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Biomedical subjects

D Mitchell

Publications and source records attributed to D Mitchell.

At least 289 records · Page 16Linked to original sources

Immunohistochemical localisation of keratin in human lung tumours.

Antisera against total keratin extracts of human callus have been used to identify keratins in lung tumours of different histological type. Forty-three were classified by the WHO scheme. Keratin immunoreactive cells were identified in all 8 epidermoid carcinomas; 6 out of 12 large cell carcinomas; 2 out of 6 adenocarcinomas; 2 out of 15 small cell carcinomas and in the only muco-epidermoid carcinoma. These cases demonstrate the heterogeneity of phenotypic expression in lung tumours not recognisable without the use of immunohistochemical techniques.

Adenocarcinoma↗

Effects of heat and cold exposure and exercise on the interstitial fluid proteins of the rat.

1. Interstitial fluid (obtained from capsules implanted subcutaneously) and plasma were obtained from rats before and after heat and cold exposure and exercise. 2. In the case of plasma, cold and heat exposure and exercise decreased A/G ratios. Albumin concentrations also decreased after heat and cold and protein concentration increased after exercise. 3. Cold decreased interstitial protein and albumin concentrations and A/G ratios. Heat exposure increased protein concentration and decreased the A/G ratio. Exercise decreased decreased protein concentrations. 4. The results are discussed in relation to previous findings.

Albumins↗

On the pyrogenic action of intravenous lipid A in rabbits.

1. Previous evidence purporting to show that lipid A is the pyrogenic moiety of endotoxin is demonstrably inconclusive. 2. We have extracted lipid A from endotoxin of Salmonella typhosa and tested the pyrogenic action of the lipid A, the residual polysaccharide and the parent endotoxin, by intravenous injection in conscious rabbits. 3. Lipid A dissolved in an aqueous solution of rabbit serum albumin induced a significant pyrexia of short latency, while neither rabbit serum albumin alone, nor the polysaccharide from S. typhosa, affected body temperature. The physical presence in the injectate of the polysaccharide from S. typhosa did not enhance the pyrogenicity of the lipid. 4. Dose-response curves for lipid A and the parent endotoxin, over the dose range 10 ng-20 micrograms, showed that lipid A incorporated in endotoxin was much more pyrogenic than pure lipid A in solution. When separated from the polysaccharide component of endotoxin, lipid A lost more than 99.9% of its pyrogenic activity, at threshold doses.

Animals↗

Distribution of myoepithelial cells and basement membrane proteins in the resting, pregnant, lactating, and involuting rat mammary gland.

Using antisera to specific proteins, the localization of the rat mammary parenchymal cells (both epithelial and myoepithelial), the basement membrane, and connective tissue components has been studied during the four physiological stages of the adult rat mammary gland, viz. resting, pregnant, lactating, and involuting glands. Antisera to myosin and prekeratin were used to localize myoepithelial cells, antisera to rat milk fat globule membrane for epithelial cells, antisera to laminin and type IV collagen to delineate the basement membrane and antisera to type I collagen and fibronectin as markers for connective tissue. In the resting, virgin mammary gland, myoepithelial cells appear to form a continuous layer around the epithelial cells and are in turn surrounded by a continuous basement membrane. Antiserum to fibronectin does not delineate the basement membrane in the resting gland. The ductal system is surrounded by connective tissue. Only the basal or myoepithelial cells in the terminal end buds of neonatal animals demonstrate cytoplasmic staining for basement membrane proteins, indicating active synthesis of these proteins during this period. In the secretory alveoli of the lactating rat, the myoepithelial cells no longer appear to form a continuous layer beneath the epithelial cells and in many areas the epithelial cells appear to be in contact with the basement membrane. The basement membrane in the lactating gland is still continuous around the ducts and alveoli. In the lactating gland, fibronectin appears to be located in the basement membrane region in addition to being a component of the stroma. During involution, the alveoli collapse, and appear to be in a state of dissolution. The basement membrane is thicker and is occasionally incomplete, as also are the basket-like myoepithelial structures. Basement membrane components can also be demonstrated throughout the collapsed alveoli.

Animals↗

Distribution of myoepithelial cells and basement membrane proteins in the normal breast and in benign and malignant breast diseases.

An immunocytochemical method for fixed and paraffin-embedded human breast biopsies is reported for the detection of myoepithelial and epithelial cells using antibodies to myosin and keratin, respectively, and of basement membranes using antibodies to laminin and type IV collagen. Using these markers, myoepithelial cells can be clearly distinguished in the normal breast and in the benign breast diseases sclerosing adenosis, epitheliosis, and fibroadenoma. In sclerosing adenosis, myoepithelial cells form a major cellular component. A stromally derived spindle cell is identified which stains with myosin but not with keratin antibodies (myofibroblast). These cells are seen in one-fifth of the fibroadenomas. Although cells staining with myosin antibodies are seen in the infiltrating component of all 18 carcinomas examined, elongated cells staining with both myosin and keratin antibodies (myoepithelial-like) are seen in only one infiltrating carcinoma where they are interposed at the stromal-epithelial junction of the infiltrating tumor cells. In contrast to the situation in benign breast diseases, mature myoepithelial cells form a very minor component of the majority of infiltrating ductal carcinomas. Basement membrane proteins, laminin, and type IV collagen are present in normal breast, benign breast disease, and grade I infiltrating ductal carcinomas but are absent in carcinomas of grades II and III.

Basement Membrane↗

Development of horse embryos up to twenty two days after ovulation: observations on fresh specimens.

Forty nine embryos, twenty unfertilized eggs and five other fresh eggs of 'doubtful' status have been recovered from 58 pony mares in 122 flushes up to 22 days after ovulation. The fresh egg or embryo recovery rate was 78% with surgical methods (or at slaughter) and 40-60% with non-surgical methods of recovery. The fertilization rate was about 70%. It has been confirmed that horse embryos normally enter the uterus as blastocysts 5-6 days after ovulation. Three features of early embryo morphology have become clearer upon comparison with unfertilized eggs of similar ages; early embryos are often ellipsoidal in shape; dispersal of most of a thick gel coat seems to be hastened by fertilization; gradual disappearance of refractile granules from the perivitelline space is similar in fertilized and unfertilized eggs. A tense, transparent, acellular capsule (considered to be different from the zona pellucida) is acquired by the spherical blastocysts within the uterus and persists at least until a diameter of 34 mm is attained (at 21 days in the present series). The capsule seems to be analogous, in part, with the 'neozona' described in rabbit blastocyst before attachment, and trophoblastic cells appear to be involved in its formation. Cleavage stages of oviductal embryos and diameters of uterine blastocysts from this series have been described and illustrated and used to extend previous knowledge of early growth patterns in horse embryos.

Animals↗

Slow-wave sleep: a recovery period after exercise.

Sleep recordings were carried out on athletes on four successive nights after completing a 92-kilometer road race. Significant increases in total sleep time and slow-wave sleep were found after this metabolic stress. The results show a definite exercise effect on sleep and support sleep-restoration hypotheses.

Adolescent↗

The effect of water deficit on body temperature during rugby.

Sweat losses, water deficits and changes in rectal temperature were measured in 13 first-league players during a rugby match. Changes in plasma volume, serum electrolyte and blood glucose levels were also determined. Rectal temperatures were markedly elevated after the match. Both temperatures reached levels which are known to be associated with an impairment of physical, mental and psychological function, and could have caused a deterioration in performance during the second half of the match. Body temperatures were high enough to have predisposed to aggressive behaviour. Increases in rectal temperature were related to water deficit. The small volumes of fluid ingested by the players just before and during the match suggest that they are unaware of the importance of preventing dehydration. Recommendations are made to reduce the risk of hyperthermia. Glucose and electrolyte supplementation is not required just before and during rugby.

Adult↗

The effects of cycloheximide on the biosynthesis and secretion of proteoglycans by chondrocytes in culture.

Proteoglycans synthesized by rat chondrosarcoma cells in culture are secreted into the culture medium through a pericellular matrix. The appearance of [35S]sulphate in secreted proteoglycan after a 5 min pulse was rapid (half-time, t 1/2 less than 10 min), but that of [3H]serine into proteoglycan measured after a 15 min pulse was much slower (t 1/2 120 min). The incorporation of [3H]serine into secreted protein was immediately inhibited by 1 mM-cycloheximide, but the incorporation of [35S]sulphate into proteoglycans was only inhibited gradually(t 1/2 79 min), suggesting the presence of a large intracellular pool of proteoglycan that did not carry sulphated glycosaminoglycans. Cultures were pulsed with [3H]serine and [35S]sulphate and chased for up to 6 h in the presence of 1 mM-cycloheximide. Analysis showed that cycloheximide-chased cells secreted less than 50% of the [3H]serine in proteoglycan of control cultures and the rate of incorporation into secreted proteoglycan was decreased (from t 1/2 120 min to t 1/2 80 min). Under these conditions cycloheximide interfered with the flow of proteoglycan protein core along the route of intracellular synthesis leading to secretion, as well as inhibiting further protein core synthesis. The results suggested that the newly synthesized protein core of proteoglycan passes through an intracellular pool for about 70-90 min before the chondroitin sulphate chains are synthesized on it, and it is then rapidly secreted from the cell. Proteoglycan produced by cultures incubated in the presence of cycloheximide and labelled with [35S]sulphate showed an increase with time of both the average proteoglycan size and the length of the constituent chondroitin sulphate chain. However, the proportion of synthesized proteoglycans able to form stable aggregates did not alter.

Animals↗

Pyrogens fail to produce fever in a cordylid lizard.

We investigated the effects on body temperature of the lizard Cordylus cataphractus of intracardiac injections of leucocyte pyrogen (LP) synthesized from rabbit blood and of killed Aeromonas hydrophila, a gram-negative bacterium reputed to be pathogenic in lizards. Lizards were placed in a photothermal gradient that allowed them to select a preferred body temperature following the injections. Neither injection of 0.5 ml rabbit LP nor of 4 X 10(9) organisms of A. hydrophila in 0.2 ml sterile saline caused body temperature of lizards to differ from that of control lizards injected with sterile saline. Following injection of these solutions in the lizards placed in a thermal gradient where ambient temperature ranged from 20-88 degrees C, body temperature was maintained between 32 and 34 degrees C. Pyrogens failed to elevate body temperature even when body temperature was elevated artificially to 36 degrees C before injection. We conclude that C. cataphractus does not respond with fever to either rabbit LP or A. hydrophila. Fever may not be ubiquitous even among lizards.

Aeromonas↗

A subcutaneous capsule for long-term studies.

In assessing interstitial fluid dynamics, perforated capsules have a limited existence because of the ingrowth of connective tissue. A permanently patent capsule (1 yr) can be obtained by implanting 1.9-cm lengths of Tygon tubing (OD 7.9 mm, ID 4.8 mm). After implant, the capsule is invested in connective tissue, and a thin strand of connective tissue invades both ends of the capsule. In 2-3 wk, the connective tissue joins in the capsule and there is no further ingrowth of connective tissue. This tissue bridge through the center of the capsule is richly vascularized, eventually containing small central arteries and veins. Protein content of capsule fluid was 50-60% of plasma, with albumin proportionately higher in the capsule. Intracapsule pressures averaged -2.08 mmHg. Communication between capsule contents and vascular volume appeared to be size-dependent in that the [35S]sulfate and [3H]inulin count could be measured in tail blood 5 min after intracapsule injection and it increased over 30 min. This did not occur with [14C]dextran (mol wt 70,000) and [14C]globulins (mol wt 150,000). This capsule appears to lend itself to long-term studies related to interstitial fluid dynamics and/or capillary exchange.

Animals↗

Effects of intracerebroventricular floctafenine and indomethacin on body temperature in febrile rabbits.

1. We injected the potent prostaglandin synthesis inhibitors, floctafenine and indomethacin, intravenously and intracerebroventricularly in rabbits made febrile by intravenous injection of leucocyte pyrogen. 2. Floctafenine (75 mumol) injected intravenously failed to affect the fever, whereas indomethacin (15 mumol) markedly reduced the fever. 3. When injected into the cerebral ventricles, floctafenine was feebly antipyretic, and then only at a dose ten times the antipyretic dose of indomethacin. 4. Our results support the suggestion that floctafenine has no antipyretic action when administered peripherally. However, its lack of antipyretic effect cannot be explained solely on the grounds that it fails to cross the blood-brain barrier.

Animals↗

Chromosomal analysis of 159 bovine embryos collected 12 to 18 days after estrus.

One hundred and fifty-nine embryos were analysed in conjunction with embryo transfer studies. Chromosome preparations were made from small biopsy fragments of trophoblast, from large portions of trophoblast and the inner cell mass, or from the entire embryo. Results obtained from fragments were similar to those obtained from large portions of trophoblast and inner cell mass. No structural chromosomal abnormalities were observed. Single triploid, diploid-triploid and diploid-hexaploid and 66 diploid-tetraploid embryos were found. The 41.5% incidence of diploid-tetraploid embryos was relatively high, and appeared to be associated with a donor factor. The transfer of 49 biopsied and analysed embryos to recipients resulted in 15 pregnancies, seven with diploid-tetraploid embryos having up to 25% of polyploid cells. The diploid-triploid and diploid-hexaploid embryos were among the transfers that did not result in pregnancy. The low incidence of embryos with chromosomal abnormalities, excluding the diploid-tetraploid embryos, may have been due to the embryos being analysed at 12 to 18 days of age rather than at an earlier age before death or degeneration could have occurred.

Animals↗

An educational program for psoriatics: an evaluation.

Patients with psoriasis referred to the Dermatology Service at Women's College Hospital and satisfying certain criteria relating to percentage body involvement, age, and the absence of serious coincident conditions were assigned at random to three weeks of day care and education at the Psoriasis Education and Research Centre (PERC) or to the Dermatology Service at Women's College Hospital (WCH) for normal hospital care. On admission, all study patients received normal history and physical examinations and were photographed by a standardized procedure that provided an accurate estimate of type and extent of body involvement. A functional history was taken from PERC patients that provided information concerning their ability to cope at home, at work, and socially; the extent and appropriateness of their self-care practices; and their knowledge concerning the pathophysiology and etiology of psoriasis and the names and actions of the medications they were using. Individualized patient education programs were designed with reference to the medical and functional information and implemented in the three weeks of day care. Photographic assessment and the functional history were repeated at three weeks, six months and twelve months. Hospital patients were reassessed at six and twelve months and a functional history was taken at six months. The functional status of PERC and hospital patients was compared at six months. The results of this study reinforced the belief that in the case of psoriasis, education coupled with treatment is more effective than treatment alone.

Evaluation Studies as Topic↗

Collection, description and transfer of embryos from cattle 10--16 days after oestrus.

Of 226 donor cattle treated with PMSG to induce superovulation, 76.5% responded with 3 or more ovulations. Flushing at surgery or slaughter 10-16 days after oestrus recovered eggs and embryos that represented 49.3% of the number of ovulations. Of those recovered, 73.3% were embryos, an average yield of 4.0 embryos/treated cow or 4.8 embryo/flushed cow. The location of eggs and embryos was determined in 65 of the donors. Embryos and unfertilized eggs (6.1% of those recovered) were occasionally found in the oviducts. Empty zonae pellucidae were also found in the uterus on all days. The lengths, or diameters, of embryos were extremely variable within days and within donors, but mean values indicated logarithmic growth between Days 10 and 16. Eighty-four synchronous (+/- 1 day) recipients received single embryos, and 51 recipients twin embryos, by surgical transfer. Pregnancies were obtained in recipients up to Day 16 but not on Day 17, indicating the stage by which an embryo must be present to prevent luteolysis. The overall pregnancy rate at Day 42 was 50.4% and further 18.1% of the recipients exhibited extended oestrous cycles. Of 35 recipients that were allowed to go to term, 12 lost their pregnancies, most often between Days 42 and 63.

Abortion, Veterinary↗