Immunohistological study of senile brains by using a monoclonal antibody recognizing β amyloid precursor protein: significance of granular deposits in relation with senile plaques

Summary Immunochemical analyses revealed that a monclonal antibody Am-3 recognized amyloid precursor protein (APP) in senile plaques extracted from Alzheimer's brain, but did not recognize amyloid protein. Immunohistochemically, however, the staining pattern of Am-3 in frozen section of Alzheimer's brain was almost the same with that of rabbit polyclonal antibody to amyloid peptide which could recognize both amyloid protein and APP. In other words, APP was present in senile plaques of various types, cerebrovascular amyloid and granular deposits. The granular deposits were 5–10 m in size and laminarily distributed in the 1st, 3rd and 4th layers of cerebral cortex. They were especially abundant in 1st and 4th layers where senile plaques were usually fewer in number. Although the distribution in the cerebral cortex was different between the senile plaques and the granular deposits, the number of the granular deposits was well correlated with that of senile plaques. The granular deposits were negative in Congo-red birefringence, but contained amyloid protein as well as APP fragment judging from positive staining by both Am-3 and polyclonal antibody to synthetic amyloid peptide. Thus, they could be regarded as pre-amyloid.     

Hyperkinetic children: Early indicators of potential school failure

Hyperkinetic children are identified as a population-at risk upon admission to kindergarten. The etiology of hyperkinetic behavior is controversial. Organic driveness, hyperkinetic behavior disorder, postencephalitic behavior, brain damage with behavioral and conceptual deficit, Strauss syndrome, have all been used to label essentially similar symptom constellations. Bypassing the area of controversy, a study is reported that demonstrates that children who were identified as hyperkinetic (using behavioral criteria developed in an earlier study) were (1) absent from school more frequently, and (2) did remarkably less well on standardized tests of school readiness than their peers rated nonhyperkinetic. The implications are discussed and suggestions made for the development of intervention programs.An earlier version of this paper was presented at the Annual Meeting of the American Orthopsychiatric Association, March, 1967.     

Immunohistochemical study on the distribution of α and β subunits of S-100 protein in brain tumors

Summary The immunohistochemical distribution of and subunits of S-100 protein (S-100, S-100, respectively) in 138 cases of human brain tumors was investigated by the avidin-biotin immunoperoxidase method. Brain tumors can be divided into four groups: group 1 [S-100 (+) and/or S-100 (+)]; astrocytoma, glioblastoma, ependymoma, subependymoma, oligodendroglioma, choroid plexus papilloma, gangliocytoma, meningioma, chordoma, malignant melanoma. Group 2 [S-100 (+) and S-100 (-)]; pineoblastoma, pituitary adenoma, craniopharyngioma, rhabdomyosarcoma. Group 3 [S-100 (-) and S-100 (+)]; acoustic Schwannoma. Group 4 [S-100 (-) and S-100 (-)]; medulloblastoma, malignant lymphoma, germinoma. The S-100 immunoreactivity pattern in brain tumors was similar to those obtained using conventional anti-S-100 protein sera. In the first group of brain tumors both the number of positively stained tumor cells and the staining intensity were generally greater for S-100 than for S-100 with a few exceptions including one gemistocytic astrocytoma, one subependymoma, one malignant melanoma, and some cases of glioblastomas. As to the relationship between malignancy and S-100 protein in glioma, S-100 immunoreactivity decreased according to degree of malignancy, while that of S-100 varied, suggesting a heterogeneity of tumor cells in glioblastomas. Immunostaining for S-100 and S-100 might become a useful diagnostic procedure in brain tumors and may give us more detailed and precise data of S-100 protein in brain tumors.     

Comparison of integrin adhesion molecules expressed by primary brain lymphomas and nodal lymphomas

The expression of 17 adhesion molecules was immunohistochemically examined in 5 primary cerebral lymphomas (PCL) and in 5 histologically similar nodal lymphomas (NL) to evaluate their possible involvement in selective targeting of lymphoma cells to the brain. PCL and NL tumor cells showed very similar expression patterns: they were consistently positive for ₃, ₄ and ₁ integrin chains; negative for ₂, ₆, ₃ and ₄ integrin chains; and heterogeneous for ₅, _L, _M, _X, ₂ and ₇ integrin chains, as well as for intercellular adhesion molecule-1 (ICAM-1) and the selectin LECAM-1. Loosely infiltrating PCL showed lower levels of the _L2 integrin than compact cell clusters. Vessels stained for ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). We conclude that the adhesion molecules implicated in the extravasation of non-neoplastic leukocytes (₄₁/VCAM-1 and _L2/ICAM-1) are also expressed by both PCL and NL. The adhesion molecules examined are apparently not selective mediators of lymphoma cell homing to the brain, but at least _L2 integrin might be related to the infiltration pattern of PCL within the brain parenchyma.Supported by the Sander Foundation     

Experience and philosophy with regard to case registers in health and welfare

A well designed and executed case register for mental illness or other conditions can provide information not readily obtainable by any other method. This includes unduplicated counts of diagnosed cases of the disease and longitudinal information such as changes in diagnosis, outcome, and survival information. Registers often are the only way in which new cases can be identified with any certainty. Also, the register can serve as a sampling frame for more intensive studies of services and of prevalence of the disease in the community, genetic studies, studies of the cost of treating various types of patients, before and after comparisons, and many other sociological and epidemiologic investigations. At the same time, there are many problems and pitfalls to case registers. This paper outlines some of these difficulties and suggests that registers be established only after careful planning and preparation.This paper is based on a presentation for a Workshop on Case Registers, American Orthopsychiatric Association Meeting, Chicago, Illinois, March 20, 1964. An extended bibliography on case registers is available from the author.     

Quantitative analysis of “synaptic” ribbon profiles in the pineal complex of male and female Pirbright-White guinea pigs

Summary Previous studies have pointed in the direction of sex differences as well as regional differences in the pineal gland of guinea pigs. In the present investigation these aspects were studied at the electron-microscopic level by quantitating different types of synaptic bodies, intrinsic to pinealocytes. The two major types of synaptic organelles, ribbons and spherules, did not exhibit regional or sex differences. Synaptic structures intermediate in appearance to ribbons and spherules were significantly larger in number in males in the distal region of the pineal gland, compared to females. As previous studies have shown that ribbon and spherule numbers undergo characteristic changes depending on the functional state of the pineal gland, it is concluded that, as far as the synaptic organelles are concerned, no clear-cut sex or regional differences appear to exist in the guinea pig pineal gland.     

“Sporadic” prealbumin-related amyloid polyneuropathy: report of two cases

Summary Two sporadic cases of amyloid polyneuropathy are reported. There was no family history or plasma cell dyscrasia. Both showed sensorimotor and autonomic polyneuropathy with onset in the seventh decade. Amyloid deposits in both cases reacted with anti-human prealbumin sera but not with antisera to human AA and anti-human immunoglobulin light-chain amyloids, including A and A. One patient had the abnormal serum prealbumin and abnormal DNA sequence found in type I familial amyloid polyneuropathy (FAP) (Japanese type). Investigations in sporadic amyloid polyneuropathy should include immunohistochemistry, using antisera to the different amyloid proteins, and the radioimmunoassay and recombinant DNA techniques for diagnosis of FAP.     

Die Hamburger Schätzskala für Psychische Störungen nach Herzoperationen (HRPD)

Zusammenfassung An einer Stichprobe von 99 herzoperierten Patienten wurde zur Erfassung, Beschreibung und Klassifikation früh-postoperativer psychischer Störungen aus dem psychopathologischen Befundbogen des AMP/AMDP-Systems eine Kurzform (HRPD) entwickelt. Weitgehend mit Hilfe einer klassischen Itemanalyse wurde eine Auswahl von 36 Symptomen vorgenommen.Eine Faktorenanalyse dieser Kurzform ergab 8 Merkmalsfaktoren bzw. Syndromskalen: Desorientierung, Konzentrations-/Denkstörungen, paranoid-halluzinatorische Symptomatik, Angstsymptomatik, gehemmt-depressive Symptomatik, Hostilität, Kontrollverlust sowie Selbstaufgabe.Clusteranalytisch wurden 6 psychopathologisch verschiedene Patientengruppen gefunden: unauffällig, fast unauffällig, leichte psychoorganische Symptomatik mit Affektstörungen, schwere psychoorganische Symptomatik mit Kontrollverlust, Hostilität mit paranoid-halluzinatorischer und psychoorganischer Symptomatik, sowie delirante Symptomatik.Ein Vergleich der Ergebnisse der HRPD mit Syndrombeschreibungen anderer AMP/AMDP-Untersucher ergab zum Teil gute Übereinstimmungen, zum Ted aber auch deutliche Unterschiede, die am ehesten durch die besondere Situation herzoperierter Patienten bedingt sein dürfte.Vorform in englischer Sprache: HRPD = Hamburg Rating Scale for Psychic Disturbances     

Does social deprivation during gestation and early life predispose to later schizophrenia?

Summary We employed a case-control study design to investigate whether schizophrenic patients differed from non-psychotic psychiatric patients in terms of place of birth and paternal occupation. Cases were first-contact schizophrenic patients ascertained from the Camberwell Cumulative Psychiatric Case Register. Controls were the next (non-psychotic) patient on the Register matched for age and sex. In comparison with controls, cases were more likely to have: (1) been born in the deprived innercity Camberwell catchment area (odds ratio 2.3), and (2) had fathers who had manual as opposed to non-manual occupations (odds ratio 2.1). The results were compatible with the notion that socio-economic deprivation during gestation and early life predisposes to later schizophrenia.     

Single drug therapy for intractable epilepsy

Summary Single drug therapy with either phenytoin or primidone resulted in complete seizure control in 11 of 35 patients (31%) referred to an epilepsy clinic for treatment of uncontrolled chronic epilepsy with complex-partial seizures. Complete seizure control was associated with an increase in the mean plasma concentrations from 14 g/ml to 23 g/ml phenytoin and from 34 g/ml to 40 g/ml phenobarbitone with no change in the antiepileptic drug. Insufficiently low plasma concentrations of less than 11 g/ml phenytoin or phenobarbitone were measured at the first visit in 14 patients (40%). Non-compliance was admitted by eight patients (23%). Optimum single drug therapy is of considerable clinical value in intractable epilepsy with complex-partial seizures.

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Zusammenfassung Eine Monotherapie mit Phenytoin oder Primidon führte zur Anfallsfreiheit bei 11 von 35 Patienten (31%), die wegen schwerbehandelbarer psychomotorischer Anfälle eine Epilepsieambulanz aufsuchten. Anfallsfreiheit trat auf bei einem Anstieg der mittleren Plasmakonzentration von 14 g/ml auf 23 g/ml Phenytoin und von 34 g/ml auf 40 g/ml Phenobarbital. Ein Wechsel der Medikamente war nicht notwendig. Während der ersten Untersuchung wurden bei 14 Patienten (40%) zu niedrige Plasmakonzentrationen von weniger als 11 g/ml Phenytoin oder Phenobarbital gefunden. 8 Patienten (23%) gaben eine unregelmäßige Einnahme der Medikamente (non-compliance) zu. Eine konsequente Monotherapie ist von klinischem Wert für die Behandlung von schwerbehandelbaren Epilepsien mit psychomotorischen Anfällen.

     

Potential role of transforming growth factor-β1 in terminating the immune response in patients with Guillain-Barré syndrome

T-cell activation and proinflammatory cytokines seem to be important in promoting the disease activity in Guillain-Barré syndrome (GBS). Transforming growth factor-1 (TGF-1) is a multifunctional peptide with potent immunosuppressive activity, and can therefore be considered a putative disease-limiting cytokine. We determined levels of soluble TGF-1 in the serum of 12 patients with GBS in serial investigations during the course of the disease, in 12 patients with other non-inflammatory neurological diseases (OND), and in 12 healthy control subjects. Levels of biologically active and total TGF-1 were significantly increased in patients with GBS compared with patients with OND and healthy controls. During the course of GBS, levels of TGF-1 peaked in the plateau phase before onset of recovery. During the recovery phase levels of TGF-1 decreased but still exceeded significantly the levels in patients with OND and healthy controls. The differences were more marked with biologically active than with total TGF-1. The temporal relationship between increased serum levels of TGF-1 and the end of the progressive phase indicates that TGF-1 has a role in terminating the pathological immune response in GBS. These findings suggest that TGF-1 may be important in recovery from GBS.     

Über Xanthurensäure-Bestimmung bei Ertrankungen des Nervensystems

Zusammenfassung Bei 91 Patienten und zehn Normalpersonen wurde die Xanthurensäure-Ausscheidung kontrolliert. Der Begriff Normalperson wird diskutiert. Für die Vergleichsgruppen werden Extrem- und Durchschnittswerte der Urin- und Xanthurensäure-Ausscheidung in 12- und 24 Std-Portionen vor und nach Belastung angegeben. Unter 39 sicher pathologischen Reaktionen fallen als relativ geschlossene Gruppen die Schizophrenien, Depressionen, Manien und die Fälle mit Chorea Huntington und chronischem Alkoholismus auf. In einigen Fällen, besonders solchen mit symptomatischem Parkinson-Syndrom ist eine negative Belastungsreaktion zu beobachten. Differenzen zwischen diagnostischen Gruppen und verschiedenen Altersklassen werden ebenso wie die Deutung der Befunde an Hand der einschlägigen Literatur besprochen.     

Extraocular muscles light microscopy and ultrastructural features

Summary Thirty extraocular muscles (EOM) from 20 patients were evaluated by light microscopy (LM), electron microscopy (EM), and enzyme histochemistry (EZH). Twenty-one EOM were obtained from 13 patients with strabismus, 9 EOM from 4 patients undergoing eye surgery for other reasons and from 3 autopsy cases. One m thick sections revealed marked variation in muscle fibre shape and size and in myofibrillar structure; also noted were small, hypertrophied, whorled, and ringbinden fibres. Dense and granular material in the central portion of some fibres and sarcomere disruption in 2–3 m sections was observed. EZH revealed the absence of the classical mosaic pattern usually found in skeletal muscles. ATPase studies were inconsistent and did not correlate with the expected reciprocal activity of NAD-H diaphorase, particularly on the large fibres.Ultrastructural features consisted of vacuoles within myofilament bundles, smearing of Z bands, and nemaline rods. Occasional myelin figures and lipid-like droplets were observed in subsarcolemmal spaces, associated with scattered clusters of glycogen granules. Abnormal mitochondria and subsarcolemmal inclusions of dense and granular material were conspicuous. Leptomeric profiles, Zebra bodies, or striated bodies were noted in 8 EOM's, and an Hirano body was found in 1. The intramuscular nerves contained structures resembling Luse bodies in 7 cases.These observations suggest that EOM from individuals with and without strabismus possess unique structural characteristics suggestive of developmental and morphological disarrangement of contractile elements. Some of these changes might play a role in the pathogenesis of strabismus and in the development of clinical symptoms.These features are significantly different from striated skeletal muscle. Therefore the criteria used in the pathological evaluation and diagnosis of skeletal muscle disorders cannot be unequivocally applied to EOM investigations. These data establish the necessity to determine histological norms, ultrastructural patterns, and develop new enzyme histochemistry criteria for the evaluation of EOM. Only then can an acceptable comparison of EOM and skeletal muscle be made.     

Somatosensory evoked potentials in patients with thalamic lesions

Summary Somatosensory evoked potentials (SEPs) were recorded in 20 patients with thalamic lesions confirmed by CT (10 with infarction, 10 with haemorrhage). The changes in SEP configuration are discussed in their relationship to clinical symptoms. Four types of SEP abnormality produced by thalamic lesion are distinguished: (1) FF type, (2) N20/P23 dissociation type, (3) N18/N20 false shift type, and (4) reduced early component type. It was shown that clinically similar lesions might produce different SEP patterns.     

Lomest psychiatric case register: Old and new long-stay patients

Summary Data derived from a psychiatric case-register are presented on the attrition of the cohort of theold long-stay in-patients, and the accumulation of thenew long-stay cases in Lomest, a town in northern Italy, from 1975 to 1980. The characteristics of high user groups of out-patients attending the non-residential services are also described. The analysis seeks to provide some information on who has been left behind by the massive deinstitutionalization programme that has been carried out in Italy since 1970.     

Neuroectodermal tumors of the peripheral and the central nervous system share neuroendocrine N-CAM-related antigens with small cell lung carcinomas

Summary The current study describes the presence of neuroendocrine antigens of peripheral and central neural tumors using eight monoclonal antibodies raised to small cell lung carcinoma (SCLC), which recognize neural/neuroendocrine or neural antigens, as defined by their reaction pattern in normal tissues and tumors. At least five of them recognize different epitopes of the neural cell adhesion molecule (N-CAM). It was found that all of 12 neuroblastomas, 2 ganglioneuroblastomas and 4 ganglioneuromas as well as 23 central primitive neuroectodermal tumors, 13 astrocytomas and 4 ependymomas share neural/neuroendocrine antigens (as defined by the anti-N-CAM antibodies Moc-1,-21,-32,-52 and-191) with SCLC. The neural/neuroendocrine antigen defined by Moc-171 was also found in all peripheral tumors, but only in further differentiated central tumors. Non-N-CAM related neural antigens (as defined by Moc-51 and-172) were found only in better-differentiated peripheral and central tumors, but they could be demonstrated in all three medulloblastoma cell lines studied. In addition, the antigen defined by Moc-51 was demonstrated in an immunoblot of a neuroblastoma cell line. Antibodies recognizing epithelia antigens of SCLC and other epithelia and their tumors (Moc-31 and-181) were non-reactive. It was concluded that these findings give further support for a relation between neural and neuroendocrine tumors and that some of the antibodies may be useful for the detection of differentiation in neural tumors. Antibodies with an epithelia recognition pattern may serve to distinguish neural from neuroendocrine tumors.Supported by NIH grant CA 36245 W.M.M. was a Fullbright scholar     

The Rituals, Fears and Phobias of Young Children: Insights from Development, Psychopathology and Neurobiology

This study examined the relationship between ritualistic, compulsive-like behaviors and normative fears and phobias in 61 children ranging from 1 to 7 years of age. Parents reported on their children's ritualistic habits, and perfectionistic behaviors that reflect what we have previously called compulsive-like behaviors. Parents also reported on their children's fears and phobias. Results indicated that various aspects of children's ritualistic and compulsive-like behaviors are correlated with children's fears and phobias. Developmental differences existed such that younger children's (< 4 years) repetitive, compulsive-like behaviors were related to prepotent fears such as stranger and separation anxieties, whereas the compulsive-like behaviors of older children (> 4 years) were correlated with more specific, contextual fears such as fears of contamination, death, and fears often associated with concerns of the inner city such as burglars, assault, etc. These findings are discussed in terms of the phenomenologic and possible neurobiological continuities between normative and pathologic rituals, fears and phobias.     

Intraventricular blood after “traumatic” lumbar puncture: a report of two cases

Blood was detected in the lateral ventricles on head computed tomograms performed after traumatic lumbar punctures in two children. This finding has not previously been observed or reported. The likely mechanisms by which blood from the spinal thecal sac reached the ventricles are discussed. This potentially confusing observation, if not correctly accounted for, may lead to an unnecessary, fruitless search for the site of a supposed primary intraventricular haemorrhage.     

Visual pattern evoked responses and blink reflexes in assessment of MS diagnosis

Summary VEPs were measured after pattern reversal in 135 MS patients and 30 control subjects. Neurological findings were documented in a standard manner. An extensive ophthalmological examination of all subjects was part of the study. The latency of P₂ was abnormally delayed in 82% of the definite, in 60% of the probable and in 65% of the possible MS groups respectively. The VEP was more often delayed in relation to ophthalmological disturbances. Changes in the MS classification had to be made in more than 10% of the patients, due to delay of VEP latency. These were patients with a spinal form of MS, which is known to create diagnostic problems.Optically and electrically evoked blink reflexes were recorded in 107 MS patients. All patients with mesencephalic lesions had delayed responses of the optically evoked reflex. 74% of the patients with caudal brainstem lesions had delayed latencies of the components of the electrically evoked blink reflex. The blink reflex was delayed in 18 additional patients without brainstem signs. The possibility of delineating clinically silent brainstem lesions by investigating blink reflexes is discussed.Supported by the Deutsche Forschungsgemeinschaft (Dr. Fischer Bosch-Stiftung).     

Psychometric properties of the parental bonding instrument in a spanish sample

Summary The Parental Bonding Instrument was translated into Spanish and administered to a sample of 205 Spanish primiparae 3 days after childbirth. Reliability, factorial structure and predictive validity for affective disorders were evaluated. The Spanish version of the PBI has psychometric features similar to those described in other cultures. However, the results suggest that in future research the predictive power of the Control factor in affective disorders might be improved by splitting it into two subfactors: Overprotection and Restraint.