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Biomedical subjects

W L Dunn

Publications and source records attributed to W L Dunn.

At least 55 records · Page 3Linked to original sources
PubMed1984

Studies of the degraded carrageenan-induced colitis of rabbits. I. Changes in the epithelial glycoprotein O-acylated sialic acids associated with ulceration.

Ulceration of the large intestine, induced in New Zealand white rabbits by the administration of 1% w/v degraded carrageenan for periods of up to nine weeks, was studied by a combination of histochemical and chemical procedures for the identification of O-acylated sialic acid. The onset of the disease was rapid, visible faecal blood being observed within five days. Caecal ulceration was diffuse throughout the mucosa being more prominent and frequent on the transverse folds. In some cases large, discrete ulcers were observed in the rectal portion of the lower colon, while in a small number of cases there were ulcers at the caecal end of the upper colon. The ulceration was characterized by oedema, congestion, haemorrhage, inflammation and mucosal ulceration. The inflammatory exudate consisted of macrophages, lymphocytes, a few plasma cells and, in animals treated for a long period, aggregates of eosinophils. The ulceration was associated with a marked reduction in the proportion of the caecal epithelial glycoprotein sialic acids which were neuraminidase-resistant and/or substituted in the side chain. Histochemical studies indicated that changes in side chain substitution were more marked at the margins of the ulcers and could be observed in sections of colon that showed no evidence of ulceration.

Animals↗
PubMed1984

Studies of the degraded carrageenan-induced colitis of rabbits. II. Changes in the epithelial glycoprotein O-acylated sialic acids associated with the induction and healing phases.

Rabbits fed freely with a 1% aqueous solution of degraded carrageenan developed a progressive colitis characterized after five days by severe inflammation and mucosal ulceration of the caecum. Histochemical and chemical studies indicated that there was a marked reduction in intracellular mucin and in the proportion of the epithelial glycoprotein sialic acids with substituents in the side chain and at position C4. Changes in the O-acylated sialic acids occurred rapidly and, apparently, prior to either mucosal ulceration or a significant inflammatory response. Following the removal of carrageenan from the diet, there was evidence of progressive healing characterized by re- epitheliazation and a reduction in the inflammatory response until, at 12 days, the mucosa was comparatively normal. Healing was accompanied by an apparent increase in intracellular mucin and in the proportion of the epithelial glycoprotein sialic acids with substituents in the side chain and at position C4. Animals sacrificed 20 days after withdrawal of the carrageenan showed a renewal of ulceration characterized by an active inflammatory process, congestion, haemorrhage, and an inflammatory exudate consisting of a massive aggregation of eosinophils together with lymphocytes and plasma cells. This was accompanied by a reduction in the proportion of side chain and C4 substituted sialic acids.

Animals↗
PubMed1984

Assessment of bone mineral. Part 2.

A number of different techniques are available to study bone mineral. Those based on radiographs are helpful as an initial approach to the symptomatic patient with advanced disease, but they do not have the sensitivity to detect early bone loss, to assist in the estimation of fracture risk, or to monitor effects of treatment in controlled drug studies. A radiograph of the spine and hip, however, should be the first step before other tests are ordered. Photon absorptiometry methods or CT-based tests are currently most attractive as second-line approaches. Of these, photon absorptiometry is more widely tested clinically and allows studies of predominantly cortical or trabecular bone sites and total skeletal calcium. Although all of this cannot be done reliably with one instrument under routine laboratory conditions at present, it may well become possible in the near future. Of the CT-based procedures, the forearm scanner is very attractive because of its high precision and accuracy and the fact that it allows measurement of trabecular bone only. The technique is restricted to the forearm and may not be versatile enough for modern clinical requirements. A similar comment may be applicable to neutron-activation techniques of the hand, forearm, or spine. Low-level counting and the handling of neutron sources are not widely known techniques in many laboratories, and this will restrict their use in clinical practice. At this time there is no optimal technique available for mass screening for early osteoporosis. Dual-photon absorptiometry of the spine has been in use in our institution as the method of choice in selected patients for early detection of osteoporosis. However, for screening purposes the radius is still a very attractive bone to measure. At the currently used measuring sites, however, it does not have the sensitivity required to indicate spinal bone loss. Perhaps measurements closer to the distal end, where the trabecular-to-cortical bone ratios approach that in the spine, could be more sensitive. The difficulty of relocating the arm for photon absorptiometry can perhaps be solved for photon absorptiometry, or may be resolved by CT of the forearm. Correlation of the extreme distal radius with the spine is necessary to answer this question.

Activation Analysis↗
PubMed1983

Use of secretin in the roentgenologic and biochemical diagnosis of duodenal gastrinoma.

The use of secretin in the biochemical and roentgenologic diagnoses of a duodenal gastrinoma has been described. Preoperatively, the secretin test indicated that a gastrinoma and not a retained antrum was the cause of hypergastrinemia in a patient who had previously undergone Billroth II gastrectomy. Intravenous infusion of secretin during selective angiography resulted in greatly enhanced visualization of the tumor which allowed it to be localized to the duodenal stump. Several months postoperatively, the secretin test result had become negative, which presumably suggested that the tumor had been excised completely. Our experience has revealed that intravenous secretin might improve the diagnostic usefulness of selective angiography.

Aged↗
PubMed1983

Noninvasive bone mineral measurements.

Single and dual photon absorptiometry are now available to aid the physician in diagnosis and management of generalized bone diseases. Both methods are reviewed in detail. They allow an accurate and reproducible assessment of bone mineral at predominantly cortical (appendicular skeleton) and trabecular (axial skeleton) bone sites. Newer findings show that cortical and trabecular bone behave differently and that the effect of endocrine dysfunction on bone appears to be both disease and site specific. These qualitative and quantitative differences in cortical and trabecular bone loss require that an optimal sampling site has to be found for a given bone problem if maximum benefit is to be derived from these tests.

Adult↗
PubMed1983

Removal of O-acetylated sialic acids from rat colonic epithelial glycoproteins by cell-free extracts of rat faeces.

Sterile, cell-free, extracts of freshly defaecated Wistar rat faeces in a pH 7.0 "minimal medium" contain neuraminidase(s), capable of removing sialic acids both with and without side-chain substituents from bovine submandibular mucin and rat colonic epithelial glycoproteins, and an esterase which removes O-acetyl substituents from the side chain of sialic acid residues. Studies of the removal of sialic acids from bovine submandibular mucin and rat colonic epithelial glycoproteins indicated that (i) the faecal enzymes removed a greater proportion of the sialic acid of both the de-O-acetylated and native glycoproteins than was removed with Vibrio cholera neuraminidase, (ii) sialic acids were removed more rapidly from de-O-acetylated glycoproteins, and (iii) the resistance to removal of sialic acids was apparently dependent at least in part upon the O-acetyl sialic acid content of the substrate.

Acetylation↗
PubMed1982

Changes in bone mineral density of the proximal femur and spine with aging. Differences between the postmenopausal and senile osteoporosis syndromes.

We measured bone mineral density (BMD) of the proximal femur, lumbar spine, or both by dual photon absorptiometry in 205 normal volunteers (123 women and 82 men; age range 20 to 92 yr) and in 31 patients with hip fractures (26 women and 5 men; mean age, 78 yr). For normal women, the regression of BMD on age was negative and linear at each site; overall decrease during life was 58% in the femoral neck, 53% in the intertrochanteric region of the femur, and 42% in the lumbar spine. For normal men, the age regression was linear also; the rate of decrease in BMD was two-thirds of that in women for femoral neck and intertrochanteric femur but was only one-fourth of that in women for lumbar spine. This difference may explain why the female/male ratio is 2:1 for hip fractures but 8:1 for vertebral fractures. The standard deviation (Z-score) from the sex-specific age-adjusted normal mean in 26 women with hip fracture averaged -0.31 (P < 0.05) for the femoral neck, -0.53 (P < 0.01) for the intertrochanteric femur, and +0.24 (NS) for the lumbar spine; results were similar for 5 men with hip fractures. By contrast, for 27 additional women, ages 51-65 yr, with only nontraumatic vertebral fractures, the Z-score was -1.92 (P < 0.001) for the lumbar spine. Thus, contrary to the view that osteoporosis is a single age-related entity, our data suggest the existence of two distinct syndromes. One form, "postmenopausal osteoporosis," is characterized by excessive and disproportionate trabecular bone loss, involves a small subset of women in the early postmenopausal period, and is associated mainly with vertebral fractures. The other form, "senile osteoporosis," is characterized by proportionate loss of both cortical and trabecular bone, involves essentially the entire population of aging women and, to a lesser extent, aging men, and is associated with hip fractures or vertebral fractures or both.

Adult↗
PubMed1981

Elevation of brain GABA content by chronic low-dosage administration of hydrazine, a metabolite of isoniazid.

When gamma-aminobutyric acid aminotransferase (GABA-T) activity was measured in vitro in rat brain, neither isoniazid (INH) nor for of its known metabolites (isonicotinic acid, acetylisoniazid, acetylhydrazine, diacetylhydrazine) inhibited the enzyme in concentrations (5 mM) far higher than those likely to be achieved when INH is administered to man. In contrast, hydrazine (5 micrometers) caused a 50% inhibition of GABA-T without inhibiting glutamic acid decarboxylase (GAD). Rats were injected daily for 109 days with hydrazine (0.08 or 0.16 mmol/kg/day), after which amino acid contents and enzyme activities were measured in their brains. Both hydrazine doses caused significant elevations of whole brain GABA content and reductions of GABA-T activity, but did not affect GAD activity. Chronic administration of hydrazine at these doses did not reduce weight gain or alter rat behavior, nor did it produce any irreversible pathologic changes in liver or alterations in hepatic aryl hydrocarbon hydroxylase activity. However, hydrazine treatment caused changes in the contents of many brain amino acids besides GABA, and markedly increased concentrations of ornithine, tyrosine, and alpha-aminoadipic acid in rat plasma. Inhibition of GABA-T activity and the other biochemical alterations observed in patients given high doses of INH probably result from hydrazine formed in the metabolic degradation of INH. Thus administration of hydrazine might be a more direct means of elevating brain GABA content in patients where this seems indicated, and might not entail a greater risk of adverse effects.

4-Aminobutyrate Transaminase↗
PubMed1981

Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis.

Patterns of bone loss in the axial and the appendicular skeleton were studied in 185 normal volunteers (105 women and 82 men; age range, 20--89 yr) and in 76 women and 9 men with vertebral fractures due to osteoporosis. Bone mineral density was measured in vivo at the lumbar spine (predominantly trabecular bone) by dual photon absorptiometry and at the midradius (greater than 95% cortical bone) and distal radius (75% cortical and 25% trabecular bone) by single photon absorptiometry. In normal women, bone diminution from the vertebrae began in young adulthood and was linear. In the appendicular skeleton, bone diminution did not occur until age 50 yr, was accelerated from aged 51 to 65 yr, and then decelerated somewhat after age 65 yr. Overall bone diminution throughout life was 47% for the vertebrae, 30% for the midradius, and 39% for the distal radius. In normal men, vertebral and appendicular bone diminution with aging was minimal or insignificant. Mean bone mineral density was lower in patients with osteoporosis than in age- and sex-matched normal subjects at all three scanning sites, although spinal measurements discriminated best; however, there was considerable overlap. By age 65 yr, half of the normal women (and by age 85 yr, virtually all of them) had vertebral bone mineral density values below the 90th percentile of women with vertebral fractures and, thus, might be considered to have asymptomatic osteoporosis. For men, the degree of overlap was less. The data suggest that disproportionate loss of trabecular bone from the axial skeleton is a distinguishing characteristic of spinal osteoporosis.

Adult↗
PubMed1980

Measurement of bone mineral content in human vertebrae and hip by dual photon absorptiometry.

An instrument for clinical measurement of bone mineral content in the axial skeleton was constructed. Components include a modified dual probe scanner, a PDP-11 computer, a 153Gd source, and a NaTI) detector. The results were accurate and highly reproducible, and distinction of osteoporotic women from normal age-matched women was superior to that accomplished with single photon absorptiometry in the radius.

Adult↗
PubMed1980

Differences between the O-acetylated sialic acids of the epithelial mucins of human colonic tumors and normal controls: a correlative chemical and histochemical study.

Chemical analyses, together with histochemical assessments, were carried out on specimens of adenocarcinoma of the colon and histologically normal colonic epithelium (from resection margins from cases of carcinoma of the colon). In the epithelial glycoproteins of the normal tissue, both chemical and histochemical investigations indicated that the great majority of the sialic acids contained a side-chain O-acyl substituent located at position C8, whereas the side-chain substitution of the sialic acids of tumor glycoproteins was markedly reduced. Chemical analysis of the normal glycoproteins indicated that the great majority of the sialic acids were resistant to digestion with Vibrio cholerae neuraminidase, presumably due to an ester substituent at C4. The sialic acids of the tumor glycoproteins were significantly different from normal, in that they were less resistant to digestion with neuraminidase (p greater than 0.01), and therefore had a lower percentage of substitution at C4 (p greater than 0.01).

Adenocarcinoma↗
PubMed1979

A histochemical comparison of the O-acylated sialic acids of the epithelial mucins in ulcerative colitis, Crohn's disease, and normal controls.

Two histochemical techniques, the PAT/KOH/PAS and the PBT/KOH/PAS, were used to investigate the side chain O-acyl substitution patterns of the sialic acids of the colonic epithelial mucins in cases of ulcerative colitis and Crohn's disease. In both diseases there was, as compared to normal, a reduction in the proportion of sialic acids O-acylated at C7C8, the reduction being greater in ulcerative colitis. Further, there appeared to be an association between the severity of the disease and the reduction in the staining of O-acylated sialic acids. This relationship was more marked in ulcerative colitis. In some cases of both diseases there was evidence for epithelial mucins containing predominantly C7-substituted sialic acids. This study has confirmed our previous conclusion that, in Crohn's disease of the terminal ileum, the disease is associated with an increase in the proportion of sialic acids bearing side chain substituents.

Colitis, Ulcerative↗
PubMed1978

A correlative chemical and histochemical study of the O-acetylated sialic acids of human colonic epithelial glycoproteins in formalin fixed paraffin embedded tissues.

Procedures are described for the isolation and identification of epithelial glycoproteins from formalin fixed, paraffin embedded specimens of human large intestine. The side chain O-acetylation patterns of the sialic acids of these glycoproteins were surprisingly similar to those of purified glycoproteins prepared from epithelial cells obtained from the same tissue before fixation. These results were consistent with those obtained by histochemical procedures performed on representative sections taken from the same tissue blocks. The methodology described permits a direct correlation of chemical and histochemical results obtained from the study of colonic epithelial glycoproteins of both normal and diseased tissues. It eliminates some of the difficulties associated with interpretation of the results by either discipline and may provide new information which would be unavailable by either chemistry or histochemistry alone.

Acetylation↗
PubMed1978

A histochemical method for the identification of 9-O-acyl sialic acid. An investigation of bovine submaxillary gland and intestinal mucins.

Prolongation of the initial periodate oxidation step of the periodate-borohydride technique/potassium hydroxide/periodic acid-Schiff and periodic acid-Thionin Schiff/potassium hydroxide/periodic acid-Schiff sequences produced little or no change in the diagnostic staining for the potassium hydroxide/periodic acid-Schiff effect, exhibited by the colonic epithelial mucins of man and rat and the Brunner's gland mucin of rabbits. In contrast, there was a gradual, but clear decrease in the intensity of such staining of bovine submaxillary gland mucins. It was concluded that, in the intestinal mucins studied the potassium hydroxide/periodic acid-Schiff effect was due to sialic acids bearing O-acyl substitutents at positions C7 and/or C8 whereas in bovine submaxillary gland mucin the potassium hydroxide/periodic acid-Schiff effect is probably due, at least in part, to the presence of 9-O-acyl sialic acids. This investigation has led to the development of a technique which can be used to identify 9-O-acyl sialic acids.

Animals↗