Analysis of White Matter Damage in Patients with Multiple Sclerosis via a Novel In Vivo MR Method for Measuring Myelin, Axons, and G-Ratio.

BACKGROUND AND PURPOSE: Myelin and axon volume fractions can now be estimated via MR imaging in vivo, as can the g-ratio, which equals the ratio of the inner to the outer diameter of a nerve fiber. The purpose of this study was to evaluate WM damage in patients with MS via this novel MR imaging technique. MATERIALS AND METHODS: Twenty patients with relapsing-remitting MS with a combined total of 149 chronic plaques were analyzed. Myelin volume fraction was calculated based on simultaneous tissue relaxometry. Intracellular and CSF compartment volume fractions were quantified via neurite orientation dispersion and density imaging. Axon volume fraction and g-ratio were calculated by combining these measurements. Myelin and axon volume fractions and g-ratio were measured in plaques, periplaque WM, and normal-appearing WM. RESULTS: All metrics differed significantly across the 3 groups (P < .001, except P = .027 for g-ratio between periplaque WM and normal-appearing WM). Those in plaques differed most from those in normal-appearing WM. The percentage changes in plaque and periplaque WM metrics relative to normal-appearing WM were significantly larger in absolute value for myelin volume fraction than for axon volume fraction and g-ratio (P < .001, except P = .033 in periplaque WM relative to normal-appearing WM for comparison between myelin and axon volume fraction). CONCLUSIONS: In this in vivo MR imaging study, the myelin of WM was more damaged than axons in plaques and periplaque WM of patients with MS. Myelin and axon volume fractions and g-ratio may potentially be useful for evaluating WM damage in patients with MS.

Identification of hemiclonal reproduction in three species of Hexagrammos marine reef fishes.

Natural hybrids between the boreal species Hexagrammos octogrammus and two temperate species Hexagrammos agrammus and Hexagrammos otakii were observed frequently in southern Hokkaido, Japan. Previous studies revealed that H. octogrammus is a maternal ancestor of both hybrids; the hybrids are all fertile females and they frequently breed with paternal species. Although such rampant hybridization occurs, species boundaries have been maintained in the hybrid zone. Possible explanations for the absence of introgressions, despite the frequent backcrossing, might include clonal reproduction: parthenogenesis, gynogenesis and hybridogenesis. The natural hybrids produced haploid eggs that contained only the H. octogrammus genome (maternal ancestor) with discarded paternal genome and generated F1 -hybrid type offspring by fertilization with the haploid sperm of H. agrammus or H. otakii (paternal ancestor). This reproductive mode was found in an artificial backcross hybrid between the natural hybrid and a male of the paternal ancestor. These findings indicate that the natural hybrids adopt hybridogenesis with high possibility and produce successive generations through hybridogenesis by backcrossing with the paternal ancestor. These hybrids of Hexagrammos represent the first hybridogenetic system found from marine fishes that widely inhabit the North Pacific Ocean. In contrast with other hybridogenetic systems, these Hexagrammos hybrids coexist with all three ancestral species in the hybrid zone. The coexistence mechanism is also discussed.

Decreasing urinary PAH metabolites and 7-methylguanine after smoking cessation.

OBJECTIVE: Humans are exposed to various carcinogens by smoking. Urinary metabolites of polycyclic aromatic hydrocarbons (PAH), one of the major carcinogens in cigarette smoke, were measured as the environmental carcinogen exposure marker for humans. We evaluated urinary exposure markers for smoking cessation. METHOD: In this study, we measured cigarette smoke exposure markers, such as urinary cotinine, PAH exposure markers, such as urinary 1-hydroxypyrene (1-OHP), 2-naphthol (2-NP) and 1-naphthol (1-NP), as well as a methylating chemical exposure marker, 7-methylguanine (7-MeG). The before smoking cessation levels of these markers, and the after smoking cessation levels were then compared. Eighteen subjects participated in this smoking cessation program. RESULTS: Levels of all of four markers were found to have decreased by 19-54% after smoking cessation. Urinary cotinine, 1-OHP, 2-NP and 7-MeG levels were found to have significantly decreased after smoking cessation. There were positive correlations between cotinine and three urinary PAH markers and between 1-OHP, 2-NP and 7-MeG. CONCLUSION: PAH metabolites were better biomarkers of smoking cessation than 7-MeG. Analyzing urinary metabolites or urinary DNA adducts is suitable for epidemiological studies.

Sleep and daytime sleepiness in upper airway resistance syndrome compared to obstructive sleep apnoea syndrome.

This study has investigated differences in the nocturnal sleep and daytime sleepiness among patients with obstructive sleep apnoea syndrome (OSAS), upper airway resistance (UARS), sleep hypopnoea syndrome, and normal control subjects, using sleep scoring and spectral activity analysis of the electroencephalogram (EEG). Twelve nonobese males with UARS aged 30-60 yrs were recruited. These subjects were strictly matched for age and body mass index with twelve OSAS patients, 12 sleep hypopnoea syndrome patients, and 12 normal controls, all male. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT). The macrostructure of sleep was determined using international criteria and spectral analysis of the sleep EEG was obtained from a central lead. The sleep macrostructure of OSAS and UARS patients was significantly different from that of controls. These patients were also sleepier during the daytime than controls. Complaints of tiredness and daytime sleepiness, ESS and MSLT scores were similar in the different patient groups. Mild dysmorphia was present in all three patient groups. However, nocturnal sleep was significantly different among the different groups. OSAS patients had significantly more awake time during sleep than the UARS patients. The spectral activity of the total sleep time of the patient groups also differed significantly from that of controls. When the sleep spectral activity of UARS and OSAS patients were compared, OSAS patients had less slow wave sleep activity than UARS patients. UARS patients had a significantly higher absolute power in the 7-9 Hz bandwidth than OSAS patients. The absolute delta power over the different sleep cycles was also different between controls and patients, and between UARS and OSAS patients. There are clear differences in the macrostructure and spectral activity of sleep between upper airway resistance and obstructive sleep apnoea syndrome patients, demonstrated by differences in the cortical activity recorded in the central lead during sleep. Despite these nocturnal sleep differences, the tests of subjective daytime sleepiness are not significantly different.

Genetic Diversity of Japanese Strains of Ralstonia solanacearum.

ABSTRACT The genetic diversity of 74 Japanese strains of Ralstonia solanacearum was assessed by pathogenicity tests and the repetitive sequencebased polymerase chain reaction (rep-PCR) fingerprint method. Based on their genomic fingerprints, biovar N2 strains were divided into two distinct groups, one consisting of potato isolates belonging to race 3, and the other consisting of tomato, eggplant, pepper, and tobacco isolates belonging to race 1. Biovar 3 strains had low average similarity and were divided into five groups that differed in original host or pathogenicity. Biovar 4 strains consisted of only one group at the 80% similarity level. Comparative analysis of the rep-PCR fingerprints of 78 strains, including six biovars from Japan and various countries, revealed two main clusters. Cluster 1 comprised all biovar 3, 4, and 5 strains, biovar 1 strains from Reunion, and some biovar N2 strains from Japan. Cluster 2 included most of the biovar 1, 2, and N2 strains. The fingerprints showed low average similarity with biovar N2 strains from Japan and Brazil.

The potent role of increased sympathetic tone in pathogenesis of essential hypertension with neurovascular compression.

OBJECTIVE: To study the role of increased sympathetic tone in pathogenesis of hypertension in patients with essential hypertension with neurovascular compression. METHODS: Twenty-three patients with essential hypertension, 13 patients with secondary hypertension, and 46 normotensive subjects were investigated. Neurovascular compression was evaluated by MRT. The power spectral components of heart rate variability as indices of autonomic nerve tone were determined to investigate the possibility that sympathetic tone mediates the neurovascular compression-induced increase in blood pressure. RESULTS: Neurovascular compression of the rostral ventrolateral medulla (RVLM) was observed in 70% of essential hypertension group, none of secondary hyperension group and 16% of normotensive group (P < 0.001). The age-adjusted low-frequency power spectral density (A-PSD) (0.04 to 0.15 Hz), which is an index of sympathetic tone, was significantly higher in patients with essential hypertension (139.5 +/- 6.7%) with neurovascular compression than in essential hypertension patients without neurovascular compression (92.2 +/- 6.8%), normotensive subjects with (102.8 +/- 13.0%) and without neurovascular compression (100.1 +/- 4.1%), and patients with secondary hypertension (95.7 +/- 10.2%) (P < 0.001). There was no significant difference in the high-frequency A-PSD (0.15 to 0.40 Hz), which is an index of vagal tone, among groups. CONCLUSIONS: Neurovascular compression was not always associated with an increase in sympathetic nerve tone. Hypertension was present in subjects with neurovascular compression, who had increased sympathetic tone but not in those with normal sympathetic tone. An increase in sympathetic tone may mediate the neurovascular compression-induced increase in blood pressure. Journal of Human Hypertension (2000) 14, 807-811

Blockade of the Bcr-Abl kinase activity induces apoptosis of chronic myelogenous leukemia cells by suppressing signal transducer and activator of transcription 5-dependent expression of Bcl-xL.

Bcr-Abl-expressing leukemic cells are highly resistant to apoptosis induced by chemotherapeutic drugs. Although a number of signaling molecules have been shown to be activated by the Bcr-Abl kinase, the antiapoptotic pathway triggered by this oncogene has not been elucidated. Here, we show that the interleukin 3-independent expression of the antiapoptotic protein, Bcl-xL, is induced by Bcr-Abl through activation of signal transducer and activator of transcription (Stat)5. Inhibition of the Bcr-Abl kinase activity in Bcr-Abl-expressing cell lines and CD34(+) cells from chronic myelogenous leukemia (CML) patients induces apoptosis by suppressing the capacity of Stat5 to interact with the bcl-x promoter. Interestingly, after inhibition of the Bcr-Abl kinase, the expression of Bcl-xL is downregulated more rapidly in chronic phase than in blast crisis CML cells, suggesting an involvement of this protein in disease progression. Overall, we describe a novel antiapoptotic pathway triggered by Bcr-Abl that may contribute to the resistance of CML cells to undergo apoptosis.

Noninvasive, continuous evaluation of peripheral vascular resistance in humans.

We sought a noninvasive alternative method of monitoring peripheral vascular resistance continuously in humans, based on the analysis of arterial pressure waveforms. Radial arterial pressure waveforms were recorded noninvasively with a tonometer and analysed using a neural network method. To test the accuracy of this method, the peripheral vascular resistance was also determined by an invasive thermodilution method using a Swan-Ganz catheter in 20 subjects. To test the method in a clinical application, peripheral vascular resistance was determined by the noninvasive method before and after administration of nifedipine in 6 patients with essential hypertension. Neural network analysis of waveforms reliably yielded values between 0.00 and 1.00. Peripheral vascular resistance determined by neural network analysis and according to the invasive method showed a significant (p< 0.005) positive linear correlation. The peripheral vascular resistance measured by neural network analysis showed a significant (p< 0.05) decrease 30 min after administration of nifedipine, paralleling a decrease in blood pressure. Neural network analysis of tonometric radial artery waveforms provides an accurate, noninvasive, and continuous index of peripheral vascular resistance in human subjects. This simple method should permit more extensive homodynamic studies and larger epidemiological surveys in contrast to those undertaken using invasive techniques.

[A patient with Goodpasture's syndrome revealed a poor prognosis regardless of receiving intensive therapy from an early stage after onset].

Goodpasture's syndrome has been reported as a disease that has a favorable prognosis when the patient receives intensive immunosuppressive drug-therapy from an early stage after onset. The present report describes a 50-year-old woman, who exhibited progressive renal failure accompanied by pulmonary hemorrhage, and an increase in serum level of antiglomerular basement membrane (GBM) antibody. Initial histological examination of a renal specimen indicated a severe fibrocellular crescentic glomerulonephritis with a linear deposition of Ig-G and C3 along the glomerular capillary wall. The patient was thus diagnosed as having Goodpasture's syndrome. Therapy with pulse treatment of steroid (corticosteroid hormone), immunosuppressive agents, or plasma-exchange for the removal of anti-GBM antibody was adopted a week after the clinical onset. However, histological amelioration of the glomeruli did not occur with this treatment in the second biopsy, while glomerular damage advanced progressively. In contrast to other patients with Goodpasture's syndrome, our case revealed an unfavorable outcome regardless of receiving intensive therapy from an early period after onset, which suggests that more intensive therapy of another approach to this patient may have been necessary.

Purification and Properties of a New Chitin-binding Antifungal CB-1 from Bacillus licheniformis.

CB-1, a new antifungal, was purified from Bacillus licheniformis. The molecular mass of CB-1 was estimated as 42 kDa by gel filtration column chromatography. CB-1 seemed to be an aggregation product from 4 kinds of peptides. CB-1 contained 10 amino acids and some fatty acids of C14-18:0 and C18:1. CB-1 irreversively bound with chitin powder.

Secondary amyloidosis associated with Castleman's disease.

A rare case of secondary amyloidosis associated with Castleman's disease is reported. A 53-year-old woman was referred for investigation of proteinuria. Biopsy specimens from kidney and gastric mucosa revealed numerous amyloid deposits, defined as AA amyloidosis by immunohistological staining. Castleman's disease was found in the abdomen as the primary disease for the amyloidosis. Although the urinary protein was somewhat reduced and the inflammatory findings were improved after removal of the lymphoma, renal insufficiency progressed and hemodialysis was begun.

[Sex differences in EEG background activity: a study with quantitative analysis in normal adults].

The present study performed quantitative EEG analysis in normal 20 males and 20 females, aged 18-26 years, in order to examine the sex differences in EEG activity at rest. The females had more absolute EEG power than the males, with significant differences observed for delta, theta and beta bands. In contrast, no significant difference was found in peak alpha frequency or relative EEG power for any frequency band. The present findings provide further evidence that females have more absolute power in resting EEG, and emphasize the importance of matching patients and control populations for sex in future investigations dealing with the relationship between resting EEG and various pathological conditions.

[Quantitative analysis of EEG background activity in drug-naive schizophrenic patients].

In this study we performed quantitative EEG analyses in 12 drug-naive patients who fulfilled DSM-IIIR criteria for schizophrenia and in a group of 12 healthy subjects. The schizophrenic patients were found to have slower activity (delta and theta) than the controls. These differences were most marked in the frontal region for delta band and in the occipital region for theta band. The schizophrenic patients also had more beta 1 activity, particularly in the occipital leads. Conversely, they had less alpha 2 activity over all regions examined. Our findings indicate cerebral dysfunction in schizophrenia and are in line with the hypothesis of hypofrontality in this disorder.

Agreement of visual scoring of sleep stages among many laboratories in Japan: effect of a supplementary definition of slow wave on scoring of slow wave sleep.

The purpose of this study was to elucidate the agreement of visual scoring of all-night polysomnographic recordings among many scores from different laboratories. Ten scorers including the author from different laboratories in Japan scored the same paper recordings of two young male subjects. We calculated the agreement rate for each stage using an epoch by epoch analysis. In both records, the agreement rates for stages 2 and R were high; on the contrary, those for stages 3 and 4 were low. After adding a supplementary definition of high voltage slow wave in deep sleep, we scored the first NREM period of another subject. The mean agreement rate for stage 3 among 10 scorers was significantly higher than those of the two former subjects. However, the agreement for stage 4 did not change so much. This result demonstrates that there is much interrater (laboratory) variability of visual scoring, especially in slow wave sleep. When the result of automatic scoring is compared to that of the visual scoring to evaluate the reliability of automatic scoring, these findings must be considered.

A novel antibody from rheumatoid arthritis patients.

A 106 base-pair length DNA sequence was isolated from rheumatoid synovium. Base sequence analysis showed this fragment to correspond to sequences already reported as the non-transcribed spacer of ribosomal DNA. Base sequence analysis also revealed that a fused protein has a unique five amino acid sequence. This five amino acid sequence was considered to be an epitope for an antibody. This antibody was named BUNGO antibody (BUNGO is the old name for Oita prefecture). An antigen peptide was synthesized chemically in accordance with the amino acid sequence of the epitope. Using this synthetic peptide, BUNGO antibody in serum was measured. Twelve of 32 patients (37.5%) with RA (rheumatoid arthritis) tested positive for the antibody. Five of 32 (15.6%) age and sex-matched control subjects were positive, indicating a significant difference from the RA group (chi 2 = 3.9, p < 0.05).

Allergic granulomatosis and angiitis with severe cardiac disease: a case in which cardiac function was extremely improved by long-term steroid therapy.

A 38-year-old man with a history of bronchial asthma developed marked eosinophilia, mononeuritis multiplex and transient pulmonary infiltration. Pathological findings from the lung and nerve biopsy were helpful in determining the diagnosis as allergic granulomatosis and angiitis (AGA). Echocardiogram indicated dilation of the left ventricle with impaired systolic contraction. Coronary arteriography demonstrated significant stenosis only in the peripheral segment of the circumflex artery. After 1 year of corticosteroid therapy, echocardiogram revealed improvement of left ventricular contractility evaluated by ejection fraction (from 28% to 67%). To our knowledge, no previous reports have described amelioration of severe cardiac lesions during long-term steroid treatment in patients with AGA.

A case of primary biliary cirrhosis associated with Hashimoto's thyroiditis, scleroderma and Sjögren's syndrome.

A 53-year-old woman was admitted because of Raynaud's phenomenon, polyarthralgia and polymyalgia. Biopsy specimens of the liver and thyroid gland revealed characteristic findings of primary biliary cirrhosis (PBC) (stage I by Scheuer's classification) and chronic thyroiditis. Her clinical features were also complicated by scleroderma (type I by Barnett's classification) and Sjögren's syndrome (Sjs) with keratoconjunctivitis sicca. Thyroid hormone replacement therapy led to improvement in thyroid function, normalization of the biliary tract enzymes and alleviation of subjective symptoms.