Risk factors to cause tooth formation anomalies in chemotherapy of paediatric cancers.

This study aimed to investigate the risk factors of tooth formation anomalies in anti-cancer chemotherapies. Long-term survivors treated by conventional chemotherapy (n = 26), conventional chemotherapy with high-dose chemotherapy (HDC) (n = 14), and HDC with total body irradiation (TBI) (n = 6) were analysed for the incidence of tooth agenesis, microdonts, and short-rooted teeth. The tooth agenesis and/or microdonts were found in second premolars and second molars, but not in first molars or central incisors. The ratio of subjects with tooth agenesis and/or microdonts was 66.7% and 18.2% in subjects administered conventional chemotherapy at <4 years and ≥ 4 years of age, respectively, while it was 100% and 25% in subjects administered HDC at <4 years and ≥ 4 years of age. The incidence of tooth formation anomalies did not related with the duration of conventional chemotherapy but increased by HDC. The incidence of tooth formation anomalies did not show significantly differences between the HDC with and without TBI groups, and was higher in busulfan-administered subjects than in subjects given cyclophosphamide. It may be concluded that the high-risk group of tooth agenesis is the subjects with HDC under 4 years of age. However, protocols of conventional chemotherapy are not an important risk factor to cause the tooth formation anomalies.

Imaging single atoms using secondary electrons with an aberration-corrected electron microscope.

Aberration correction has embarked on a new frontier in electron microscopy by overcoming the limitations of conventional round lenses, providing sub-angstrom-sized probes. However, improvement of spatial resolution using aberration correction so far has been limited to the use of transmitted electrons both in scanning and stationary mode, with an improvement of 20-40% (refs 3-8). In contrast, advances in the spatial resolution of scanning electron microscopes (SEMs), which are by far the most widely used instrument for surface imaging at the micrometre-nanometre scale, have been stagnant, despite several recent efforts. Here, we report a new SEM, with aberration correction, able to image single atoms by detecting electrons emerging from its surface as a result of interaction with the small probe. The spatial resolution achieved represents a fourfold improvement over the best-reported resolution in any SEM (refs 10-12). Furthermore, we can simultaneously probe the sample through its entire thickness with transmitted electrons. This ability is significant because it permits the selective visualization of bulk atoms and surface ones, beyond a traditional two-dimensional projection in transmission electron microscopy. It has the potential to revolutionize the field of microscopy and imaging, thereby opening the door to a wide range of applications, especially when combined with simultaneous nanoprobe spectroscopy.

Keratin attenuates tumor necrosis factor-induced cytotoxicity through association with TRADD.

Keratin 8 and 18 (K8/18) are the major components of intermediate filament (IF) proteins of simple or single-layered epithelia. Recent data show that normal and malignant epithelial cells deficient in K8/18 are nearly 100 times more sensitive to tumor necrosis factor (TNF)-induced cell death. We have now identified human TNF receptor type 1 (TNFR1)-associated death domain protein (TRADD) to be the K18-interacting protein. Among IF proteins tested in two-hybrid systems, TRADD specifically bound K18 and K14, type I (acidic) keratins. The COOH-terminal region of TRADD interacted with the coil Ia of the rod domain of K18. Endogenous TRADD coimmunoprecipitated with K18, and colocalized with K8/18 filaments in human mammary epithelial cells. Overexpression of the NH2 terminus (amino acids 1-270) of K18 containing the TRADD-binding domain as well as overexpression of K8/18 in SW13 cells, which are devoid of keratins, rendered the cells more resistant to killing by TNF. We also showed that overexpressed NH2 termini of K18 and K8/18 were associated with endogenous TRADD in SW13 cells, resulting in the inhibition of caspase-8 activation. These results indicate that K18 may sequester TRADD to attenuate interactions between TRADD and activated TNFR1 and moderate TNF-induced apoptosis in simple epithelial cells.

Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB).

BACKGROUND AND PURPOSE: Transient receptor potential melastatin 2 (TRPM2) is a non-selective Ca(2+)-permeable cation channel and is known to be activated by adenosine 5'-diphosphoribose (ADP-ribose) and hydrogen peroxide. TRPM2 current responses are reported to be drastically potentiated by the combination of each of these ligands with heat. Furthermore, the combination of cyclic ADP-ribose with heat also activates TRPM2. Although flufenamic acid, antifungal agents (miconazole and clotrimazole), and a phospholipase A(2) inhibitor (N-(p-amylcinnamoyl)anthranilic acid) inhibit TRPM2, their inhibition was either gradual or irreversible. EXPERIMENTAL APPROACH: To facilitate future research on TRPM2, we screened several compounds to investigate their potential to activate or inhibit the TRPM2 channels using the patch-clamp technique in HEK293 cells, transfected with human TRPM2. KEY RESULTS: 2-aminoethoxydiphenyl borate (2-APB) exhibited a rapid and reversible inhibition of TRPM2 channels that had been activated by its ADP-ribose or cADP-ribose and heat in a dose-dependent manner (IC(50) about 1 microM). 2-APB also inhibited heat-evoked insulin release from pancreatic islets, isolated from rats. CONCLUSIONS AND IMPLICATIONS: 2-APB proved to be a powerful and effective tool for studying the function of TRPM2.

Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19.

Hypercalcemia is relatively rare but clinically important complication in childhood leukemic patients. To clarify the clinical characteristics, mechanisms of hypercalcemia, response to management for hypercalcemia, incidence of t(17;19) and final outcome of childhood acute lymphoblastic leukemia (ALL) accompanied by hypercalcemia, clinical data of 22 cases of childhood ALL accompanied by hypercalcemia (>12 mg/dl) reported in Japan from 1990 to 2005 were retrospectively analyzed. Eleven patients were 10 years and older. Twenty patients had low white blood cell count (<20 x 10(9)/l), 15 showed hemoglobin> or =8 g/dl and 14 showed platelet count > or =100 x 10(9)/l. Parathyroid hormone-related peptide (PTHrP)-mediated hypercalcemia was confirmed in 11 of the 16 patients in whom elevated-serum level or positive immunohistochemistry of PTHrP was observed. Hypercalcemia and accompanying renal insufficiency resolved quickly, particularly in patients treated with bisphosphonate. t(17;19) or add(19)(p13) was detected in five patients among 17 patients in whom karyotypic data were available, and the presence of E2A-HLF was confirmed in these five patients. All five patients with t(17;19)-ALL relapsed very early. Excluding the t(17;19)-ALL patients, the final outcome of ALL accompanied by hypercalcemia was similar to that of all childhood ALL patients, indicating that the development of hypercalcemia itself is not a poor prognostic factor.

Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats.

Delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) causes cerebral ischemia and infarction. To date, the pathogenesis and gene expression associated with vasospasm remain poorly understood. The present study used fluorescent differential display to identify differentially expressed genes in a rat model of SAH. By using quantitative RT-PCR, we found that heme oxygenase-1 (HO-1) mRNA was prominently induced in the basilar artery and modestly in brain tissue in a rat vasospasm model. A significant correlation was observed between the degree of vasospasm and HO-1 mRNA levels in the basilar arteries exhibiting vasospasm. Intracisternal injection of antisense HO-1 oligodeoxynucleotide (ODN) significantly delayed the clearance of oxyhemoglobin and deoxyhemoglobin from the subarachnoid space and aggravated angiographic vasospasm. Antisense HO-1 ODN inhibited HO-1 induction in the basilar arteries but not in the whole brain tissue. This phenomenon was not observed in the nontreated, sense HO-1 ODN-treated, or scrambled ODN-treated arteries. We report the protective effects of HO-1 gene induction in cerebral vasospasm after SAH, a finding that should provide a novel therapeutic approach for cerebral vasospasm.

Modulation of basal nitric oxide-dependent cyclic-GMP production by ambient glucose, myo-inositol, and protein kinase C in SH-SY5Y human neuroblastoma cells.

Defective tissue perfusion and nitric oxide production and altered myo-inositol metabolism and protein kinase C activation have been invoked in the pathogenesis of diabetic complications including neuropathy. The precise cellular compartmentalization and mechanistic interrelationships of these abnormalities remain obscure, and nitric oxide possesses both neurotransmitter and vasodilator activity. Therefore the effects of ambient glucose and myo-inositol on nitric oxide-dependent cGMP production and protein kinase C activity were studied in SH-SY5Y human neuroblastoma cells, a cell culture model for peripheral cholinergic neurons. D-Glucose lowered cellular myo-inositol content, phosphatidylinositol synthesis, and phosphorylation of an endogenous protein kinase C substrate, and specifically reduced nitric oxide-dependent cGMP production a time- and dose-dependent manner with an apparent IC50 of approximately 30 mM. The near maximal decrease in cGMP induced by 50 mM D-glucose was corrected by the addition of protein kinase C agonists or 500 microM myo-inositol to the culture medium, and was reproduced by protein kinase C inhibition or downregulation, or by myo-inositol deficient medium. Sodium nitroprusside increased cGMP in a dose-dependent fashion, with low concentrations (1 microM) counteracting the effects of 50 mM D-glucose or protein kinase C inhibition. The demonstration that elevated D-glucose diminishes basal nitric oxide-dependent cGMP production by myo-inositol depletion and protein kinase C inhibition in peripheral cholinergic neurons provides a potential metabolic basis for impaired nitric oxide production, nerve blood flow, and nerve impulse conduction in diabetes.

Radiotherapy modulates expression of EGFR, ERCC1 and p53 in cervical cancer.

Cervical cancer is a public health problem and the molecular mechanisms underlying radioresistance are still poorly understood. Here, we evaluated the modulation of key molecules involved in cell proliferation, cell cycle and DNA repair in cervical cancer cell lines (CASKI and C33A) and in malignant tissues biopsied from 10 patients before and after radiotherapy. The expression patterns of epidermal growth factor receptor (EGFR), excision repair cross-complementation group 1 (ERCC1) and p53 were evaluated in cancer cell lines by quantitative PCR and western blotting, and in human malignant tissues by immunohistochemistry. The mutation status of TP53 gene was evaluated by direct sequencing. Among cell lines, absent or weak modulations of EGFR, ERCC1 and p53 were observed after exposure to 1.8 Gy. Conversely, increased expressions of p53 (5/10 patients; P=0.0239), ERCC1 (5/10 patients; P=0.0294) and EGFR (4/10 patients; P=0.1773) were observed in malignant tissues after radiotherapy with the same radiation dose. TP53 mutations were found only in one patient. Here we show that a single dose of radiotherapy induced EGFR, ERCC1 and p53 expression in malignant tissues from cervical cancer patients but not in cancer cell lines, highlighting the gap between in vitro and in vivo experimental models. Studies on larger patient cohorts are needed to allow an interpretation that an upregulation of p53, EGFR and ERCC1 may be part of a radioresistance mechanism.

Effect of ZnO addition on bioactive CaO-SiO2-P2O5-CaF2 glass-ceramics containing apatite and wollastonite.

Some ceramics show bone-bonding ability, i.e. bioactivity. Apatite formation on ceramics is an essential condition to bring about direct bonding to living bone when implanted into bony defects. A controlled surface reaction of the ceramic is an important factor governing the bioactivity and biodegradation of the implanted ceramic. Among bioactive ceramics, glass-ceramic A-W containing apatite and wollastonite shows high bioactivity, as well as high mechanical strength. In this study, glass-ceramics containing zinc oxide were prepared by modification of the composition of the glass-ceramic A-W. Zinc oxide was selected to control the reactivity of the glass-ceramics since zinc is a trace element that shows stimulatory effects on bone formation. Glass-ceramics were prepared by heat treatment of glasses with the general composition: xZnOx(57.0-x)CaOx35.4SiO(2)x7.2P(2)O(5)x0.4CaF(2) (where x=0-14.2mol.%). Addition of ZnO increased the chemical durability of the glass-ceramics, resulting in a decrease in the rate of apatite formation in a simulated body fluid. On the other hand, the release of zinc from the glass-ceramics increased with increasing ZnO content. Addition of ZnO may provide bioactive CaO-SiO(2)-P(2)O(5)-CaF(2) glass-ceramics with the capacity for appropriate biodegradation, as well as enhancement of bone formation.

Delirium during intravenous sedation with midazolam alone and with propofol in dental treatment.

A 62-year-old man visited our clinic for dental implantation under intravenous sedation. He demonstrated increased psychomotor activity and incomprehensible verbal contact during intravenous sedation. Although delirium caused by midazolam or propofol in different patients has been reported, the present case represents a delirium that developed from both drugs in the same patient, possibly because of the patient's smaller tolerance to midazolam and propofol.

Activities of newly synthesized dihydropyridines in overcoming of vincristine resistance, calcium antagonism, and inhibition of photoaffinity labeling of P-glycoprotein in rodents.

Newly synthesized 1,4-dihydropyridine derivatives (NK-compounds) were screened to determine whether they could overcome vincristine (VCR) resistance in VCR-resistant (P388/VCR) leukemia-bearing mice. Among the 57 NK-compounds examined, six compounds had strong reversing ability (Grade A), 18 partially overcame the resistance (Grade B), and 33 did not reverse the resistance (Grade C). The ability to overcome resistance varied considerably with the nature of substituents at positions 3.5 of the 1,4-dihydropyridine, and the most suitable substituents were the pyridylalkyl-including esters. Calcium antagonistic activity of NK-compounds having pyridylalkyl-including esters at positions 3.5 and dithiene ring at position 4 of the 1,4-dihydropyridine was greater than in those compounds having the dioxene ring at position 4. NK-242, which was assessed at Grade A and had no calcium antagonistic activity, improved therapeutic effects in both VCR-sensitive (P388/S) leukemia- and P388/VCR leukemia-bearing mice when combined with VCR. Fourteen NK-compounds were screened to determine whether they could inhibit photoaffinity labeling of the P-glycoprotein (Mr 170,000 glycoprotein) in a multidrug-resistant cell line by [3H]azidopine. All six compounds of Grade A and two of the three compounds of Grade B almost completely inhibited the labeling of Mr 170,000 glycoprotein at 1 to 10 microM. Thus there was a good correlation between the ability to reverse VCR resistance in vivo and the inhibition of photoaffinity labeling of Mr 170,000 glycoprotein.

Risk factor analyses for macrovascular complication in nonobese NIDDM patients. Multiclinical Study for Diabetic Macroangiopathy (MSDM).

To examine the characteristic features of risk factors for macroangiopathy (MA) in nonobese Japanese NIDDM patients, 899 NIDDM patients with and without MA were registered from 40 facilities. Of these, 386 subjects were identified as having any form of MA (total MA); these included 211 with ischemic heart disease (IHD), 163 with cerebrovascular disease (CVD), and 77 with peripheral vascular disease (PVD). Univariate analyses revealed the following common risk factors for total MA, IHD, CVD, and PVD: age, hypertension, systolic blood pressure (sBP) or diastolic blood pressure (dBP), duration of diabetes, diabetic microangiopathy (retinopathy, nephropathy, and neuropathy), low HDL cholesterol level, and higher LDL cholesterol/HDL cholesterol ratio. Additional significant risk factors for specific conditions were also identified, respectively, as male sex for total MA, IHD, and PVD, smoking for IHD and PVD, and high fasting plasma glucose level for total MA and CVD. With stepwise multivariate logistic regression analysis, older age, duration of diabetes, smoking, and low LDL cholesterol/HDL cholesterol ratio were identified as significant and independent risk factors for total MA, IHD, CVD, and PVD. Other risk factors identified were high dBP for IHD, CVD, and PVD, high sBP for total MA, and low BMI for PVD. These results clearly demonstrated that duration of diabetes, smoking, hypertension, and dyslipidemia are major risk factors for MA in NIDDM patients. Since the mean BMI was similar for both groups (approximately 23 kg/m2) and there were no significant differences in immunoreactive insulin levels before and after 75-g oral glucose challenge testing, obesity and hyperinsulinism at the time of the analyses were not considered to play an important role for the pathogenesis of MA in Japanese NIDDM patients. By using the chi 2 test, cutoff points were determined for six of the most commonly measured risk factors. The cutoff point was the level beyond which a significantly higher prevalence of MA occurred. The cutoff points (rounded slightly upward in some cases) for fasting plasma glucose, sBP, dBP, serum total cholesterol level, serum triglyceride level, and BMI were 140 mg/dl, 140 mmHg, 80 mmHg, 180 mg/dl, 120 mg/dl, and 23 kg/m2, respectively. When these cutoff points were used as control criteria, the prevalence of MA was significantly lower in subjects whose risk factor measurements remained under the proposed control criteria for four or more of the six variables. In conclusion, in nonobese NIDDM patients, age, hypertension, and dyslipidemia were found to be risk factors for MA. Duration of diabetes was also demonstrated as an independent risk factor, indicating the close association of deranged glucose metabolism with the pathogenesis of MA in NIDDM patients. It seems to be crucial to control these risk factors for the prevention of MA in NIDDM patients.

Therapy-related myelodysplastic syndrome in childhood: a retrospective study of 36 patients in Japan.

We report here a retrospective analysis of 36 children with therapy-related myelodysplastic syndrome (t-MDS) diagnosed between 1990 and 1999 in Japan. Their median age was 7.7 years and the median latency period for the development of t-MDS was 38.5 months. The primary tumors were hematologic in 15 of the cases and nonhematologic in 21. Chromosomal abnormalities were detected in 32/34(94%) patients: abnormalities of chromosomes 5and/or 7 in 41% and notably, 11q23 abnormalities in 31%. The prognosis of children with t-MDS was very poor as compared to children with primary MDS (5 year survival: 16% versus 54%, p<0.0001).

Impaired retinal artery blood flow in IDDM patients before clinical manifestations of diabetic retinopathy.

OBJECTIVE: To determine whether hemodynamic changes in retinal arteries precede clinical manifestations of diabetic retinopathy and to examine the effects of control of hyperglycemia on retinal artery blood flow. RESEARCH DESIGN AND METHODS: We assessed blood flow in bilateral central retinal arteries in 50 insulin-dependent diabetes mellitus (IDDM) patients without retinopathy and 20 sex- and age-matched control subjects using duplex Doppler sonography. We determined the peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged velocity (TAV), resistance index (RI), and pulsatility index (PI). RESULTS: PSV, EDV, and TAV were significantly lower in IDDM patients than in control subjects (P < 0.05, P < 0.01, and P < 0.01, respectively). The RI was significantly higher in IDDM patients than in control subjects (P < 0.01) and was significantly correlated with plasma levels of glucose in IDDM patients (r = 0.0.310, P = 0.0248). Multiple regression analysis identified the plasma levels of glucose as a significant determination of RI in IDDM patients. After 14 days of intensive insulin therapy in 7 IDDM patients, the RI and plasma levels of glucose showed significant decreases (P = 0.018, P = 0.001, respectively). CONCLUSIONS: Our results showed that changes in retinal hemodynamics were present before the clinical detection of overt diabetic retinopathy and suggest that the presence of short-term hyperglycemia partly contributes to impaired retinal circulation.

Surface determination through atomically resolved secondary-electron imaging.

Unique determination of the atomic structure of technologically relevant surfaces is often limited by both a need for homogeneous crystals and ambiguity of registration between the surface and bulk. Atomically resolved secondary-electron imaging is extremely sensitive to this registration and is compatible with faceted nanomaterials, but has not been previously utilized for surface structure determination. Here we report a detailed experimental atomic-resolution secondary-electron microscopy analysis of the c(6 × 2) reconstruction on strontium titanate (001) coupled with careful simulation of secondary-electron images, density functional theory calculations and surface monolayer-sensitive aberration-corrected plan-view high-resolution transmission electron microscopy. Our work reveals several unexpected findings, including an amended registry of the surface on the bulk and strontium atoms with unusual seven-fold coordination within a typically high surface coverage of square pyramidal TiO5 units. Dielectric screening is found to play a critical role in attenuating secondary-electron generation processes from valence orbitals.

Interactions between steroid hormones and insulin-like growth factor-I in rabbit chondrocytes.

The mechanism of action of steroid hormones on skeletal growth is not understood in detail. We examined the interactions of steroid hormones and insulin-like growth factor-I (IGF-I) during DNA and sulfated proteoglycan synthesis in rabbit costal chondrocytes. Progesterone at 0.05 nM stimulated the incorporation of [3H]thymidine into DNA by 30% above the control level in confluent cultures, but neither testosterone nor 17 beta-estradiol stimulated DNA synthesis. None of the hormones affected [3H]thymidine incorporation stimulated by IGF-I when chondrocytes were incubated with one of the hormones and IGF-I simultaneously. In contrast, when confluent cultures were incubated with one of the sex steroids for 24 h before the addition of IGF-I, stimulation of DNA synthesis by the growth factor was enhanced about 45% above the control value by 0.5 nM progesterone, 50% by 0.5 nM testosterone, and 80% by 50 nM 17 beta-estradiol. The effects of IGF-I on proteoglycan synthesis, as judged by the incorporation of [35S]sulfate, were stimulated by treatment with progesterone or testosterone. Dexamethasone at physiological concentrations inhibited chondrocyte DNA synthesis in confluent cultures to 10% of the control level. At 50 nM, dexamethasone suppressed IGF-I induction of DNA synthesis by 60%. This suppression was greater when dexamethasone was added before IGF-I than when the additions were simultaneous. When chondrocytes were treated with hydrocortisone or dexamethasone for 24 h before the addition of IGF-I, the glucocorticoids synergistically accelerated proteoglycan synthesis mediated by IGF-I. These findings suggest that steroid hormones have priming effects on the biological action of IGF-I in cartilage metabolism.

Molecular characterisation of glutamate dehydrogenase gene defects in Japanese patients with congenital hyperinsulinism/hyperammonaemia.

Congenital hyperinsulinism and hyperammonaemia (CHH) is caused by dysregulation of glutamate dehydrogenase (GDH). We characterised the GDH gene in two Japanese patients with CHH. Patient 1 showed late-onset and mild hypoglycaemic episodes and mild hyperammonaemia, compared with patient 2. In GDH activity of lymphoblasts, patient 1 showed twofold higher basal GDH activity than control subjects and mild insensitivity for GTP inhibition. Patient 2 showed severe insensitivity for GTP inhibition, and similar allosteric stimulation by ADP in the controls. Genetic studies identified heterozygous and de novo L413V and G446D mutations in patients 1 and 2, respectively. COS cell expression study confirmed that both mutations were disease-causing gene. The insensitivity for GTP inhibition in L413V and G446D was emphasised in COS cell expression system as a result of the dosage effect of mutant GDH gene. L413V showed less impairment of GDH than G446D based on biochemical and genetic results, which was consistent with the clinical phenotype. Based on the structure of bovine GDH, G446D was located in GTP binding site of pivot helix and its surroundings, while L413V was located in alpha-helix of antenna-like structure. These different locations of mutations gave different effects on GDH enzyme. The antenna-like structure plays an important role in GDH activity.

Phosphorylation of vimentin head domain inhibits interaction with the carboxyl-terminal end of alpha-helical rod domain studied by surface plasmon resonance measurements.

The amino-terminal head domain of vimentin is the target site for several protein kinases and phosphorylation induces disassembly of the vimentin intermediate filaments in vivo and in vitro. To better understand molecular mechanisms involved in phosphorylation-dependent disassembly, we examined domain interactions involving the head domain and the effect of phosphorylation on the interaction, using surface plasmon resonance. We observed that the head domain binds to the carboxyl-terminal helix 2B in the rod domain, under physiological ionic strength. This interaction was interfered with by A-kinase phosphorylation of the head domain. Deletion of the carboxyl-terminal 20 amino acids of helix 2B resulted in loss of the interaction. Furthermore, peptide representing the carboxyl-terminal 20 residues of helix 2B had a substantial affinity with the head domain but not with the phosphorylated one. These findings support the idea that the interaction between the head domain and the last 20 residues of helix 2B is essential for association of vimentin tetramers into the intermediate filaments and that the phosphorylation-dependent disassembly is the result of loss of the interaction.

First-pass radionuclide angiography using iodine-123 myocardial tracers and a multicrystal gamma camera.

UNLABELLED: The purpose of this study was to validate the accuracy of the assessment of ventricular function by first-pass radionuclide angiography (FPRNA) with 123I myocardial tracers and a multicrystal gamma camera. METHODS: Left ventricular ejection fraction (LVEF) and right ventricular ejection fraction were measured in 69 patients by FPRNA using 123I myocardial tracers (126 +/- 7 MBq) and 99mTc tracers (541 +/- 141 MBq) on a multicrystal gamma camera with a high-sensitivity collimator. For 44 patients, ejection fraction values measured by 123I-FPRNA were compared to those estimated by equilibrium radionuclide angiography (ERNA). Visual wall-motion analysis was also performed to judge clinical acceptability of 123I-FPRNA images for identification of wall-motion abnormality. RESULTS: Mean LVEFs (%) estimated by 123I-FPRNA and by 99mTc-FPRNA were 49.6 +/- 13.6 and 49.1 +/- 14.1, respectively (nonsignificant p value). An excellent correlation was found between LVEFs estimated by 123I-FPRNA and 99mTc-FPRNA (r = 0.96, s.e.e. = 1.9%). Values of LVEF measured by 123I-FPRNA also demonstrated excellent correlation with those measured by ERNA (r = 0.95, s.e.e. = 2.2%). A good correlation was also noted between right ventricular ejection fractions measured by 123I-FPRNA and 99mTc-FPRNA (r = 0.72, s.e.e. = 4.0%). The Spearman rank correlation coefficient between 123I-FPRNA and ERNA wall-motion scores was 0.87 (n = 135, p < 0.001). CONCLUSION: Resting ventricular function can be reliably measured with 123I-FPRNA in combination with a multicrystal gamma camera. This indicates that the assessment of ventricular function is feasible in conjunction with 123I myocardial imaging without an increase in cost or radiation dose to patients.

T cell repertoire in the liver of patients with primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune chronic liver disease characterized by the destruction of the bile ducts with an accumulation of lymphocytes. To investigate the roles of T cells accumulating around the bile ducts, we analyzed the clonality of alphabeta T cell populations in the livers of patients with PBC by size spectratyping and sequencing of the T cell receptor (TCR) Vbeta transcripts.TCR Vbeta spectratyping of PBC patients showed several skewed complementarity determining region 3 (CDR3) size patterns suggestive of clonal predominance as well as Gaussian-like patterns suggestive of polyclonal expansion. We observed Vbeta4 clones sharing the Gly (G)-G motif in the CDR3 nDn regions and a Vbeta4-Jbeta2.7 combination in three patients bearing HLA-DR2 and -DQ1. G-Leu (L)-Ala (A) or G-L motifs were also seen in the nDn regions of Vbeta17 with Jbeta2.1 of the two patients having HLA-A26. However, there were no whole CDR3-shared clones in any of the patients. In conclusion, we have observed that T cell clones are heterogeneous in each patient, but that they have some common motifs in the TCR Vbeta CDR3. We strongly suggest that these clonally expanded T cells might be involved in the immunopathogenesis of PBC.