Influence of the anatomical form of the posterior maxilla on the reliability of superior maxillary repositioning by Le Fort I osteotomy.

Certain patients with facial deformities require superior repositioning of the maxilla via Le Fort I osteotomy; however, the magnitude of superior repositioning of the maxilla is often less than expected. In this study, the correlation between the accuracy of superior repositioning of the maxilla and the anatomical form of the maxillary posterior region was examined. Seventy-five patients who underwent Le Fort I osteotomy without forward movement of the maxilla but with superior repositioning of the maxilla were included in this study. The bone volume around the descending palatine artery (DPA), the angle of the junction between the pterygoid process and the tuberosity, and the distance between the upper second molar and the pterygoid process were measured via three-dimensional analysis. A significant negative correlation (r=-0.566) was found between the bone volume around the DPA and the ratio of repositioning (actual movement divided by expected movement). It is possible that the superior repositioning of the maxilla expected prior to surgery was not sufficiently attained because of the large volume of bone around the DPA. The results of this study show that in some patients, superior repositioning was not achieved at the expected level because of bone interference attributable to the anatomical form of the maxillary posterior region.

Treatment of refractory non-union after maxillary osteotomy: A case report.

Maxillary non-union is a rare complication that occurs after an orthognathic surgery such as Le Fort I osteotomy. Here, we report a case of refractory non-union after maxillary osteotomy, which required a second surgery with bone graft. A 33-year-old man who had undergone bimaxillary osteotomy complained of an abnormal sensation in the right alar part about 1 year after the surgery. The patient was diagnosed as having maxillary non-union. Although surgical stabilization was performed using titanium plates, the non-union remained. The re-fusion surgery was performed about 3 years after the bimaxillary osteotomy with autologous bone graft using a biodegradable fixation system. At the 1-year follow up, the maxillary non-union was healed both clinically and radiographically. Re-fusion surgery using bone graft with biodegradable fixation might be an effective treatment option in cases of prolonged non-union that becomes evident after a long period following the initial maxillary osteotomy.

[A case of Japanese encephalitis presenting with unilateral lesions in diffusion-weighted MRI].

We report the findings of diffusion-weighted MRI (DWI) taken serially in a patient with Japanese encephalitis (JE). The patient was a 43-year-old woman presenting with headache, high fever and consciousness disturbance. The diagnosis of JE was made based on more than fourfold elevation of serum complement fixation antibody titer for JE virus in the convalescent phase of illness. The DWI on the second day of illness (Day-2) disclosed high-signal intensity lesions in the left thalamus, substantia nigra and frontal lobe cortex. The signal intensity of these lesions on the DWI increased on Day-3 but gradually decreased thereafter and normalized on Day-28. The improvement of the DWI findings was paralleled with that of the consciousness level and the cell number and neuron specific enolase concentration in the CSF, suggesting that DWI is useful for evaluation of the disease activity in JE. The lesions in the brain suffering from Japanese encephalitis are usually bilateral and diffuse. To our knowledge, this is the first report of JE presenting with unilateral lesions on MRI, of which phathomechanism remains to be elucidated.

Changes in the cell structure of Flavobacterium psychrophilum with length of culture.

Flavobacterium psychrophilum, the pathogen of bacterial cold-water disease, causes serious problems in ayu Plecoglossus altivelis culture. This study investigated the effect of the culture period of F. psychrophilum and on the structure of its cells. From the SDS-PAGE of total proteins of cellular components, much difference was found between the 36 hr culture and the 48 and 72 hr cultures. A SEM observation of the cells showed many fragments, especially on the cell surface of the 36 hr culture. These fragments consisted of an outer membrane, seen by TEM observation, and may contain substances causing the virulence. Specific proteins observed by the SDS-PAGE and fragments in the 36 hr culture may be related to the virulence of F. psychrophilum.

An enzyme-linked immunosorbent assay to quantify 14-3-3 proteins in the cerebrospinal fluid of suspected Creutzfeldt-Jakob disease patients.

The detection of 14-3-3 protein by Western immunoblot is a sensitive and specific cerebrospinal fluid marker of Creutzfeldt-Jakob disease (CJD). We developed a quantitative enzyme-linked immunosorbent assay (ELISA) that reliably detects 14-3-3 in cerebrospinal fluid. In a prospective study of 147 cerebrospinal fluid samples, the mean 14-3-3 concentration among pathologically confirmed CJD patients (28.0+/-20.6 ng/ml, n = 41) is significantly higher than the mean in the cerebrospinal fluid of those with other neurological disorders (3.1+/-2.9 ng/ ml, n = 84). At a cutoff value of 8.3 ng/ml, the ELISA has a sensitivity of 92.7% and a specificity of 97.6%. The 14-3-3 ELISA supports a diagnosis of CJD in patients who fulfill clinical criteria for possible CJD.

Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum to chromosome 15A13-15.

To date, three loci for autosomal recessive hereditary spastic paraplegia (ARHSP) linked to chromosomes 8p12-q13, 16qter, and 15q13-15 have been characterized. We have clinically characterized 13 Japanese ARHSP families and performed genetic linkage analyses. All 13 families were classified as having the "complicated" form, which manifests with mental impairment and thin corpus callosum. Linkage to the 8p12-q13 and 16qter loci was excluded, although 10 of the 13 families showed marker data consistent with linkage to the 15q13-15 locus. The multipoint LOD score of the 10 families linked to chromosome 15 was above 9.00 in the 3-centimorgan segment flanked by D15S994 and D15S659, with a maximum multipoint LOD score of 9.68 at a position 1.2 centimorgans telomeric from D15S994 to D15S659. We have shown that ARHSP with thin corpus callosum, a subtype of recessive spastic paraplegia, maps to chromosome 15q13-15.

Meltrin beta (ADAM19) gene: cloning, mapping, and analysis of the regulatory region.

Meltrin beta (ADAM19) is a member of the metalloprotease-disintegrin family. We report here chromosomal mapping of the mouse and rat meltrin beta genes and cloning and analysis of the mouse upstream regulatory regions. The meltrin beta transcript shows a spatially and temporally restricted expression pattern during morphogenesis, indicating that the actions of this membrane-bound protease are regulated, at least in part, at the transcriptional level. Analysis of the promoter revealed positive and negative regulatory regions upstream of the gene. The former includes a GC-box that appears to be a critical cis-element for activation of the promoter in muscle cells.

The 14-3-3 protein detectable in the cerebrospinal fluid of patients with prion-unrelated neurological diseases is expressed constitutively in neurons and glial cells in culture.

The 14-3-3 protein belongs to a family of 30-kD proteins originally identified by two-dimensional analysis of brain protein extracts. Recently, the detection of the 14-3-3 protein in the cerebrospinal fluid (CSF) is utilized as a highly reliable test for the premortem diagnosis of prion diseases such as Creutzfeldt-Jakob disease. For the initial step, to clarify the biological implication of the CSF 14-3-3 protein in these diseases, its expression was investigated in neural tissues and cultures and CSF samples from patients with a variety of neurological diseases by Western blot analysis and immunocytochemistry. The constitutive expression of the 14-3-3 protein was identified in all neural and nonneural tissues examined. It was expressed in all neurons, astrocytes, oligodendrocytes, and microglia in culture with its location in both cytoplasmic and nuclear regions. The 14-3-3 protein was detected in the CSF of 8 out of 71 patients, including 1 Gerstmann-Sträussler-Scheinker disease patient and 7 patients with prion-unrelated neurological diseases, such as meningoencephalitis of viral, bacterial, or tuberculous origin, multiple sclerosis, and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. These results suggest that the 14-3-3 protein expressed constitutively at substantial levels in both neurons and glial cells might be released into the CSF as a disease-nonspecific consequence of the extensive brain damage and indicate that the analysis of the 14-3-3 protein in the CSF is not useful as a screening test for prion diseases.

Cultured skin fibroblasts isolated from mice devoid of the prion protein gene express major heat shock proteins in response to heat stress.

Recent evidence has suggested that molecular chaperones participate in the conformational change between the normal cellular prion protein (PrPC) and its scrapie isoform (PrPSc). To study a role of PrPC in the regulation of expression of heat shock proteins (HSPs), a group of molecular chaperones, heat-induced expression of major HSPs (HSP105, HSP90alpha, HSP72, HSC70, HSP60, and HSP25) was investigated in cultured skin fibroblasts isolated from the mice homogeneous for a disrupted PrP gene (PrP-/- mice) by Western blot analysis and immunocytochemistry. Two lines of fibroblasts were established and designated SFK derived from the PrP-/- mice and SFH derived from the PrP+/+ mice, respectively. In both SFK and SFH cells, HSP105, HSP72, and HSP25 were expressed at low levels under unstressed conditions but they were induced markedly following exposure to heat stress (43 degreesC/20 min) at 3-72 h postrecovery. In both cell types, HSC70 and HSP60 were expressed at high levels under unstressed conditions and their levels remained unchanged after heat shock treatment. HSP90alpha was undetectable in both cell types under any conditions examined. The pattern of expression, induction, and subcellular location of HSP105, HSP72, HSC70, HSP60, and HSP25 was not significantly different between SFK and SFH cells under unstressed and heat-stressed conditions. Furthermore, the levels of constitutive expression of HSP105, HSC70, HSP60, and HSP25 were similar between the brain tissues isolated from the PrP-/- and PrP+/+ mice. These results indicate that HSP induction is not affected by either the existence or the absence of PrPC in the cells.

Constitutive and cytokine-inducible expression of prion protein gene in human neural cell lines.

Prion diseases are a group of neurodegenerative disorders characterized by intracerebral accumulation of a protease-resistant prion protein (PrP(Sc)) that causes extensive neuronal degeneration and astrogliosis. The regulation of prion protein (PrP) gene expression by a panel of glial and neuronal cytokines (TNF-alpha, IFN-gamma, IL-1beta, IL-10, and TGF-beta1) was investigated in human neural cell lines by reverse transcription-polymerase chain reaction and Northern blot analysis. The constitutive expression of PrP mRNA was identified in all human neural cell lines and tissues examined including Y79 retinoblastoma, IMR-32 neuroblastoma, SK-N-SH neuroblastoma, U-373MG astrocytoma, KG-1-C glioma, NTera2 teratocarcinoma, NTera2-derived differentiated neurons (NTera2-N), peripheral nerve, and cerebral and cerebellar tissues. In SK-N-SH cells, a 48 hour (h) treatment with 100 ng/ml IL-1beta, 100 ng/ml TNF-alpha, or 100 nM phorbol 12-myristate 13-acetate induced a 2.7- to 4.2-fold increase in the level of PrP mRNA, while the exposure to 100 ng/ml IFN-gamma resulted in a 50% decrease. By contrast, none of these cytokines significantly altered the levels of PrP mRNA in IMR-32, NTera2-N, or U-373MG cells. These results indicate that the PrP gene expression is constitutive in a wide range of human neural cell lines and tissues where it is controlled by cell type-specific regulatory mechanisms.

Interleukin-15, a T-cell growth factor, is expressed in human neural cell lines and tissues.

Interleukin-15 (IL-15) is a novel cytokine which shares activities and receptor components with IL-2. To investigate the biological roles of IL-15 in the human nervous system, we examined the expression of mRNAs for IL-15 and the IL-15 receptor three subunits (IL-15alpha, IL-2Rbeta and IL-2Rgamma) in human neural cell lines and tissues using reverse transcription-polymerase chain reaction and Southern blot analysis. The constitutive expression of high levels of IL-15 mRNA was observed in all the cell lines examined, including Y79 retinoblastoma, IMR-32 neuroblastoma, SK-N-SH neuroblastoma, U-373MG glioma, KG-1-C glioma, NTera2 teratocarcinoma and neurons derived from NTera2 cells following treatment with retinoic acid (RA). Among these cell lines, IL-15 protein was detectable at high levels in culture supernatants of SK-N-SH cells and NTera2-derived neurons. The expression of an alternatively-spliced transcript of the IL-15 gene was up-regulated in NTera2 cells during RA-induced neuronal differentiation, suggesting the existence of differentiation-dependent transcriptional regulation. The expression of IL-15 mRNA was also identified in the human cerebral and cerebellar tissues, peripheral nerve and skeletal muscle, while the mRNAs for the complete set of IL-15R components were detectable only in U-373MG cells, cerebral and cerebellar tissues at significant levels. These results indicate that the expression of IL-15 but not of IL-15R mRNA is universal in human neural cell lines and tissues and raise the possibility that IL-15 acts as a neuroimmune regulatory factor in the human central nervous system.

Adult-onset Krabbe disease with homozygous T1853C mutation in the galactocerebrosidase gene. Unusual MRI findings of corticospinal tract demyelination.

A 51-year-old woman developed a slowly progressive spastic paraparesis and diminished vibration sense beginning at age 38. Intellectual capacity was normal. Krabbe disease was confirmed by markedly reduced leukocyte galactocerebrosidase (GALC) activity, typical inclusions in Schwann cell cytoplasm, and an identification of the homozygous point mutation T1835C (Leu618Ser) in the GALC gene. T2-weighted MRI of the brain showed symmetric high-signal-intensity lesions in the bilateral frontoparietal white matter, the centrum semiovale, and the posterior limb of the internal capsule with sparing of the periventricular white matter. This case is unusual because of the late onset, protracted clinical course, and MRI findings of demyelination confined to the corticospinal tracts.

[A case of axonal form of Guillain-Barré syndrome associated with anti-GM1b IgG antibody following Penner 4 Campylobacter jejuni infection].

A 41-year-old woman was admitted to the hospital because of diarrhea followed by progressive weakness of all extremities and dysphagia. On neurological examination, she showed facial diplegia, bulbar palsy, flaccid quadriplegia, and absence of all deep tendon reflexes in addition to Laségue's sign. The Campylobacter jejuni Penner type 4 was isolated from the culture of stool. The test of anti-GM1b antibody (IgG) was positive in the serum. The protein content was elevated in the cerebrospinal fluid without pleocytosis. The studies of motor nerve conduction velocity showed a pattern of the axonal neuropathy. This is a case of Guillain-Barré syndrome presenting with the axonal neuropathy possibly due to the immune response directed to GM1b which is triggered by the Campylobacter jejuni Penner type 4 infection.

Homozygosity for an allele carrying intermediate CAG repeats in the dentatorubral-pallidoluysian atrophy (DRPLA) gene results in spastic paraplegia.

We report a family with autosomal recessive spastic paraplegia. Patient 1 was a 37-year-old woman and patient 2 was her 35-year-old sister. They showed spastic paraplegia with mild truncal ataxia and dysarthria but no dementia, epilepsy, myoclonus, or other involuntary movements. They were the products of a consanguineous marriage but the parents were neurologically normal. We analyzed the CAG repeats of the dentatorubral-pallidoluysian atrophy (DRPLA) gene in the family members. The patients were homozygous for an allele carrying an intermediate size of CAG repeats (41 or 40 repeats) in the DRPLA gene; the parents were heterozygous for an intermediate allele and a normal allele in this gene. Homozygosity for an intermediate allele in the DRPLA gene appears to have resulted in spastic paraplegia different from any DRPLA phenotype.

Occurrence of Borrelia garinii oculo-neuroborreliosis in Japan.

We report a 64-year-old Japanese man with oculo-neuroborreliosis. His clinical features consisted of polyarthralgia, keratoconjunctivitis, chorioretinitis, optic neuritis, confusion, and polyradiculitis. Assay of antibodies to Borrelia species detected IgG-antibody to B. garinii in both serum and CSF. Progressive declining of serum IgG antibody titer against Borrelia garinii, in parallel with clinical improvement, was observed after administration of ceftriaxone.

[Improvement of ophthalmoplegia by 5-hydroxytryptophan in two cases of progressive supranuclear palsy].

We report two patients with clinically diagnosed progressive supranuclear palsy (PSP): a 69-year-old man and a 73-year-old woman. Both patients showed supranuclear ophthalmoplegia, postural instability, pseudobulbar palsy, and Parkinsonism. In the first patient, we administered L-dopa/carbidopa (300 mg/30 mg/ day), which moderately improved gait disturbance, but exerted no beneficial effects on gaze palsy. Then, we administered amitriptyline, bromocriptine, pergolide, l-threo-DOPS or 5-hydroxytryptophan (5-HTP) in addition to L-dopa/carbidopa. The second patient was treated by the monotherapy of L-dopa/carbidopa, amitriptyline, l-threo-DOPS or 5-HTP. We interposed two to three weeks between administration of each drug. In both patients, amitriptyline (75 mg/day) markedly improved both gait disturbance and horizontal gaze palsy. 5-HTP (600 mg/day) also improved horizontal gaze palsy, but failed to alleviate gait disturbance. The results suggest the involvement of impaired serotonergic system in ophthalmoplegia of PSP.

A follow-up study on spastic paraparesis in Japanese HAM/TSP.

We followed 24 patients with HTLV-I-associated myelopathy (HAM) for 4-12 years (mean 7 years) and assessed longitudinal changes of their spastic paraparesis by Kurtzke's Disability Status Scale (DSS). The DSS score of spastic paraparesis was unchanged in 18 patients (75%), advanced (worsened) by two in 1 patient and by one in 3 patients, and declined (improved) by one in 2 patients during the follow-up period. The results demonstrated that HAM presents with a variety of clinical courses including spontaneous improvement.

Assessment of MRI criteria for MS in Japanese MS and HAM/TSP.

We evaluated the usefulness of the MRI criteria for multiple sclerosis (MS) proposed by Paty et al and Fazekas et al in 36 Japanese MS patients, using HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) as the control. Although 30 of 36 HAM/TSP patients had multiple white matter lesions on T2-weighted cranial MRI, only two fulfilled the MRI criteria for MS. At the same time, 31 of the 36 MS patients fulfilled the primary MRI criterion, yielding 93% specificity and 86% sensitivity for the criterion. MS has disease-specific MRI abnormalities.