IDENTICAL TWIN SISTERS WITH CLOSE ONSET OF GRAVES' DISEASE AND WITH MULTIPLE HLA SUSCEPTIBILITY ALLELES FOR GRAVES' DISEASE.

CONTEXT: Autoimmune thyroid disease is considered a multifactorial disorder in which autoimmunity against thyroid antigens is facilitated by exposure to endogenous and environmental factors. We present here a rare case of identical female twins who developed consecutively Graves' disease within a few months and had three HLA susceptibility alleles for the development of Graves' disease. SUBJECTS: A 28-year-old woman was referred to our hospital complaining of thirst, sweating, palpitations, tremor and skin rash. Laboratory data showed hyperthyroidism with antibodies against the thyroid stimulating hormone receptor and ultrasonography of the thyroid revealed enlargement with hypervascularity. Her identical twin was referred to our hospital because of similar symptoms. RESULT: We diagnosed them with Graves' disease and both were treated with methimazole. Human leukocyte antigen genotyping showed that both twins possessed the DRB1*04:05, DQB1*04:01:01, DPB1*05:01 haplotype, which confers susceptibility to Graves' disease. CONCLUSIONS: This case supports the hypothesis that interaction of multiple human leukocyte antigen susceptibility alleles as well as genetic background and environmental factors might synergistically contribute the close timing in Graves' disease onset.

Time-dependent CP-violating asymmetry in B0-->rho0gamma decays.

We report the first measurement of CP-violation parameters in B0-->rho0gamma decays based on a data sample of 657x10(6)BB pairs collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. We obtain the time-dependent and direct CP-violating parameters, Srho0gamma=-0.83+/-0.65(stat)+/-0.18(syst) and Arho0gamma=-0.44+/-0.49(stat)+/-0.14(syst), respectively.

Observation of time-dependent CP violation in B0 --> eta'K0 decays and improved measurements of CP asymmetries in B0 --> phiK0, KS0KS0KS0 and B0 --> J/psiK0 decays.

We present improved measurements of CP-violation parameters in B(0) --> phiK(0), eta(')K(0), KS(0)KS(0)KS(0) decays based on a sample of 535 x 10(6) BB pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB energy-asymmetric e(+)e(-) collider. We obtain sin2phi1(eff)=+0.64+/-0.10(stat)+/-0.04(syst) for B(0) --> eta(')K(0), +0.50+/-0.21(stat)+/-0.06(syst) for B(0) --> phiK(0), and +0.30+/-0.32(stat)+/-0.08(syst) for B(0) --> KS(0)KS(0)KS(0) decays. We have observed CP violation in the B(0) --> eta(')K(0) decay with a significance of 5.6 standard deviations. We also perform an improved measurement of CP asymmetries in B(0) --> J/psiK(0) decays and obtain sin2phi1=+0.642+/-0.031(stat)+/-0.017(syst).

Measurement of the time-dependent CP-violating asymmetry in B(0)-->K(0)(S)pi(0)gamma decays.

We present a new measurement of CP-violation parameters in B(0)-->K(0)(S)pi(0)gamma decay based on a sample of 275 x 10(6) BB pairs collected at the Gamma(4S) resonance with the Belle detector at the KEKB energy-asymmetric e(+)e(-) collider. One of the B mesons is fully reconstructed in the B(0)-->K(0)(S)pi(0)gamma decay. The flavor of the accompanying B meson is identified from its decay products. CP-violation parameters are obtained from the asymmetry in the distribution of the proper time intervals between the two B decays. We obtain SK(0)(S)(pi(0)gamma) = -0.58(+0.46)(-0.38)(stat) +/- 0.11(syst) and AK(0)(S)(pi(0)gamma) = +0.03 +/- 0.34(stat) +/- 0.11(syst), for the K(0)(S)pi(0) invariant mass covering the full range up to 1.8 GeV/c2. We also measure the CP-violation parameters for the case B(0)-->K(*0)(-->K(0)(S)pi(0))gamma and obtain S(K(*0)gamma) = -0.79(+0.63)(-0.50)(stat) +/- 0.10(syst) for A(K(*0)gamma) fixed at 0.

Measurement of time-dependent CP-violating asymmetries in B0 --> K(s)0K(s)0K(s)0 decay.

We present a measurement of CP-violation parameters in the B0 --> K(s)0K(s)0K(s)0 decay based on a sample of 275 x 10(6) BB pairs collected at the upsilon(4S) resonance with the Belle detector at the KEKB energy-asymmetric e+e- collider. One neutral B meson is fully reconstructed in the decay B0 --> K(s)0K(s)0K(s)0, and the flavor of the accompanying B meson is identified from its decay products. CP-violation parameters are obtained from the asymmetry in the distributions of the proper-time interval between the two B decays: S = +1.26 +/- 0.68(stat) +/- 0.20(syst) and [symbol: see text] = +0.54 +/- 0.34(stat) +/- 0.09(syst).

Multiple endocrine neoplasia type 1 associated with malignant lymphoma and other complications.

A 49-year-old female with multiple endocrine neoplasia (MEN) type 1 associated with malignant lymphoma, lipoma, functioning adenomatous goiter, non-functioning adrenal tumor, polyneuropathy, postoperative primary hyperparathyroidism, and hepatitis B virus was a human T lymphotropic virus type 1 (HTLV-1) carrier. She underwent parathyroidectomy for primary hyperparathyroidism at age 44. At age 49, examinations of the enlarged para-aortic lymph nodes revealed diffuse small non-cleaved B cell lymphoma in stage II, and other various complications were also found. Multiple tumorigenetic factors were considered to be involved in the present case.

Interaction of 6-p-toluidinylnaphthalene-2-sulfonate with beta-cyclodextrin.

The interaction of 6-p-toluidinylnaphthalene-2-sulfonate (TNS) with beta-cyclodextrin was investigated in 0.1 M phosphate buffer at pH 7.4 by fluorescence spectroscopy. Using the fluorescence enhancement of TNS in the presence of beta-cyclodextrin, the thermodynamic parameters for the formation of two kinds of the inclusion complex (molar ratio of beta-cyclodextrin to TNS = 1:1 and 2:1) were determined as follows: delta G degree 1 (1:1 complex) = -20.0 kJ mol-1 at 25 degrees C, delta H degree 1 = -19.6 kJ mol-1, delta S degree 1 = -1.7 J mol-1 K-1, delta G degree 2 (2:1 complex) at 25 degrees C = -6.14 kJ mol-1, delta H degree 2 = -2.80 kJ mol-1, delta S degree 2 = 16.7 J mol-1 K-1. From the thermodynamic parameters, the main driving force for the 1:1 inclusion complex formation was considered to be the van der Waals-London dispersion force, while the contribution of the hydrophobic interaction was small. Also, the hydrogen bonding was suggested to contribute to the inclusion complex formation. The main driving force for the 2:1 inclusion complex formation was the hydrophobic interaction. Also, from the measurements of proton nuclear magnetic resonance spectra and studies with Corey-Pauling-Koltun atomic models, the probable structure was determined and discussed in connection with the thermodynamic parameters.

Increased serum immunoreactive parathyroid hormone-related protein levels in chronic hypocalcemia.

To elucidate possible negative feedback regulation of circulating PTH-related protein (PTHrP) by serum calcium levels, we measured serum immunoreactive PTHrP (iPTHrP) by a specific RIA for PTHrP-(1-34) in patients with hypocalcemia due to PTH deficiency or resistance. Serum iPTHrP levels were not detectable (< 4 pmol/L) in 9 of 11 patients with postoperative hypocalcemia who presented with transient tetany, in 1 patient with hypocalcemia due to hypomagnesemia induced by cisplatin treatment, in normal subjects (n = 60), or in 1 normocalcemic patient with pseudopseudohypoparathyroidism. In contrast, the other 2 patients with postoperative hypocalcemia who had had hypocalcemic symptoms for longer periods (6 months and 3 yr, respectively) showed increased iPTHrP levels (6.3 and 5.3 pmol/L). All 6 patients with idiopathic hypoparathyroidism showed undetectable or low PTH, but increased iPTHrP, ranging from 6.5-19.5 pmol/L (mean +/- SD, 10.8 +/- 4.8 pmol/L). Elevated serum iPTHrP levels (7.4 and 8.1 pmol/L) were also found in both patients with pseudohypoparathyroidism type I. When chronic and profound hypocalcemia in these patients was normalized by treatment with 1 alpha-hydroxyvitamin D3, the elevated serum iPTHrP levels were normalized (undetectable, < 4 pmol/L) in all 6 patients examined. These results suggest that chronic and profound hypocalcemia and/or vitamin D deficiency can stimulate endogenous PTHrP secretion via a negative feedback mechanism, although elevated iPTHrP does not normalize the decreased serum calcium levels.

Characterization of parathyroid hormone-related protein in the human term placenta.

To characterize parathyroid hormone-related protein (PTHrP) in the human placenta, we measured PTHrP-like immunoreactivity (PRP-LI) in the term placenta and studied the elution profiles of placental tissue extracts on Sephadex G-75 chromatography with a specific RIA. We also examined the gene expression of PTHrP mRNA by Northern blot analysis and the localization of PRP-LI in the placenta by immunohistochemistry. The amount of PRP-LI in placental extracts (n = 7) was 20.9 +/- 2.2 pg/g wet tissue (mean +/- SE). Dilution curves of placental tissue ran parallel to those of synthetic PTHrP (1-34) standards. Sephadex G-75 gel chromatography demonstrated two major PRP-LI peaks; the first peak was eluted around the molecular size between 10 kilodaltons (Kda) and 20 Kda and the other around 5 Kda. Northern blot analysis of PTHrP mRNA extracted from placental tissues showed a major hybridization signal around 18S. PTHrP immunohistochemistry showed PRP-LI staining in the cytoplasm of syncytiotrophoblasts and stroma cells (Hofbauer cells) in the term placenta. These results suggest that syncytiotrophoblasts and stroma cells in the term placenta synthesize PTHrP in two major molecular forms, 10 Kda-20 Kda and around 5 Kda.