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Biomedical subjects

C Allen

Publications and source records attributed to C Allen.

At least 55 records · Page 3Linked to original sources

The interaction between Pseudomonas aeruginosa and the corneal epithelium. An electron microscopic study.

The interaction between Pseudomonas aeruginosa and the rabbit corneal epithelium during the first hour after inoculation was studied using scanning and transmission electron microscopy. Fifteen minutes after inoculation, adherent bacteria were found on damaged or exposed basal epithelial cells at the edge of an epithelial defect, and this adherence was the result of an interaction between the bacterial and epithelial cell membranes. Thirty minutes after inoculation, the adherent bacteria began to penetrate the epithelial cells by the formation of "pockets" surrounding the organisms, and after an additional 15 minutes the bacteria further penetrated the cells as the pockets began to fill in with cellular material. One hour after inoculation, only rare bacteria were seen on the cell surfaces or within the margins of the epithelial defect. Transmission electron microscopy, however, revealed many intracellular bacteria or bacteria that had migrated between the basal epithelium and corneal stroma. Therefore, it appears that the initiating events in Pseudomonas corneal ulceration involve adherence to the damaged or exposed basal epithelial cells by an interaction between the bacterial and cellular membranes, after which the organisms are engulfed by the epithelial cell and reach the corneal stroma by a process of transcellular migration.

Adhesiveness

Prevalence and clinical associations of intraocular pressure changes in Graves' disease.

We investigated an unselected series of 55 patients with treated or untreated hyperthyroid Graves' disease, assessing their clinical and laboratory status and ophthalmological findings, including the difference in intraocular pressure (dIOP) between upgaze and straight gaze using applanation tonometry. An increased dIOP (greater than 2 mm Hg) was detected in only 22% of Graves' patients [who had a mean dIOP of 3.5 +/- 1.6 (+/- SEM) mm Hg]. dIOP did not correlate with age, sex, age at disease onset, duration of disease, mode of antithyroid treatment, or thyroid function testing at the time of examination. Mean Hertel exophthalmometry measurements in patients with a dIOP greater than 2 mm Hg were 22.0 +/- 2.9 mm compared with 18.4 +/- 3.7 mm in those with a dIOP less than 2 mm Hg (P less than 0.027, by Wilcoxon rank sum test). Only 58% of patients with increased dIOP had clinical exophthalmos, but all had other evidence of Graves' eye disease. Computed tomographic scanning revealed significant proptosis and/or orbital muscle involvement in all of the patients with increased dIOP.

Adult

Ancrod: normalization of fibrinolytic enzyme abnormalities in patients with systemic lupus erythematosus and lupus nephritis.

Ancrod is a thrombinlike enzyme from Malayan pit viper (Agkistrodon rhodostoma) venom that has a selective enzyme substrate specificity for fibrinogen. Unlike thrombin, it splits only fibrinopeptide A from the fibrinogen molecule and does not activate factor XIII. Simultaneously with the occurrence of hypofibrinogenemia there is a reduction of plasma plasminogen and a rise in fibrin degradation products, suggesting secondary recruitment of the fibrinolytic enzyme system. Ancrod was given to 18 patients with systemic lupus erythematosus and glomerular and vascular microthrombi. Before treatment vascular plasminogen activator (VPA) was low or unmeasurable in 14, an inhibitor of urokinase-induced plasminogen activation (IPA) was elevated in 18, and an inhibitor of plasmin (PI) was elevated in five. Ancrod treatment resulted in prompt normalization of IPA levels in 13 patients; they were classified as fibrinolysis responders. In five patients IPA levels remained elevated throughout treatment with ancrod; they were classified as fibrinolysis nonresponders. In these five the PI level was elevated before treatment and decreased slowly toward the normal range during ancrod administration. The PI did not appear related to the nonspecific serine protease inhibitors, and was shown to be identical with alpha 2-antiplasmin. In the fibrinolysis responders serial histologic studies showed a striking decrease of disappearance of microvascular thrombosis; in the fibrinolysis nonresponders microvascular thrombosis persisted. The action of ancrod is discussed.

Adult

Features of synovial membrane identified with monoclonal antibodies.

As part of a study of the characteristics of the synovial membrane which make it susceptible to inflammatory reactions, we tested a number of monoclonal antibodies (MoAb) which revealed novel features of the synovium using tissue from rheumatoid, osteoarthritic and traumatized (mechanically deranged) joints. In a previous study we detected macrophages (Mph) lining the synovial membrane by means of Mph specific and HLA-DR specific MoAb. These may account for the type A synoviocytes. Type B synoviocytes are thought to be fibroblastic and we used an anti-Thy 1 MoAb to identify these cells. Many fibroblasts were seen in a subintimal position but only few in the lining layer, not in sufficient numbers to account for the type-B category of synoviocyte. Staining with a new MoAb, 67, was found to precisely delineate the lining layer. This MoAb was previously seen to react with dendritic reticulum cells (DRC) of germinal centres, cells involved in B lymphocyte activation. However, other MoAb which react with germinal centre DRC did not label the synovial lining layer. Several MoAb revealed features of the vasculature not previously recognized. In rheumatoid samples, MoAb10 labelled small capillaries near the synovial surface and larger vessels deeper in the intima were labelled with a second MoAb, SM phi. This dichotomy of staining was not so apparent in synovium from control osteoarthritis and trauma (OA/T) samples. In addition, the Thy 1 epitope, identified previously on a variety of human cells, was strongly expressed on all vascular endothelium. Finally a new vessel or duct like structure was identified in OA/T samples, located subintimally. These ducts contained keratin, detected with MoAb LE61 and may be the normal counterpart for the rare malignancy, biphasic synovial sarcoma.

Adult

Monocytes and other infiltrating cells in human colorectal tumours identified by monoclonal antibodies.

Monoclonal antibodies have been used to examine the patterns of infiltrating cells in colorectal tumours staged according to Dukes' classification. MAbs reacting with monocytes, but not tissue Mph, revealed a six-fold increase in monocytes in metastasizing C tumours compared to normal gut. The non-metastasizing B tumours could be divided into one group containing increased numbers of monocytes, and a second group comparable to control gut. T-cell numbers were increased in all tumour stages by an average 1.4-fold, which disguised the lack of consistent pattern in T-cell subset ratios in the tumour stromal tissue. However, in the tumour epithelium, there was a constant decrease in the Ts + c cell subset and a subsequent alteration in T-cell subset ratio in favour of Th + i cells. With the progression from Dukes' Stage B to C, there was an increase in the proportion of monocytes and T cells which were activated as detected by mAbs to the C3b receptor and IL-2 receptor, respectively. These observations suggest that an immune response is in progress in these colorectal tumours and that it is most active in the metastasizing Dukes' C tumours. Whether this response is elicited by the tumour or other elements, whether it is detrimental to tumour growth, or whether it is actively assisting tumour growth and possibly dissemination, are matters of conjecture.

Antibodies, Monoclonal

State of unesterified fatty acids in skim milk.

By a multiple extraction procedure the unesterified fatty acids of skim milk have been shown in at least three entities: a) free dissociated and undissociated fatty acids, b) fatty acids associated with the membrane material in skim milk, and c) fatty acids of unknown origin requiring acidification to pH 1.5 for extraction.

Animals

Photodegradation of riboflavin in milks exposed to fluorescent light.

Photodegradation of riboflavin in 50-ml samples of fluid milks exposed to fluorescent light (2690 lux) followed first-order reaction kinetics, and the reaction rate (s-1) averaged 1.86 x 10(-5) in skim milk and 1.47 x 10(-5) in whole milk. Additional evidence led us to conclude that photodegradation of riboflavin proceeds prior to the appearance of a light-induced off-flavor.

Animals

Vasopressin in the rat with spontaneous hypertension.

Because vasopressin is one of the most potent naturally occurring pressor agents, and because of its importance in the regulation of blood volume and composition, we have undertaken a study of the role of vasopressin in the pathogenesis of the hypertension in the Okamoto-Aoki spontaneously hypertension (SH) rat. In SH rats, systolic blood pressure increased from 135 +/- 3 (SE) mmHg at age 33 days to 184 +/- 3 mmHg at age 75 days (P less than 0.01). In the Wistar-Kyoto (WKY) control rats, blood pressure increased from 100 +/- 2 to 120 +/- 2 mmHg (P less than 0.01). The differences in blood pressure between the SH and WKY rats at all ages were significant (P less than 0.01). During the age period 33-75 days, the 24-h urinary excretion of vasopressin in the SH rat was consistently more than twofold greater (P less than 0.01) than in the WKY rat. Plasma vasopressin concentration and pituitary vasopressin content were also elevated in the SH rat (P less than 0.01 and P less than 0.02, respectively). Changes in systolic blood pressure in the SH rat, however, were not paralleled by changes in the urinary excretion of vasopressin. The data indicate that the secretion of vasopressin is elevated in the SH rat. However, the magnitude of this elevation, in and of itself, may not be sufficient to account for the rising blood pressure in the young SH rat.

Animals

Loss of body weight and fat during exercise in a cold chamber.

Ten men spent one week in a cold climatic facility performing a simulated arctic military exercise demanding an energy expenditure of 13-16 MJ-day-1. Although the ration pack was adequate, extensive plate wastage led to a negative energy balance of 2.2 MJ-day-1. Fluid intake was also insufficient, with a 3.25% decrease of body weight, and a 9.7% decrease in skin thickness over the cold exposure. Extensive fat mobilization was indicated by a decrease of skinfold thicknesses, an increase of body density, and associated ketonuria and glycosuria. The fat breakdown far exceeded the calculated energy deficit, and it is postulated that much of the "surplus" energy was required for synthesis of additional muscle protein. In the arctic environment, both energy and fluid balances are better maintained because there are few distraction from the simple pleasure of preparing and eating meals.

Adipose Tissue

Treatment of obesity by exercise in the cold.

Six obese men aged 25 to 46 years exercised vigorously for 3 1/2 hours in a cold chamber (-34 degrees C) on 10 successive days. There was an early water loss of about 1 kg, probably due to mobilization of glycogen stores, and a subsequent fat loss of about 4 kg (as estimated from readings of skinfold thickness and confirmed by underwater weighing). The total fat loss was much greater than the calculated external energy deficit (as estimated from dietary records, an activity diary and use of a Kofranyi-Michaelis respirometer). Although some energy was "wasted" through ketosis, much of the additional energy was apparently used for synthesis of additional muscle protein. Both readings of skinfold thickness and underwater weighing indicated that the loss of adipose tissue was well sustained in the first 2 months after the exercise program. Further experiments are recommended to determine whether cold exposure makes a specific contribution to the observed weight loss, and whether this approach would be equally effective in a larger and less selected sample of obese patients.

Adult

LaTulippe--a case study of a one hundred and sixty kilometre runner.

A 55 year old runner covered 160 km within a 20 hour period. His speed averaged 8.16 km/h, at an estimated 59.1% of maximum oxygen intake. After the first four hours of running, one of five fluids was taken in rotation every twelve minutes. Volumes ingested whe heart rate for the final four hours (125/min) was not increased relative to oxygen consumption for this portion of the run. Constancy of heart rate, continued urine production and formal fluid balance calculations all indicate that hydration was well maintained over the run. Caloric intake averaged 480 kcal/h (2.01 MJH), being greatest fro the ice-creas/syrup mixture; the energy deficit (56/KA/H, 235 kJ/h) was small during that part of the run in which food was provided.

Blood Pressure

Loss of body fat during an arctic winter expedition.

Fifty-five soldiers have been observed over a vigorous 10-day sledging patrol in the Canadian arctic and subarctic. Initial observations showed a low level of physical fitness (26% body fat, aerobic power 41.9 +/- 7.8 ml kg-1 min-1, handgrip force 43.7 +/- 7.2 kg). Over 2-week northern sojourn, energy expenditures as measured by a Kofranyi-Michaelis respirometer and diary observation averaged 3248 kcal (13.6 MJ) day-1, with a small (152 kcal (633 kJ)) positive daily energy balance. A weight loss of 1 kg, presumably water, was made good within 1 week of return to the south. A fat loss of some 3.9 kg was probably attributable largely to the demands of lean tissue synthesis. The lean mass was increased by 3.9 kg over the trial, with parallel gains of muscle force and aerobic power. The rapid mobilization of depot fat led to marked ketonuria.

Adipose Tissue