PubMed Health⌕ Search

Biomedical subjects

P Coates

Publications and source records attributed to P Coates.

At least 37 records · Page 2Linked to original sources

Sural nerve biopsies in Guillain-Barre syndrome: axonal degeneration and macrophage-associated demyelination and absence of cytomegalovirus genome.

T-cell infiltration was detected by immunohistochemistry in only 2 of 10 sural nerve biopsies from patients with Guillain-Barré syndrome (GBS). The number of endoneurial macrophages, identified by the monoclonal antibody MAC 387, was increased, compared with the number in 10 cases of axonal neuropathy. Macrophage-associated demyelination was identified in 7 and axonal degeneration in 8 cases. Cytomegalovirus (CMV) genome was not detected with the polymerase chain reaction.

Adult↗

Characterization of integrin chains in normal and neoplastic human pancreas.

Integrins are a complex family of non-covalently linked heterodimeric glycoproteins which function as cell adhesion molecules, interacting with extracellular matrix molecules such as laminin, fibronectin, vitronectin, and collagen, and also having a role in intercellular adhesion. Each integrin subfamily is characterized by a common beta chain associated with variable alpha chains. We have examined, using immunohistological methods, the expression of the VLA (very late activation) family comprising beta 1 in association with alpha 1-6, and also alpha 6 in association with beta 4, the LFA beta chain beta 2, and the vitronectin receptor, in association with beta 1 or beta 5 and as the complex alpha v beta 3. Cryostat sections of normal pancreas, pancreatic adenocarcinomas, and ampullary tumours were studied together with six pancreatic carcinoma cell lines. Normal pancreas showed expression of beta 1 in all parenchyma. alpha 2 and alpha 6 had a similar distribution whereas alpha 3 expression was confined to ducts, including the very smallest radicles. Staining along the basement membranes of ducts was seen with beta 4 and the anti-vitronectin alpha v chain receptor antibody 13C2. Islet cells failed to stain with any antibody. No staining of epithelial components was seen with antibodies to alpha 1, alpha 4, alpha 5, or to the alpha v beta 3 form of the vitronectin receptor (beta 3 and alpha v beta 3 using the antibody 23C6). Pancreatic adenocarcinomas and ampullary tumours showed expression of alpha 2, alpha 3, alpha 6, beta 1, beta 4, and the vitronectin receptor (alpha v associated with beta 1 or beta 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Basement Membrane↗

An open study to compare the pharmacokinetics, safety and tolerability of a multiple-dose regimen of azithromycin in young and elderly volunteers.

An open, parallel study was conducted to compare the pharmacokinetics of oral azithromycin in young and elderly healthy volunteers. A total of 12 young subjects (six males, six females) with a mean age of 29 (range 22-39) years and another 12 elderly subjects (six males, six females) with a mean age of 72 (range 67-80) years were given a standard five-day therapeutic regimen of azithromycin (500 mg single dose on day 1 and 250 mg once daily on days 2-5). Pharmacokinetic results indicated that Cmax, Cmin and urinary excretion were similar in the two age groups. Mean AUC0-24 was significantly greater (2.7 micrograms.h/ml) at day 5 in the elderly subjects compared with the younger age group (AUC0-24 = 2.1 micrograms.h/ml) (p = 0.041). Similarly, tmax values on days 1 and 5 were significantly greater in the elderly subjects; 3.8 h compared with 2.5 h in young subjects (p = 0.005) on day 1 and 4.4 h, compared with 3.2 h (p = 0.047) on day 5. There was also evidence of an inverse relationship between creatinine clearance and AUC0-24 (p less than 0.01) but not urinary excretion or Cmax. Despite these observations, it is concluded that the differences between the two age groups were of insufficient magnitude to warrant a dose modification in elderly subjects with only mild renal impairment. Side effects, chiefly headache and gastrointestinal symptoms, were reported by seven subjects in each group. No subject, however, was withdrawn from the study and there were no treatment-related abnormalities in any of the laboratory parameters measured.

Administration, Oral↗

In vitro and in vivo analysis of the processing and fate of the peptide products of the short proopiomelanocortin mRNA.

Many peripheral tissues express the proopiomelanocortin (POMC) gene as an 800-base mRNA that lacks the 5' end of the 1200-base pituitary transcript. The missing region encodes the peptide signal sequence, and thus, it is unlikely that any translation product would be secreted. We have found that a RNA transcript equivalent to this short message, generated by transcription in vitro from a T7 polymerase promoter, is translatable in a rabbit reticulocyte lysate, generating peptides of 27.5, 22.5, and 15.5 kD. None of these peptides appears to be processed or protected from proteinase-K digestion by a microsomal membrane fraction. In vivo studies were undertaken by transfecting into GH3 cells one of two expression vectors containing sequences that would produce either a full-length mRNA or a short (800-base) mRNA. The neomycin resistance gene was cotransfected with these plasmids, and 30 permanent cell lines were produced after selection in G418. Cell lines containing the full-length RNA secreted large quantities of ACTH and beta-endorphin immunoreactivity, whereas those expressing the short transcript secreted neither of these peptides. However extractable peptide was present in this latter type of cell line, thereby suggesting that the 800-base mRNA was translated, and that no peptide reached the secretory vesicle. These findings raise important questions about the role of peripheral POMC gene expression.

Adrenocorticotropic Hormone↗

Survival of cultured allogeneic keratinocytes transplanted to deep dermal bed assessed with probe specific for Y chromosome.

To determine the survival of cultured allogeneic keratinocytes transplanted to a deep dermal bed 24 tattoos that had been removed by deep shave excision in 19 patients were grafted with sheets of cultured allogeneic keratinocytes from donors of the opposite sex. Cells carrying the Y chromosome were identified in biopsy specimens taken from the graft site by in situ DNA hybridisation with a biotinylated Y probe (pHY 2.1) and visualised with a technique using immunoperoxidase. The cultured allograft sites were biopsied one, two, and three weeks after transplantation. No male cells were identified in any biopsy specimen from female patients who were given transplants of male cultured keratinocytes, and all biopsy specimens from male patients, who received female cultured keratinocytes, showed percentages of male cells within the normal range for male skin. The beneficial effects of cultivated allogeneic keratinocytes result from effects on wound healing other than forming a successful graft that "takes."

Bandages↗

The effects of transsphenoidal surgery on endocrine function and visual fields in patients with functionless pituitary tumours.

Twenty-eight patients with functionless pituitary tumours have been treated by transsphenoidal surgery over the last 28 months. Mean age at presentation was 55 years. Tumor size was graded according to the extent of suprasellar extension on CT headscan from above the interclinoid line: four were small, 15 medium and nine large. Before surgery in 25 per cent of patients visual acuity and visual fields were normal. In the immediate postoperative period, 24 per cent of the patients with visual defects before surgery had normal vision, and in 38 per cent of the others it was improved. Six months after surgery, there had been further improvement; 43 per cent had normal vision and 48 per cent showed an overall improvement. In no patient did vision deteriorate following surgery. In the patients who presented with visual symptoms of one year or less, there was no correlation between the length of symptoms and the extent of visual recovery after surgery. Average age of the patients with full visual recovery was 47 +/- 4 years (mean +/- SEM); average age of the patients with only partial visual recovery was 63 +/- 3 years. Prolactin levels before surgery were elevated in 77 per cent of patients and fell significantly after operation, remaining elevated in 28 per cent of patients six months later. Fifty per cent of patients were treated with long-term hormone replacement therapy. Transsphenoidal surgery led to improved vision in the majority of patients, the results being comparable with those obtained with transfrontal surgery. Surgical complications were few, and long-term morbidity low. We suggest that the first-line treatment for patients with functionless pituitary tumours should be transsphenoidal surgery, even when large suprasellar extensions are present.

Adenoma↗

Immunoreactive human chorionic gonadotrophin from the cyst fluid and CSF of patients with craniopharyngioma.

A specific radioimmunoassay for the beta-chain of human chorionic gonadotrophin irHCG beta has demonstrated HCG-like material to be present in craniopharyngioma cyst fluid in nine consecutive patients with craniopharyngioma. There was no detectable LH/HCG bioactivity as assessed using testosterone production from isolated Leydig cells from rat testis in seven samples tested. One patient was also found to have measurable irHCG beta in the cerebrospinal fluid (CSF), which fell to undetectable levels following surgery; in this patient, there was clinical evidence that the cyst fluid had leaked into the CSF pre-operatively. Immunocytochemical staining for HCG beta and intact HCG was positive in five of the tumours. irHCG beta was not measurable in the serum of any of the patients.

Biological Assay↗

Structural complexity of Y chromosome heterochromatin.

Following a standard C-banding procedure early metaphase chromosomes demonstrate a discontinuous distribution of heterochromatin in the long arm of the human Y chromosome. The discrete blocks of heterochromatin can be shown to be separated into nonrepeating sequences by in situ hybridization using probe pHY 2.1. The number of heterochromatin blocks vary from person to person.

Chromosome Banding↗

"Is it functional?" A question for music therapists who work with the institutionalized mentally retarded.

The criterion of ultimate functioning is beginning to be the standard for treatment in institutions for the mentally retarded. The medical and developmental models are being replaced as standards because they are not considered sufficiently effective for deinstitutionalizing adult severely and profoundly retarded clients. Music therapists are being required to devise treatment plans to develop functional leisure time skills that clients can pursue independently in a community setting.

Adult↗

A phaeochromocytoma presenting with Cushing's syndrome associated with increased concentrations of circulating corticotrophin-releasing factor.

The case is described of a 61-year-old male who presented with hypertension and Cushing's syndrome which resolved on excision of a unilateral adrenal mass. Histology of the tumour revealed a benign phaeochromocytoma which immunostained for corticotrophin-releasing factor (CRF-41) but not for ACTH. Preoperative plasma concentrations of immunoreactive CRF-41 were increased, and gradients for both CRF-41 and ACTH were demonstrated across the tumour. Post-operatively, CRF-41 was undetectable in plasma. The tumour contained high concentrations of immunoreactive CRF-41 which co-eluted with synthetic human CRF-41 on reversed-phase high-performance liquid chromatography. Tumour CRF-41 stimulated the release of ACTH in a dose-dependent manner from isolated rat anterior pituitary cells. We conclude that this tumour secreted CRF-41 and ACTH and had the capacity to produce ACTH-dependent Cushing's syndrome directly by secreting ACTH and indirectly by secreting CRF-41 to stimulate ACTH secretion from the anterior pituitary.

Adrenal Gland Neoplasms↗

An HPLC assay for sulphapyridine in plasma and its use to assess small bowel transit time after the administration of sulphasalazine.

An HPLC assay for sulphapyridine is described. The use of the assay to measure sulphapyridine produced by the action of large bowel flora on 2 g of orally administered sulphasalazine as a means of assessing oro-colonic transit time is discussed. The assay is applied to show the action on oro-colonic transit time of a novel gastrokinetic agent BRL 24924 which brought about a 62.8% median reduction in transit time at a dose of 5 mg.

Adult↗

Increased activity of rat intestinal lactase due to increased intake of alpha-saccharides (starch, sucrose) in isocaloric diets.

The adaptability of intestinal microvillar alpha-disaccharidases to the variation of alpha-saccharide content in the diets is well established, but the influence of these sugars on the activity of microvillar lactase (neutral beta-galactosidase) has heretofore been considered negligible or non-existing. In two experiments rats were fed isocaloric diets where the carbohydrate (starch or sucrose) content versus fat content was varied. (High carbohydrate diets: 71% of calories as carbohydrate and 5% of calories as fat; low carbohydrate diets: 6 and 73% calories, respectively). Experiment 1: male and female rats had access to experimental diets only from day 12 postnatally and were killed at age 56 days. Experiment 2: male rats were fed experimental diets starting on day 73 postnatally and killed 3, 7, 14 and 28 days later. Rats fed the high carbohydrate diets exhibited a significant increase in activity (specific and total per segment) of lactase in all three intestinal segments compared to rats fed the low carbohydrate diets. Changes in the activity of sucrase and maltase paralleled those of lactase activity. These experiments have thus demonstrated clearly the influence of variation in alpha-saccharide content in the diet upon lactase activity. Further experiments are needed to determine the active principle of this dietary adaptation.

Adaptation, Physiological↗

Interstitial deletion 13q33 resulting from maternal insertional translocation.

A 32-month-old female with a unique interstitial deletion of 13q is presented, including cytogenetic and gene marker studies. The deleted 13 in the patient is a result of malsegregation of a maternal insertional translocation involving chromosomes 7 and 13, 46,XX,ins(7;13)(q22;q32q34). The demonstration of two esterase D alleles in this patient excludes band 13q33 as the site of the ESD locus, previously assigned to the distal long arm of chromosome 13. The BUdR dye studies reveal that the replicative pattern for 13q31 and 13q21 is not altered by deletion of 13q33 and permit precise delineation of the breakpoints of the rearrangement.

Abnormalities, Multiple↗