Feasibility of HLA-haploidentical hematopoietic stem cell transplantation between noninherited maternal antigen (NIMA)-mismatched family members linked with long-term fetomaternal microchimerism

Based on the hypothesis that long-term fetomaternal microchimerism is associated with acquired immunologic hyporesponsiveness to noninherited maternal antigens (NIMAs) or inherited paternal antigens (IPAs), several groups have recently reported successful cases of non-T-cell-depleted hematopoietic stem cell transplantation (SCT) from HLA-haploidentical family members mismatched for NIMAs. In this study, we examined the outcomes of 35 patients with advanced hematologic malignancies who underwent HLA-2-antigen- or HLA-3-antigen-incompatible SCT from a microchimeric NIMA-mismatched donor. After standard-intensity or reduced-intensity preparative regimens, all patients had sustained hematopoietic recovery with tacrolimus-based graft-versus-host disease (GVHD) prophylaxis. Grade II/IV acute GVHD occurred in 19 (56%) of 34 evaluable patients, while extensive chronic GVHD developed in 13 (57%) of 23 patients who could be evaluated. Multivariate analysis demonstrated that NIMA mismatch in the GVH direction was associated with a lower risk of severe grade III-IV acute GVHD when compared with IPA mismatch (P = .03). Fifteen patients were alive and 14 of them were disease-free with a median follow-up of 20 (range, 8 to 37) months. These results indicate that T cell-replete SCT from an HLA-haploidentical NIMA-mismatched donor can offer durable remission with an acceptable risk of GVHD in selected patients with advanced hematologic malignancies who lack immediate access to a conventional stem cell source.     

Creutzfeldt-Jakob disease with the M232R mutation in the prion protein gene in two cases showing different disease courses: a clinicopathological study

We report two autopsy cases of Creutzfeldt-Jakob disease (CJD) with the M232R mutation of the prion protein (PrP) gene that exhibited different clinicopathological features (age at death, 64/54 years; disease duration, 13/26 months). Both cases showed myoclonus, hyperintensity on diffusion-weighted MRI, and increased 14-3-3 protein in the cerebrospinal fluid. The initial sign in each case was memory disturbance and abnormal pharyngeal sensation, respectively. In the first case, the disease progressed rapidly with akinetic mutism developing 6 months after onset, while it occurred 23 months after onset in the second case. Pathologically, both cases had severe neuronal loss with gliosis and spongiform change in the cerebral cortex, basal ganglia, and cerebellum. PrP deposition was the diffuse synaptic type in the first case, but the second case had both diffuse synaptic and perivacuolar types. PrP(sc) immunoblotting revealed a type 1 band pattern in the first case, but both types 1 and 2 in the second case. Based on these findings, together with the results in previous CJD cases with M232R, we noted the possibility that the presence of type 2 PrP(sc) may be associated with both morphological features of PrP deposition and slow disease progression in this genetic prion disease.     

High salivary alpha-amylase levels in patients with schizophrenia: A pilot study

Previous studies have demonstrated the autonomic dysregulation in patients with schizophrenia using electrophysiological methods, such as electrodermal measures and heart rate analysis. Several theories have been proposed to explain the underlying mechanisms of schizophrenia and its autonomic function. Recently, the measurement of salivary alpha-amylase has been considered to be a useful tool for evaluating the sympathetic-adrenal-medullary (SAM) system. Psychosocial stress increases the release of salivary alpha-amylase. Although some studies have evaluated salivary alpha-amylase under psychosocial stress, no studies have demonstrated the change in the salivary alpha-amylase (sAA) activity level in schizophrenic patients. We examined the relationship between sAA level and psychiatric state in patients with schizophrenia (n = 54) using a portable and rapid hand-held monitor to investigate sAA. The sAA activity in the patients was significantly higher than that in the control subjects (n = 55) (p < 0.01). The correlation between amylase level and psychiatric symptoms was highly significant (r = 0.37, p < 0.01). These findings indicate that higher increases in sAA may indicate severe psychiatric symptoms. These results indicate a predominant role of the sympathetic nervous system in the secretion of sAA, together with parasympathetic withdrawal, under psychosocial stress.     

Clinical evaluation of choline measurement by proton MR spectroscopy in patients with malignant tumors

PURPOSE: To examine whether choline measurement by proton magnetic resonance (MR) spectroscopy in patients with malignant tumors is clinically meaningful in addition to routine MR imaging. MATERIALS AND METHODS: MR spectroscopy and MR imaging were performed in 27 consecutive patients with suspected malignant disease. Malignancy was assessed based on total choline compound levels using proton MR spectroscopy, and the results were compared with MR imaging findings. RESULTS: The sensitivity of MR imaging (84%, 21/25) was not significantly different from that of MR spectroscopy (88%, 22/25) among the 25 actual malignant diseases. Both MR imaging and MR spectroscopy produced two false-negative results. In one case, MR spectroscopy produced a false-negative result, whereas MR imaging produced a true-positive result. In two cases of benign breast disease, MR imaging produced false-positive results. MR spectroscopy produced one true-negative result and one false-positive result. CONCLUSION: Although choline measurement by MR spectroscopy is a useful tool in the evaluation of malignant disease, it should be reserved for patients with suspected malignant disease that cannot be detected by MR imaging, such as those with non-palpable prostate tumor with elevated sPSA levels.     

Gender difference in brain perfusion 99mTc-ECD SPECT in aged healthy volunteers after correction for partial volume effects

BACKGROUND: Previous reports have yielded controversial results concerning gender differences in regional cerebral blood flow (rCBF). To elucidate this issue, we compared 99mTc ethyl cysteinate dimer single photon emission computed tomography (SPECT) images for brain perfusion between aged-matched healthy men and women after correction for partial volume effects (PVEs). METHODS: Brain perfusion SPECT in the resting state was performed on 40 healthy, right-handed subjects, 20 men and 20 women, with an age range of 58-86 years, who did not differ sociodemographically. PVE correction was performed using grey matter volume measured by magnetic resonance imaging. Statistical parametric mapping was used for the analysis of the adjusted rCBF images of relative flow distribution. RESULTS: The PVE correction revealed that women had higher rCBF in left inferior frontal gyrus, bilateral middle temporal gyri, and left superior temporal gyrus. Men had higher rCBF in left superior frontal gyrus, right medial frontal gyrus, right superior parietal lobule, right postcentral gyrus, right cerebellum, right middle frontal gyrus, right fusiform gyrus, and right precuneus. CONCLUSION: Significant gender differences in rCBF existed in these healthy volunteers. The PVE correction of SPECT images revealed gender differences that were consistent with the universal findings of better performance on verbal tasks in women and on visuospatial tasks in men.     

Availability of N-isopropyl-p-[125I]iodoamphetamine (IMP) as a practical cerebral blood flow (CBF) indicator in rats

Since a very complicated technique is necessary to measure cerebral blood flow (CBF) with [14C]iodoantipyrine in small animals, a practical and easy method is needed. In this paper, the differential uptake ratio (DUR) at 5 min after injection of N-isopropyl-p-[125I]iodoamphetamine (IMP) was estimated as an index of CBF in normal rats and compared with the quantitative CBF value measured using [15O]H2O and dynamic PET scan. A good correlation between the two values was obtained. The results indicate that DUR of [125I]IMP at 5 min after injection in rats is a useful and practical indicator of CBF since neither arterial blood sampling nor metabolite correction is necessary.     

In vitro hypertrophy and calcification of human fracture haematoma-derived cells in chondrogenic differentiation

Purpose

The haematoma at a fracture site plays an important role in fracture healing. Previously, we demonstrated that a fracture haematoma contains multilineage mesenchymal progenitor cells. We postulated that the haematoma provided a source of chondrogenic cells for endochondral ossification during fracture healing and preservation of the cells contributed to biological fracture healing. In this study, we investigated whether haematoma-derived cells (HCs) could differentiate into hypertrophic chondrocytes and finally induce calcification of the extracellular matrix in vitro.

Methods

Fracture haematomas were obtained from four patients. HCs were cultured for five weeks under conditions that induce chondrogenic differentiation, followed by two weeks of hypertrophic induction using a pellet culture system. The pellets were analysed histologically and immunohistochemically. The gene expression levels of chondrogenic, hypertrophic, osteogenic, and angiogenic markers were measured by real-time PCR.

Results

The histological and immunohistochemical analyses revealed that HCs differentiated into chondrocytes and hypertrophic chondrocytes, followed by calcification of the extracellular matrix. This sequential differentiation was also reflected in the gene expression profiles. After chondrogenic induction, expression of osteogenic and angiogenic markers was not significantly upregulated. However, the expression of these markers was significantly upregulated following hypertrophic induction. These in vitro observations mimicked the process of endochondral ossification during fracture healing.

Conclusions

Our results suggest that the fracture haematoma may offer a source of cells with chondrogenic potential that play key roles in endochondral ossification during fracture healing. These findings support the opinion that the haematoma should be preserved for biological fracture healing.     

Improved Long-term Survival after Liver Resection for Hepatocellular Carcinoma in the Modern Era: Retrospective Study from HCV-endemic Areas

Introduction It remains unclear whether recent progress in perioperative management and treatment for recurrent hepatocellular carcinoma (HCC) has improved patient outcomes in hepatitis C virus-endemic areas. Methods The clinicopathologic and follow-up data of 218 consecutive HCC patients who underwent curative resection between 1982 and 2003 were analyzed. Patients were assigned to one of two groups: before 1992 (early group; n = 82) and 1992 and later (late group; n = 136). Factors influencing survival rates were investigated by multivariate analysis. The effects of the period during which the hepatic resection was done on the patients’ outcome were examined with respect to tumor size. Results The 5-year cancer-related and disease-free survival rates were 51.4% and 20.4%, respectively. The late group showed better 5-year cancer-related survival than the early group (64.1% vs. 33.8%), but disease-free survival did not differ significantly between the groups. On multivariate analysis, the period of the hepatic resection was identified as an independent prognostic factor for cancer-related survival (relative risk 0.70, P < 0.01) but not disease-free survival. There were no differences in the cancer-related and disease-free survival rates between the two groups for patients with tumors ≤ 25 mm. In patients with HCCs > 50 mm, both cancer-related and disease-free survival rates were better in patients in the late group. Conclusions During the past two decades, improvements in the treatment of recurrent HCC tumors have contributed to controlling large HCCs but not to controlling the multicentric development of HCCs. It may be important to control multicentric recurrence of HCC to improve patient survival in areas where the hepatitis C virus is endemic.