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Biomedical subjects

J M Osborne

Publications and source records attributed to J M Osborne.

9 recordsLinked to original sources

Insulin-like growth factor-I levels and gene expression in ovine hereditary chondrodysplasia (spider lamb syndrome).

Hereditary Chondrodysplasia or Spider Lamb Syndrome (SLS) is an inherited, semi-lethal, musculo-skeletal disease affecting lambs primarily of Suffolk or Hampshire breeding. Deformities of the limbs and spinal column along with multiple sites of ossification at the anconeal process are diagnostic for the disease. Muscle atrophy is also predominant. We have investigated the relationship between SLS and circulating levels of IGF-I and the IGF-BPs in older (50-80 d of age) animals. Serum IGF-I levels were lower (P less than 0.01) in SLS affected lambs (117 ng/ml) than in phenotypically normal lambs (188 ng/ml) while serum levels of the 32 kDa BP increased (P less than 0.01) 77% in SLS affected lambs as compared to contemporary controls. All other IGF-BPs appeared to be unaffected in this group. Gene expression of IGF-I and -II in the liver and muscle of younger (16-22 d of age) lambs was also measured. There were no differences in IGF-II expression in either muscle or liver between SLS affected and phenotypically normal control lambs. Muscle IGF-I expression also did not differ. However, liver IGF-I expression in SLS affected lambs was nearly double that of control lambs (P less than 0.01). These data suggest that the regulation of IGF-I and the IGF-BPs may be involved in the physical manifestations of this disorder.

3-Hydroxybutyric Acid

Ultrastructural studies of the reaction of urate crystals with a cultured renal tubular cell line.

Hypotheses concerning the development of uric acid and gouty nephropathy suggest that the initiating disease mechanism involves an interaction between uric acid or monosodium urate monohydrate (MSUM) crystals and renal tubular epithelial cells. We have studied the interaction of these crystals with Madin-Darby canine kidney (MDCK) cells, which exhibit many of the characteristics of cells of the collecting duct epithelium. Addition of MSUM crystals to monolayer cultures of MDCK cells leads to the formation of reaction sites, localised areas which are raised above the monolayer forming a 3-dimensional structure. These reaction sites are evident within 4-8 h and appear to be initiated by the interaction of a single crystal or small number of crystals with a single cell. With time, both cells and crystals accumulate at the site. By 24 h most reaction sites involve 6-12 cells and numerous crystals. Interaction of MSUM crystals and MDCK cells not only involves the attachment of crystals to cells but, by 8 h, some crystals appear to be completely or partially covered by the cell membrane, and MDCK cells appear to react by growing around the crystals. Transmission electron microscopy shows that crystals are found not only within cells, but also within the intercellular spaces. Within the cells, crystals have been shown in vacuoles containing lysosomal enzymes, indicating the formation of a phagolysosome. Ultimately, enzyme release occurs. These studies support the hypothesis that some interstitial deposits of urate and uric acid in the kidney may be derived from intratubular deposits that react with the tubular epithelium and pass into the interstitium; loss of tubular integrity may not be a prerequisite for crystal migration.

Animals

Effect of weaning at different ages on serum insulin-like growth factor I (IGF-I), IGF binding proteins and serum in vitro mitogenic activity in swine.

We investigated the effects of weaning or fasting of 21- or 35-d-old swine by monitoring serum mitogenic activity, circulating insulin-like growth factor I (IGF-I) and its binding proteins using L6 myoblast bioassays, RIA and ligand blotting techniques. Serum samples were collected from 21- or 35-d-old animals just before and 36 h after weaning or fasting. Sera from 21- and 35-d-old weaned animals were not significantly altered in their ability to promote myoblast proliferation, whereas sera from 21- and 35-d-old fasted animals caused 29 and 21% decreases (P less than .05) compared with preweaning. The mitogenic activity of control serum was inhibited by serum from fasted animals but not by preweaned or weaned sera. Serum IGF-I levels were decreased 65 to 70% (P less than .05) with weaning or fasting at both ages. Unoccupied binding sites on circulating IGF binding proteins in the 155 kDa range decreased 18 to 19% with weaning at both ages and decreased 40% (P less than .05) with fasting at 21 d but only 17% at 35 d. Ligand blotting revealed that the 43 and 39 kDa IGF binding protein bands decreased with weaning and fasting at both ages, whereas the 29-kDa band increased with weaning and fasting. These data indicate that serum IGF-I and specific IGF binding protein bands decrease during weaning or fasting at 21 and 35 d of age. However, serum mitogenic activity did not always follow serum IGF-I levels.

Age Factors

The abnormal mammogram--what to do.

When an abnormality is detected in a mammogram the following questions should be answered: 1. Does a significant abnormality exist, that is, is the abnormality present in at least two views? 2. Should special imaging techniques, such as ultrasound, be used? 3. What is the conclusion of the radiologist? 4. Is the radiological abnormality clinically palpable? 5. Is the opinion of a breast specialist required? 6. Can fine needle aspirations cytology of the area be performed accurately and without trauma? 7. Should biopsy be undertaken? By posing these questions in sequence and obtaining firm answers, small cancers should not be missed and the biopsy rate will be kept to an acceptably low level.

Biopsy

Reaction of MDCK cells to crystals of monosodium urate monohydrate and uric acid.

Madin-Darby canine kidney (MDCK) cells exhibit many of the characteristics of cells of the cortical collecting tubule. Since hypotheses concerning the development of gouty and uric acid nephropathy involve a reaction between such cells and crystals, either of monosodium urate monohydrate (MSUM) or uric acid, the reaction between MDCK cells in culture and the above crystals was studied, both morphologically and functionally. In monolayer cultures, reaction sites developed within four hours of exposure to urate crystals. These increased in number for up to 72 hours and subsided gradually after removal of the crystals. At these reaction sites, crystals were observed to have passed beneath the cell surface and could be demonstrated both within intra-cellular lysosomes as well as within the inter-cellular spaces. When the MDCK cells were maintained as single cells in suspension, phagocytosis of crystals by the majority of the cells could be observed, but the response was much more rapid than in monolayers. During the cell/crystal reaction, significant amounts of lysosomal enzymes and prostaglandin E2 were released and, to a less significant degree, cytosolic enzymes, presumably due to cell lysis. This enzyme release did not occur in MDCK cells grown in protein-free medium, and protein coating of the crystals was necessary for reactivity with cells. In this regard, coating with IgG or lysozyme was more effective than albumin. The reaction with uric acid crystals revealed a reactivity which was lesser in degree but qualitatively similar to that of urate crystals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Evaluation of the mammographic lesion.

Radiologists have all too often been vague about mammographic problems presenting on films. Their reports are often too equivocal. However, with a thorough mammographic evaluation, most lesions can be classified as benign, malignant or spurious. We have listed thirteen positions, apart from the routine craniocaudal and oblique views, that may help decide the malignant potential of a mammographic problem.

Breast Neoplasms

Scimitar etcetera--the dysmorphic right lung.

'Dysmorphic lung' is introduced as a term to describe any complex congenital malformation which involves both abnormal vascular morphology and disordered growth of a whole lung. The major group within this definition is the scimitar syndrome, which we choose to mean a hypoplastic lung with anomalous venous drainage and various degrees of collateral arterial supply. Nine typical cases of scimitar are presented, with three closely related cases. Six other cases of dysmorphic lungs are also present. The relationships between the groups are discussed, and an effort is made to clarify the nomenclature used in this condition.

Humans

Expression of 20-alpha-hydroxysteroid dehydrogenase in mouse macrophages, hemopoietic cells, and cell lines and its induction by colony-stimulating factors.

The enzyme 20-alpha-hydroxysteroid dehydrogenase (20 alpha SDH) has been proposed as a T lymphocyte marker that is specifically induced by interleukin 3. We have examined the expression of 20 alpha SDH and its relationship to interleukin 3 responsiveness in other hemopoietic lineages. The enzyme is expressed at high levels in the bone marrow of athymic nu/nu mice, but only at low levels in nu/nu spleen and normal adult bone marrow. 20 alpha SDH is induced in nu/nu spleen and in normal fetal liver cells by granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as by interleukin 3. In longer term cultures of fetal liver and adult marrow, macrophage colony-stimulating factor (M-CSF) also induces the enzyme, which is expressed in proliferating adherent macrophages. The high levels of 20 alpha SDH in purified bone marrow-derived macrophages are maintained by M-CSF, GM-CSF, or interleukin 3. Expression of 20 alpha SDH in these cells is associated with resistance to growth inhibition by progesterone. Additional evidence against the restriction of 20 alpha SDH to T lymphocytes is found in its presence in peritoneal macrophages, myelomonocytic and macrophage-like cell lines, and the L929 fibrosarcoma line. We conclude that 20 alpha SDH is a normal enzyme of proliferating hemopoietic cells irrespective of their lineage or growth factor responsiveness.

20-Hydroxysteroid Dehydrogenases