In vitro growth of epithelial cells from mucosa derived from different regions of the gastrointestinal tract

Attempts have been made to culture the mucosa from various parts of the gastrointestinal tract. In this study, using an explant culture method, epithelial cells have been successfully cultured from all major regions of the gastrointestinal tract. The success rate, as judged by outgrowth of epithelial cells for at least 4 weeks, varied with the tissue studied with 19/50 colonic biopsies, 5/11 small intestinal biopsies, 9/12 stomach biopsies and 42/47 gallbladder biopsies yielding outgrowth of epithelial cells. Differentiation of the epithelial cells along the mucus cell pathway could be demonstrated on the monolayer cultures using Periodic acid Schiff or Alcian blue staining. Because the cultures were very heterogeneous and many morphological cell types were present in most cultures, differentiation along the other known differentiation pathways of the gastrointestinal mucosa, such as development of absorptive cells and endocrine cells, could not be excluded.
The problem of bacterial contamination, which has hindered previous studies on tissue from these sites, was overcome by decontaminating the biopsy by soaking in dilute sodium hypochlorite (0.04%).     

THE PITUITARY-LEYDIG CELL AXIS IN MEN WITH SEVERE DAMAGE TO THE GERMINAL EPITHELIUM

Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of acute exercise on colonie motility

Abstract Changes in colonic motor activity during aerobic exercise were investigated in ten regularly exercising volunteers (five males and five females) aged 27–70 years. Motility was recorded with a catheter containing three solid-state pressure transducers spaced 5 cm apart. The motility catheter was advanced 40–50 cm from the anal verge by flexible sigmoidoscope without anesthesia at least 60 min prior to testing. Manometric recordings were made from the colon during a 1-h pre-exercise rest period, 1 h of jogging at 70–80% maximum heart rate, and 1-h post-exercise rest period. The dominant frequency of contractile activity in the colon shifted from 1–4 cpm during rest, to 4–9 cpm with the onset of exercise. Activity also shifted from sporadic, isolated contractions to regular, propagated contractions in six of ten subjects, five of whom reported a history of runner's diarrhoea. The dominant frequency returned to 1–4 cpm during the post-exercise period. These changes in distal colonie motility may account for the diarrhoea which some subjects experience during intense, acute exercise.     

The effect of estrone on thrombin generation may explain the different thrombotic risk between oral and transdermal hormone replacement therapy

Summary. Background: The metabolism of estrogen contained within hormone replacement therapy (HRT) is influenced by the route of administration, and this may affect the risk of venous thromboembolism. Thrombin generation, a global coagulation assay, is a marker of hypercoagulability and is of potential use in determining the thrombotic risk associated with particular HRT administration routes. Objectives: To determine whether any effect of oral and transdermal HRT on thrombin generation is related to the plasma estrogen profile. Methods: We investigated the effects of oral, transdermal and no HRT (controls) in 52, 39 and 52 postmenopausal women, respectively, on thrombin generation, standard markers of thrombophilia, estradiol level and estrone level. Results: All parameters of thrombin generation were altered in women using oral HRT as compared with controls (P < 0.001 for all comparisons). No such differences were found in women using transdermal HRT. Estrone levels correlated with peak thrombin generation (R = 0.451, P < 0.001) in women using oral HRT, but there was no correlation in women using the transdermal route. Conclusions: Thrombin generation is significantly increased in women who use HRT administered by the oral route. This is probably mediated by the hepatic first‐pass metabolism of estrone, the main metabolite of oral estradiol, which is avoided by the transdermal route. The effect of estrone on thrombin generation may provide the explanation for the higher thrombotic risk seen in women using oral rather than transdermal HRT.     

Effect on plasma lipids and lipoproteins of postmenopausal oestrogen therapy with added dydrogesterone

Summary. In a prospective, randomized, cross-over study, 14 postmenopausal women completed 9 months of treatment with conjugated equine oestrogens, 1.25 mg daily. Seven women added dydrogesterone 20 mg daily for 12 days during months 2, 3 and 4, and then 10 mg daily for an identical time in months 5,6 and 7. The other seven women added the two dydrogesterone doses in reverse sequence. No dydrogesterone was taken during months 8 and 9. Lipids and lipoproteins were measured before treatment and at the end of months 4, 7 and 9. Lipids were also estimated in an untreated (reference) group of eight postmenopausal women on two occasions 6 months apart; these showed significant changes in HDL₂- and HDL₃-cholesterol. In the treatment group, HDL-cholesterol and apolipoprotein (apo) Al were significantly higher and LDL-cholesterol and apo B were significantly lower at months 4, 7 and 9 compared with baseline values. Triglyceride levels were increased significantly over baseline values, but remained within the normal range. No significant differences between the two dydrogesterone doses were observed on any lipid and lipoprotein fraction, nor were there any differences between the oestrogen-only and oestrogen/dydrogesterone treatment phases. Dydrogesterone appears to cause little, if any, lipid and lipoprotein changes and assessment in a larger population of postmenopausal women is warranted.     

Congenital self-healing Langerhans cell histiocytosis with persistent cellular immunological abnormalities

We describe an infant who presented at birth with numerous haemorrhagic and encrusted skin lesions, hepatomegaly, lymphadenopathy, raised hepatic transaminases, leucopenia and thrombocytopenia. The diagnosis of Langerhans cell histiocytosis was confirmed by immunohistochemistry, which demonstrated the presence of CD1, S-100 and DR positive cells in the skin infiltrate. The skin lesions resolved spontaneously after 6 weeks but recurred at 3 months and again were self involuting with resolution by 9 months. Persistent circulating T-cell abnormalities, including T-cell lymphopenia and the presence and persistence of peripheral blood CD1 + cells were noted throughout the first year of life.     

Wallaby Serum Amyloid A Protein: cDNA Cloning, Sequence and Evolutionary Analysis

A serum amyloid A (SAA) clone was isolated from a Tammar wallaby cDNA library, the most distantly related mammalian species for which an SAA has been described to date. The clone predicts a premolecule of 127 amino acids with good homology to other mammalian SAAs, and consists of an 18 residue leader peptide and a mature protein of 109 amino acids. Evolutionary analysis at both the protein and nucleotide level indicate that the wallaby SAA clone clusters with the acute phase SAAs. However, as the SAA superfamily has undergone concerted evolution it is not possible to determine at this point which acute phase SAA it is most like. The grouping of wallaby SAA inside the acute phase SAA cluster demonstrates that at least some of the duplication events giving rise to multiple acute phase genes occured prior to the divergence of the eutherian and metatherian mammals.