Prevention of collagen-induced arthritis (CIA) by treatment with polyethylene glycol-conjugated type II collagen; distinct tolerogenic property of the conjugated collagen from the native one

Administration of a soluble protein into animals prior to challenge immunization induces immunological tolerance which is specific for the protein. In addition, chemical modification of proteins with polyethylene glycol (PEG) has been reported to convert the immunogenic proteins to become tolerogenic. However, differences in tolerogenic properties between PEG-modified proteins and the native counterparts have never been analysed. The ability of PEG-conjugated type II collagen (PEG-CII) to attenuate CIA, an animal model for rheumatoid arthritis, was compared with the native unconjugated CII. Groups of DBA/1 J mice were treated weekly with i.p. injections with PEG-CII, native CII, or vehicle alone for 3 weeks, before they were challenged with CII in adjuvants. The induction of tolerance was confirmed in both PEG-CII- and CII-pretreated mice when suppression of lymph node T cell proliferation in response to CII was noted. The degrees of suppression of T cell proliferation were comparable between the two pretreated groups. However, induction of arthritis and production of IgG anti-CII antibody were more markedly suppressed in PEG-CII-pretreated mice than in native CII-pretreated mice, although the severity of arthritis and antibody levels in the latter group were also lower than in control mice. IgG2a and IgG2b antibody levels were equally suppressed in the two pretreated groups, whereas the IgG1 level was significantly lower in the PEG-CII-pretreated group than in the native CII-pretreated group. The results provide the first evidence that attachment of PEG to CII renders the protein more tolerogenic.     

PSEUDO-INTRACELLULAR COLLAGEN TANGLES IN HUMAN SPINAL GANGLIA

Pseudo-intracellular collagen tangles in human spinal ganglia
A new structure was found in the spinal ganglia of 6 out of 215 human autopsy cases with various disorders. It was composed of ballooned cells fully packed with fibrillar structures showing the same staining properties as collagen. Ultrastructurally the fibrillar structures were bundles of collagen fibres with a striation of about 70nm periodicity, and they were enclosed by the cell membrane invaginated in a very complex manner into the cytoplasm. This structure, which we named 'pseudo-intracellular collagen tangle', was considered to result from a disturbance in the releasing process of collagen fibre from fibroblasts. The aetiology of the structure is unknown, but it might represent one of regressive or senile changes in human spinal ganglia.     

Evaluation of Mini Mental State Examination and Brief Psychiatric Rating Scale on aged schizophrenic patients

Abstract  Mini Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS) and subscales of the BPRS were performed on 73 elderly inpatients (mean age: 67.9 years; standard deviation: 7.2; range: 60–89) diagnosed with DSM-III-R chronic schizophrenia. Forty of the subjects were men and 33 were women. A significant negative correlation was observed between MMSE and the age, factor negative, factor depressive, and total score of BPRS. We believe, however, that it is relatively sufficient to screen for demented illness of schizophrenics using MMSE when considering the age and the psychiatric symptoms (especially negative or depressive symptoms). Forty-eight (66%) of the 73 patients were categorized as 'demented' by MMSE. These results suggest that the aged inpatients with schizophrenia in a hospital showed certain kinds of cognitive deficits (including senile dementia) more frequently than the general population.     

Alpha-delta sleep in a case with non-24 h sleep-wake syndrome: Quantitative electroencephalogram analysis of alpha and delta band waves

Abstract  Four all-night polysomnograms of a 39-year-old male patient with non-24 h sleep-wake syndrome were recorded. We analysed electroencephalograms (EEG) with the power spectrum method and the wave pattern recognition analysis of Fujimori. The EEC of the rest waking condition showed normal patterns. High-voltage diffuse alpha band waves were observed in sleep stages 2, 3 and 4. The integrated area of the alpha band waves in the analysis epochs showed a strong positive correlation to the delta hand components in the power spectrum of the same epoch during sleep (correlation coefficients r = 0.762–0.815). Alpha hand waves during sleep were clearly different from the alpha waves in the rest waking condition, with respect to slower peak frequency and the frontal dominant voltage distribution.     

Mucinous adenocarcinoma of the renal pelvis associated with transitional cell carcinoma in the renal pelvis and the bladder

We report a case of mucinous adenocarcinoma of the renal pelvis associated with bladder carcinoma in situ (CIS). Transitional cell carcinoma (TCC) of the renal pelvis and CIS were also observed adjacent to the adenocarcinoma. Immunohistochemical assessment of the pelvic adenocarcinoma revealed positive expressions for mucin, epithelial membrane antigen, cytokeratin 7, cytokeratin 19 and carcinoembryonal antigen, but not vimentin or chromogranin. Based on the histopathological examinations, the adenocarcinoma of the renal pelvis in the present case may have a similar biological nature to conventional TCC and probably originated by development of pre-existing TCC of the renal pelvis.     

ETHANOL INDUCES HETEROGENEOUS REDUCTION OF CYTOCHROME aa3 WITHIN PERFUSED RAT LIVER LOBULE ASSESSED USING MICROSPECTROSCOPY

The redox state of cytochrome aa₃ was measured at microspots(20µm diameter) within the lobule of perfused rat livers,using reflectance microspectroscopy, and the effect of ethanolinfusion on sublobular distribution of the redox states wasevaluated. A sigmoidal relationship was observed between oxygendelivery and the reduction of cytochrome aa₃ in both the periportaland pericentral regions of the liver lobule when the influentO₂ concentration was decreased in a graduated manner. This sigmoidalcurve was shifted to the more reduced state by ethanol infusion,with ethanol (25–100mM) increasing the degree of cytochromeaa₃ reduction in a dose-dependent manner according to the distancefrom the periportal region along a sinusoid. This increase wasspatially heterogeneous within a liver lobule. These data indicatethat ethanol accelerates cytochrome aa₃ reduction, with a distinctgradient of reduction along sinusoids but a heterogeneous distributionwithin the liver lobule.     

Diaphragmatic Hernia Induced in Rat Fetuses by Administration of Bisdiamine

Administration of N, N'-bis (dichloroacetyl)-l,8-octamethylenediamine, bisdiamine, to pregnant Donryu rats on a single day of gestation induced unilateral and bilateral diaphragmatic hernias in fetuses with high incidence. The protruded liver was not covered with a serous membrane or a muscular layer. Incidence of unilateral diaphragmatic hernia on the left side was high when bisdiamine was administered on day 9 or 13 of gestation, and that on the right side was high when administered on day 12 of gestation. Incidence of bilateral diaphragmatic hernia was high when bisdiamine was administered on day 12 of gestation. Differences in sensitivity to hernia formation according to day of bisdiamine administration between right and left sides may reflect differences in developmental chronology between the two sides. Two distinct times for induction of left diaphragmatic hernia might be attributed to at least two different mechanisms. The present model is expected to help analyzing not only anatomical characteristics of congenital diaphragmatic hernia but also possible mechanisms responsible for their development.