Utility of osteopontin in cerebrospinal fluid as a diagnostic marker for neuropsychiatric systemic lupus erythematosus.

The whole protein of osteopontin (OPN full) and its cleaved form (OPN N-half) are involved in the immune response and the migration of immune cells to an inflammatory lesion. We have reported that serum OPN full and urine OPN N-half are elevated in lupus nephritis (LN). Neuropsychiatric systemic lupus erythematosus (NPSLE) is a refractory complication of SLE. To investigate whether OPN full and OPN N-half could serve as diagnostic markers for NPSLE, and to elucidate their role in NPSLE pathogenesis, the concentrations of OPN full and OPN N-half in cerebrospinal fluid (CSF) were measured in NPSLE and non-NPSLE patients. We found that the concentration of OPN full in the CSF was significantly higher in NPSLE than in non-NPSLE, and it decreased after treatment. When the cutoff value of OPN full in CSF was set to 963.4 ng/ml, the sensitivity and specificity for the diagnosis of NPSLE were 70% and 100%, respectively. The correlation analysis of OPN full, OPN N-half and various cytokines/chemokines suggested that the cytokines/chemokines could be divided into two clusters: cluster A, which contains OPN full and cluster B, which contains interleukin-6. OPN full in CSF could be a novel diagnostic marker for NPSLE.

An anaerobic-aerobic sequential batch process with simultaneous methanogenesis and short-cut denitrification for the treatment of marine biofoulings.

Although combination of denitritation and methanogenesis for wastewater treatment has been widely investigated, an application of this technology to solid waste treatment has been rarely studied. This study investigated an anaerobic-aerobic batch system with simultaneous denitritation-methanogenesis as an effective treatment for marine biofoulings, which is a major source of intermittently discharged organic solid wastes. Preliminary NO2--exposed sludge was inoculated to achieve stable methanogenesis process without NO2- inhibition. Both high NH4+-N removal of 99.5% and high NO2--N accumulation of 96.4% were achieved on average during the nitritation step. Sufficient CH4 recovery of 101 L-CH4 kg-COD-1 was achieved, indicating that the use of NO2--exposed sludge is effective to avoid NO2- inhibition on methanogenesis. Methanogenesis was the main COD utilization pathway when the substrate solubilization occurred actively, while denitritation was the main when solubilization was limited because of substrate shortage. The results showed a high COD removal efficiency of 96.0% and a relatively low nitrogen removal efficiency of 64.4%. Fitting equations were developed to optimize the effluent exchange ratio. The estimated results showed that the increase of effluent exchange ratio during the active solubilization period increased the nitrogen removal efficiency but decreased CH4 content in biogas. An appropriate effluent exchange ratio with high anaerobic effluent quality below approximately 120 mg-N L-1 as well as sufficient CH4 gas quality which can be used as fuel for gas engine generator was achieved by daily effluent exchange of 80% during the first week and 5% during the subsequent 8 days.

The long-term outcome of high tibial osteotomy: a ten- to 20-year follow-up.

We carried out a prospective study of 132 patients (159 knees) who underwent closed-wedge high tibial osteotomy for severe medial compartment osteoarthritis between 1988 and 1997. A total of 94 patients (118 knees) was available for review at a mean of 16.4 years (16 to 20). Seven patients (7.4%) (11 knees) required conversion to total knee replacement. Kaplan-Meier survival was 97.6% (95% confidence interval 95.0 to 100) at ten years and 90.4% (95% confidence interval 84.1 to 96.7) at 15 years. Excellent and good results as assessed by the Hospital for Special Surgery knee score were achieved in 87 knees (73.7%). A pre-operative body mass index > 27.5 kg/m(2) and range of movement < 100 degrees were risk factors predicting early failure. Although our long-term results were satisfactory, strict indications for osteotomy are required if long-term survival is required.

[In vivo biomechanics of unicondylar knee replacement performed using minimally invasive technique]. / Die In-vivo-Biomechanik von unikondylären Knieprothesen in minimal-invasiver Technik.

Disturbed kinematics of the knee plays an important role in early failure of a unicondylar knee prosthesis (UNI). Recent studies on kinematics have shown that an intact anterior cruciate ligament (ACL) is important for a successful UNI. In this study, in vivo fluoroscopic analysis of knee kinematics was performed for 30 patients with a successful medial UNI implanted with the use of minimally invasive technique. The three-dimensional data of the CAD model were used for evaluating the sagittal translation as well as the axial rotation during deep knee bending and one gait cycle. The anteroposterior translation for flexion was, on average, -5.3 mm (-15.7-3.3; standard deviation 5.3). In most cases, the contact point was more posterior compared with the normal knee. During gait, the average anteroposterior translation was 0.8 mm, which is comparable to that of the normal knee. Axial rotation for deep knee bending was, on average, 8 degrees (-1.3-22.0; standard deviation 5.7), whereas 28 of the 30 knees showed normal axial rotation. During gait, an average axial rotation of 0.94 degrees was observed. The kinematic pattern of each of the subjects did not replicate the average pattern in most of the patients. An insufficient ACL may be suspected as the cause of the pathological kinematic pattern observed in some of these patients.

High-resolution analysis of DNA copy number alterations and gene expression in renal clear cell carcinoma.

We analysed chromosomal copy number aberrations (CNAs) in renal cell carcinomas by array-based comparative genomic hybridization, using a genome-wide scanning array with 2304 BAC and PAC clones covering the whole human genome at a resolution of roughly 1.3 Mb. A total of 30 samples of renal cell carcinoma were analysed, including 26 cases of clear cell carcinoma (CCC) and four cases of chromophobe renal cell carcinoma (ChCC). In CCCs, gains of chromosomes 5q33.1-qter (58%), 7q11.22-q35 (35%) and 16p12.3-p13.12 (19%), and losses of chromosomes 3p25.1-p25.3 (77%), 3p21.31-p22.3 (81%), 3p14.1-p14.2 (77%), 8p23.3 (31%), 9q21.13-qter (19%) and 14q32.32-qter (38%) were detected. On the other hand, the patterns of CNAs differed markedly between CCCs and ChCCs. Next, we examined the correlation of CNAs with expression profiles in the same tumour samples in 22/26 cases of CCC, using oligonucleotide microarray. We extracted genes that were differentially expressed between cases with and without CNAs, and found that significantly more up-regulated genes were localized on chromosomes 5 and 7, where recurrent genomic gains have been detected. Conversely, significantly more down-regulated genes were localized on chromosomes 14 and 3, where recurrent genomic losses have been detected. These results revealed that CNAs were correlated with deregulation of gene expression in CCCs. Furthermore, we compared the patterns of genomic imbalance with histopathological features, and found that loss of 14q appeared to be a specific and additional genetic abnormality in high-grade CCC. When we compared the expression profiles of low-grade CCCs with those of high-grade CCCs, differentially down-regulated genes tended to be localized on chromosomes 14 and 9. Thus, it is suggested that copy number loss at 14q in high-grade CCC may be involved in the down-regulation of genes located in this region.

Survival analysis of a cementless, cruciate-retaining total knee arthroplasty. Clinical and radiographic assessment 10 to 13 years after surgery.

We performed a prospective study of 54 patients (76 knees) who underwent Osteonics series 3000 cruciate-retaining cementless total knee arthroplasty between December 1990 and June 1993. Five patients (seven knees) were lost to follow-up (90.7% completion). One patient required revision at 10.5 years after operation. The rate of survival was 100% at ten years and 96.7% at 13 years. The mean ten-year knee and function scores were 79 and 59 respectively. Both were significantly better than the pre-operative scores. The range of movement also improved. Although a radiolucent line around the tibial component enlarged in six knees (20.7%) at ten years, the clinical outcome was generally good. In a patient who died after 5.5 years, post-mortem examination of the knee showed no bony ingrowth into the tibial component. Despite poor bony ingrowth, press-fit fixation was satisfactory and good results can be obtained with this cementless, cruciate-retaining prosthesis.

Fixation of a hydroxyapatite-tricalcium phosphate-coated cementless knee prosthesis. Clinical and radiographic evaluation seven years after surgery.

Miller-Galante II total knee arthroplasty (MG II TKA) was performed on 32 knees in 30 patients. On both the femoral and tibial components, the fibre-metal area was plasma-sprayed with hydroxyapatite-tricalcium phosphate (HA-TCP). The clinical and radiographic outcome was evaluated. A mean preoperative knee score of 26.0 +/- 18.6 (SD) increased to 97.5 +/- 3.5 and a mean pre-operative functional score of 21.7 +/- 15.0 (SD) increased to 83.4 +/- 12.4 at follow-up of seven years. Clear zones were common around the components at one month post-operatively but had completely disappeared after six months. An autopsy of a patient who underwent MG II TKA with HA-TCP two years previously, showed osteogenesis in all parts of the fibre-metal, and bone tissue comprised 77.7% of the interface. This coated prosthesis has good early fixation which is maintained at seven years with good clinical and radiographic outcomes.

Pharmacokinetics and adverse events following 5-day repeated administration of lenograstim, a recombinant human granulocyte colony-stimulating factor, in healthy subjects.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) (lenograstim) was administered to healthy subjects at doses of 2, 5 and 10 micrograms/kg/day for 5 days (twice a day subcutaneously) to examine the optimal dose and schedule of lenograstim in mobilizing peripheral blood progenitor cells (PBSC) for allogeneic transplantation. Lenograstim administration significantly increased CD34+ cells in a dose-related manner. A significant correlation was observed between the maximal post-dosing counts and the pre-dosing baseline counts of CD34+ cells. Peripheral neutrophils increased markedly by seven to 13 times from the baseline to a peak of approximately 40,000/microliter on day 5 for the 5 and 10 micrograms/kg/day doses. After peak serum concentration (Cmax) was attained 4 h following administration, serum G-CSF declined with time in a log-linear fashion. The Cmax and 12 h area-under-the-curve increased dose dependently, but minimum drug level increased up to day 2 and then decreased until day 5. Clearance decreased with increasing dosage at the first dose, and increased significantly at the last dose. We found a highly significant correlation between absolute neutrophil counts and clearance for each dose. Adverse events most frequently occurred on day 6, with increases of alkaline phosphatase and lactate dehydrogenase and onset of bone pain. Increases of aspartate aminotransferase and alanine aminotransferase occurred as delayed events. Platelet count gradually decreased after the end of drug administration to 57% of the pre-dosing count on day 10, but was still within the normal range. These preliminary results suggest that repeated doses of lenograstim induce mobilization of PBSC in a dose-dependent manner and the pre-dosing baseline count of PBSC may predict the post-dosing maximal mobilization. The drug treatment may cause delayed-onset moderate thrombocytopenia and increased transaminase, and the drug clearance changes in a complex manner during repeated dosing.

Endometrioid adenocarcinoma arising from adenomyosis.

In spite of many references to carcinoma arising from endometriosis at extrauterine sites, there are few documented cases of carcinoma developing in association with adenomyosis. We present 2 rare cases of adenocarcinoma arising from adenomyosis. The relationship between prior frequent estrogen use and carcinogenesis and the possible effects of chemotherapy and radiation therapy are reviewed.

[A case of systemic lupus erythematosus with interstitial myocarditis leading to sudden death].

A 29-year-old female with systemic lupus erythematosus (SLE) was admitted because of exertional dyspnea in January, 1996. The diagnosis of SLE was made on the basis of malar rash, discoid rash, polyarthritis, leukopenia, positive antinuclear antibody and focal glomerulonephritis in 1991. She did not have any cardiac symptoms in 1994, when the electrocardiogram (ECG) abnormalities, such as poor R wave progression and right axis deviation, were present. On admission, she developed congestive heart failure without any signs of active SLE. Laboratory findings were unremarkable. There were new ECG abnormalities, such as left atrial overload and low voltage in limb leads. Chest roentgenogram showed mild pulmonary congestion and marked cardiomegaly. Echocardiography showed enlargement and diffuse hypokinesis of the left ventricle. Cardiac catheterization confirmed that the coronary arteries were normal and that the left ventricular function was poor (ejection fraction, 21%). Myocardial biopsy obtained from left ventricle revealed interstitial fibrosis. After furosemide, digoxin and captril were administered with predonisolone (PSL), her symptoms gradually improved. Since the Holter monitoring showed nonsustained ventricular tachycardia, the doses of PSL and mexiletine were increased up to 20 mg and 300 mg daily, respectively. Unexpectedly, she was found dead in her hospital room in May, 1996. The postmortem findings of the heart revealed mild infiltration of inflammatory cells, predominantly lymphocytes, and plasma cells, and interstitial fibrosis, which were consistent with interstitial myocarditis. In this case ECG abnormalities preceded cardiac symptoms, which may suggest that myocarditis subclinically developed. Serum creatinine kinase levels had not been elevated throughout the entire course. While several cases of acute myocarditis associated with a flare of SLE have been reported, there were few cases regarding interstitial myocarditis that chronically progress and can be fatal. This case is thought to be suggestive of elucidating the pathogenesis of lupus myocarditis.

[Dibucaine number (DN) and fluoride number (FN) of L330 I mutant recombinant cholinesterase by use of various substrates].

Dibucaine number (DN) and fluoride number (FN) of the recombinant 330 I mutant ChE (r330 I) expressed in human kidney cells (293 cell) were compared with recombinant usual ChE (rUU), by several assay kits and substrates. All of them showed lower the values compared with rUU. However, the r330 I/rUU ratios about FN determined by several substrates were higher than that determined by propionyl thiocholoneiodide (PTCI), which was recommended by American Association for Clinical Chemistry. In conclusion, commercially available assay kits may not be suitable for the determination of L330 I.

[A case of pulmonary fat embolism and cardiac arrest after prosthetic replacement of the femoral stem].

We experienced a case of cardiac arrest which occurred after prosthetic replacement of the femoral stem. The patient died three hours and fifty minutes after the end of operation, following hypouresis, pulmonary edema and hypoxia. According to the autopsy, extensive and severe fat embolism was documented in the lung and kidney, and this is considered to be the cause of the death. When prosthetic replacement of the femoral head is performed, we have to keep in mind the danger of fat embolism.

CD14 transgenic mice expressing membrane and soluble forms: comparisons of levels of cytokines and lethalities in response to lipopolysaccharide between transgenic and non-transgenic mice.

Two different metallothionein promoter-mouse CD14 fusion genes were constructed. The membrane form of the CD14 fusion gene, designated M14M, contained the full-length CD14 cDNA sequence, whereas the soluble form of the fusion gene, designated M14S, was truncated to lack the sequence for the phosphatidylinositol-anchoring site. Expression of transgenic RNA in M14M and M14S mice on the basal diet was abundant in the liver. After maintenance with water containing ZnSO4 (50 mM) for 4 days, expression of transgenic RNA in M14M and M14S mice was strong in the small intestine. Immunohistochemical analysis demonstrated CD14 expression in these organs in M14S and M14M mice. Levels of CD14 in sera from M14S mice after zinc administration were significantly higher than these animals maintained with normal water, M14M mice after zinc administration and non-transgenic mice. Sera from M14S and M14M mice after stimulation with lipopolysaccharide LPS (LPS) demonstrated significantly lower levels of tumor necrosis factor-alpha and IL-6 than those from non-transgenic mice. Lethality in endotoxin shock produced by i.p. injection of 30-40 microg/g body wt LPS was not different between M14S, M14M and non-transgenic mice. However, survival rates in the lethal Shwartzman reaction induced by priming and challenge injections of LPS were significantly higher in M14M and M14S mice than in non-transgenic mice.

A novel in-frame deletion mutation in a case of lactate dehydrogenase (LD) H subunit deficiency showing an atypical LD isoenzyme pattern in serum and erythrocytes.

OBJECTIVE: We report a case showing an atypical lactate dehydrogenase (LD) isoenzyme pattern involving deficiency only of LD-1 and LD-2 in serum and erythrocytes. LD activity in serum from this patient was extremely low, similar to complete LD-H deficiency, and also that in erythrocytes was low. DESIGN: The DNA fragment containing exon 1 through 7 of the LD-H gene were amplified by PCR and directly sequenced. Total RNA was prepared from venous blood and the proportion of LD-H cDNA to total LD cDNA was semiquantified. RESULTS: Genetic analysis by DNA sequencing detected a three base deletion (AAT) at codon 220 of exon 5, which caused a deletion of one asparagine. The present case did not show reduced LD-H expression at the mRNA level in whole blood. Residue 220 is involved in turning beta-J to alpha1-G and is not buried in the interior of the protein. The novel homozygous in-frame deletion mutation at codon 220 may cause a three-dimensional change of the subunit-binding domain.

[Diminution of the number of gamma delta T lymphocytes in hepatocellular carcinoma patients treated with transcatheter arterial embolization].

gamma delta T lymphocytes, which are CD3+ lymphocytes that express gamma delta chains of the T-cell antigen receptor (TCR) on their surface, are functionally distinct from alpha beta T lymphocytes, which express alpha beta chains of the TCR. gamma delta T lymphocytes are thought to differentiate in mouse hepatic sinusoids, to play a role in antitumor action, and to act as natural killer cells. The purpose of this study was to examine whether gamma delta T lymphocytes in the peripheral blood are suppressed when hepatic sinusoids are damaged during transcatheter arterial embolization (TAE). The numbers of alpha beta T lymphocytes and gamma delta T lymphocytes in the peripheral blood were examined with monoclonal antibodies and flow cytometry before and after TAE in 32 patients (from 46 to 78 years of age) with liver cirrhosis and hepatocellular carcinoma. The number of alpha beta T lymphocytes before and after TAE was unchanged. However, the number of gamma delta T lymphocytes and the ratio of gamma delta T lymphocytes to CD3+ lymphocytes were significantly decreased for 3 weeks after TAE treatment. This decrease suggests that TAE suppresses the supply of gamma delta T lymphocytes to the peripheral blood. In addition, TAE may weaken a patient's antitumor immunity, because gamma delta T lymphocytes that have antitumor activity decrease after TAE.

Familial neurilemoma of the spinal cord in a mother and daughter.

Neurilemoma of the spinal cord occurred in a mother and daughter. Case 1 was a 75-year-old woman with gait disturbance. Examination revealed weakness of the lower extremities, and magnetic resonance (MR) imaging showed an intradural extramedullary tumor at T12. After laminectomy, the histologic diagnosis was mixed Antoni type A and B neurilemoma. Case 2 was a 48-year-old woman (daughter of case 1). She presented with cervical pain and numbness of both hands. Examination revealed weakened intrinsic muscles of the right hand and paresthesia of the right upper arm. MR imaging showed a giant hourglass-shaped extradural tumor at C2 and C3. The histologic diagnosis was Antoni type A neurilemoma. Only six families with neurilemoma have been reported, including our patients. Gene analysis of such patients may clarify the etiology of neurilemoma.

Clinicopathologic characteristics of the lungs of patients with human T cell lymphotropic virus type 1-associated myelopathy.

Lung autopsy specimens were evaluated histologically in the six patients with human T cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM). The results revealed two histologic changes. First, lymphoid infiltrates were distributed widely in peribronchiolar and perivascular regions, subpleural regions, and the alveolus. Lymphoid infiltrates were also observed in bronchial mucosal glands in relatively large bronchi, in which the acinar epithelium was sometimes degenerated. Second, chronic inflammatory changes, such as smooth muscle hypertrophy, fibrosis, or squamous cell metaplasia, were increased significantly in the membranous bronchioles of HAM patients compared with specimens from lung cancer control patients. Such histologic changes were subclinical in most cases, but one case had an abnormal chest shadow, and two cases had recurrent pneumonia. In HAM patients, high levels of HTLV-1-specific cytotoxic T lymphocytes are believed to attack the HTLV-1-bearing cells in the lung, resulting in inflammatory reactions.

Foreign body gonitis caused by a broken poly-L-lactic acid screw.

Poly-L-lactic acid (PLLA), a biodegradable polymer, is generally considered to be gradually degraded without causing any severe tissue reaction. However, we encountered a patient who developed foreign body gonitis caused by screw breakage after fixation of an intercondylar prominence fracture with PLLA screws. This case suggests that care should be taken when PLLA materials are used to fix intraarticular fractures.