Anti-host isohemagglutinin production is associated with a higher risk of acute GVHD in ABO-incompatible transplantation.

We retrospectively analyzed the association between anti-host isohemagglutinin (IH) production and the development of acute GVHD. Of 189 patients who received minor or major/minor ABO-incompatible hematopoietic SCT (HSCT) at our hospital, 36 patients (19%) showed IH production. IH was detected before the onset of acute GVHD in 10, around the same time in 8, and after the onset of acute GVHD in 17 patients. The cumulative incidence of grade II-IV acute GVHD was significantly higher in the IH+ group compared with the IH- group (P<0.0001). The higher risk of acute GVHD that was associated with IH production occurred irrespective of human leukocyte Ag compatibility and donor type. Furthermore, the incidence of acute GVHD in the IH- group was comparable to that seen in major ABO-incompatible or -compatible HSCT. Our findings not only showed a strong association between IH production and acute GVHD development, but also suggested that IH production might be a useful predictor of subsequent acute GVHD after ABO-incompatible HSCT.

Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3beta-mediated phosphorylation of beta-catenin.

The Wnt signaling pathway is essential for embryonic development and carcinogenesis. Upon Wnt stimulation, beta-catenin is stabilized and associates with T-cell factor or lymphoid enhancing factor, thereby activating transcription of target genes. In the absence of Wnt stimulation, the level of beta-catenin is reduced via glycogen synthase kinase (GSK)-3beta-mediated phosphorylation and subsequent proteasome-dependent degradation. Here, we report the identification of Ajuba as a negative regulator of the Wnt signaling pathway. Ajuba is a member of LIM domain-containing proteins that contribute to cell fate determination and regulate cell proliferation and differentiation. We found that enforced expression of Ajuba destabilized beta-catenin and suppressed target gene expression. Ajuba promoted GSK-3beta-mediated phosphorylation of beta-catenin by reinforcing the association between beta-catenin and GSK-3beta. Furthermore, Wnt stimulation induced both accumulation of beta-catenin and destabilization of Ajuba. Our findings suggest that Ajuba is important for regulation of the Wnt signaling pathway.

Recovery of Valpha24+ NKT cells after hematopoietic stem cell transplantation.

Human Valpha24+ natural killer T (NKT) cells have an invariant T-cell receptor-alpha chain and are activated in a CD1d-restricted manner. Valpha24+ NKT cells are thought to regulate immune responses and to play important roles in the induction of allograft tolerance. In this report, we analyzed the recovery of Valpha24+ NKT cells after hematopoietic stem cell transplantation and its correlation with graft-versus-host disease (GVHD). Patients who received a dose-reduced conditioning regimen, antithymocyte globulin- or CAMPATH-1H-containing conditioning regimen were excluded. NKT cells were reconstituted within 1 month after transplantation in peripheral blood stem cell transplantation recipients, while their numbers remained low for more than 1 year in bone marrow transplantation (BMT) recipients. The number of Valpha24+ NKT cells in BMT recipients with acute GVHD was lower than that in patients without acute GVHD, and both the CD4+ and CD4- Valpha24+ NKT subsets were significantly reduced. With regard to chronic GVHD, BMT recipients with extensive GVHD had significantly fewer Valpha24+ NKT cells than other patients. Furthermore, the number of CD4+ Valpha24+ NKT cells was also significantly reduced in patients with chronic extensive GVHD. Our results raise the possibility that the number of Valpha24+ NKT cells could be related to the development of GVHD.

Contamination by mercury and cadmium in the cetacean products from Japanese market.

Cetaceans hunted coastally in Japan include several species of odontocete (dolphins, porpoises and beaked whales), and fresh and frozen red meat and blubber, as well as boiled internal organs, such as liver, lung, kidney and small intestine, are still sold for human consumption. Furthermore, red meat and blubber products originating from mysticete minke whales caught in the Antarctic and Northern Pacific are also sold for human consumption. We surveyed mercury and cadmium contamination levels in boiled liver, lung, kidney and red meat products being marketed in Japanese retail outlets. We also analyzed the DNA of these products to obtain information concerning gender and species. Total mercury (T-Hg) and methyl mercury (M-Hg) contamination levels in all the cetacean products were markedly higher in odontocete species than in mysticete species, and slightly higher in females than in males. T-Hg contamination in the organs was seen in the following order: boiled liver>boiled kidney=boiled lung>red meat. In particular, T-Hg concentrations in the boiled liver were high enough to cause acute intoxication even from a single ingestion: the mean +/-SD (range) of T-Hg was 388+/-543 (0.12-1980) microg/wetg. In contrast, although M-Hg contamination in the liver was not markedly higher than that in other organs, M-Hg contamination was in the following order: boiled liver>odontocete red meat>boiled kidney>boiled lung. The contamination levels of T-Hg and M-Hg in odontocete red meat, the most popular whale product, were 8.94+/-13.3 and 5.44+/-5.72 microg/wetg, respectively. These averages exceeded the provisional permitted levels of T-Hg (0.4 microg/wetg) and M-Hg (0.3 microg/wetg) in marine foods set by the Japanese Ministry of Health, Labor and Welfare by 22 and 18 times, respectively, suggesting the possibility of chronic intoxication by T-Hg and M-Hg with frequent consumption of odontocete red meat. Cadmium contamination levels in boiled liver, kidney and lung were 8.59+/-12.0, 10.4+/-8.6 and 1.66+/-1.27 (microg/wetg), respectively.

MR detection of iliac bone marrow involvement by malignant lymphoma with various MR sequences including diffusion-weighted echo-planar imaging.

OBJECTIVE: To assess the diagnostic accuracy of MR imaging for detecting bone marrow infiltration by malignant lymphoma. PATIENTS AND DESIGN: Fifty-three patients with malignant lymphoma underwent MR imaging and bone marrow biopsy. In 80 iliac crests of the 53 patients (13 positive specimens in 9 patients and 67 negative specimens in 44 patients), biopsy results and the signal intensity characteristics were compared. MR sequences included T1-weighted SE, T2-weighted FSE with fat suppression, FSE STIR, and diffusion-weighted EPI with fat suppression at 1.5 T. RESULTS AND CONCLUSIONS: To detect lymphoma infiltration, T1-weighted SE had the highest sensitivity (92%) and diffusion-weighted EPI with fat suppression and FSE STIR had the highest specificity (92.5% and 92%, respectively). A combination of T1-weighted SE and FSE STIR yielded the highest sensitivity and specificity (85% and 97%, respectively). A combination of T1-weighted SE and FSE STIR sequences seems to be the current choice of imaging protocol for detecting bone marrow infiltration by malignant lymphoma.

Osteoblastic response to osteoarthrosis of the hip does not predict outcome of cementless cup fixation: 79 patients followed for 5-11 years.

We evaluated the influence of osteoblastic response to osteoarthrosis of the hip on the outcome of cementless acetabular cup after 91 total hip replacements in 79 patients. Of the 91 hips, 23 were atrophic, 37 normotrophic, and 31 hypertrophic, according to Bombelli's criteria. There were no clinical or radiographic differences among the three groups at the final follow-up (average 7 (5-11) years), when stable bone growth had been achieved by all of the acetabular cups in patients with the atrophic type, 35/37 of the normotrophic type, and all the hypertrophic type. Revision of the acetabular cup was performed on 1 hip of the normotrophic type, in connection with severe polyethylene liner wear and progressive osteolysis.

Phase transformation of a zirconia ceramic head after total hip arthroplasty.

We report two cases of surface deterioration of a zirconia ceramic femoral head associated with phase transformation after total hip arthroplasty. One head was retrieved at revision due to recurrent dislocation after six years and the other because of failure of the locking mechanism of the polyethylene liner after three years. The monoclinic content of the zirconia ceramics rose from 1% to about 30% on the surface of the heads. SEM revealed numerous craters indicating extraction of the zirconia ceramics at the surface. Surface roughness increased from an initial value of 0.006 microm up to 0.12 microm. This is the first report to show that phase transformation of zirconia ceramics causes deterioration of the surface roughness of the head in vivo after total hip arthroplasty.

Dome (modified Chiari) pelvic osteotomy: 10- to 18-year followup study.

Ninety-six dome (modified Chiari) pelvic osteotomies in 87 patients with pain and disability because of osteoarthrosis secondary to hip dysplasia were reviewed. The mean age of the patients at the time of surgery was 29 years (range, 16-55 years). The mean followup was 13 years (range, 10-18 years). Forty-one hips were classified into a hip dysplasia stage, 32 hips into an early stage of osteoarthrosis, and 23 hips into an advanced stage of osteoarthrosis according to the radiographic grading of the Japanese Orthopaedic Association. The average preoperative Merle d'Aubigné and Postel hip score was 13.8, and the average score at final followup was 16.6. Excellent or good results with a score greater than 14 were achieved in 96% of the hips at final followup. Radiographically, signs of progression of osteoarthrosis were not seen in 87% of the hips. Osteoarthrosis progressed during the postoperative course in 13% of the hips. Four patients (four hips) eventually had a total hip arthroplasty at 13.8 years (range, 12.5-15.3 years) after surgery. The survival rate of dome pelvic osteotomy, using clinical failure as an end point, was 82% at 15 years. Using radiologic failure as an end point, 61 hips in 54 patients (survival rate, 78%) survived at 15 years. Using hip replacement as an end point, 92 hips in 83 patients (survival rate, 82%) survived at 15 years. Dome pelvic osteotomy is an excellent and effective operation for pain relief and functional maintenance of the hip.

Ligands for peroxisome proliferator-activated receptor gamma inhibit growth and induce apoptosis of human papillary thyroid carcinoma cells.

Ligands for peroxisome proliferator-activated receptor gamma (PPARgamma) induce apoptosis and exert antiproliferative effects on several carcinoma cell lines. The present study investigates the expression of PPARgamma and the possibility that agonists for PPARgamma also inhibit the growth of human thyroid carcinoma cells. We examined this hypothesis using six cell lines, designated BHP thyroid carcinoma cells, which originated from patients with papillary thyroid carcinoma. RT-PCR analysis revealed that the thyroid carcinoma cell lines BHP2-7, 7-13, 10-3, and 18-21 express PPARgamma. More PPARgamma was expressed in carcinoma than in adjacent normal thyroid tissue in three of six samples of human papillary carcinoma of the thyroid. PPARgamma-positive thyroid carcinoma cells were treated with agonists of PPARgamma, troglitazone, BRL 49653, and 15-deoxy-12,14-prostaglandin J2. Troglitazone (10 micromol/L), BRL 49653 (10 micromol/L), and 15-deoxy-12,14-prostaglandin J2 (1 microg/mL) decreased [(3)H]thymidine incorporation and reduced cell number, respectively, in BHP carcinoma cell lines that expressed PPARgamma. Under low serum conditions, ligands for PPARgamma induced condensation of the nucleus and fragmentation of chromatin into nucleosome ladders. These findings indicate that the death of thyroid carcinoma cells is a form of apoptosis. To investigate the molecular mechanism of the apoptosis, we assessed expression of the apoptosis-regulatory genes bcl-2, bax, and c-myc. Troglitazone significantly increased the expression of c-myc messenger RNA but had no effect on the expression of bcl-2 and bax in thyroid carcinoma cells. These results suggest that, at least in part, the induction of apoptosis in human papillary thyroid carcinoma cells may be due to an increase of c-myc. Troglitazone (500 mg/kg.day) significantly inhibited tumor growth and prevented distant metastasis of BHP18-21 tumors in nude mice in vivo. Taken together, these results suggest that PPARgamma agonist inhibit cell growth of some types of human thyroid cancer.

Relationship between bone marrow cellularity and apparent diffusion coefficient.

This study was performed to determine if there is a relationship between apparent diffusion coefficient (ADC) and cellularity of bone marrow of the posterior ilium. Four groups of various marrow cellularity underwent diffusion-weighted echo-planar imaging: 1) adults with normal hypocellularity (21 patients); 2) adults with normal normocellularity (13 patients); 3) young children with normal hypercellularity (5 patients); and 4) adults with lymphoma-related hypercellularity (3 patients). In all adults, marrow cellularity was confirmed by uni-or bilateral bone marrow biopsies. In children, the iliac marrow was presumed hypercellular because of their ages. A total of 66 ADC values of bone marrow calculated from diffusion-weighted images with b-values of 30 and 300 seconds/mm(2) was evaluated. Hypercellular marrow (normal and lymphoma-related) showed the highest mean ADC, and hypocellular the lowest ADC. Statistically significant differences were found between three groups of normal marrow: hypocellular, normocellular, and hypercellular. There is a positive correlation between ADC and cellularity of bone marrow. J. Magn. Reson. Imaging 2001;13:757-760.

Full weight-bearing after cementless total hip arthroplasty.

In a prospective study of cementless total hip arthroplasty, 19 hips in 17 patients (Group A) were allowed full weight-bearing immediately after the operation while 18 hips in 16 patients (Group B) were first allowed weight-bearing after 6 weeks. Patients were matched for sex, age at surgery, height, weight, and follow-up period and there were no significant differences in hip scores between the two groups. Rehabilitation to gain walking ability with a cane lasted 5.8 days for Group A and 44.8 days for Group B (P = 0.0001). The hospital stay after surgery was 30.1 days for Group A and 46.7 days for Group B (P = 0.006). All patients showed bone ingrowth radiographically. There were no complications in either group.

Influence of polyethylene and femoral head surface quality on wear: a retrieval study.

Thirty-two polyethylene sockets and 22 femoral heads were retrieved because of aseptic loosening more than 9 years after total hip arthroplasty. The volumetric wear rates of the retrieved polyethylene sockets were significantly greater in those coupled with an alumina head (P < 0.05). The retrieved alumina heads showed significantly better surface roughness and roundness than heads of Co-Cr and of stainless steel (P < 0.05). However, no significant difference was found in polyethylene quality demonstrated as fusion defects among the three different groups. The present study suggests that maintaining better surface roughness and roundness of the femoral heads does not always result in an in vivo reduction of polyethylene wear.

Transcriptional activation of the thyroglobulin promoter directing suicide gene expression by thyroid transcription factor-1 in thyroid cancer cells.

Gene therapy with thyroglobulin (TG) promoter and a prodrug/suicide gene combination may prove useful as a treatment for thyroid carcinoma. However, most poorly differentiated and anaplastic thyroid carcinomas have lost the ability to express the TG gene expression accompanied by loss of transcription factors [thyroid transcription factor-1 (TTF-1), TTF-2, or Pax-8] interacting with the TG promoter. In anticipation of developing transcriptionally targeted gene therapy of TG-nonproducing thyroid carcinomas, we investigated the effect of TTF-1 gene transfer on TG promoter activity and the cytotoxic effect obtained by the TG promoter-driven HSV-TK gene along with ganciclovir in thyroid carcinoma and nonthyroidal cells. Using a chimeric construct containing the 5'-flanking region of the rat TG gene between -826 and +39 bp and the luciferase gene, TG promoter activity was detected in a normal rat thyroid cell line (FRTL-5), but not in a dedifferentiated line of thyroid cells (FRT) expressing Pax-8 but not TTF-1, TTF-2, or TG [TTF-1(-)/TTF-2(-)/Pax-8(+)/TG(-)], or in a human papillary thyroid carcinoma cell line [BHP15-3; TTF-1(-)/TTF-2(-)/Pax-8(-)/TG(-)], a human pulmonary cell line [H441; TTF-1(+)/TTF-2(-)/Pax-8(-)/TG(-)], or a dog kidney epithelial cell line [MDCK; TTF-1(-)/TTF-2(-)/Pax-8(+)/TG(-)]. Cotransfection of the TTF-1 expression vector stimulated TG promoter activity in FRT and BHP15-3 dedifferentiated thyroid cells, but not in H441 pulmonary cells. Only weak activation was observed in MDCK kidney cells. We then constructed recombinant adenovirus vectors, AdTTF-1 and ADTGTK: AdTTF-1 contained cytomegalovirus promoter and rat TTF-1 cDNA; AdTGTK carried the TG promoter-driven HSV-TK gene. Infection with AdTGTK and combined with GCV treatment induced a cytotoxic effect in FRTL-5 cells but not in dedifferentiated thyroid or nonthyroid cells. Cotransduction of AdTTF-1 and AdTGTK permitted 90% cytotoxicity for BHP15-3 and >95% cytotoxicity for FRT, as well as for BHP7-13 and BHP18-21v thyroid cancer cell lines [both/TTF1(-)/TTF-2(-)/Pax-8(+)/TG(-)]. In contrast, little cytotoxicity was seen for H441 and MDCK cell lines even with 300 microg/ml of ganciclovir. These results suggest that cotransduction of a TG promoter-controlled suicide gene and the TTF-1 gene by adenoviral vectors confers transcriptionally targeted gene-mediated cytotoxicity in poorly differentiated thyroid carcinoma cells unable to express the TG gene.

Early MRI findings of rapidly destructive coxopathy.

To diagnose rapidly destructive coxopathy (RDC) in its early stages and understand the pathomechanism of associated joint destruction, ten cases of RDC were followed by periodic MRI from onset of the disease. In the initial stage (stage 1) of RDC, when radiographs revealed slight narrowing of the joint space, a small subchondral area of low signal intensity was observed on T(1)-weighted images (T1WI) and inhomogeneous high intensity was observed on T(2)-weighted images (T2WI) in the antero-lateral portion of the femoral head. When radiographs showed obliteration of the joint space (stage 2), MRI revealed a diffuse area of low intensity on TIWI and high intensity on T2WI in the proximal femur, including the femoral neck and head, suggesting extensive bone marrow edema. The femoral head and acetabulum were aggressively destroyed (stage 3) in all cases 3 to 6 months after the diffuse abnormal pattern was observed on MRI. MRI in stage 3 cases showed low intensity areas on both T1WI and T2WI. RDC did not show the band-like pattern of low intensity on T1WI and high intensity on T2WI that typify MRI findings in cases of osteonecrosis. When joint space narrowing is observed radiographically, the diffuse abnormal pattern of low intensity on T1WI and high intensity on T2WI induced by a subchondral small lesion might be an early sign of RDC.

Comparison of fit and fill between anatomic stem and straight tapered stem using virtual implantation on the ORTHODOC workstation.

The objective of this article was to determine the influence of stem design on fit and fill using the preoperative planning workstation of the ROBODOC system. Anatomic ABG and straight Osteolock femoral components were virtually implanted into 50 femora (25 from patients with developmental dysplasia of the hip (DDH), 25 morphologically normal) on the workstation display. Fit and fill, and length of the proximal posterolateral femoral cortex removed by milling (LPFCR), were measured on the cross-sectional images. Lateral curvature (alpha angle) and anteversion of the femur were evaluated. The ABG components showed significantly better fit than the Osteolock components at the levels proximal to the lesser trochanter. The Osteolock components showed significantly greater LPFCR than the ABG components, especially in the patients with DDH. The patients with DDH showed significantly greater alpha angle and femoral anteversion than those with morphologically normal femora. With the Osteolock components, the alpha angle correlated significantly with femoral anteversion and LPFCR. Use of an anatomic proximal body of the stem helped to improve the proximal canal fit. Greater LPFCR was required when a straight stem was implanted in patients with a relatively high alpha angle.

The hDLG-associated protein DAP interacts with dynein light chain and neuronal nitric oxide synthase.

BACKGROUND: Postsynaptic density (PSD)-95 interacts with and mediates clustering of the N-methyl-D-aspartate-receptors (NMDA-R). PSD-95 also interacts with the hDLG-associated protein DAP, which is also called Synapse-associated protein 90-associated protein (SAPAP), and Guanylate kinase-associated protein (GKAP). RESULTS: DAP interacted directly with the dynein light chain (DLC) family of proteins. DLC was contained in the NMDA-R-PSD-95-DAP-neuronal nitric oxide synthase (nNOS) complex. Furthermore, DAP interacted with nNOS and recruited it into the Triton X-100-insoluble fraction of transfected cells. CONCLUSION: DAP interacts directly with DLC and nNOS, and links these proteins to the NMDA-R-PSD-95 complex.

[A case of Terson's syndrome with an interesting MRI finding].

We report a case of a 62-year-old woman admitted to our hospital in a semicomatose state. CT scan and MRI on admission revealed a dense subarachnoid hemorrhage and intracerebral hematoma in the right frontal lobe. Digital subtraction angiography showed a saccular aneurysm located in the anterior communicating artery, so radical neck clipping of the aneurysm was performed via the right pterional approach. The operation was unevential. The patient complained of bilateral visual disturbance on the next day and FLAIR image of MRI demonstrated clearly crescent shaped and mobile high intense lesions corresponding to subhyaloid vitreous hemorrhage in both eye balls. The fundoscopic examination revealed an intravitreous hemorrhage which gradually disappeared over the next 12 days. Terson's syndrome after subarachnoid hemorrhage has been linked to an entity of poor prognosis, so it is beneficial that characteristic findings in FLAIR image of MRI can lead to correct diagnosis of Terson's syndrome earlier.

[Benefits of 0.5T MR diffusion-weighted images for super-acute-phase cerebral infarction].

Though diffusion-weighted images (DWI) have been increasingly used to detect super-acute-phase cerebral infarction in recent years, they have primarily been obtained through the use of high magnetic machines of more than 1.5T. In this study, we discussed the usefulness of DWI obtained using 0.5T MRI in comparison with CT, MRI (FLAIR and T2 weighted image) and SPECT (99mTc-HMPAO). DWI were able to detect ischemic lesions earlier than FLAIR or T2-weighted images. Scanning time was short at four seconds for eight slices, and the quality of image was sufficient for clinical usage. The most available b-value seems to be 800. There were less susceptibility artifacts in the 0.5T DWI than in the 1.5T DWI. From these data, we presume that it is possible to detect super-acute-phase cerebral ischemia on the 0.5T DWI, proving the clinical usefulness of DWI. Furthermore, DWI is considered useful in observing chronological changes in cerebral infarction, differentiation of abscess or brain tumor, diagnosis of moyamoya disease, degenerative disease and so on.

[Craniopharyngioma presenting a symptom of pituitary apoplexy and hyponatremia: a case report].

We report a case of a 70-year-old woman admitted to our hospital with sudden headache, drowsiness and hyponatremia. MRI on admission showed an intrasellar mass with suprasellar extension. Serum examination revealed decreased sodium and hypopituitarism, but they were normalized gradually by compensation using hydrocortisone, thyroid hormone and salt. Afterwards, masked diabetes insipidus appeared and required aqueous pitressin for the control of urine volume. A removal operation was performed uneventfully using the transsphenoidal approach and histological examination confirmed squamous-papillary type craniopharyngioma. Intratumoral hemorrhage of the craniopharyngioma is extremely rare. These cases tend to occur after over 15 years of maturation and the squamous-papillary type tend to bleed more than the adamantinomatous type. However, it is very difficult to make a differential diagnosis between craniopharyngioma with intratumoral hemorrhage and pituitary apoplexy, judging only by symptoms or interventional radiology. The definite mechanism of hyponatremia associated with a parasellar lesion is still obscure, but compression to the anterior hypothalamus or pituitary gland by an enlargement of the parasellar tumor is generally hypothesized.