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Biomedical subjects

D Parker

Publications and source records attributed to D Parker.

At least 235 records · Page 13Linked to original sources

Serum lipid response to oat product intake with a fat-modified diet.

Healthy adult volunteers (no. = 208), men and women aged 30 to 65 years, participated in a 12-week study on dietary fat modification plus oat product ingestion (60 gm/day) to test whether moderate daily intake of oat bran and oatmeal enhanced serum lipid response. During weeks 0 to 6, all participants followed the American Heart Association fat-modified eating style. At 6 weeks, participants were randomly assigned to one of three groups. All participants continued to follow the fat-modified eating pattern; groups 1 and 2 were asked during weeks 7 to 12 to consume two servings of either oat bran or oatmeal per day, for a total of 60 gm/day isocalorically substituted for other carbohydrates. Group 3 ingested no oat products. At baseline, the group mean cholesterol level was 208.4 mg/dl. After 6 weeks of dietary fat intervention, the level was 197.6--a fall of 10.8 mg/dl (5.2%). At 12 weeks, the mean serum cholesterol level fell further, by 5.6, 6.5, and 1.2 mg/dl for groups 1, 2, and 3, respectively. Group mean weight loss was small--1.9 lb during the first 6 weeks and 0.6 to 0.8 for the three groups during weeks 7 to 12. Reported oat product ingestion was 39 and 35 gm per person per day, respectively, for groups 1 and 2 (2.2 and 1.4 servings per person per day, respectively). Dietary fat composition remained similar among the three groups during weeks 7 to 12. Pooled results indicated that the addition of oat products at a moderate and practical level enhanced serum lipid response (p less than .05) to a fat-modified eating pattern among free-living adults.

Adult↗

Regulation of protein synthesis and accumulation during murine erythroleukemia cell differentiation.

We have examined the repertoire of cytoplasmic proteins present at different times during murine erythroleukemia (MEL) cell differentiation. Our laboratory has developed an improved differentiation system in which the use of rapidly inducing MEL subclones and culture conditions which stabilize terminally differentiated cells results in highly synchronous differentiation and the accumulation of large numbers of cells in the end stages of differentiation. Using two-dimensional gel electrophoresis, the proteins of MEL cell cytoplasm have been fractionated at different times of induction in the improved system. The protein composition of MEL cell cytoplasm changes dramatically during the differentiation program, in contrast to previously reported results. We observe patterns of changes that are consistent with alterations in the relative degradative rates as well as the relative synthetic rates of the different proteins. We find that the rate of incorporation of labeled amino acid into protein is reduced in induced cultures of MEL cells. We demonstrate that the contribution of uninduced cells to the protein patterns observed late in differentiation is minor in our system, and argue that the results previously obtained for differentiating MEL cells were influenced by the heterogeneity of the induced populations.

Animals↗

Expression of the human calcitonin/CGRP gene in lung and thyroid carcinoma.

Nucleotide sequence analysis of a partially processed polyadenylated precursor RNA transcript shows that the human calcitonin gene in common with the rat calcitonin gene, encodes calcitonin and the calcitonin gene related peptide (CGRP). Using hybridisation probes specific to calcitonin mRNA, intron, coding and non-coding regions of the CGRP mRNA, we demonstrate by Southern blotting the existence of a second human CGRP gene, and by RNA blotting and S1 mapping, the differential expression of calcitonin and CGRP in medullary thyroid carcinoma and human lung tumour cell-lines. These studies implicate the requirement for separate post-transcriptional events in the differential expression of calcitonin and CGRP from a single gene, the preferential use of splice acceptor sites for the synthesis of CGRP mRNA, and post-transcriptional cleavage modulated by a trans-acting gene product for the synthesis of calcitonin mRNA. Studies using antisera raised against CGRP and calcitonin, demonstrate elevated circulating levels of plasma CGRP in medullary thyroid carcinoma which do not parallel calcitonin levels, and the presence of CGRP in secretions from lung tumour cell-lines. These studies indicate that CGRP is a tumour marker of diagnostic and possibly prognostic value in the management of lung and thyroid tumours.

Amino Acid Sequence↗

Correlation between prostaglandin and thromboxane levels and clinical signs in cyclosporine A-treated guinea pigs with acute experimental allergic encephalomyelitis.

Prostaglandin E, prostaglandin F2 alpha and thromboxane B2 levels were measured in the spinal cord and cerebellum of guinea pigs with acute experimental allergic encephalomyelitis treated with Cyclosporine A in a schedule which delayed the onset of the disease and completely suppressed it in 40% of the animals. A correlation was found between the eicosanoid levels in the central nervous system and clinical signs of the disease. Where lesions were completely suppressed the levels of eicosanoids were normal. The number of lesions found correlated well with the clinical state of the animals.

Animals↗

A comparison of the effects of hydrocortisone on peritoneal inflammatory exudates, the tuberculin reaction and contact sensitivity-to DNFB in the guinea pig.

Hydrocortisone acetate, injected subcutaneously in five doses in a depot producing vehicle, causes prolonged suppression of the ability of guinea pigs to produce a chronic inflammatory reaction in the peritoneal cavity and also of the tuberculin reaction. This suppression of the tuberculin reaction persists for at least 65 days after the last dose of hydrocortisone. Suppression of both peritoneal exudate and the tuberculin reaction was associated with a preferential depletion of macrophages at the reaction site. A similar regime had no effect on the ability of guinea pigs to manifest contact sensitivity reactions to 2,4-dinitrofluorobenzene although there was a similar drop in macrophages in the lesion. It appears that the effect of hydrocortisone on delayed hypersensitivity reactions is not directly related to the functional contribution of macrophages in the inflammatory reactions, and may be related to the site of the inflammatory reaction in the skin.

Animals↗

Management of maternal vegetative state during pregnancy.

A pregnant patient with irreversible anoxic brain damage was maintained by life-support measures from 14 weeks' gestation until delivery of a healthy male infant at 34 weeks. Because two patients (the mother and the fetus), as well as the surviving family members, will be affected by decisions about life support, each case should be assessed individually.

Adult↗

Predictive value of assessment of lymph node weight and T-lymphocyte proliferation in contact sensitivity in acrylates.

An assessment of T-lymphocyte proliferation and lymph node weight is proposed as a predictive test for contact sensitizers of industrial origin. Data are presented showing increased T-lymphocyte proliferation following epicutaneous application of a variety of industrially important acrylate-like chemicals which appear to correlate well with their ability to sensitize in the guinea pig. These data were compared with those obtained after application of 2,4-dinitro-1-fluorobenzene (DNFB) a strong sensitizer, and 2,4-dinitrothiocyanatebenzene (DNTB) a nonsensitizer when given epicutaneously. It is suggested that this quantitative approach, in parallel with a simple one-dose immunization, may provide a better picture of sensitization potential than the longer multidose immunizations currently in use.

Acrylates↗

Synthesis of thymosin alpha 1 by fragment condensation using tert.-butyl side chain protection.

A novel synthesis of thymosin alpha 1 by classical methods using seven tert.-butyl side chain protected fragments is described. Optimum conditions were found for the final DCC/HOBt coupling of the two key intermediates; decapeptide and octadecapeptide. Thymosin alpha 1 was purified by two stages of preparative HPLC (partial purification with C8 and final purification with C18 reverse phase silica gel) to give a 30% overall yield for the final four stages of synthesis (including catalytic hydrogenation of octadecapeptide, coupling, deprotection and purification). The product was shown to be homogeneous by thin-layer and paper high voltage electrophoresis, isoelectric focusing analysis, thin-layer chromatography and high performance liquid chromatography. Amino acid analysis, optical rotation, 1H-n.m.r. spectroscopy, FAB mass spectroscopy and peptide mapping after tryptic digestion confirmed the structure of thymosin alpha 1. Three minor stereoisomer contaminants were isolated by HPLC and characterized as [D-Lys14]-thymosin alpha 1, [D-Lys17]-thymosin alpha 1 and [D-Ala3]-thymosin alpha 1 resulting from racemization at Lys14, Lys17 and Ala3 during the coupling of the fragments. A final contaminant, isolated by HPLC, was characterized as N alpha-isobutyloxycarbonyl-thymosin alpha 1 (15-28), which results from "wrong way opening" of an activated mixed anhydride.

Amino Acid Sequence↗

Epicutaneous induction of tolerance with acrylates and related compounds.

Epicutaneous application of acrylates and related compounds 14 and 7 days before sensitization with either methyl acrylate or trimethylol propane triacrylate induced tolerance to the resultant contact reactions. This tolerance could not be correlated with either the degree of cross reactivity between these compounds or with their ability to react covalently with amino or sulphydryl groups of proteins. These results are discussed in relation to other epicutaneous tolerizers in the dinitrobenzene and poison ivy systems.

Acrylates↗

Immune response to a thymus-independent antigen (DNP-Ficoll) in the guinea pig.

Guinea pigs immunized with DNP30-Ficoll produced IgM antibody only. No IgG1, IgG2, IgE antibodies or delayed hypersensitivity were detected in these animals. However, Arthus reactions, induced by the hapten coupled to a foreign carrier or the whole antigen, were found. The time course of the IgM response was limited and the response to reinjection of the antigen reduced. Cyclophosphamide (CY), given 3 days before primary immunization, prolonged the IgM response. Given on the day of immunization or 3 days after CY reduced this response. CY given on days +3 or +7 after primary immunization completely suppressed the response to antigen reinjected 42 days later. Arthus reactions were totally suppressed by CY given on the day of immunization, or 3 or 7 days later.

Animals↗

Hereditary motor-sensory neuropathy (HMSN): possible X-linked dominant inheritance.

The inheritance of the hereditary motor and sensory neuropathies (HMSN) is usually autosomal dominant. We studied a kinship with a pattern of X-linked dominant inheritance. The phenotype was similar to HMSN of the "intermediate" type. Men were more severely affected than women, and hypertrophic nerves were not found. Nerve conduction was very slow in men, but it was mildly slow or normal in women. No male-to-male transmission was found in six generations.

Adolescent↗

Isolation and analysis of circulating immune complexes in leprosy.

Circulating immune complexes (CIC) were isolated by two antigen nonspecific methods from 60 leprosy patients belonging to borderline tuberculoid (BT) and lepromatous (LL) types with and without reactions. CIC were elevated in both BT and LL reactions. CIC from BT in reaction (BTR) were found to consist largely of IgG and C3, whereas, C-reactive protein could be found in CIC from LL reactions (LR). In addition, IgM and rheumatoid factor were demonstrated in the complexes of LR patients who had mainly arthritis. Antimycobacterial antibody was seen in the complexes of two-thirds of LR patients who had predominantly skin manifestations as part of their reaction. The relevance of these findings to the clinical manifestations of different types of reactions is discussed.

Animals↗

Potentiation of T-lymphocyte function by bleomycin.

Bleomycin, an anti-cancer drug, hitherto thought to have no effect on the immune response, was found to increase contact sensitivity in the guinea pig to 2,4-dinitrofluorobenzene. The drug was given in a single dose (125 mg/kg) on the day of or up to 3 days after sensitization, to achieve this effect. The drug was ineffective if given 3 days before or 4 days after sensitization. In addition, if given 2 or 3 days after sensitization, it caused increased T-cell proliferation in lymph nodes draining the skin sensitization site. It is suggested that the potentiating effect of bleomycin is not on suppressor cell function, as with cyclophosphamide, but might have an effect on local interleukin 2 production, particularly if given when T-cell proliferation is on the increase.

Adjuvants, Immunologic↗