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C Stewart

Publications and source records attributed to C Stewart.

At least 163 records · Page 9Linked to original sources

Osteocalcin: characterization and regulated expression of the rat gene.

An osteocalcin gene was isolated from a rat genomic DNA library, and sequence analysis indicated that the mRNA is represented in 953 nucleotide segment of DNA consisting of 4 exons and 3 introns. Although the introns in the rat gene are larger, its overall organization is similar to the human gene. Analysis of the 5' flanking sequences of the rat gene shows a modular organization of the promotor as reflected by the the presence of at least 3 classes of regulatory elements. These include (1) typical sequences associated with most genes transcribed by RNA polymerase II (e.g. TATA, CAAT, AP1, AP2), (2) a series of consensus sequences for cyclic nucleotide responsive elements and several hormone receptor binding-sites (estrogen, thyroid and clusters of AG-rich putative Vitamin D responsive elements); and (3) a 24 nucleotide highly conserved sequence between the rat and human gene having a CAAT motif as a central element, designated as an "osteocalcin box." Two regulatory factors of osteocalcin gene expression have been identified. First, contained within the 600 nucleotides immediately upstream from the transcription initiation site are sequences which support Vitamin D dependent transcription of the rat osteocalcin gene. 1,25(OH)2D3 increases osteocalcin mRNA by 6-20 fold increases. In contrast, up to a 200 fold increase in osteocalcin gene expression occurs with mineralization of the extracellular matrix produced by osteoblasts. We propose osteocalcin is a bone-specific marker protein of the mature osteoblast in a mineralizing matrix.

Animals↗

Isolation of additional polymorphic clones from the cystic fibrosis region, using chromosome jumping from D7S8.

The cystic fibrosis (CF) locus has been located, by both linkage analysis and physical mapping, to a 900-kb region of 7q22-31 flanked by D7S8 (J3.11) and D7S23 (XV-2c). Using a 100-kb general jumping library, we isolated two sequential jump clones, J31 and J29, to one side of the D7S8 region and one jump clone, J32, to the other side of D7S8, so that the total region covered is about 300 kb. Three new RFLPs were detected by J29 and J32. Using PFGE mapping and the three jump clones, we found it possible to orient D7S8 on the chromosome and, by linkage analysis, to further narrow the CF region by 100 kb. The orientation of D7S8 will be useful for directing the isolation of other jump clones toward the CF locus. Though the newly described RFLPs are in considerable linkage disequilibrium with D7S8 polymorphisms, they increase the informativeness of genetic markers in the D7S8 region and should be useful in prenatal diagnosis.

Chromosomes, Human, Pair 7↗

The distribution of immunoreactive interferon-alpha in normal human tissues.

The cellular distribution of immunoreactive interferon-alpha (IFN-alpha) was studied in formalin-fixed paraffin-embedded normal human tissues from 36 different organs. These samples were drawn from over 300 individuals none of whom had evidence of viral infection. Tissue histiocytes from all organs in the body, with the exception of brain and renal cortex and medulla, stained positively for IFN-alpha. Kupffer cells, pulmonary alveolar macrophages and lymph node macrophages were also positive. Parenchymal cells in some other organs also appeared to contain immunoreactive IFN-alpha. These included cuboidal lining cells of the choroid plexus in the brain, thyroid follicular cells, pituitary endocrine cells, adrenocortical cells and parathyroid principal and oxyphil cells. These findings are compatible with previous suggestions that IFN-alpha may be synthesized and released in the absence of viral infection and may thus have a role in normal physiology. The presence of IFN-alpha in most cells of the mononuclear phagocyte system suggests that these cells may play a major part in defence against viral infection.

Endocrine Glands↗

Synthesis and immunoreactivity of neoglycoproteins containing the trisaccharide unit of phenolic glycolipid I of Mycobacterium leprae.

The trisaccharide segment, O-(3,6-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-O-(2,3-di-O-methyl- alpha-L-rhamnopyranosyl)-(1----2)-3-O-methyl-L-rhamnopyranose, of the Mycobacterium leprae-specific phenolic glycolipid I has been synthesized as its 8-(methoxycarbonyl)octyl glycoside and coupled to a carrier protein, to produce a leprosy-specific neoglycoprotein, the so-called natural trisaccharide-octyl-bovine serum albumin (NT-O-BSA). Special features of the synthetic strategy were the use of silver trifluoromethanesulfonate (triflate) to promote glycosylation, resulting in the rhamnobiose in high yield and absolute stereospecificity. The terminal 3,6-di-O-methyl-D-glucopyranosyl group was introduced after O-deallylation of the rhamnobiose. Removal of protecting groups yielded the trisaccharide hapten suitable for coupling to carrier protein. Poly(acrylamide)-gel electrophoresis of the neoglycoprotein demonstrated its purity, and subsequent immunoblotting with a monoclonal antibody directed to the terminal 3,6-di-O-methyl-beta-D-glucopyranosyl epitope of the native glycolipid demonstrated its antigenicity. Comparative serological testing in enzyme-linked immunosorbent assays of NT-O-BSA, the corresponding disaccharide-containing products, and another trisaccharide-containing neoglycoprotein, O-(3,6-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-O-(2,3-di-O- methyl-alpha-L-rhamnopyranosyl)-(1----2)-(3-O-methyl-alpha-L-rhamnopy ran osyl)- (1----4')-oxy-(3-phenylpropanoyl)-BSA (NT-P-BSA) [Fujiwara et al., Agric. Biol. Chem., 51 (1987) 2539-2547] against sera from leprosy patients and control populations showed concordance; the presence of the innermost sugar did not contribute significantly to sensitivity or specificity. The di- and tri-saccharide-containing neoantigens, on account of ready availability and solubility, provide greater flexibility than the native glycolipid for the serodiagnosis of leprosy.

Antigens, Bacterial↗

Familial risk of cancer among randomly selected cancer probands.

Several investigators have reported that relatives of lung cancer probands have a greater-than-normal likelihood for developing some form of cancer. To evaluate whether this familial risk is general for probands with cancer at any site or limited to lung cancer probands, we did a case-control study in which probands having cancer affecting any body site were identified and their pedigree data were tabulated. Telephone interviews and a mailed questionnaire were used to obtain cancer histories and environmental exposures on the families of 41 lung cancer probands, 105 probands with cancer other than lung, and 127 spouse families. Cumulative tobacco exposure (P less than .05), occupational hazards (P less than .005), and age of the family relatives (P less than .0001) were found to be statistically significant predictors of cancer risk. With consideration given for these variables, we determined that siblings of lung cancer probands were at slightly greater risk of cancer of any kind (odds ratio [OR] = 1.43, P = .06) than siblings in the control group. Much of the elevated risk was attributable to an excess of lung cancer (OR = 2.49, P = .06). Siblings of non-lung/non-breast cancer probands were also determined to be at increased risk of lung cancer as well (OR = 1.61, P = .06). For parents, the risk was lower, although parental information may have been underreported.

Family↗

Experimental drug therapy of peritumoral brain edema.

Four drugs with potential anti-peritumoral brain edema activity were studied using the VX2 rabbit brain tumor model. Meclofenamate and indomethacin were tested in an attempt to confirm recent reports of anti-edema activity in non steroidal anti-inflammatory drugs (NSAID's). The 'angiostatic' steroids 17 hydroxyprogesterone and epicortisol were tested because of their lack of glucocorticoid and mineralocorticoid effects and their structural similarity to glucocorticoids. The protein and water component of brain edema were indirectly quantitated. None of the test drugs demonstrated significant anti-edema activity. This work does not confirm reports that NSAID's have anti-edema activity and suggests that there may be no correlation between 'angiostatic' and anti-edema activity in certain steroid compounds.

17-alpha-Hydroxyprogesterone↗

Magnetic resonance imaging for monitoring relapse of acute myeloid leukemia.

Magnetic resonance provides a non-invasive tool for monitoring normal and leukemic bone marrow. Measurements of the T1 relaxation times are elevated in acute myelogenous leukemia. However, interpatient variability diminishes the usefulness of MR measurements for diagnosing leukemia. In following the time course of individual patients, T1 relaxation time measurements appear to give an early and sensitive indication of leukemic relapse after remission and this may serve a clinical role in the management of leukemia by reducing the regularity of necessary marrow aspirates and biopsies.

Bone Marrow↗

Further experience in the healing rate of lower limb amputations.

Results of lower limb amputation in the Tayside Region in the years 1981-1985 have been analysed. Three-hundred and twenty-four amputations were performed on three-hundred and eight patients. Two-hundred and thirty-six amputations were attempted at the below-knee level. Only 19 required proximal revision. Prior to amputation, all patients should have a detailed vascular assessment, and the operation should be performed by experienced amputation surgeons using meticulous technique.

Adult↗

Immunological significance of Mycobacterium leprae cell walls.

Cell walls of Mycobacterium leprae, prepared by differential solvent extraction, were shown to contain arabinogalactan, mycolates, and peptidoglycan. In addition, amino acid analysis revealed the unexpected presence of large amounts of protein that retained potent immunological reactivity. Purified cell walls stimulated proliferation of T cells from tuberculoid, but not from lepromatous leprosy, patients and elicited delayed-type hypersensitivity skin reactions in guinea pigs and patients sensitized to M. leprae. Analysis of the precursor frequency of antigen-reactive human peripheral T cells revealed that as many cells (approximately equal to 1/6000) proliferate to antigen contained in cell walls as to intact M. leprae. Sequential removal of mycolates and arabinogalactan resulted in a large peptidoglycan-protein complex that retained all the immunological activity. This immunological reactivity and the inherent protein were destroyed by proteolysis. Thus, cell wall protein is a major contributor to cell-mediated immune reactivity to this pathogenic mycobacterium.

Amino Acids↗

Vaccination as a possible means of preventing lantana poisoning.

The toxic triterpene acids lantadene A and lantadene B were isolated from Lantana camara and conjugated to bovine serum albumen or haemocyanin. The conjugates were emulsified with complete Freund's adjuvant and injected into sheep and cattle. Vaccinated animals produced antibodies against the toxic compounds. Cholestasis was less severe in vaccinated than in non-vaccinated sheep challenged with a toxic dose of lantana. The results indicated a mild protective effect of vaccination against the hepatotoxic effects of lantana toxins.

Animals↗

Prostatitis.

Prostatitis is a poorly defined group of syndromes with multiple causes, some of which are not yet determined. Although treatment of acute prostatitis is well defined and almost uniformly successful, chronic prostatitis, either of bacterial or undetermined etiology, remains a perplexing problem in both diagnosis and treatment. Identification of the etiologic agent of chronic "nonbacterial" prostatitis, if one exists, has not yet been accomplished. Undoubtedly, more than one organism may be responsible for these cases. Treatment is ineffective for a high percentage of patients with chronic prostatitis, both from proven bacterial and nonbacterial causes. Few drugs penetrate the prostatic tissues well, and few of those that do have an appropriate antimicrobial spectrum. An excellent, or even adequate, antibiotic for chronic prostatic infections has yet to be developed. Prostatodynia remains as a "wastebasket" syndrome of miscellaneous pains, aches, and pelvic discomforts. With this collection of symptoms, no easy approach to diagnosis or treatment is possible. Only when more detailed diagnosis has been developed can one hope for better therapy of this condition.

Bacterial Infections↗

Nephrolithiasis.

The management of the patient presenting to the Emergency Department with nephrolithiasis or renal colic should include evaluation of the patient for concurrent diseases, risk factors for stone formation, and possible etiologies for stones. Suspicion of ureterolithiasis is based on a cogent history and physical examination and reinforced by a finding of hematuria. Diagnosis should be based upon a promptly performed intravenous pyelogram, unless the patient is truly allergic to contrast media or has substantial risk of a contrast-induced renal failure. A solitary flat plate of the abdomen adds no useful information and is an unnecessary expense to the patient. Essential laboratory data include a urinalysis, CBC, and electrolyte, BUN, creatinine, and serum calcium levels. A urine culture should be obtained in all patients because urinalysis alone may not be sufficient to exlude a urinary tract infection. Initial treatment of the patient with an uncomplicated renal colic should include hydration, relief of pain, and reassurance. Evaluation by a consultant may be done as an outpatient on a nonemergent basis. If the colic has not resolved after 72 hours, hospitalization generally is recommended. If the patient has vomiting, dehydration, a complete obstruction, or a solitary kidney, hospitalization in indicated and urgent consultation recommended. If the patient has fever or other signs of infection, emergent consultation and immediate hospitalization are essential. Retained obstructing stones are generally managed by urologic consultants. It is in the care of the patient with the retained stone that greatest advances have been made in the past 10 years. Patients should be counseled that the retained stone no longer calls for extended hospitalization and convalescence.

Colic↗

Teratocarcinoma stem cells and early mouse embryos contain only a single major lamin polypeptide closely resembling lamin B.

The nuclear lamina in adult mammalian somatic cells is composed of three major proteins, lamins A, B, and C. The expression of these proteins during the differentiation of teratocarcinomas and mouse embryogenesis is described. Embryos up to day 8 of gestation and embryonal carcinoma (EC) cells express only a single lamin species closely resembling, if not identical to, lamin B. Lamins A and/or C were detected in fertilized eggs, but disappear during the first 2-4 cleavage divisions, only reappearing in 8 day post-implantation embryos. These two lamins are absent from EC cells, but are strongly expressed in some of their derivatives. These results show that cells of the early mouse embryo do not have a functional requirement for lamins A and C and imply that the structural organization of the nucleus may change fundamentally during embryogenesis.

Animals↗

Fate of the vascular patient after below-knee amputation.

50 below-knee amputations were carried out in 45 patients (25 men and 20 women), mean (SD) age 73 (10.5) years. The mean survival time was 22(16) months after the operation. In each patient the healing potential of a below-knee amputation was determined preoperatively by segmental pressure studies and thermographic delineation of skin perfusion. 33 of the stumps healed by first intention, in 14 healing was delayed but occurred without the need for further surgery, and 3 stumps healed after local wedge excision. The initial mobilisation rate was 90%. Thus, there are no grounds for carrying out an initial above-knee amputation to save the patient a further operation.

Aged↗