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Nippon Ganka Gakkai Zasshi. 1999 Jan;103(1):66-71.
[A report of two cases suggesting positive influence of pregnancy on uveitis activity]

[Article in Japanese]

Taguchi C, Ikeda E, Hikita N, Mochizuki M.

Department of Ophthalmology, Kurume University School of Medicine, Japan.

BACKGROUND: Little is known about the influence of pregnancy on uveitis activity. We report two cases suggesting a favorable influence of pregnancy on the clinical course of uveitis. CASE: A 30-year-old woman who was three months pregnant was suspected Vogt-Koyanagi-Harada disease based on the systemic symptoms and ocular findings of iritis and multi-focal serous retinal detachment. She was positive to human leukocyte antigen (HLA)-DR 4. She was treated only with topical corticosteroids. One month later, the retinal detachment disappeared. Six month later, a healthy baby was born. The fundus of both eyes took on a sunset glow appearance and there has been no recurrence of uveitis. The other case was a 23-year-old woman with Behcet's disease who had several episodes of uveitis in a year even on tacrolimus. Because of pregnancy, all systemic drugs including tacrolimus were discontinued since then. Interestingly, the frequency of uveitis was remarkably decreased during the pregnancy. A normal healthy baby was born. The uveitis has almost completely disappeared since parturition until now. CONCLUSION: It is considered that the increase of intrinsic hormone, especially corticosteroid, and some other factors with pregnancy may give the suppressive influence on uveitis in our cases.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10036927&dopt=Abstract

J Clin Endocrinol Metab. 1999 Feb;84(2):590-5.
Growth hormone (GH) substitution in hypogonadotropic, GH-deficient women decreases the follicle-stimulating hormone threshold for monofollicular growth.

de Boer JA, van der Meer M, van der Veen EA, Schoemaker J.

Institute for Endocrinology, Reproduction and Metabolism, Vrije Universiteit, Department of Obstetrics and Gynecology, Free University Hospital, Amsterdam, The Netherlands.

The FSH threshold concept for monofollicular growth (which means that at the time the largest follicle reaches 18 mm there are no other follicles with a diameter of 13-18 mm also present) was used during ovulation induction in hypogonadotropic women, who appeared to be GH deficient. This concept was used to investigate whether 1) GH influences the FSH threshold for monofollicular growth and 2) whether such an influence would depend upon the endogenous GH/insulin-like growth factor I (IGF-I)/IGF-binding protein-3 (IGFBP-3) levels. In six hypogonadotropic women the GH response after an insulin challenge did not exceed 6 microg/L. Patients underwent ovulation induction according to a low dose step-up protocol by hMG during two consecutive cycles. GH substitution was provided only during the second cycle. Except for one GH treated cycle, all cycles were ovulatory. IGF-I levels as well as IGFBP-3 levels significantly increased (P < 0.01) during GH substitution. Monofollicular growth was not achieved in the first cycles. In five of six GH-substituted cycles, monofollicular growth was obtained. FSH threshold levels decreased in all patients during GH substitution. The FSH area under the curve was negatively correlated to IGF-I (r = -0.6; P < 0.05) and IGFBP-3 (r = -0.6; P < 0.05). The results of this study indicate that GH may play a role in the physiological growth of the follicle; most likely this occurs by influencing the IGF-I or IGFBP-3 levels. GH appears to selectively increase the sensitivity of the dominant follicle to FSH, facilitating monofollicular growth.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10022421&dopt=Abstract

J Bone Miner Res. 1999 Mar;14(3):431-8.
Demonstration of the predominant urine osteocalcin fragments detectable by two-site immunoassays.

Matikainen T, Kakonen SM, Pettersson K, Karp M, Lovgren T, Vaananen H, Hellman J.

Department of Anatomy, University of Turku, Turku, Finland.

We have isolated and characterized human osteocalcin (OC) fragments from pubertal urine. The fragments were isolated by immunoaffinity chromatography based on monoclonal antibody 6F9 and further purified by reverse phase chromatography. The major isolated forms, which were detectable with two-site immunofluorometric assays for serum OC, span residues 6-30 and 7-30 as determined by mass spectrometry and N-terminal amino acid sequencing. Full-length OC was not detectable in the supernatant fraction of urine but could be extracted with guanidinium hydrochloride from the sediment of urine samples. Urine samples from subjects with different menopausal status were measured by two different two-site assays. Urine OC (uOC) concentrations were 12- to 16-fold higher in the pubertal group than in the adult group. Also, the uOC concentration in a postmenopausal group was significantly higher than in a premenopausal group. The difference was 125% and 75% (values for p < 0.0001), respectively, when measured with the two assays. uOC concentrations in postmenopausal subjects on hormone replacement therapy were indistinguishable from the premenopausal subjects. The fact that uOC can be measured by a noncompetetive two-site assay design offers improved analytical sensitivity. Urine as the sample matrix is also especially interesting because the predominant markers of bone resorption, collagen type I peptides or cross-links, are performed on urine samples. Our results from the technical validation of two-site assays for uOC and from applying these to human pubertal and pre- and postmenopausal samples calls for more extensive clinical validation.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10027908&dopt=Abstract

Oncogene. 1999 Jan 28;18(4):917-24.
Thyroid hormone effects on Krox-24 transcription in the post-natal mouse brain are developmentally regulated but are not correlated with mitosis.

Ghorbel MT, Seugnet I, Hadj-Sahraoui N, Topilko P, Levi G, Demeneix B.

Laboratoire de Physiologie Generale et Comparee, U.R.A.90 CNRS, Museum National d'Histoire Naturelle, Paris, France.

Krox-24 (NGFI-A, Egr-1) is an immediate-early gene encoding a zinc finger transcription factor. As Krox-24 is expressed in brain areas showing post-natal neurogenesis during a thyroid hormone (T3)-sensitive period, we followed T3 effects on Krox-24 expression in newborn mice. We analysed whether regulation was associated with changes in mitotic activity in the subventricular zone and the cerebellum. In vivo T3-dependent Krox-24 transcription was studied by polyethylenimine-based gene transfer. T3 increased transcription from the Krox-24 promoter in both areas studied at post-natal day 2, but was without effect at day 6. An intact thyroid hormone response element (TRE) in the Krox-24 promoter was necessary for these inductions. These stage-dependent effects were also seen in endogenous Krox-24 mRNA levels: activation at day 2 and no effect at day 6. Moreover, similar results were obtained by examining beta-galactosidase expression in heterozygous mice in which one allele of the Krox-24 gene was disrupted with an inframe Lac-Z insertion. However, bromodeoxyuridine incorporation showed mitosis to continue through to day 6. We conclude first, that T3 activates Krox-24 transcription during early post-natal mitosis but that this effect is extinguished as development proceeds and second, loss of T3-dependent Krox-24 expression is not correlated with loss of mitotic activity.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10023667&dopt=Abstract

Biochem Biophys Res Commun. 1999 Feb 24;255(3):778-84.
Parathyroid hormone-regulated production of stem cell factor in human osteoblasts and osteoblast-like cells.

Blair HC, Julian BA, Cao X, Jordan SE, Dong SS.

Department of Pathology, University of Alabama School of Medicine and Veteran's Affairs Medical Center, Birmingham, Alabama, 35294, USA. Blaiath.uab.edu

We investigated stem cell factor (SCF) expression in osteoblasts because mast cells, which occur ectopically in hyperparathyroid bone, are induced by SCF. Nontransformed osteoblasts and Saos2 or MG63 cells expressed SCF in response to PTH. Western analysis showed only large, cell-associated isoforms, Mrs approximately 40-48 kD. Transfection of MG63 cells with plasmids expressing antisense SCF mRNA eliminated immunoreactive SCF. Sequencing osteoblast SCF cDNAs showed that exon 6 was omitted. mRNAs without exon 6 produce membrane-associated SCF isoforms in rodents, suggesting that human SCFs are processed similarly. The major osteoblastic SCF mRNA, approximately 5 kB, was augmented by PTH. Neither protein or mRNA was increased by vitamin D, however, 6-7 kB transcripts were predominant in other tissues but not detectable in osteoblasts. We conclude that osteoblasts express SCF in response to PTH, with mRNA and protein processing differences relative to other cells. SCF stimulates osteoclasts, suggesting that PTH-induced osteoblastic SCF functions to accelerate bone turnover. Mast cells may occur due to SCF overexpression at extreme PTH levels. 1999 Academic Press.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10049787&dopt=Abstract

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