Recombination of a maternal pericentric inversion results in 22q13 deletion syndrome

We describe a 10-month-old boy with 22q13 deletion syndrome. Chromosomal analysis showed a partial duplication of 22p11.2-pter and a terminal deletion of 22q13.31-qter. Maternal chromosomal analysis showed a pericentric inversion of chromosome 22, with breakpoints at p11.2 and q13.31 [inv(22)(p11.2q13.31)]. The deleted chromosome resulted from a recombinant chromosome inherited from his mother. This is a rare case of 22q13 deletion syndrome associated with parental pericentric inversion of chromosome 22.     

Repeated Necrotizing Lymphadenitis with MEFV Gene Mutations

We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient''s chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis.     

Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients

Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of systemic autoinflammatory disorders in which the majority of patients have mutations in the cold-induced autoinflammatory syndrome (CIAS)1 gene. Despite having indistinguishable clinical features, some patients lack CIAS1 mutations by conventional nucleotide sequencing. We recently reported a CAPS patient with mosaicism of mutant CIAS1, and raised the possibility that CIAS1 mutations were overlooked in "mutation-negative" patients, due to a low frequency of mosaicism. To determine whether there were latent mutant cells in "mutation-negative" patients, we sought to identify mutation-associated biologic phenotypes of patients' monocytes. We found that lipopolysaccharide selectively induced necrosis-like cell death in monocytes bearing CIAS1 mutations. Monocyte death correlated with CIAS1 up-regulation, was dependent on cathepsin B, and was independent of caspase-1. Cell death was intrinsic to CIAS1-mutated monocytes, was not mediated by the inflammatory milieu, and was independent of disease severity or anti-IL-1 therapy. By collecting dying monocytes after lipopolysaccharide treatment, we succeeded in enriching CIAS1-mutant monocytes and identifying low-level CIAS1-mosaicism in 3 of 4 "mutation-negative" CAPS patients. Our findings reveal a novel effect of CIAS1 mutations in promoting necrosis-like cell death, and demonstrate that CIAS1 mosaicism plays an important role in mutation-negative CAPS patients.     

Structural elements influencing von Willebrand factor (vWF) binding affinity for platelet glycoprotein Ib within a dispase-digested vWF fragment

We investigated the structural elements in human von Willebrand factor (vWF) that influence binding affinity for platelet glycoprotein (GP) Ib using a dispase-digested vWF fragment as a prototype (residues Leu480/Val481-Gly718 of the vWF subunit; Andrews et al, Biochemistry 28:8326, 1989). The major structural features of this fragment are a large A1-loop formed by an intrachain disulfide bond between Cys509 and Cys695 and six O-linked sugar chains. The fragment was chemically modified by (1) reduction and S-carboxyamido-methylation (R/A), (2) desialylation (DS), or (3) a combination of both (R/A-DS). The GPIb binding affinity of these fragments was basically evaluated by competitive binding assay with anti-GPIb monoclonal antibody (LJ-Ib1), a receptor blocker for vWF (Sugimoto et al, Biochemistry 30:5202, 1991). Both the prototype and the R/A fragments were also assessed for their function in shear-induced platelet aggregation. Results unambiguously demonstrated that the presence of a disulfide bridge (Cys509-Cys695) within this domain downregulates the affinity of vWF to GPIb. In addition, it was also demonstrated that the terminal sialic acids attached to six o-linked sugar chains within this domain contribute to optimal functional modulation by the antibiotic ristocetin, but not by snake venom botrocetin.     

Prone positioning improves distribution of pulmonary perfusion: noninvasive magnetic resonance imaging study in healthy humans

The purpose of this study was to evaluate the effects of prone positioning on pulmonary perfusion using flow-sensitive alternating inversion recovery (FAIR), a noninvasive magnetic resonance imaging technique that requires no contrast medium. Seven healthy volunteers were studied in the supine and prone positions under three respiratory conditions: normal breathing of room air, unassisted breathing of 45% O₂, and controlled mechanical ventilation (CMV) with positive end-expiratory pressure. Signal intensities (SIs) were obtained from ventral, middle, and dorsal regions on sagittal lung images and dependent/nondependent SI ratios were calculated to evaluate pulmonary perfusion distribution. In the supine position, SIs increased significantly from the ventral to dorsal region under all three respiratory conditions and prone positioning inverted the perfusion distribution under all conditions. Right lung SI ratios were 2.34 ± 0.29, 2.74 ± 0.66, and 2.42 ± 0.73 in the supine position and 1.68 ± 0.48, 1.78 ± 0.36, and 1.92 ± 0.21 in prone for room air, 45% O₂, and CMV, respectively. The difference between supine and prone positions was statistically significant. The left lung showed a similar pattern and the difference was significant only under CMV. No difference was observed between the different respiratory conditions in both lungs. This study demonstrated that the distribution of pulmonary perfusion was more uniform in prone than in the supine position.     

Discordance of motion artifacts on magnetic resonance imaging in Creutzfeldt-Jakob disease: comparison of diffusion-weighted and conventional imaging sequences

Purpose Motion artifact is problematic in the diagnosis of Creutzfeldt-Jakob disease (CJD) because of dementia. The purpose was to compare the occurrence of this artifact between a diffusion-weighted (DW) magnetic resonance (MR) imaging sequence and conventional sequences. Materials and methods Ten MR examinations comprising T2-weighted, T1-weighted, DW, and fluid-attenuated inversion recovery imaging in seven CJD patients were retrospectively evaluated. The occurrence of motion artifacts on each sequence were assessed, and the examination was classified into four groups as follows: group A, motion artifact not revealed on DW imaging but revealed on one or more other sequences; group B, revealed on DW imaging and one or more other sequences; group C, not revealed on any sequences; and group D, revealed on DW imaging but not on any other sequences. Results The 10 MR examinations were classified as eight group A (80%), one B (10%), one C (10%), and zero D (0%). Conclusion Motion artifacts are likely to occur in any conventional imaging sequences in CJD, but the fast-imaging ability of DW imaging can reduce this artifact. The combination of an absence of motion artifact on DW imaging and the presence on conventional sequences may be one of the frequent findings of CJD.     

Management of pancreatic mass accompanying chronic pancreatitis

We report two patients with focal, chronic pancreatitis that was diagnosed by dynamic computed tomography (CT) combined with intraoperative biopsy. In case 1, serum carbohydrate antigen (CA) 19-9 level rose to 160 U/ml. Abdominal ultrasonography, CT, and magnetic resonance imaging demonstrated a mass, of 4.5 cm in diameter, in the pancreatic head. On dynamic CT, the mass was enhanced similarly to the normal pancreatic parenchyma. In case 2, dynamic CT demonstrated a mass, of 3.0 cm in diameter, in the pancreatic head, which was enhanced similarly to the normal pancreatic parenchyma. From such characteristics of enhancement, both masses were suspected to be chronic pancreatitis rather than cancer, and the diagnosis was confirmed by intraoperative biopsy. Three years in case 1 and 2 years in case 2 have passed since their operations, and the size of each mass has not changed. With the use of dynamic CT combined with intraoperative biopsy, focal chronic pancreatitis could be diagnosed more accurately, and this may lead to a reduction in unnecessary pancreatic resection. Received: November 16, 2001 / Accepted: February 8, 2002     

Complete paralysis of the quadriceps muscle caused by traumatic iliacus hematoma: a case report

 A 15-year-old girl who developed traumatic iliacus hematoma and complete paralysis of the quadriceps muscle is reported. The current case and literature review revealed that incomplete quadriceps paralysis associated with traumatic iliacus hematoma is likely to progress to complete paralysis in days or weeks as a result of increased intracompartmental pressure. However, surgical decompression of the femoral nerve could produce good results even in patients who have complete quadriceps paralysis preoperatively. Received: April 9, 2002 / Accepted: June 28, 2002 Offprint requests to: K. Tamai     

Congenital absence of lumbosacral articular facet joint associated with conjoined nerve root: a case report

We report a rare case of congenital absence of the L5-S1 facet joint, which was associated with a conjoined nerve root. Combination of these two anomalies has been quite rarely reported in the literature. A 39-year-old man presented with acute low back pain and right leg radiating pain. Muscle weakness and sensory disturbance of the right leg were also apparent in the region innervated by L5 and S1 nerve roots. Preoperative multidetector three-dimensional computed tomography (3D-CT) showed complete absence of the right S1 superior articular process. Magnetic resonance (MR) images showed lumbar disc herniation at right L5-S1 level that migrated cranially. Intraoperative findings revealed that the right L5 nerve root and S1 nerve root were conjoined, and the conjoined nerve root was compressed by L5-S1 disc herniation, which led to impairment of the conjoined nerve root by a single-level lumbar disc herniation. After removal of the disc herniation, his right leg pain immediately subsided, however muscle weakness and sensory disturbance persisted. Surgeons should be aware of this nerve root anomaly when examining a patient who shows an unusual clinical presentation and/or congenital osseous anomaly.     

Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis

Endoplasmic reticulum (ER) stress response is important for protein maturation in the ER. Some murine models for bone diseases have provided significant insight into the possibility that pathogenesis of osteoporosis is related to ER stress response of osteoblasts. We examined a possible correlation between osteoporosis and ER stress response. Bone specimens from 8 osteoporosis patients and 8 disease-controls were used for immunohistochemical analysis. We found that ER molecular chaperones, such as BiP (immunoglobulin heavy-chain binding protein) and PDI (protein-disulfide isomerase) are down-regulated in osteoblasts from osteoporosis patients. Based on this result, we hypothesized that up-regulation of ER molecular chaperones in osteoblasts could restore decreased bone formation in osteoporosis. Therefore, we investigated whether treatment of murine model for osteoporosis with BIX (BiP inducer X), selective inducer BiP, could prevent bone loss. We found that oral administration of BIX effectively improves decline in bone formation through the activation of folding and secretion of bone matrix proteins. Considering these results together, BIX may be a potential therapeutic agent for the prevention of bone loss in osteoporosis patients.