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Biomedical subjects

B J Collins

Publications and source records attributed to B J Collins.

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

Immunohistochemical changes in sigmoid colon after allogeneic and autologous bone marrow transplantation.

AIM: To determine whether there are characteristic immunohistological changes in the colonic mucosa in acute graft versus host disease (GvHD). METHODS: Consecutive allogeneic (n = 11) and autologous (n = 11) bone marrow transplant recipients underwent endoscopic biopsy of sigmoid mucosa before transplant and on day 30 post-transplant. Immunohistochemical staining and quantitation of intraepithelial and lamina propria mononuclear cells were undertaken using a panel of monoclonal antibodies and a Streptavidin-biotin alkaline phosphatase staining technique. RESULTS: In the allogeneic group (nine of whom had clinical acute GvHD) there was a fivefold increase in lamina propria CD16+ mononuclear cells (3.1 +/- 4.3 to 17.0 +/- 12.2 per 100 lamina propria nucleated cells), compared with autologous transplant recipients in whom this rise was twofold (5.5 +/- 4.6 to 10.6 +/- 7.1 per 100 lamina propria nucleated cells). The CD16+ mononuclear cells had morphological appearances of tissue macrophages, but in neither the allogeneic nor autologous groups was there an increase in total macrophage numbers (CD14+). In patients with acute GvHD the lamina propria CD4+:CD8+ lymphocyte ratio fell (1.97 +/- 1.12 to 1.07 +/- 1.01), primarily because of a fall in the number of lamina propria CD4+ lymphocytes. In both allogeneic and autologous groups there was a fall in intraepithelial lymphocyte numbers, but there was no change in CD19+ (B cell), CD25+ (interleukin-2 receptor positive) or CD56+ (natural killer) cell numbers. CONCLUSION: Following bone marrow transplantation, there appears to be upregulation of lamina propria tissue macrophage CD16 (an Fc receptor for IgG), a change which is more noticeable after allogeneic transplantation and which may be related to the development of acute GvHD. In patients with acute GvHD there was a fall in the lamina propria CD4+:CD8+ lymphocyte ratio. If these changes are functionally important, they may have significant implications for understanding the pathogenesis of GvHD.

Acute Disease↗
PubMed1995

Ontogeny of the GH response to phorbol ester and phospholipase C in rat pituitary cells.

GH secretory patterns undergo marked change during early mammalian development. The factors that underlie these changes and the major components of signal transduction in the immature somatotrophs are not fully understood. Increasing evidence suggests that protein kinase C (PKC) plays a central role in perinatal organ differentiation and function. To evaluate the possible role of PKC as a mediator of GH secretion from immature pituitaries, we tested the effects of the PKC activating phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), alone or together with GH-releasing factor (GRF), somatostatin (SRIF), and Ca2+ modifying agents; an inactive phorbol analogue (4 alpha-12-13-didecanoate; 4 alpha-PDD), and phospholipase C on GH release from pituitary cell cultures from perinatal and mature rats. Pituitary primary cell cultures were prepared from fetal (day 20 of 21.5 days of gestation), 2-day-old, 12-day-old, and adult male (2- to 4-month-old) rats. Each experiment was performed on at least three separate occasions. The magnitude of TPA (0.15-150 nM)-induced GH release was markedly age-dependent, fractional GH release being greatest from pituitaries of fetal and newborn rats, and least from those of adults (P < 0.001). Further, the minimum dose of TPA required to stimulate GH release over basal levels was tenfold higher for adult pituitaries (15 nM) than for perinatal pituitaries (1.5 nM). Phospholipase C (1 and 10 U/ml) also caused greater fractional GH release from neonatal pituitaries than from adult pituitaries (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Intestinal mucosal mononuclear cell chimaerism after sex-mismatched allogeneic bone marrow transplantation.

The contribution of haemopoietic cell chimaerism to the pathogenesis of GVHD after BMT is unclear. This report raises the possibility that donor lymphocyte-recipient macrophage chimaerism may occur shortly after allogeneic marrow engraftment and hence might contribute to the development of GVHD. Immunohistological studies of intestinal mucosa in an allogeneic BMT patient, who did not engraft, revealed an almost complete absence of lymphocytes 30 days after transplant, but preservation of mucosal macrophage numbers. Subsequently, combined immunohistology-Y chromosome in situ hybridization studies were performed in two female BMT recipients of male donor marrow. These studies revealed that between 25 and 40% of macrophages and between 25 and 40% of T lymphocytes were of donor origin during the first 6 months after transplant. In conclusion, whilst the immunohistological studies of intestinal mucosa from a patient who failed to engraft suggest that donor lymphocyte-recipient macrophage ('split') chimaerism may occur shortly after marrow engraftment, the subsequent in situ hybridization studies revealed 'mixed' chimaerism in the two sex-mismatched BMT recipients.

Adult↗
PubMed1994

Duodenal ulcer treated with Helicobacter pylori eradication: seven-year follow-up.

The long-term benefits of Helicobacter pylori-eradication treatment (HET) in H pylori-associated duodenal ulcer are unclear. We followed up patients with duodenal ulcers from a trial of H pylori eradication in 1985-86. 63 of 78 patients (81%) were reviewed clinically and had upper gastrointestinal endoscopy with gastric antral biopsy. Of 35 patients previously rendered H pylori negative, 32 (92%) remained H pylori negative after 7.1 years (mean). All patients initially H pylori positive remained infected, unless HET was given in the interim. Duodenal ulceration was found in 20% (5 out of 25) of patients remaining H pylori-positive, compared with 3% (1 of 38) of H pylori-negative patients (p < 0.05). The reduction of duodenal ulcer relapse obtained from H pylori eradication in H pylori-associated duodenal ulcer extends to at least 7 years after treatment, and is likely to be due to freedom from H pylori infection. However, duodenal ulcer may recur in patients rendered H pylori negative, due to factors other than reinfection with H pylori.

Adult↗
PubMed1993

Expression of Egr-1 in the brain of sleep deprived rats.

In previous research, rats subjected to prolonged sleep deprivation have shown disturbances of thermoregulation, hormonal and metabolic changes in apparent response to the thermoregulatory problems, lesions on the tail and paws, and eventual death. To search for alterations of functional activity in brain, the expression of the immediate early gene Egr-1 was examined by immunocytochemistry and Northern blotting in rats subjected to total sleep deprivation (TSD) for 10 days. Controls included yoked stimulus-control (TSC) rats, surgically implanted but otherwise undisturbed control rats, and unoperated control rats. Photographs of immunoreacted coronal sections from four sets of rats were ranked blindly for 25 brain regions. TSD rats showed tendencies for regionally specific increases in Egr-1-like immunoreactivity in dorsal raphe, lateral habenula, superior colliculus, and ventral periaqueductal grey. However, most regions showed no differences in Egr-1-like immunoreactivity between TSD and control rats. Neither was there a difference in whole brain Egr-1 mRNA by Northern blot in two additional sets of rats. Thus, this study, like previous studies of brain histology, amines, adrenoceptors, and glucose utilization, does not provide positive support for the hypothesis that sleep protects the central nervous system against massive global damage, fatigue, or dysfunction.

Animals↗
PubMed1993

When is Helicobacter pylori infection acquired?

Cross sectional surveys have shown an increasing prevalence of Helicobacter pylori (H pylori) infection with increasing age in Western populations. The aim of this study was to examine the pattern of acquisition of H pylori infection over a 21 year period in a group of 141 adults who had blood samples and serum stored in 1969, 1978, and 1990. A prevalence of H pylori antibody of 39% in 1969 serum samples, 40.9% in 1978, and 34.8% in 1990 was found when assessed by an enzyme linked immunosorbent assay (ELISA). Of the 86 subjects who were seronegative in 1969, only six (7%) were seropositive in 1990. These data suggest that a cohort effect may contribute to the pattern of increasing prevalence of H pylori infection seen with increasing age. Acquisition of infection in adults is rare. It is unlikely, therefore, that reinfection will occur after successful eradication.

Adult↗
PubMed1993

Audit of the role of oesophageal manometry in clinical practice.

This oesophageal laboratory serves a population of 1.5 million. The study aimed to review referral patterns and assess the cost effectiveness of oesophageal manometry in clinical practice. All 276 consecutive manometry studies performed between 1988 and 1991 were reviewed. Reasons for referral in the 268 first referrals were: dysphagia 50.4%, non-cardiac chest pain 23.1%, gastro-oesophageal reflux disease 14.2%, connective tissue disease 11.2%, and 'other' 1.1%. Manometry was normal in 49.3%, showed achalasia in 17.9%, diffuse oesophageal spasm in 13.4%, connective tissue disease in 7.8%, hypertensive lower oesophageal sphincter in 4.5%, nutcracker oesophagus in 2.6%, and 'other' in 4.5%. A positive diagnosis was significantly more common if dysphagia was the reason for referral (65.9% v 35.3%, p < 0.01). A positive diagnosis was established in 60% of patients referred with connective tissue disease, 30.6% with non-cardiac chest pain, and 21.1% with gastro-oesophageal reflux disease. A positive diagnosis was significantly more common in connective tissue disease when symptoms were present (85% v 10%, p < 0.05). Management was changed in 48.9% of all patients because of manometry findings. The cost of each oesophageal manometry study was calculated to be 63.00 pounds: every change in patient management cost 129.00 pounds. In conclusion, oesophageal manometry changed management in over 20% of patients with non-cardiac chest pain or gastro-oesophageal reflux disease and in over 60% of those with dysphagia. It is, therefore, a useful and cost effective test in patients with these symptoms.

Adolescent↗
PubMed1993

The effect of isobutylmethylxanthine, forskolin, and cholera toxin on growth hormone release from pituitary cell cultures of perinatal and mature rats.

The factors that regulate growth hormone (GH) release during the perinatal period are not well understood. Circulating GH levels are markedly elevated in mammalian fetuses and newborns compared with mature animals, and the immature pituitary is highly responsive to the GH-stimulatory effect of GH-releasing factor (GHRF). The etiology of these developmental changes in GH secretion is not known. In order to investigate the mechanisms underlying GH release from immature pituitaries, we tested the effects of agents that increase intracellular cyclic adenosine 3',5' monophosphate (cAMP) production independent of the GHRF receptor on GH release from pituitaries of developing and mature rats. Pituitary cell cultures from fetal (day 20 of gestation), newborn (postnatal day 2), juvenile (postnatal day 12-15), adult male (3-4 months), and adult female (3-4 months) rats were tested with isobutylmethylxanthine (IBMX; 0.001-1.0 mM), forskolin (0.01-10 microM), and cholera toxin (0.025-25 ng/ml). IBMX, forskolin, and cholera toxin stimulated GH release in a dose-dependent manner from pituitary cultures of all age groups. However, the magnitude of the GH responses to these agents was highly age-dependent. Perinatal pituitaries exhibited markedly greater GH responses to IBMX, forskolin, and cholera toxin than did those of mature animals (P < 0.001 for age effect with each agent). GH release in response to the highest dose of IBMX (1 mM) was 301 +/- 8, 389 +/- 37, 296 +/- 33, 198 +/- 14, and 187 +/- 19% of control values from pituitary cell cultures of fetal, newborn, juvenile, adult male, and adult female rats, respectively (P < 0.001). In response to the highest dose of forskolin (10 microM) GH release was 537 +/- 46, 601 +/- 75, 274 +/- 22, 270 +/- 37, and 248 +/- 35% of control values in the same respective age groups (P < 0.001). Similarly, the highest dose of cholera toxin (25 ng/ml) stimulated GH release to 407 +/- 55, 365 +/- 43, 249 +/- 26, 186 +/- 11, and 186 +/- 1% of controls in these respective age groups (P < 0.003). The marked stimulation of GH release from perinatal pituitaries by IBMX, forskolin, and cholera toxin is consistent with the concept that cAMP is a potent mediator of GH release from immature as well as mature somatotrophs. The developmental changes in the GH secretory response to these agents further suggest that signal transduction pathways mediating GH release may undergo maturation, at least in part, at intrasomatotroph loci distal to the GHRF receptor.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Characterization of a novel set of membrane antigens associated with axonal growth. I. Biochemical and functional studies.

Cranin, a prominent 120 kDa laminin-binding protein of cell membranes, was originally identified and characterized by virtue of its ability to bind laminin directly in ligand-blotting assays. We have now raised polyclonal ('3070') and monoclonal antibodies (MAbs 4 and 199) against a partially purified preparation of cranin, and have characterized the properties and expression of the corresponding antigens in further detail. In immunoblots of E14 chick brain membranes, these antibodies all recognized a single major band migrating at approximately 125 kDa, with minor bands at 115 kDa and 170/180 kDa. The major 125 kDa antigen bound to laminin affinity beads in a divalent cation- and conformation-dependent manner. The 125 and 115 kDa bands were also the most prominent HNK-1 positive proteins detected overall within E14 chick brain membranes. MAbs 4 and 199 specifically inhibited the attachment of NG108-15 cells to low, but not high amounts of substratum-bound laminin. While the relation of 3070/MAb 4 antigens to cranin requires further elucidation, these data, together with evidence presented in the companion papers and elsewhere, suggest that the antigens are important in neural development by mediating at least some of the responses of neural cells to laminin--for example, by acting as a laminin receptor guiding axonal outgrowth and neuronal migration, or by involvement in the transport and binding of laminin to the surface of neurons and reactive glial cells that synthesize laminin.

Animals↗
PubMed1992

Characterization of a novel set of membrane antigens associated with axonal growth. II. Expression in the chick central nervous system.

In the preceding paper (Dev. Brain Res., 69 (1992) 215-223), a polyclonal antiserum ('3070') and several monoclonal antibodies (MAbs 4 and 199) were used to define a novel set of laminin-binding membrane antigens in chick brain. These MAbs specifically inhibited attachment of NG108-15 cells to low, but not high amounts of laminin. Here, the immunocytochemical localization of MAb 4 and 3070 antigens was examined in frozen sections of E3-P21 chick brain, with particular reference to retina, optic tectum, cerebellum and spinal cord. Growing axons and migrating nascent neurons were stained transiently, while projection neurons were intensely labelled at all stages. Some interneurons and glial cells were stained faintly; others, apparently not at all. Finally, 3070 antiserum stained neuropil regions in mature brain. Cells in the CNS expressing high levels of MAb 4 antigens corresponded to those which, in rodents, are known to migrate in response to laminin or to synthesize forms of laminin themselves. These data, together with evidence presented elsewhere (J. Comp. Neurol., 313 (1991) 625-642) and in the next paper in this series (Dev. Brain Res., 69 (1992) 277-282), suggest that MAb 4 and 3070 antigens are important in neural development by mediating at least some of the responses of neural cells to laminin--for example, by acting as a laminin receptor guiding axonal outgrowth and neuronal migration, or by involvement in the transport and binding of laminin to the surface of neurons and reactive glial cells.

Animals↗
PubMed1992

Characterization of novel set of membrane antigens associated with axonal growth. III: Expression in the regenerating goldfish optic nerve and tectum.

In the preceding two papers in this series, a polyclonal antiserum (3070) and several monoclonal antibodies (MAbs 4 and 199) were used to define a novel set of laminin-binding membrane antigens in chick brain. In chick brain, 3070 and MAb 4 antigens stained growing axons and migrating nascent neurons transiently; though projection neurons were intensely labelled at all stages, normal glial cells were stained faintly or not at all. To learn if these antigens are associated more generally with active states of nerve growth, the present paper examined the expression of 3070 and MAb 4 antigens during regeneration of the goldfish optic nerve. Only a few optic fibers or glial cells were stained by 3070 antiserum in the resting (uninjured) optic nerve, but 10 days following a unilateral nerve crush, when the growth response is maximal in these fish, distal regenerating neuritic sprouts and glial cell bodies and processes were profusely labelled. The intensity of labelling was diminished by 135 days post-crush, when most active growth was completed. Since 3070/MAb 4 antigens exhibit properties expected for functional laminin receptors, these findings suggest several possible roles that they could play to aid nerve regeneration.

Animals↗
PubMed1992

Perendoscopic pneumatic dilatation in achalasia: assessment of outcome using esophageal scintigraphy.

Sixteen patients (nine male) underwent perendoscopic pneumatic dilatation for achalasia. The Witzel dilator was chosen as it allows placement of the balloon under endoscopic vision. Its efficacy was assessed using esophageal scintigraphy. Symptom score and esophageal transit values at 100 s and after a drink of water all improved significantly (P less than or equal to 0.014) after dilatation and there was a significant correlation between the improved symptom score and the change in transit values after 100 s (r = 0.586, P = 0.017). At follow-up at 8 (3-16) months [mean (range)], 15 of 16 patients (94%) are symptom free. The Witzel dilator is effective in the treatment of achalasia. Esophageal scintigraphy offers a quantitative assessment of esophageal function, helping the clinical investigator evaluate new forms of therapy.

Adult↗
PubMed1992

Isolation and characterization of the initial radical adduct formed from linoleic acid and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone in the presence of soybean lipoxygenase.

The spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) was used to trap the initial radical formed from [U-14C]linoleic acid in the reaction with soybean lipoxygenase. By using low levels of enzyme and relatively short incubation times it was possible to avoid the formation of secondary oxidation products and polymers. The adduct was extracted after methyl esterification, and isolated by a combination of open column chromatography on silicic acid and high pressure liquid chromatography on Spherisorb S5 CN with non-aqueous solvents. The 1:1 POBN-linoleate adduct was characterized by UV, IR and ESR spectra of the appropriate HPLC column fraction, by the ratio of the UV absorption to 14C content, and by mass spectrometry of the reduced (hydroxylamine) form. The results indicated that POBN trapped a linoleic acid carbon-centered radical such that POBN was attached to the fatty acid chain at C-13 or C-9 (two isomers), the linoleate double bonds having become conjugated in the process. The exact locations of the bridges in the two isomers were only tentatively determined. There was no evidence for the presence of oxygen-bridged adducts. The trapped linoleoyl radical adduct provides evidence for the production of a free radical as part of the enzymatic mechanism of soybean lipoxygenase.

Drug Stability↗
PubMed1992

Hypersensitivity responses and repeated infections with Lucilia cuprina, the sheep blowfly.

Sheep repeatedly infected with L. cuprina at 2- but not 4-week intervals developed partial resistance to infection after five infections, as measured by larval recovery. However, resistance did not persist for more than three infections. Skin weal responses were measured after injection of larval products simultaneously with each infection. The only correlation between weal size and larval recoveries occurred at infection 1 and indicated a relationship between skin sensitivity and innate rather than acquired resistance. The results suggest that resistance to L. cuprina can develop after repeated infections but that it is short lived and requires frequent larval exposure. A role for hypersensitivity responses was not confirmed by the weal responses but was suggested by the size of wound developed per larva recovered.

Animals↗
PubMed1992

Colorectal cancer and ischaemic heart disease: an uncommon inheritance!

This study reports the relative risk of death from cancer and from coronary artery disease in 1,811 first-degree relatives of 205 young colorectal cancer probands. The elevation in the risks of death from cancer (eg colon 3.6; rectum 2.0; uterus 1.8; cervix 2.3) is consistent with, though of lower magnitude than previous studies. An unexpected find was a highly significant deficit in coronary deaths. Recently discovered molecular associations between colon cancer and cholesterol metabolism suggest that further family studies of bowel cancer and heart disease in a variety of populations may be worthwhile.

Cause of Death↗
PubMed1992

Families at risk of colorectal cancer: who are they?

The first degree kinships of 305 index cases have been studied to determine whether an early age of onset or a particular site distribution characterizes familial aggregations of colorectal cancer. The probands comprised 100 patients aged 55-74 years and 205 patients under 55 years at diagnosis and were drawn from a large population database. Ascertainment and verification were complete for 2566 of 2657 first degree relatives. The history of cancer in 296 relatives was validated in 96% of cases from medical or other records. Among kinships ascertained through index cases under 55 years of age, less than 5% had three or more individuals affected by colorectal cancer. The comparable proportion of older probands' families was 3%. Probands with proximal disease were no more likely to have a positive family history of bowel cancer than those with disease distal to the splenic flexure. These findings are consistent with other population based studies of the epidemiology of familial colorectal cancer but contrast with reviews from referral centres and family cancer clinics.

Age Factors↗