AMYLOID PLAQUES IN THE BRAINS OF MICE INFECTED WITH SCRAPIE: MORPHOLOGICAL VARIATION AND STAINING PROPERTIES

Amyloid plaques in the brains of mice infected with scrapie: morphological variation and staining properties
Cerebral amyloid deposits predominantly in the form of plaques are associated with experimental scrapie produced by particular agents in inbred mice. In this paper the staining properties and variation in the morphology of these deposits are described. At the light microscope level a discretionary classification into six types is made: shadowy plaques; amorphous plaques; stellate plaques; giant plaques; diffuse amyloid deposits; and perivascular amyloid deposits. It is shown that Masson's trichrome technique provides the most efficient staining method for identifying cerebral amyloid of all these types. A preliminary ultrastructural examination of stellate plaques confirms the presence of amyloid on the basis of characteristic fibrils and demonstrates that microglia and distended neurites are involved in the structure of the plaques. The similarities and differences between cerebral amyloid in scrapie and other forms of amyloid deposits in the brain, particularly kuru plaques and senile plaques, are discussed.     

EFFECTS OF TRAMADOL ON NERVE ACTION POTENTIALS IN RAT: COMPARISONS WITH BENZOCAINE AND LIDOCAINE

The effects of tramadol on repetitively elicited action potentials were studied in rat sciatic nerve, using the sucrose gap method. Tramadol's local anesthetic-like effects were compared with lidocaine and benzocaine at single or 10, 40, and 100 Hz stimulations. Tramadol and lidocaine both produced approximately the same level of conduction block. The depolarization time of the compound action potentials (CAP) measured from the beginning to the peak of the CAPs, was extended by lidocaine and tramadol, but benzocaine had no effect in this respect. Tramadol extended half width of CAP more than lidocaine. Lidocaine and tramadol produced similar conduction-block patterns, which were different from benzocaine. The results suggested that tramadol enhanced the nerve conduction block like lidocaine, and extended the duration of the compound action potential more than lidocaine. However, their frequency-dependent block patterns were similar. It was concluded that tramadol may block the Na⁺ channels follow-ing the hydrophilic pathway like lidocaine and block K⁺ channels more than lidocaine. These may accounted for the local anesthetic-like effects of tramadol.     

CEREBRAL AMYLOIDOSIS IN SCRAPIE IN THE MOUSE: EFFECT OF AGENT STRAIN AND MOUSE GENOTYPE

Cerebral amyloid deposits, predominantly in the form of discrete plaques are common in mice infected with certain scrapie isolates. In this paper the incidences of cerebral amyloidois occurring with different combinations of agent strain and mouse genotype are investigated. Seven different agents from four primary sources were studied in three mouse genotypes (C57BL, VM and their F₁ cross). It is shown that the degree of amyloidosis is a passageable characteristic of the agent depending also on host genotype. However, the amyloid incidence is not influenced by the agent and mouse genotype independently but depends on a specific interaction between the two. For two scrapie agents, 22A and ME7 there is a correlation between incubation period and the incidence of cerebral amyloid in the three mouse genotypes. The degree of cerebral amyloid for ME7 remains unaffected by passage through the two genotypes of mouse, C57BL and VM, and through another species, a Cheviot sheep.     

THE CORRELATION OF ELECTRORETINOGRAPHIC AND HISTOPATHOLOGICAL FINDINGS IN THE EYES OF MICE INFECTED WITH THE 79A STRAIN OF SCRAPIE

Retinal degeneration was produced using the 79A strain of scrapie injected intracerebrally into mice of the MM inbred strain, and studied by electroretinography and light and electron microscopy during the preclinical and clinical phases of the disease. The changes in the electroretinogram (ERG), detectable in some mice at 118 days postinjection (d.p.i.), appeared to coincide with the earliest morphological evidence of photoreceptor damage. In the early stages there was a progressive reduction of b-wave amplitude without marked loss of retinal sensitivity or significant change in a- and b-wave peak implicit times. Extinction of the ERG, observed in half the mice examined at 144 d.p.i., approximated to a stage of the retinopathy in which the outer nuclear layer was reduced to about four rows of nuclei. Early morphological changes suggested that the primary lesion involved the integrity of the photoreceptor as a whole, the electrophysiological findings reflecting a primary loss of light sensitive tissue rather than impairment of the transduction mechanism or neurotransmission.     

PATHOGENESIS OF MOUSE SCRAPIE: DYNAMICS OF VACUOLATION IN BRAIN AND SPINAL CORD AFTER INTRAPERITONEAL INFECTION

At the late clinical stage of scrapie in mice, the severity and distribution of vacuolation in the brain (the lesion profile) is largely determined by the strain of agent and the genotype of the mouse: under controlled conditions, lesion profiles can be used to distinguish between scrapie strains. This paper describes the sequential development of lesions in brain at much earlier times and includes a study of spinal cord. Mice (CW) were infected intraperitoneally with 139A scrapie. Grey matter vacuolation first occurred in thoracic cord, developing later in lumbar and cervical cords, and then in various brain regions in a caudal to rostral sequence. This pattern closely matches the sequential spread of infection from mid-thoracic cord to much of the CNS that was previously found in this scrapie model. Further studies of grey matter in spinal cord suggest that agent entered the mid-thoracic region via sympathetic fibres. Vacuolation in white matter mirrored the grey matter pattern within an area but always occurred later. The severity of grey matter vacuolation in the four areas of the CNS where it developed early, reached plateau levels before the clinical stage of scrapie, but the severity was still increasing at the clinical stage in areas where vacuolation had started late. Hence the severity of lesions in a particular area may sometimes be limited by the time available for them to develop before the host dies. It appears that the distribution of vacuolation in this particular scrapie model is initially influenced by that of the infectious agent and only later does it reflect the distribution of vacuolation target areas shown by the characteristic lesion profile.     

IMMUNOSTAINING OF SCRAPIE CEREBRAL AMYLOID PLAQUES WITH ANTISERA RAISED TO SCRAPIE–ASSOCIATED FIBRILS (SAF)

Brain sections from 16 different mouse scrapie models were immunostained with antisera to scrapie-associated fibrils (SAF) from three experimental scrapie sources (hamster 263K, mouse ME7 and mouse 22L). These models involved seven strains of scrapie injected intracerebrally or intraperitoneally into a range of inbred mouse strains, producing a wide variety of neuropathological changes. The only brain structures which were positively immunostained were amyloid plaque cores in those models in which plaques could be readily identified using traditional amyloid stains. The intensity of immunostaining correlated with the density of amyloid in the cores, as detected by Congo red and thioflavine S staining. No differences in immunostaining specificity were found between antisera or between plaques in different combinations of scrapie strain and mouse genotype. There were also no differences in immunoreactivity between plaques in different parts of the brain. These results strongly suggest that SAF and histologically detectable amyloid in scrapie mice are derived from the same precursor protein. Scrapie-associated cerebrovascular amyloid and plaques in sheep and goats also gave positive immunostaining with SAF antisera, although the lesions in the natural disease could only be stained after formic acid pretreatment. Senile plaques in Alzheimer's disease and Down's syndrome, although structurally similar to scrapie amyloid plaques, were found to be completely negative for SAF, in agreement with previous biochemical and immunocytochemical findings.     

UNUSUAL DEVELOPMENT OF POLYOMA VIRUS IN THE BRAINS OF TWO PATIENTS WITH THE ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)

Two HIV-positive male patients presented with a variety of symptoms including hemiparesis, unsteadiness, progressive loss of vision and poor memory. There were multiple non-enhancing lesions shown by CT scan in the white matter of the cerebral hemispheres. Specimens obtained by burr-hole biopsy showed the features of progressive multifocal leucoencephalopathy (PML) in both cases. Electron microscopy demonstrated round and rod shaped particles of papovavirus in the nuclei and cytoplasm of oligodendrocytes and in processes of astrocytes where abnormal and florid modes of viral replication were seen. Additional features observed were viral particles suggestive of an enterovirus in Case 1 and, in both specimens, massive membrane proliferation within both nuclei and cytoplasm of infected cells together with the presence of tubuloreticular structures (TRS) in the cytoplasm of endothelial cells. At post-mortem, the brain of patient 2 showed PML and HIV encephalitis. The presence of HIV was confirmed by immunohistochemical methods. We suggest that in AIDS patients the abnormality of the immune system induced by HIV causes abnormal replication patterns of papovavirus in the brain. In addition, these cases confirm the frequent occurrence in AIDS patients of TRS, now considered to be a marker for HIV.     

LIPOPROTEIN(a) CONCENTRATION AND MOLECULAR WEIGHT OF APOLIPOPROTEIN(a) IN PATIENTS WITH CEREBROVASCULAR DISEASE AND DIABETES MELLITUS

Plasma lipoprotein(a) [Lp(a)] concentrations are genetically determined, and hyper-Lp(a)-emia is an independent risk factor for atherosclerosis and thrombosis. To study the implications of Lp(a) in cerebrovascular disease (CVD) and diabetes mellitus (DM), we examined plasma Lp(a) levels and molecular weights of apolipoprotein(a) [apo(a)] in 118 patients with CVD, and 125 cases with DM. Although mean Lp(a) concentrations were higher in those cases with atherothrombotic brain infarction than in those with brain hemorrhage and lacunar infarction, the difference was not statistically significant. Lp(a) levels were significantly higher in the DM cases treated with insulin and in those treated with oral hypoglycemic agents than in those on diet therapy alone, suggesting that insulin and oral agents modulate apo(a) expression. Lp(a) concentrations correlated significantly with the low-molecular-weight isoforms of apo(a) in all CVD and DM groups. © 1997 Elsevier Science Ltd     

AGE OF ONSET AND OUTCOME IN ''ACQUIRED APHASIA WITH CONVULSIVE DISORDER'' (LANDAU-KLEFFNER SYNDROME)

The relationship between age at onset of language disorder and eventual outcome was examined in 45 cases of Landau-Kleffner syndrome reported in the literature, all of whom had been followed up to at least 12 years of age. A strong relationship was found, which is opposite to that for childhood aphasia after structural lesions of the left hemisphere; i.e. in Landau-Kleffner syndrome, the older the child at onset the better the prognosis for language.     

AGGRESSIVE BEHAVIOUR IN THE CHINESE ELDERLY—VALIDATION OF THE CHINESE VERSION OF THE RATING SCALE FOR AGGRESSIVE BEHAVIOUR IN THE ELDERLY (RAGE) IN HOSPITAL AND NURSING HOME SETTINGS

Objective. The objective is to examine the validity of the Chinese version of the Rating Scale for Aggressive Behaviour in the Elderly (RAGE) in Hong Kong. Design. A cross-sectional study comparing the pattern of aggressive behaviour among residents of different elderly institutions. Setting. A nursing home and a psychogeriatric inpatient unit. Patients. Psychogeriatric inpatients and nursing home residents. Thirty subjects participated in the validation study of the Chinese version of the RAGE (CRAGE). Eighty-eight subjects were assessed by the CRAGE for pattern of aggressive behaviour. Measures. The CRAGE and the Chinese version of the Mini-Mental State Examination (CMMSE). Results. The CRAGE showed satisfactory validity and reliability measures. Aggressive episodes were found in 57% of the subjects, mostly mild in nature. No significant difference was found in the CRAGE total scores in different institutions and across diagnoses. Hospital and schizophrenic patients had significantly higher ratings in overall aggressiveness. Demented subjects had higher CRAGE ratings with CMMSE scores from 11 to 15. Conclusions. CRAGE is a valid instrument for use in the Chinese elderly. Although there is no significant difference in total aggressive episodes among different elderly institutions, chronic psychiatric patients were more frequently regarded as aggressive.     

THE SUITABILITY OF THE ROBERTS APPERCEPTION TEST FOR CHILDREN (RATC), THE HOUSE-TREE-PERSON (H-T-P) AND DRAW-A-PERSON (D-A-P) SCALES IN THE IDENTIFICATION OF CHILD SEXUAL ABUSE IN THE INDIAN COMMUNITY: AN EXPLORATORY STUDY

Abstract

Determining whether a child has been sexually abused is both a challenging and daunting task, since errors in this regard could have far-reaching implications. Adding to the dilemma of distinguishing between the abused and non-abused child is the fact that there is no single psychological measuring instrument to aid the forensic evaluator in this task. However, recently there have been attempts to either develop certain measures for specific use in child sexual abuse investigations or to determine the suitability of existing measures in this regard. The aim of this study was to determine the suitability of the Roberts Apperception Test for Children (RATC), the House-Tree-Person (H-T-P) test and the Draw-A-Person (D-A-P) test as measures of sexual abuse assessment in South African children. As there is particularly a lack of information in certain subcultures, this study focused on the Indian community. The research participants included 23 sexually abused girls and 17 non-sexually abused girls mostly from foster homes in KwaZulu-Natal. The results revealed that the two groups differed significantly on the four scales of the H-T-P/D-A-P, whereas there were no differences in the scale scores on the RATC. However, a larger proportion of girls who were sexually abused, gave responses of a sexual nature on the RATC. It was concluded that both these instruments seem to be suitable for inclusion in an assessment battery for sexual abuse investigations in Indian girls. It was also emphasised that none of the instruments can be used in isolation. However, they can provide an indication of possible sexual abuse which must be investigated further.     

HUMAN AFRICAN TRYPANOSOMIASIS (T.b. GAMBIENSE): A STUDY OF 16 FATAL CASES OF SLEEPING SICKNESS WITH SOME OBSERVATIONS ON ACUTE REACTIVE ARSENICAL ENCEPHALOPATHY

The principal clinical and pathological findings in 16 fatal cases of human African trypanosomiasis caused by T.b. Gambiense are described. The changes in the brain took the form of a non-specific lymphoplasmacytic meningo-encephalitis of varying intensity. Other features included morular cells, diffuse microglial hyperplasia, and large reactive astrocytes in the white matter. Carditis was identified in 10 cases. Acute reactive arsenical encephalopathy appeared to be the principal cause of death in 10 patients. Convulsions figured prominently in this type of encephalopathy in seven patients and were sufficiently severe to produce hypoxic brain damage. In three cases of acute reactive arsenical encephalopathy the structural changes in the brain were those of acute haemorrhagic leucoencephalopathy.     

TOPOGRAPHY OF NEUROFIBRILLARY TANGLES AND GRANULOVACUOLES IN HIPPOCAMPI OF PATIENTS WITH DOWN'S SYNDROME: QUANTITATIVE COMPARISON WITH NORMAL AGEING AND ALZHEIMER'S DISEASE

Ball M. J. & Nuttall, K. (1981) Neuropathology and Applied Neurobiology 7, 13–20
Topography of neurofibrillary tangles and granulovacuoles in hippocampi of patients with Down's syndrome: quantitative comparison with normal ageing and Alzheimer's disease
An XY pen recorder linked potentiometrically to a sampling stage microscope permitted the plotting of topographic 'scattergrams' to determine the precise cytoarchitectonic localization of neurofibrillary tangles and granulovacuo-lar degeneration in hippocampal neurones of Down's syndrome adult brains. The area (and hence volume) of six cortical 'zones' surveyed was measured with a digitizer and programmable calculator. In decreasing magnitude of affliction, the rank order for neurofibrillary tangles was: entorhinal > subiculum > H₁ > endplate > H₂ > presubiculum. That for granulovacuolar change was: subiculum > H₁ > H₂ > endplate > entorhinal > presubiculum. These striking regional predispositions suggest that a common neurotransmitter deficit may underlie the local selectivity of such lesions in Down's syndrome brains; and the predilections' marked similarities to ranking orders, already noted both in normal aged subjects and especially in senile dements of the Alzheimer type, enhance the importance of the Down's syndrome neuraxis as a key to the puzzle of Alzheimer's dementia.     

VARIATION WITH AGE IN THE VOLUMES OF GREY AND WHITE MATTER IN THE CEREBRAL HEMISPHERES OF MAN: MEASUREMENTS WITH AN IMAGE ANALYSER

Miller A. K. H., Alston R. L. & Corsellis J. A. N. 1980 Neuropathology and Applied Neurology 6, 119–132
Variation with age in the volumes of grey and white matter in the cerebral hemispheres of man: measurements with an image analyser
The total volumes and relative quantities of grey and white matter have been measured in sixty-five normal male and sixty-five normal female cerebral hemispheres. Fixed hemisphere volume was found to fall linearly at 35% per decade for men from 641 ml at the age of 20 to 463 ml at the age of 100. For women the decrease was 1–9% per decade from 531 ml at 20 years to 462 ml at 100 years. After correction for the effects of fixation and for the secular increase in brain size, it was concluded that mean hemisphere volume remained roughly constant between the ages of 20 and 50 years (558 ml for men, 474 ml for women). After the age of 50 the mean volume in both sexes fell at about 2% per decade. The ratio of the volumes of grey to white matter was the same for the two sexes at all ages. Its mean value was 1–3 at the age of 20, falling to 11 at the age of 50, then rising steadily to over 1–5 at 100 years. It is impossible in practice to correct these measurements for the effects of fixation or secular change. Fourteen hemispheres from thirteen elderly female dements were also measured. The total volume was 18% lower than for an age-matched group of normals, but the ratio of grey to white matter was identical.     

中国人肝豆状核变性基因（ATP7B）第16号外显子的突变特征

为探讨中国人肝豆状核变性基因（ATP7B）第16号外显子的突变特征，应用聚合酶链反应-单链构象多态（PCR－SSCP）技术对无亲缘关系的44例肝豆状核变性患者和60名正常人的ATP7B基因第16号外显子，进行了突变及多态的筛查。发现3例患者具有与正常对照不同的单链构象，进一步经DNA测序证实其中2例发生了Ileull48Thr突变，另回例发生Glull73Lys突变。上述突变均为国际上未报道过的新型错上突变。此外，还发现2种多态现象，其中Valll40Ala与文献报道一致，而3498C—T的改变则是一种本报道过的新多态、表明中国人ATP7B基因第16号外星子的突变性质与西方人具有差异性。