtained from three glands. Enzyme activity exhibited a broad pH dependence, being optimal between pH 7.4-pH 7.8, and was maximal with NADPH in the range 2 to 4.75 X 10(-4)mol/l. No microsomal 21-hydroxylase activity was detected in the absence of NADPH or substrate and when heat denatured microsomes were employed. Enzyme activity was depressed by greater than 75% in the presence of 100% oxygen or nitrogen. In a second set of experiments, microsomal fractions were prepared individually from 7 glands. In the presence of 17 alpha-hydroxy progesterone (2.0 X 10(-7) and 2.0 X 10(-6)mol/l) product formation was linear with time for up to 90 s when the microsomal protein concentration was 5, 10 and 20 micrograms/ml. Between 5 and 30% of the substrate was converted during the first 60 s. In 5/7 of the glands the addition of the autologous cytosol (20 micrograms protein/ml) was without effect, and enzyme activity (using a 60 s reaction and either 2.0 X 10(-7) or 2 X 10(-6)mol/l 17 alpha-hydroxy progesterone was directly proportional to the microsomal protein concentration (range 0-20 micrograms/ml). With the other 2 adrenals 21-hydroxylation was not proportional to the same range of microsomal protein concentrations, although it became so upon the addition of cytosol, which significantly augmented activity. There was considerable variation in enzyme activity between glands from different individuals (Vmax ranging from 2.6 to 16.6 X 10(-9) mol/min/mg protein) and in the apparent Km's (from 0.22 to 1.1 X 10(-6)mol/l). In the two preparations sensitive to cytosol, the Vmax increased 2-fold, and the Km was 3 times lower. Cytosol was without effect upon the kinetic characteristics of the other 5 microsomal preparations. Ascorbic acid (1 X 10(-3) mol/l) depressed enzyme activity by 25-43% whereas oxidised and reduced glutathione (1 X 10(-3) mol/l) showed a slight and variable effect upon 21-hydroxylation.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Wastage and disease in Bay of Plenty dairy herds.

Information on disease incidence and herd wastage was collected from 36 farms supplying the Rangitaiki Plains Dairy Company over a two-year period from June 1981 to May 1983. These herds contained 7050 milking cows and 1460 yearlings. Although 33.5% of calves horn were reared, only 21.7% entered the herd. The average wastage rate over the two seasons was 22.6%. This included a 2.5% death-rate. Main reasons for culling were infertility (6.3%), low production (3.7%) and mastitis (2.3%). Only 0.8% of cows died or were culled because of bloat and 0.4% from each of facial eczema and metabolic diseases. Treatments were administered by farmers or veterinarians to 18.8% of the cows for mastitis, to 3.9% for metabolic diseases and to 3.6% for lameness. In total, 34.6% of cows received treatment for disease. Wide differences were noted in the proportion of cases of different diseases for which veterinarians were consulted. These ranged from 83.6% for scours to 3.8% for mastitis. As well as confirming or quantifying the relative importance of various diseases and causes of wastage, the survey highlighted the problems in collecting reliable data from herd owners on the events in their herds.

Journal Article↗
PubMed1985

Immune globulin for intravenous use: enhancement of in vitro opsonophagocytic activity of neonatal serum.

Neonates born with less-than-protective levels of transplacentally derived specific antibody are at risk for the development of disease due to type III, group B Streptococcus (III-GBS). The effect of immune serum globulin modified for intravenous use (MISG) on in vitro opsonophagocytosis of III-GBS was evaluated. Cord blood was obtained from 13 healthy, full-term neonates, and bactericidal activity for III-GBS was measured. Before the addition of MISG, one of three serum specimens with moderate levels of antibody to III-GBS, and eight of 10 specimens with low antibody levels demonstrated no bactericidal activity. The mean bactericidal index increased from 27.1% before the addition of MISG to 96.5% with MISG added in a volume equal to that of serum. The effect of MISG on opsonophagocytosis decreased with its dilution in buffer, and no effect was shown at dilutions greater than or equal to 1:4. Thus, MISG can substantially increase in vitro opsonophagocytosis of III-GBS in sera from newborns.

Antibodies, Bacterial↗
PubMed1985

The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features.

An inherited syndrome characterized by recurrent or progressive necrotic soft-tissue infections, diminished pus formation, impaired wound healing, granulocytosis, and/or delayed umbilical cord severance was recognized in four male and four female patients. As shown with subunit-specific monoclonal antibodies in immunofluorescence flow cytometry and 125I immunoprecipitation techniques, in addition to a NaB3H4-galactose oxidase labeling assay, granulocytes, monocytes, or lymphocytes from these individuals had a "moderate" or "severe" deficiency of Mac-1, LFA-1, or p150,95 (or a combination)--three structurally related "adhesive" surface glycoproteins. Two distinct phenotypes were defined on the basis of the quantity of antigen expressed. Three patients with severe deficiency and four patients with moderate deficiency expressed less than 0.3% and 2.5%-31% of normal amounts of these molecules on granulocyte surfaces, respectively. The severity of clinical infectious complications among these patients was directly related to the degree of glycoprotein deficiency. More profound abnormalities of tissue leukocyte mobilization, granulocyte-directed migration, hyperadherence, phagocytosis of iC3b-opsonized particles, and complement- or antibody-dependent cytotoxicity were found in individuals with severe, as compared with moderate, deficiency. It is proposed that in vivo abnormalities of leukocyte mobilization reflect the critical roles of Mac-1 glycoproteins in adhesive events required for endothelial margination and tissue exudation. The recognition of phenotypic variation among patients with Mac-1, LFA-1 deficiency may be important with respect to therapeutic strategies.

Adolescent↗
PubMed1985

Serum steroid binding proteins and the bioavailability of estradiol in relation to breast diseases.

Serum concentrations of sex hormone binding globulin (SHBG), corticosteroid binding globulin (CBG), and albumin were found to be normal in women with breast cancer (Ca), with benign breast disease (BBD), or with a family history of breast cancer (FHCa). Comparisons between serum steroid binding capacities and immunoassayable SHBG and CBG concentrations did not reveal abnormal forms of either protein. The serum distribution of estradiol (E2) was also determined, and women with Ca were found to have a significantly (P less than .025) higher mean percentage of non-protein-bound E2 than matched controls, but the difference was very small. In general, women with Ca also had proportionately more (P less than .05) albumin-bound E2 and less (P less than .05) SHBG-bound E2 in their sera than the controls, but the serum distributions of E2 in the BBD and FHCa subjects were the same as in controls. The dissociation rates of 5 alpha-dihydrotestosterone and E2 from SHBG in serum appear to increase with time in frozen serum samples, and this factor may effect measurements of the distribution of these steroids in serum.

Aged↗
PubMed1985

The assessment of ovulation by a combination of ultrasound and detailed serial hormone profiles in 35 women with long-standing unexplained infertility.

We have examined for the presence of subtle hormonal abnormalities in women with long-standing unexplained infertility. For a full cycle serum LH, FSH, progesterone and oestradiol levels were measured about three times a week, and serial ultrasound scans of the ovaries made until the time of apparent ovulation. The results on 45 cycles in 35 women with unexplained infertility and in three normal volunteers are presented. Normal ovulatory cycles were defined by a length of 26-32 d, and progressive follicular maturation followed by disappearance or abrupt reduction in size of a follicle within 48 h of the recorded LH peak, followed by progressive and sustained rise in serum progesterone levels to more than 25 nmol/l and a luteal phase length of greater than or equal to 13 d. Thirty spontaneous cycles (28 women) were clearly normal while 15 spontaneous cycles (12 women) were abnormal. Abnormalities included luteinization of an unruptured follicle (eight cycles), absence of follicular development (two cycles), poor follicular development (two cycles), persistence of a large ovarian cyst from the preceeding cycle (two cycles) and one aluteal cycle. Six of the abnormal cycles were characterized hormonally by inappropriate elevation of serum LH levels throughout. If this study had been based only on serial ultrasound scans, all results on abnormal cycles might have been misinterpreted. If it had been conducted only with (multiple) progesterone determinations and the level of greater than 25 nmol/l had been taken as indicative of ovulation nine clearly abnormal cycles would have been considered as normal. We conclude that the combination of the hormonal and ultrasound assessment of ovulation increases our confidence for confirmation of normality and reveals various ovulatory disorders which are possibly due to an endocrinological defect or defects.

Adult↗
PubMed1985

The treatment of hirsutism with a combination of desogestrel and ethinyl oestradiol.

Some available oral contraceptive agents are unsuitable for the treatment of hirsutism since, although they suppress endogenous gonadotrophins and so ovarian androgen production, they contain a progestogen which is itself androgenic. The combination of 30 micrograms ethinyl oestradiol (EE2) and 150 micrograms desogestrel (Marvelon) does not suffer from this drawback. We have therefore assessed its value in 15 hirsute women treated for one year. Mean +/- SE androgen-dependent hair growth, assessed photographically fell from 0.31 +/- 0.01 to 0.23 +/- 0.01 mm/d at 1 year (P less than 0.001). Ten of the fifteen patients reported definite subjective improvement. Treatment was associated with a marked rise in SHBG concentration identical to that seen with 30 micrograms EE2 alone. By four months there were significant falls in serum levels of androstenedione and LH throughout the cycle, but not for testosterone, dihydrotestosterone or 5 alpha-androstane 3 alpha, beta 17 -diol. Calculated free testosterone levels were significantly suppressed. All the biochemical changes were maintained after seven months of treatment. We conclude that this preparation is a suitable oral contraceptive for the treatment of hirsute women.

Adolescent↗