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Biomedical subjects

P Hudson

Publications and source records attributed to P Hudson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Disposition of ingested olestra in the Fischer 344 rat.

Four studies were conducted in the Fischer 344 rat to determine the disposition of orally gavaged olestra. Twenty-four rats were used for each study. Three olestra samples, differing in the degree of saturation of the fatty acid chains, were tested; one sample was heated to simulate olestra's intended use in preparing fried foods. In addition, a sucrose polyester (SPE) sample containing 28% short-chain penta- and lower polyesters was tested. All test samples were uniformly labeled with 14C in the sucrose moiety. Urine, feces, and CO2 were continuously collected and counted. Urine also was analyzed for [14C]sucrose by HPLC. If olestra were absorbed and systemically metabolized, [14C]sucrose would be excreted in the urine. Rats were killed 1, 3, 7, and 21 days after dosing, and tissues were collected and counted. Tissue lipids were extracted and analyzed for intact olestra or SPE by HPLC. Less than 0.15% of the dose of 14C was absorbed from the olestra samples, and about 1.3% from the SPE sample. The disposition of the absorbed radiolabel suggested that its source was glucose and fructose resulting from the intestinal hydrolysis of short-chain penta- and lower sucrose polyesters. For rats dosed with olestra, < 8 x 10(-4)% of the dose of radiolabel was recovered in the olestra-containing fraction of lipids extracted from liver, the target organ for absorbed olestra, and no [14C]sucrose was found in urine, indications that olestra essentially was not absorbed. Heating olestra did not change this result.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Hyperthyroidism and radio-iodine therapy in a district general hospital.

A retrospective analysis was performed of 48 patients with hyperthyroidism (41 women aged 35-80, mean 56.6 years; 7 men aged 31-77, mean 52.1 years) treated with a fixed dose of 550 MBq 131I during a 12 month period May 1991-April 1992. Weight loss was common at presentation but 28.57% of women aged 35-49 years weighed over 80 kg compared to 9.98% in a standard UK population P < 0.05. Patients treated with carbimazole (73%) prior to 131I had higher FT3 levels at presentation (14.0 +/- 4.4 pmol/l) compared to those (27%) who were considered not to require such treatment (8.9 +/- 1.4 pmol/l, P < 0.001). Four months following radio-iodine, 67% were hypothyroid, 25% were euthyroid and 8% remained thyrotoxic and were retreated. Another patient became hypothyroid during 1 year of follow-up. Pre-treatment with carbimazole did not protect against the development of hypothyroidism (carbimazole treated 69% hypothyroid at 4 months, untreated 62% hypothyroid at 4 months). Patients with continuing thyrotoxicosis had very high FT3 levels at presentation (18.6, 21.1, 20 and in one patient reported only as > 10 pmol/l). A rationalized programme of follow-up assessments at 2, 3, 4, 8 and 12 months is suggested for patients treated with this dose of radio-iodine.

Adult↗
PubMed1992

Prolonged stimulation of bovine adrenal chromaffin cells with arachidonic acid and prostaglandin E2 increases expression of the proenkephalin gene and the secretion of [Met5]-enkephalin.

The effects of long-term exposure of bovine adrenal medullary chromaffin (BAMC) cells to arachidonic acid (AA) and prostaglandin E2 (PGE2) on [Met5]-enkephalin (ME) secretion and expression of the proenkephalin A (proENK) gene were studied. Treatment with various concentrations of AA or PGE2 for 24 hr increased the secretion of ME in a concentration- and time-dependent manner. At high concentrations (10-100 microM), but not low (1-3 microM), AA significantly increased ME secretion by 1 hr. In contrast, the onset time for increase of ME secretion by PGE2 was 3 hr after exposure. The magnitude of increase in ME secretion in the presence of AA or PGE2 continued to increase with time. However, intracellular ME levels in AA- or PGE2-treated cells were not significantly different from that of controls, indicating that elevated levels of ME secretion into the media may be a result of increased biosynthesis of ME. In addition, AA or PGE2 increased proENK mRNA level in a concentration- and time-dependent manner. The onset time for the increase in proENK mRNA in response to PGE2 was 6 hr after exposure. The treatment of BAMC cells with 20 microM cycloheximide (a protein synthesis inhibitor) inhibited both the increased secretion of ME and proENK mRNA level induced by AA and PGE2 in a time-dependent manner, indicating that the delayed secretion of ME and the increase in proENK mRNA level induced by AA and PGE2 require protein synthesis. Indomethacin (a cyclooxygenase inhibitor, 10 microM) effectively inhibited AA-induced responses, whereas 10 microM nordihydroguaiaretic acid (a lipoxygenase inhibitor) was inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1991

Multi-subunit proteins on the surface of filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains.

The display of proteins on the surface of phage offers a powerful means of selecting for rare genes encoding proteins with binding activities. Recently we found that antibody heavy and light chain variable (V) domains fused as a single polypeptide chain to a minor coat protein of filamentous phage fd, could be enriched by successive rounds of phage growth and panning with antigen. This allows the selection of antigen-binding domains directly from diverse libraries of V-genes. Now we show that heterodimeric Fab fragments can be assembled on the surface of the phage by linking one chain to the phage coat protein, and secreting the other into the bacterial periplasm. Furthermore by introducing an amber mutation between the antibody chain and the coat protein, we can either display the antibody on phage using supE strains of bacteria, or produce soluble Fab fragment using non-suppressor strains. The use of Fab fragments may offer advantages over single chain Fv fragments for construction of combinatorial libraries.

Amino Acid Sequence↗
PubMed1990

Burkitt's lymphoma of the testicle: report of 2 cases occurring in elderly patients.

Burkitt's lymphoma is rare in patients older than 50 years and almost never presents as a testicular tumor. We report 2 cases of primary Burkitt's lymphoma of the testicle in men 68 and 79 years old. In 1 man the extragonadal tumor had a rapid and lasting response to combination chemotherapy. The cases are of interest for the unusual presentation of the disease and for the possibility to control Burkitt's lymphoma in older patients without undue toxicity. The management of testicular lymphoma requires radical orchiectomy and prophylactic irradiation of the contralateral testis. Chemotherapy is indicated for advanced disease and may prevent relapses in patients with early disease. The role of central nervous system prophylaxis is controversial.

Aged↗
PubMed1990

Human seminal clusterin (SP-40,40). Isolation and characterization.

Molecular cloning of the human complement inhibitor SP-40,40, has revealed strong homology to a major rat and ram Sertoli cell product, sulfated glycoprotein-2, known also as clusterin. This study reports the purification and characterization of human seminal clusterin. Two-dimensional gel electrophoresis revealed charge differences between clusterin purified from semen and the serum-derived material. Both preparations demonstrate comparable hemagglutination (clustering) activity and inhibition of C5b-6 initiated hemolysis. The average clusterin concentration in normal seminal plasma is considerably higher than that found in serum. Mean seminal plasma clusterin concentrations were significantly lower in azoospermia caused by obstruction or seminiferous tubule failure than with oligospermia or normospermia. Only men with vasal agenesis had undetectable seminal clusterin, suggesting that some of the seminal clusterin is produced by the seminal vesicles. Immunofluorescence of human spermatozoa revealed that clusterin was detected on 10% of spermatozoa, predominantly those that were immature or had abnormal morphology. A pilot study of 25 patients suggests that seminal clusterin concentration, together with sperm motility and morphology, is correlated with the fertilization rate in vitro. The function of seminal clusterin is unknown. Its extensive distribution in the male genital tract and its high concentration in seminal plasma suggests an important role in male fertility.

Animals↗
PubMed1990

Localization of insulin-like growth factor-I mRNA in rat brain by in situ hybridization--relationship to IGF-I receptors.

Recent evidence has demonstrated regional synthesis of insulin-like growth factor I (IGF-I) in rat brain, which is also known to contain widespread specific type I IGF receptors. In order to precisely define sites of IGF-I mRNA synthesis, and their relationship to IGF-I receptor sites, we have applied the techniques of in situ hybridization and in vitro receptor autoradiography in rat brain. Frozen sections of adult rat brain and liver were hybridized with 32P-labeled cDNA inserts for human IGF-I (780 base pairs) or a positive control transthyretin cDNA (1430 base pairs) probe, or a series of negative probes, followed by film or emulsion autoradiography. Receptor autoradiography was performed on similar sections using 125I-IGF-I in buffer, some chambers containing excess unlabeled IGF-I. Hybridization of IGF-I probe was clearly seen only in three major brain regions: the olfactory bulb, hippocampus and cerebellum, whereas transthyretin only hybridized to choroid plexus as expected, and other probes showed no hybridization. In olfactory bulb, hybridization was greatest in the internal granular and mitral cell layers, with lower levels in the glomerular layer, where IGF-I receptors were concentrated. In hippocampus, hybridization was to pyramidal cells of Ammon's horn in CA1 and CA2 layers and dentate gyrus, with some labeling in CA3. IGF-I receptors were most dense in CA2, CA3, CA4, and dentate gyrus. In cerebellum, hybridization was to the granule cell layer, with IGF-I receptors primarily in the adjacent molecular layer. We have clearly demonstrated precise sites of local IGF-I synthesis in adult rat brain, adjacent to, and sometimes overlapping sites of high density IGF-I receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Molecular cloning and characterization of the novel, human complement-associated protein, SP-40,40: a link between the complement and reproductive systems.

The cDNA sequence encoding the human complement-associated protein, SP-40,40, is reported. The two chains of SP-40,40 are coded in a single open reading frame on the same mRNA molecule, indicating the existence of a biosynthetic precursor protein which matures post-synthetically by the proteolysis of at least one peptide bond. The precursor is preceded by a signal sequence for vectorial export and contains six N-linked glycosylation sites distributed equally between the two chains of the structure. The sequence of the SP-40,40 precursor bears a 77% identity to a rat sulphated glycoprotein-2 (SGP-2) which is the major secreted product of Sertoli cells. The presence of SP-40,40 within human seminal plasma at levels comparable to those in serum was demonstrated, indicating that SP-40,40 and SGP-2 are serum and seminal forms of the same protein. A sequence of 23 amino acids within the beta-chain of SP-40,40 exhibited significant homology to corresponding segments located within complement components C7, C8 and C9. The short cysteine-containing motif represented the only evidence of a possible vestigial relationship between SP-40,40 and other complement components. The precise role of SP-40,40 is not known in either blood or semen but the present findings document an intriguing link between the immune and the reproductive systems.

Amino Acid Sequence↗
PubMed1989

Production of parathyroid hormone-related protein by a rat parathyroid cell line.

Parathyroid hormone-related protein (PTHrP), the peptide associated with humoral hypercalcemia of malignancy, has been identified in fetal and adult parathyroid glands. We here report a sub-clone of a rat parathyroid cell line which secretes a single peptide species corresponding in size to PTHrP(1-84). Biological activity of the secretion product was blocked by a specific antiserum against PTHrP, but not by parathyroid hormone (PTH) antiserum. Secretion of PTHrP by these cells was regulated by extracellular calcium in the physiological range. A single messenger RNA species for PTHrP was identified, though PTH mRNA could not be shown in these cells. Hybrid CAT genes containing 700-1000 bp of 5'-flanking DNA from the human PTH or PTHrP genes were transfected into these cells, and the PTHrP gene was expressed at 10-fold higher levels than the PTH gene. These cells thus provide a valuable model system for investigation expression of PTHrP in a non-transformed cell line.

Adenylyl Cyclases↗
PubMed1989

Evaluation of the effect of cicletanine on genetic atherosclerosis in the rabbit.

This study was designed to evaluate the hypolipidaemic and anti-atherosclerotic potential of cicletanine in a genetic hypercholesterolaemic rabbit model. In a pilot study the effect of 8 weeks oral administration of 2 treatment levels of cicletanine (10, 30 mg.kg-1.day-1) was compared with vehicle alone. In the main study, 8 weeks oral administration of 2 treatment levels of cicletanine (5, 30 mg.kg-1.day-1) was compared with parallel treatment with probucol (15 mg.kg-1.day-1) and with nifedipine (10 mg.kg-1.day-1). At the start of each study and at scheduled points throughout, blood samples were collected for routine biochemical and lipid/lipoprotein analyses. At the end of each test period all animals were examined at post mortem. Aortae were dissected and examined for the presence ans degree of atheroma. Hearts were examined for the presence of lesions. Sections of aortae were stained for lipid, examined histologically and scored for extent of atheroma using an atherosclerotic index. In the pilot study cicletanine had no effect on blood lipid levels. Gross pathology indicated a reduction in the extent of aortic atheroma in cicletanine-treated animals. Histopathological examination of thoracic and abdominal regions of the aortae confirmed these gross findings. The atherosclerotic index was significantly reduced (p less than 0.06) in all drug treated animals. In the main study similar data were achieved. None of the test drug affected plasma lipid/lipoprotein levels. Gross pathology indicated a reduction in the extent of aortic atheroma in all cicletanine-treated animals and also in the nifedipine-treated group. This was confirmed by histopathological examination of thoracic and abdominal regions of the aortae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Fatal iatrogenic salicylate intoxication in a long-term user of enteric-coated aspirin.

A 64-year-old woman, who was taking long-term enteric-coated aspirin therapy for rheumatoid arthritis, was prescribed approximately twice her normal dosage (7.1 g daily) during a ten-day convalescence following surgery. Although she presented with features mimicking sepsis, biochemical analysis, ie, a spuriously high carbon dioxide content, suggested salicylate intoxication (admission salicylate concentration, 5.13 mmol/L). She died on the third day after admission. Autopsy showed no major source of infection except for bronchopneumonia. Long-term users of a high-dose aspirin are at risk for potential salicylate intoxication. The metabolism of salicylate, particularly its excretion kinetics, can make small upward dosage adjustments hazardous. Salicylate has widespread metabolic effects that can mimic other medical conditions, leading to delayed diagnosis of salicylate intoxication. Increased mortality and morbidity may result.

Arthritis, Rheumatoid↗
PubMed1989

Three cases of fatal anaphylaxis to antibiotics in patients with prior histories of allergy to the drug.

Three cases of fatal anaphylaxis to penicillin and cephalexin are described. All three patients had prior histories of severe allergic reactions to the antibiotics they were given. The radioallergosorbent test was positive on post-mortem blood to the appropriate antibiotic in all three cases. RAST can be performed on post-mortem specimens of serum, sodium fluoride-treated blood, or whole blood.

Adult↗
PubMed1988

Molecular cloning and characterization of ovine homeo-box-containing genes.

The sheep genome contains at least eleven homeo-boxes (hox). Using two hox-specific 36-mer oligodeoxynucleotides to screen a sheep genomic library, constructed in lambda Charon28, clones of nine of the hox were identified. Six of the hox clones were analysed by nucleotide sequencing, Southern-blot hybridization and Northern-blot analysis. Two of the hox appear to be cognates of the human Hu-1 (or mouse Hox 2.1) and the mouse Hox 1-3, while another is closely related to the mouse Hox 1-4. These results suggest that there is strong sequence conservation in the hox-containing genes of different mammals, and highlight the possible occurrence of an ubiquitous set of hox-containing genes in mammals. Northern-blot analysis of four sheep hox-containing genes indicates that they are all expressed during embryogenesis and that expression is temporally regulated allowing hierarchical-regulatory interaction. Interestingly, none of the cloned hox-containing sequences contain repetitive sequences.

Amino Acid Sequence↗
PubMed1988

Structure and expression of the rat transthyretin (prealbumin) gene.

The rat transthyretin gene, 7.3 kilobase pairs (kb) long, with 14.5 kb of 5' flanking and 12.2 kb of 3' flanking region was cloned and characterized. The gene contained four exons. A "TATA box" sequence (5'-TATATAA-3') and a "CAAT box" sequence (5'-GTCAAT-3') were located 23 and 95 nucleotides upstream, respectively, from the major transcription start site. Nucleotides -51 to -189 were highly conserved (93% homology between rats and humans, 97% homology between rats and mice). Tandem repeats of sequences of 5'-AC-3' and 5'-ACACATGC-3' in the 5' flanking region, of 5'-GAAA-3' in the first intron, and of 5'-GT-3' in the third intron of the gene were observed. Using specific cDNA probes, tissue specificity and regulation of transthyretin mRNA biosynthesis during embryogenesis were analyzed. Transthyretin expression occurred first in the yolk sac, then decreased when expression increased in fetal liver. Presumptive choroid plexus cells in the inner lining of the neural tube expressed transthyretin early in gestation (11 days before birth) with a maximum immediately preceding the spurt of brain growth around birth. Partial hepatectomy of adult rats induced both an acute phase response and regenerative growth in liver. The decrease in transcription of the transthyretin gene in liver, which is characteristic for the acute phase response, was overridden by stimulation of gene expression after partial hepatectomy. This stimulation also affected transthyretin expression in choroid plexus.

Amino Acid Sequence↗
PubMed1988

The expression of transthyretin mRNA in the developing rat brain.

Specific cDNA and oligonucleotide probes were used to study the appearance of transthyretin mRNA in developing rat brain using Northern gel analysis, cytoplasmic dot hybridization, and in situ hybridization. Transthyretin mRNA in embryonic rat brain was found to be confined to the epithelial layer of the choroid plexus primordia appearing first in the fourth ventricle, followed by appearance in the lateral ventricles, and subsequently in the third ventricle. Transthyretin mRNA was localized in these cells from early stages of neuroepithelium differentiation, showing that it is a sensitive marker for the differentiation of the choroid plexus within the fetal brain.

Animals↗
PubMed1988

Hepatitis B markers in Lancashire police officers.

A total of 284 Lancashire police officers each with a minimum of 5 years experience was tested for evidence of hepatitis B infection. None was hepatitis B surface antigen positive (HBsAg). Three were positive for both antibody to hepatitis B core antigen (anti-HBc) and HBsAg (anti-HBs). Five were positive for anti-HBc alone. Thus the overall prevalence was 2.8% which is within the range reported for blood donors in the UK. There was no association with working in the drug squad or custody office but there was a higher prevalence in those who had worked in the scene-of-crime's squad. However, the numbers were small, and of this group of 28 officers, 2 of the 3 with detectable hepatitis B markers were positive for anti-HBc alone. Therefore for police officers in mixed rural/urban areas of the UK, routine administration of hepatitis B vaccine is not justified although special consideration should be given to those working in selected groups. Further studies are required to ascertain whether there may be an increased risk for police officers working in conurbations.

Adult↗