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Biomedical subjects

C M Dwyer

Publications and source records attributed to C M Dwyer.

At least 37 records · Page 2Linked to original sources
PubMed1994

Papuloerythroderma and cutaneous T cell lymphoma.

An 83-year-old man had the typical cutaneous features of papuloerythroderma of Ofuji. There were reduced numbers of lymphocytes and platelets in his peripheral blood but the eosinophil count was normal. Skin biopsy showed a nondiagnostic infiltrate of T lymphocytes in the dermis. Treatment with topical steroids and UVB phototherapy was ineffective. Twelve months after presentation, a further skin biopsy revealed atypical lymphoid cells invading the epidermis and the skin adnexae. A diagnosis of malignant lymphoma was made; no evidence of extracutaneous spread was found. Photochemotherapy produced rapid resolution of the skin eruption and clearance of the cutaneous infiltrate. Papuloerythroderma may be a manifestation of a cutaneous lymphoma.

Aged↗
PubMed1994

The influence of maternal nutrition on muscle fiber number development in the porcine fetus and on subsequent postnatal growth.

In the pig, undernutrition in utero causes low birth weight, a decrease in muscle fiber number, and a reduction in postnatal growth rate. The effect on fiber number is mediated via a reduced secondary fiber population. Within a litter of pigs, lighter-weight pigs have probably suffered some deficit in muscle fiber number. In an attempt to improve the number of fibers in the lighter-weight pig fetuses, four maternal feeding regimens were used, one serving as the control. Maternal feed intake was doubled for one of three time periods during pregnancy: 1) d 25 to 50 (HE) immediately before fiber hyperplasia; 2) d 50 to 80 (HL) during fiber hyperplasia; or 3) d 25 to 80 (HT) covering both developmental events. Controls were fed at levels routinely used for pregnant sows on the farm. Sows farrowed normally and pig birth weights were recorded. Estimates were made of total myofiber number, total primary fiber number, and mean secondary:primary fiber number ratio (S:P) for the semitendinosus of each pig at 5 wk postnatal or 80 kg (HT and two control litters only). The progeny of all supplemented sows had a significantly greater mean S:P ratio (P < .05), and the HE pigs tended to have a greater number of muscle fibers than control pigs (403,840 +/- 8,197 vs 370,970 +/- 12,720). Postnatal growth rate to 80 kg was also investigated for the HT group of pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Skin pigmentation due to minocycline treatment of facial dermatoses.

Fifty-four patients taking minocycline for acne or rosacea were assessed for adverse effects. Their mean duration of treatment was 17 months, and their average cumulative dose was 47 g. No symptoms attributable to the therapy were reported. Biochemistry and haematology profiles were normal. There was no evidence of an adverse effect on thyroid function. Skin pigmentation was detected in eight patients (14.8%). Five patients had diffuse facial pigmentation, and three patients had localized pigmentation at the site of a scar or injury. Diffuse pigmentation occurred only in patients who had been on treatment for 3 years or more; 50% of such patients were affected. Age and solar damage may also have been factors in this type of pigmentation. Localized pigmentation occurred at sites of previous tissue damage, and was not directly related to the duration of therapy. Patients who receive long-term minocycline therapy should be regularly monitored for the development of pigmentation.

Acne Vulgaris↗
PubMed1993

Ulceration in necrobiosis lipoidica--a case report and study.

A case of aggressive ulceration of necrobiosis lipoidica was successfully treated with oral prednisolone. A retrospective study of 23 cases of necrobiosis lipoidica revealed a 13% incidence of ulceration. The pathogenesis, clinical features and treatment of ulceration in necrobiosis lipoidica are discussed.

Administration, Oral↗
PubMed1993

Contact allergy to aluminium in 2 brothers.

A 10-year-old boy reacted to aluminium Finn Chambers during routine patch testing. Further patch tests with aqueous aluminium chloride confirmed contact allergy to aluminium. The boy's 8-year-old brother also reacted to aluminium Finn Chambers. Both boys had suffered from a scaling eruption on their face and limbs since infancy.

Aluminum↗
PubMed1993

Muscle cellularity and postnatal growth in the pig.

Fast-growing strains of pigs and of other animals tend to have more muscle fibers than do slow-growing strains. The relationship between fiber number and growth rate was extended by examining pigs within the same strain. Seven litters of pigs (n = 66) were weighted at monthly intervals from birth to approximately 80 kg. The semitendinosus muscle was removed and an estimation of total fiber number, total primary fiber number, and mean secondary:primary fiber number (S:P) ratio was made for each animal. Pig growth was divided into three approximately linear phases: birth to 6 kg, 6 to 25 kg, and 25 kg to slaughter weight. Average daily gain in the first two phases was correlated with birth weight (r = .3614, P < .05 and r = .5873, P < .001, respectively) but was not correlated with total muscle fiber number. In the third growth phase ADG was correlated with muscle fiber number (r = .4149, P < .001) and was not correlated with birth weight. The gain:feed ratio was also calculated for each pig during the third growth phase and was found to be correlated with fiber number (r = .4191, P < .001). These results suggest that muscle fiber number is an important determinant of postnatal growth such that pig littermates with a high fiber number tend to grow faster and more efficiently than littermates with a lower fiber number.

Animals↗
PubMed1992

Cloning and expression of murine IL-12.

Human IL-12 (NK cell stimulatory factor, cytotoxic lymphocyte maturation factor) is a heterodimeric cytokine that can act as a growth factor for activated human T and NK cells, enhance the lytic activity of human NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting human PBMC. Because in our hands, human IL-12 did not elicit similar responses in murine lymphocytes, we have cloned and expressed the murine IL-12 subunit cDNA in order to obtain recombinant protein for murine studies. Comparison of the predicted amino acid sequences of the murine subunits with their human counterparts revealed that the p40 subunits are more highly conserved than the p35 subunits (70% vs 60% identity, respectively). The sizes of the p35 and p40 subunit mRNA were estimated to be 1.5 kb and 2.6 kb, respectively. RNA blot analysis showed that p35 mRNA was expressed in lymphoid tissues (spleen, thymus) and nonlymphoid tissues (lung, brain), whereas p40 mRNA expression was only detected in lymphoid cells. Incubation of splenocytes with pokeweed mitogen did not significantly affect p35 mRNA levels, however, it resulted in a decrease of p40 mRNA. Coexpression of the murine p35 and p40 cDNA clones in COS cells resulted in the secretion of IL-12, which was active in human and mouse T cell proliferation, murine NK cell activation, and murine IFN-gamma induction assays. Transfection of each subunit cDNA alone did not result in measurable secreted IL-12 activity. A hybrid heterodimer consisting of murine p35 and human p40 subunits retained bioactivity on murine cells; however, the combination of human p35 and murine p40 was completely inactive on murine cells. These results indicate that the observed inability of human IL-12 to act on murine cells is largely determined by the p35 subunit.

Amino Acid Sequence↗
PubMed1992

Does the anatomical location of a muscle affect the influence of undernutrition on muscle fibre number?

Nutritional restriction during muscle fibre number development invariably has a more detrimental effect on the biceps brachii than on the soleus. The difference may be due to the relative proportions of fibre types in the muscles or the anatomical location of the muscles. To distinguish between the effects of location and fibre type the biceps (fast, cranial and proximal), soleus (slow, caudal and distal), and extensor digitorum longus (EDL) (fast, caudal and distal) were examined from control and undernourished guinea pig neonates. A 40% reduction in maternal intake resulted in a reduction in neonate body and muscle weights (P < 0.005), biceps (P < 0.05) and EDL fibre numbers (P < 0.005), but did not affect soleus fibre number. At birth the ratio of fast fibres to slow was 7.5 for the biceps, 7.0 for the EDL, and 1.5 for the soleus. The effect of undernutrition on muscle fibre number therefore seems to be a function of the fibre types in that muscle.

Adenosine Triphosphatases↗
PubMed1992

The effect of maternal undernutrition on the growth and development of the guinea pig placenta.

Fetal growth is known to be correlated with the size of the placenta and the exchange surface area. Reduction in the growth of the materno-fetal exchange surface areas may be a mechanism by which the effects of maternal undernutrition on fetal growth are mediated. In the compact placenta of the guinea pig the exchange surface is equivalent to the peripheral labyrinth. The effect of a 40% reduction in maternal feed intake on the growth of the peripheral labyrinth was investigated in pregnant guinea pigs between gestational days 25 and 65. Fetal and placental weights were significantly reduced in the last trimester by 32% and 38% respectively (P < 0.01). Placental efficiency in early gestation was significantly impaired in restricted animals but equivalent to ad lib. fed controls by the last trimester. The volume of the peripheral labyrinth increased as a percentage of the total placental volume with gestational age. Restricted placentae tended to be composed of a smaller volume of peripheral labyrinth tissue in early gestation. It is suggested that maternal undernutrition results in an impaired or delayed expansion of the peripheral labyrinth in early gestation causing a reduction in placental efficiency. By the last trimester the weight of the peripheral labyrinth of restricted animals was reduced by 33% (P < 0.05). The weight of the peripheral labyrinth was also significantly correlated with fetal weight is limited by the size of the peripheral labyrinth in the later stages of gestation.

Animals↗
PubMed1992

The effects of maternal undernutrition on maternal and fetal serum insulin-like growth factors, thyroid hormones and cortisol in the guinea pig.

The insulin-like growth factors (IGF-I and -II) are potential mediators of the effects of maternal undernutrition on fetal growth and muscle development. The effects of a 40% reduction in maternal feed intake on serum levels of the IGFs, the thyroid hormones and cortisol, were investigated for the last two trimesters (day 25 to birth). This level of undernutrition is known to cause a 35% reduction in fetal and placental weights, and a 20-25% reduction in muscle fibre number. Maternal IGF-I level was greater than non-pregnant levels on day 25 gestation, in both control and restricted dams, and declined with gestational age. The increase in IGF-I level in the 40% restricted group was approximately two-thirds that of control animals. Fetal serum IGF-I was also reduced in undernourished fetuses throughout gestation. Maternal IGF-II did not change with gestational age and was unaffected by undernutrition. Fetal IGF-II reached a peak at day 55 of gestation, this peak was greatly diminished by maternal feed restriction. Both IGF-I and IGF-II tended to be related to fetal, placental and muscle weights at day 65 of gestation. Thyroid hormone concentration declined in maternal serum and increased in fetal serum with increasing gestational age. Levels were not significantly affected by undernutrition. Both triiodothyronine (T3) and thyroxine (T4) were correlated with IGF-I in maternal serum (P < 0.05), but not in fetal serum. Cortisol levels were elevated by undernutrition in both maternal and fetal serum, and increased with gestational age. Cortisol was inversely correlated with serum IGF-I in both maternal and fetal serum. Maternal serum IGF-I may mediate the effects of undernutrition on fetal growth by affecting the growth and establishment of the feto-placental unit in mid-gestation. Fetal IGF-I may mediate the effects on muscle growth, whereas IGF-II seems to be related to hepatic glycogen deposition. Cortisol may play a role via its effect on the IGFs, but the thyroid hormones are unlikely to be important until the late gestation/early postnatal period.

Animals↗
PubMed1991

Regulation of human lymphocyte proliferation by a heterodimeric cytokine, IL-12 (cytotoxic lymphocyte maturation factor).

IL-12 is a heterodimeric cytokine that was identified on the basis of its ability to synergize with IL-2 in the induction of cytotoxic effector cells and was originally called cytotoxic lymphocyte maturation factor (CLMF). IL-12 was also found to stimulate the proliferation of PHA-activated lymphoblasts which were greater than 90% CD3+ T cells. In this report we further characterize the effects of IL-12 on lymphocyte proliferation. Studies with purified subpopulations of PHA-activated lymphoblasts and with cloned lines of human T cells indicated that IL-12 caused the proliferation of activated T cells of both the CD4+ and CD8+ subsets. This effect of IL-12 was independent of IL-2 because it was not blocked by antibodies to either IL-2 or IL-2R. The maximum proliferation induced by IL-12 was 31 to 72% of the maximum caused by IL-2; however, IL-12 was active at a lower effective concentration (EC50 = 8.5 +/- 1.3 pM) than IL-2 (EC50 = 52 +/- 8 pM). Combination of suboptimal amounts of IL-12 and IL-2 resulted in additive proliferation, up to the maximum induced by IL-2 alone. IL-12 also caused the proliferation of lymphocytes activated by culture with IL-2 for 6 to 12 days. CD56+ NK cells were among the IL-12-responsive cells in the IL-2-activated lymphocyte population. Unlike IL-2 or IL-7, IL-12 caused little or no proliferation of resting peripheral blood mononuclear cells (PBMC). In this regard, IL-12 was similar to IL-4. However, IL-12 could enhance the proliferation of resting PBMC caused by suboptimal amounts of IL-2, whereas IL-4 inhibited IL-2-induced PBMC proliferation. Thus, IL-12 is a growth factor for activated human T cells and NK cells; however, its spectrum of lymphocyte growth-promoting properties is distinct from that of IL-2, IL-4, or IL-7.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor.

Cytotoxic lymphocyte maturation factor (CLMF) is a disulfide-bonded heterodimeric lymphokine that (i) acts as a growth factor for activated T cells independent of interleukin 2 and (ii) synergizes with suboptimal concentrations of interleukin 2 to induce lymphokine-activated killer cells. We now report the cloning and expression of both human CLMF subunit cDNAs from a lymphoblastoid B-cell line, NC-37. The two subunits represent two distinct and unrelated gene products whose mRNAs are coordinately induced upon activation of NC-37 cells. Coexpression of the two subunit cDNAs in COS cells is necessary for the secretion of biologically active CLMF; COS cells transfected with either subunit cDNA alone do not secrete bioactive CLMF. Recombinant CLMF expressed in mammalian cells displays biologic activities essentially identical to natural CLMF, and its activities can be neutralized by monoclonal antibodies prepared against natural CLMF. Since this heterodimeric protein displays the properties of an interleukin, we propose that CLMF be given the designation interleukin 12.

Amino Acid Sequence↗