DECREASED BIOACTIVITY OF CIRCULATING PROLACTIN IN PATIENTS WITH RHEUMATOID ARTHRITIS

Growth hormone and prolactin (PRL) were measured by radio-immunoassayin sera of 36 patients with rheumatoid arthritis (24 femalesand 12 males) and of 50 normal blood donors (25 males and 25females). The bioactivity of PRL was also determined for bothgroups, using the Nb2 rat lymphoma proliferation assay. Althoughno significant difference was found between serum PRL valuesof patients and controls when determined by radio-immunoassay,the bioactivity of PRL was significantly decreased in patientssera, when compared to values obtained in age and sex-matchedcontrols. This decreased PRL bioactivity could not be attributedto drug treatments administered to the patients examined. KEY WORDS: Rheumatoid arthritis, Prolactin bioactivity, Prolactin immunoreactivity ^* Present address: Shaughnessy Hospital, 4500 Oak St., Vancouver,B.C., Canada. Present address: MRC Reproductive Biology Unit, 37 ChalmersSt., Edinburgh EH3 9EW, UK.     

Hydrodynamic Function of Second Generation Porcine Bioprosthetic Heart Valves

The hydrodynamic function and leaflet dynamics of second generation porcine valves prepared with low- or zero-pressure fixation have been studied and compared to first generation porcine bioprostheses, bileaflet, and tilting disc mechanical valves. The Carpentier-Edwards Supra-Annular and Hancock II valves showed lower pressure drops than the Medtronic Intact valve and first generation porcine valves, and comparable overall energy losses to mechanical valves at normal cardiac outputs. Only the zero-pressure fixed Intact valve showed synchronous leaflet opening. Delayed leaflet opening and high opening pressures were found in both low- and high-pressure fixed porcine valves. All porcine bioprostheses showed high open leaflet bending strains. Fixation of valve leaflets with "near zero" pressure fixation and a more physiological neutral geometry is necessary to ensure synchronous leaflet opening at low flows and a reduction in commissural bending strains.     

An Alzheimer's Disease-Relevant Presenilin-1 Mutation Augments Amyloid-Beta-Induced Oligodendrocyte Dysfunction

研究表明,家族性阿尔茨海默病(FAD)患者处于无症状或临床前阶段时,脑白质即出现病理改变.此种改变在髓鞘破坏及阿尔茨海默病(AD)病理生理中的作用有待进一步研究阐明.笔者前期研究证实,三重转基因AD小鼠(人淀粉前体蛋白基因的Swedish突变,早老素-1 M146V (PS1M146V)敲入突变及tauP301L突变)...     

Decrease in intrahepatic CD56+ lymphocytes in gastric and colorectal cancer patients with liver metastases

Gulubova M, Manolova I, Kyurkchiev D, Julianov A, Altunkova I. Decrease in intrahepatic CD56⁺ lymphocytes in gastric and colorectal cancer patients with liver metastases. APMIS 2009; 117: 870–9. The aim of the study was to examine the main intrahepatic lymphocyte subpopulations, namely CD3⁺ lymphocytes, natural killer (NK)‐like T lymphocytes (NKT) expressing the CD3⁺ CD56⁺ phenotype, CD56⁺ NK cells, CD4⁺, and CD8⁺ T cells in livers of patients with gastric and colorectal cancer with and without hepatic metastases. The proportion of each lymphocyte subset was determined in 34 patients with gastric or colorectal cancer (18 with and 16 without liver metastasis) by two‐color flow cytometry after extraction of hepatic mononuclear cell fraction. The distribution of lymphocyte subpopulations in selected areas of liver metastases and adjacent liver tissue was evaluated using immunohistochemistry for CD4, CD8, and CD56. Flow cytometry analysis revealed a significant decrease in the proportion of CD3⁺ CD56⁺ cells in metastatic livers, but not in nonmetastatic livers (11.9 ± 10.3 vs 24.2 ± 13.6%, p = 0.02). The percentage of intrahepatic CD3^?CD56⁺ cells was also decreased in patients with metastases compared to those without (10.1 ± 11.6 vs 16.6 ± 8.9%, p = 0.039). Immunohistochemically, three types of lymphocytes (CD4⁺, CD8⁺, and CD56⁺) were present in the metastatic tissue, although the number of CD56⁺ cells was almost twice lower. We found a low prevalence of tumor‐infiltrating CD4⁺, CD8⁺, and CD56⁺ cells in livers with multiple metastases, whereas in cases with solitary metastasis a higher degree of lymphocyte infiltration was observed. The number of CD3^?CD56⁺ and CD3⁺ CD56⁺ cells was decreased in metastatic livers compared to those unaffected by metastases. Therefore the prevalence of tumor‐infiltrating lymphocytes seems to be related to the progression of metastatic liver disease. Depletion of hepatic innate lymphocytes may reveal susceptibility to metastatic liver disease and could be a reason for the escape of metastatic cells from the mechanisms of liver immune control.     

Differential expression of LAMPs and ubiquitin in human thymus

Lysosome‐associated membrane proteins 1 and 2 (LAMP‐1 and LAMP‐2) are implicated in a variety of normal and pathological processes. LAMP‐2 is proposed to participate in chaperone‐mediated autophagy. Autophagy regulates T‐lymphocyte homeostasis by promoting both survival and proliferation. The biological importance of this process in the thymic gland and especially the involvement of LAMPs are far from being elucidated. The aim of the study was to examine the parallel expression of LAMPs and ubiquitin, a key molecule in autophagy, in normal human thymic glands and thymomas. The immunohistochemical expression of both markers was compared with that of cyclin D1 – an important regulator of cell cycle progression. Novel evidence for differential expression of LAMPs and ubiquitin is presented. Most Hassal's corpuscules in thymoma were negative for LAMPs, but positive in normal thymus. Both lymphocytes and epithelial cells in pathological thymus showed higher intensity for LAMP‐2 compared with LAMP‐1. In thymoma, ubiquitin was more intensively positive in these cell types compared with the normal thymus, suggesting activated autophagy in the course of this pathological state. A deregulation in cyclin D1 expression in thymoma is also reported. The functional importance of these molecules in autoghagy accompanying normal and pathological processes in the thymic gland is reviewed.     

INTERACTION BETWEEN SECRETION OF THE GONADOTROPHINS, PROLACTIN, GROWTH HORMONE, THYROTROPHIN AND CORTICOSTEROIDS IN MAN: THE EFFECTS OF LH/FSH-RH, TRH AND HYPOGLYCAEMIA ALONE AND IN COMBINATION

The interaction between the mechanisms involved in the LH, FSH, growth hormone, prolactin, ACTH and TSH responses to the synthetic LH and FSH releasing hormone, thyrotrophin releasing hormone and insulin induced hypoglycaemia was studied in twelve normal male volunteers. Each subject acted as his own control and the test procedures were performed individually and in combination. The simultaneous administration of one releasing hormone with another or with insulin in no way modified the hormonal responses to either releasing hormone or to hypoglycaemia. Clinical testing with these procedures may therefore be performed simultaneously, so that the pituitary reserve for the five anterior pituitary hormones may be assessed together in under 2 hr. In addition it has been shown that TRH releases a small amount of FSH but not LH in male subjects.     

CHANGES IN PLASMA LEVELS OF PROLACTIN, IN RELATION TO THOSE OF FSH, OESTRADIOL, ANDROSTENEDIONE AND PROGESTERONE AROUND THE PREOVULATORY SURGE OF LH IN WOMEN

Plasma samples were obtained at 8 hourly intervals around the preovulatory surge of LH in three groups of women with spontaneously ovulatory menstrual cycles, in order to clarify the hormonal events around the time of ovulation. In 21 of 25 women in whom samples were collected every 8 hours the start of the LH surge occurred between midnight and 0800. In 16 of these women the concentration of LH, FSH and progesterone was measured every 8 hours around the pre-ovulatory surge of LH. A progressive increase in progesterone started with the onset of the LH surge, with a transient fall after 32-40 h at a time coincident with that of ovulation. In 10 women oestradiol, androstenedione and prolactin were measured 8 hourly around the pre-ovulatory surge of LH beginning at 0800 h. Prolactin showed a sustained increase in levels beginning at the start of and lasting for the duration of the pre-ovulatory LH surge; oestradiol levels did not rise around this time, and declined by 24 h after the onset of the LH surge. These results suggest that (1) the pre-ovulatory LH surge begins between midnight and 0800 h in the majority of women, (2) luteinization of the granulosa cells within the pre-ovulatory follicle occurs in response to the LH surge, (3) the increase in prolactin at the time of the LH surge is not directly related to increasing levels of oestradiol but may be due to a decrease in hypothalamic inhibition of prolactin secretion which occurs coincident with the release of LHRH associated with the preovulatory LH surge.     

FERTILITY AFTER CHILDBIRTH: CHANGES IN SERUM GONADOTROPHIN LEVELS IN BOTTLE AND BREAST FEEDING WOMEN

Changes in basal serum gonadotrophin levels during the resumption of ovarian activity post partum have been studied longitudinally in breast and bottle feeding mothers. On the basis of urinary steroid levels, ovarian activity was classified as showing complete suppression, follicular activity only, deficient luteal phases or normal menstrual cycles. Complete suppression of ovarian activity during lactation was associated with normal levels of FSH but low levels of LH. The resumption of follicular development was not accompanied by any increase in levels of either LH or FSH when compared with the phase of complete suppression and this pattern persisted during menstrual cycles characterized by deficient luteal phase progesterone secretion. Basal LH levels did not rise to normal levels during lactation until the resumption of normal ovulatory cycles. FSH secretion remained at a level comparable with the follicular phase of normal ovulatory cycles throughout the post partum period. In mothers who did not breast feed, LH levels rose more rapidly than in breast feeding mothers and had returned to within normal limits by three weeks post partum. At 4 weeks post partum FSH levels were lower in bottle feeding mothers than in breast feeders probably in response to the early rise in oestrogen levels among bottle feeders. These results suggest that decreased LH but not FSH secretion may be important in maintaining infertility associated with breast feeding.(ABSTRACT TRUNCATED AT 250 WORDS)