Biomedical subjects
Publications and source records attributed to G E Moore.
Supravalvular aortic stenosis (SVAS) may occur as an isolated autosomal dominant trait or as a feature of Williams syndrome. It has been suggested that a defect in calcitonin function may play a role in Williams syndrome. We have excluded calcitonin as a candidate gene for SVAS using a gene specific probe.
We examined cardiac troponin T (TnT) isoform expression in rabbit left ventricular myocardium at three different stages of postnatal development. Using sodium dodecyl sulfate gel electrophoresis (PAGE), we resolved five isoforms: TnT1, TnT2, TnT3, TnT4, and TnT5. TnT1 had the slowest electrophoretic mobility and TnT5 the fastest. The predominant isoforms were TnT2, TnT3, and TnT4. The relative amounts of TnT2, TnT3, TnT4, and TnT5 were examined in myocardium from three age-groups: 3 days (Group 1), 21-22 days (Group 2), and 99-109 days (Group 3). The amount of TnT2 relative to the total amount of TnT (determined by the ratio of the areas under the densitometric curves) decreased significantly (p less than 0.01) with age from 42 +/- 4% in Group 1 to 25 +/- 3% in Group 3. In contrast, the relative amount of TnT4 increased with age from 23 +/- 2% in Group 1 to 33 +/- 4% in Group 3 (p less than 0.01). The relative amounts of the other two isoforms change biphasically with development: TnT3 decreased from Group 1 to Group 2 and increased from Group 2 to Group 3. TnT5, a minor isoform, increased from Group 1 to Group 2 and decreased from Group 2 to Group 3. These developmental changes in troponin T expression may account for some of the maturational changes observed in the physiological and biochemical properties of the myocardium.
The distribution of troponin T (TnT) species in typed single muscle fibres was analysed using one- and two-dimensional polyacrylamide gel electrophoresis (PAGE) and a monoclonal antibody specific for fast TnT. Fibres taken from erector spinae (Es), plantaris (Plt), diaphragm (Dia) and soleus (Sol) muscles of adult rabbits were pretyped as fast-twitch-glycolytic (FG), fast-twitch-oxidative-glycolytic (FOG), slow-twitch-oxidative (SO) or promiscuous (P) using a combination of histochemical staining and PAGE. Although none of the four size classes of TnT was either muscle or fibre type specific, their pattern of expression differed in each muscle and between the fibre types. FG fibres expressed TnT1f or TnT2f as predominant species, depending on the muscle; TnT3f and TnT4f were minor components. In contrast, all size classes of TnT were expressed in varying proportions in FOG fibres from Es and Plt, while those from Dia resembled FG fibres, expressing TnT1f as their major species. P fibres from Es, Plt, and Sol exhibited a distinctive pattern of fast TnT expression, TnT3f being the predominant species. Dia differed from the other muscles as TnT1f was the dominant fast TnT species in its P fibres as it is in the Dia fast fibres. Quantitative analysis of one- and two-dimensional gels revealed that the P fibres could be divided into two classes, those that exhibited discoordinate expression of fast and slow TnTs, myosin light chains and myosin heavy chains and those in which their expression was coordinate. In addition low levels of TnT4f were detected in SO fibres and of slow TnT in fast fibres.
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The pathologic changes in myotonic dystrophy (DM) skeletal muscle biopsies have been analyzed at both the histochemical and molecular level. A histochemical stain for pretyping single fibers in conjunction with sodium dodecyl sulphate-polyacrylamide gel electrophoresis allowed biochemical differences to be pinpointed in specific histochemical fiber types. These biochemical differences can be related to histochemical changes in fiber type observed in cross-section of the DM biopsies. Such changes included specific fiber type atrophy, hypertrophy, and disproportion. The pathogenesis of DM appears to be characterized by a large increase in the number of promiscuous fibers, that is, those fibers that express both fast and slow myosins. This promiscuity, which is rare in control muscle (less than 2%), is also prevalent at high levels in some family members at risk for DM. The observed promiscuity, although probably not a primary effect of DM, appears to be linked to the histochemical changes in fiber type observed in the DM biopsies.
Traumatic bilateral renal artery thrombosis is rare, and attempts to reestablish life-sustaining renal function have had dismal results. This case describes a successful outcome of such an injury, the gradual return of adequate renal function without surgical intervention. This experience raises an argument against both strict limitation of the acceptable time interval between injury and revascularization, and early nephrectomy.
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Extramedullary plasmacytoma of the parotid gland is an extremely rare lesion of which there have been only four other reported cases. The importance of these lesions rests in the possibility of their being a harbinger of multiple myeloma or their subsequent transformation to multiple myeloma. Because of its extreme rarity, the proper management remains unclear.
The relationship between histochemical fibre type and contractile protein expression was analysed in three rabbit skeletal muscles, the erector spinae, the plantaris and the diaphragm. A procedure for staining fibre bundles was developed using the same histochemical methods as those for typing fibres in cross-section. This allowed pretyped fibres to be selected and their molecular composition to be analysed by gel electrophoresis. The balance of expression of the two predominant fast troponin species, TnT1f and TnT2f, and alpha and beta tropomyosin subunits were studied in type IIA and IIB fast fibres. Type IIA fibres exhibited a restricted pattern of thin filament expression, exhibited TnT1f and both tropomyosin subunits in all three muscles. The expression in type IIB fibres, however, ranges from predominantly TnT2f and the alpha tropomyosin subunit in the erector spinae to TnT1f with both alpha and beta subunits in the diaphragm. These results indicate that there is not a simple one-to-one relationship between the fast muscle fibre subtypes and the expression of different thin filament protein isoforms.
The effects of reduced activity (immobilisation) on the development of the contractile enzyme, Mg2+-activated myofibrillar ATPase was studied in a tonic muscle, the anterior latissimus dorsi and in a phasic muscle, the posterior latissimus dorsi of the chicken. Mg2+-activated myofibrillar ATPase activity showed a decreased and delayed activity peak in both the immobilised muscles. Large differences between the two muscles were observed using this marker enzyme. These data indicate that the activity of Mg2+-activated myofibrillar ATPase and the associated differential gene expression involved in fibre type differentiation are influenced by the early activity pattern of the muscles.
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Citrate synthase and malate dehydrogenase bind to mitochondrial membrane preparations obtained from various species of animals and lemon fruit. The amount of enzyme bound per mg mitochondrial protein was comparable in all tissues studied. The effect of various substrates, products, and substrate analogs on citrate synthase binding to rat liver mitochondrial inner membrane was examined. OAA was the most effective inhibitor of binding followed by AcCoA , CoA, citrate, ATP, and MgATP. Neither D- nor L- malate were effective in blocking binding. The wide distribution of binding of citrate synthase and malate dehydrogenase to the inner membrane and specificity of substrate effects on the binding of citrate synthase are discussed in relation to the possible physiologic nature of these phenomena.
This review was undertaken to analyze critically the complications resulting from operative splenic salvage. Over a 6 year period, 200 adults who sustained splenic trauma underwent laparotomy. The mechanism of injury was blunt in 138 patients (69 percent), a stab wound in 32 patients (16 percent), and a gunshot wound in 30 patients (15 percent). Splenorrhaphy was accomplished in 85 patients (42 percent). Methods of repair included cautery and hemostatic agents in 24 patients (28 percent), debridement and suturing in 42 patients (50 percent), and partial resection in 19 patients (22 percent). Six patients died, four from head trauma and two from multiple organ failure. Postoperative complications occurred in 14 patients. Four were intraabdominal. Three patients required reoperation for splenic hemorrhage; one (2 percent) after suture repair and two (11 percent) after partial resection. A left subphrenic abscess developed in another patient. Splenic reimplantation was performed in 43 patients (22 percent). Five deaths occurred. One was due to head trauma, three to multiple organ failure, and one to overwhelming pneumococcal infection. Eleven postoperative complications occurred, but none was related to splenic autotransplantation. Despite the enthusiasm for splenic salvage, the number of patients suitable for splenorrhaphy plateaued at 56 percent. Complications of splenorrhaphy are infrequent, and the risk increases with more complex salvage attempts. We believe that splenic reimplantation remains a safe procedure.
The metabolic and contractile activity of muscle was determined in immature cockerels made hypothyroid by surgical thyroidectomy at 6 weeks of age. Four weeks after thyroidectomy the activity of Mg2+-activated myofibrillar ATPase and total phosphorylase was reduced in the fast-phasic, posterior latissimus dorsi (PLD) and scapulotriceps (ST) muscles. The activities of these enzymes were unaffected in the slow-tonic, anterior latissimus dorsi (ALD) muscle. Thyroidectomy had no effect on length of the muscles studied but reduced the weight of the ALD and ST muscles. These results suggest that hypothyroidism results in a "slowing down" of fast-phasic muscles, although it does not affect the activity of slow-tonic muscles.
The amine precursor uptake and decarboxylation (APUD) system of cells has been claimed to derive from the embryological neural crest. This assertion has been uncritically accepted. There is much contradictory evidence, especially about the origin of the gastrointestinal and respiratory APUD cells. There is further evidence that the embryological derivation of a particular cell does not relate to the possibility of ectopic peptide hormone synthesis by malignant tumours arising from that cell type. There are many reports of APUD activity by endodermally and mesodermally derived tumours, and of "APUDomas" with endodermal microscopic features. It seems that the concept of dedifferentiation explains the observed data much more satisfactorily and that the presence of double minute chromosomes may denote gene amplification and cellular production of peptides.
Cellular immunoadsorbents were employed to isolate xenogeneic antibodies that reacted with a restricted group of antigens on human melanoma cells. Melanoma cells and autologous lymphoid cells were grown in tissue culture. Cellular immunoadsorbents were prepared by coupling formalin-treated melanoma and lymphoid cells to diethylaminoethyl cellulose. Rabbits were immunized with melanoma cells and antisera were passed sequentially through immunoadsorbents made of fetal bovine serum, and lymphoid cells. Unbound effluents were then passed through an immunoadsorbent prepared with melanoma cells. Antibodies binding to melanoma cells were eluted and their reactivity to melanoma-derived antigens was tested using a solid-phase radioimmunoassay. Antigens for this assay were NP-40 lysates of melanoma and lymphoid cells and fetal bovine serum. Radioactive Staphylococcal protein A was used to detect binding by the antibodies to the test antigens. The effects of formalin-fixation and storage of melanoma and lymphoid cells were studied. Storage of fixed melanoma cells for periods up to 4 months did not affect their capacity to bind antibodies. A single exposure of formalin-fixed cells to a low-pH elution buffer which was followed by neutralization did not affect binding by these cells. Antibodies isolated in this manner were of the IgG class and reacted with antigens derived from melanoma cells but not from autologous lymphocytes or fetal bovine serum. This study demonstrated the feasibility of using cellular immunoadsorbents to prepare xenogeneic polyclonal antibodies with a high degree of reactivity to antigens derived from human melanoma cells.