Action of chloroquine on in vivo RNA and protein biosynthesis in the retina and the optic pathway of the rabbit

The in vivo action of chloroquine on RNA and protein metabolism in the optic pathway of the albino or pigmented rabbit was examined. To study the acute effects, chloroquine in a dose of 500 μg was injected into the vitreous body of one eye. The following day the animals were injected into both eyes with [³H]uridine or [³H]leucine. At various time intervals following the isotope injections the retinal synthesis and the axonal transport of labelled RNA or protein was studied. The results showed no significant difference between the drug-treated and the control side with respect to synthesis and axonal transport of RNA or protein. Nor was any selective effect noticed on the synthesis of different RNA fractions from the retina.

In long-term experiments chloroquine (100 mg/kg body weight) was administered via their drinking water 3 days a week for a period of 6 or 8 months. Following an intraocular injection of [³H]leucine no significant change in rapid axonal transport could be found in those chronically treated rabbits.     

Effect of experimental status epilepticus on the pattern of RNA synthesis in cerebral cortex

The pattern of RNA synthesis during status epilepticus was studied in the cerebral extrafocal cortex of cats. The results indicated a change in the pattern of RNA synthesis suggesting an inadequate processing of precursor RNA molecules into mature products. The newly synthesized cytoplasmic RNA was composed of discrete species whereas the corresponding RNA of the controls showed a heterogeneous distribution. Such discrete species might be involved in cellular processes of particular importance in this functional state.     

Separation of cerebrospinal fluid-enriched proteins: A methodological study, Part 2

Beta-trace protein, beta₂-microglobulin and prealbumin were identified in a cerebrospinal fluid fraction containing proteins enriched in CSF-characteristic proteins obtained through affinity chromatography. The prealbumin amount was somewhat higher among CSF-enriched proteins from ventricular CSF than in the same fraction from lumbar CSF. Otherwise no variations in the CSF-enriched protein pattern were found in a ventriculo-spinal CSF-gradient analysed with isoelectric focusing. Affinity chromatography was done using insolubilized antisera against human serum proteins or against human cerebrum. Soluble brain proteins were analysed similarly and compared to the CSF-enriched protein pattern.     

Blood-brain barrier dysfunction to peroxidase after air embolism, aggravated by acute ethanol intoxication

Ethanol-intoxicated and non-intoxicated rats were injected with horseradish peroxidase and Evan's blue-labelled albumin and given a small air embolus in the right common carotid artery after ligation of the external carotid branch. In both ethanol-intoxicated and non-intoxicated rats, some endothelial cells, mainly in arteries and arterioles, showed a diffuse distribution of peroxidase in the cytoplasm. In some arterioles with a diffuse endothelial distribution of peroxidase there was a detachment of endothelial cells from the vessel wall, with an exposure of the adluminal basement membrane to blood elements. This endothelial detachment was mainly observed in ethanol-intoxicated rats. The vascular basement membranes underlying detached endothelial cells contained peroxidase, both in ethanol-intoxicated and in non-intoxicated rats. There was a considerable leakage of peroxidase via endothelial pinocytotic vesicles into the vascular basement membranes, mainly in arterioles, but also in capillaries and venules of the embolised hemisphere. This transendothelial pinocytotic transport of peroxidase was more prominent in ethanol-intoxicated than in non-intoxicated rats.     

Muscle changes in protein-deprived young rats. A morphometrical, histochemical and ultrastructural study

Rats were reared on a standard diet up to the age of 6 weeks when they were divided into two groups. One was fed on a diet containing 14% protein and the other on a diet with only 1.5% protein. The size of the various fibre types of the EDL muscle of both groups was assessed at 6 and 25 weeks of age. All the fibre types of protein-deprived rats were smaller compared to the age-matched controls, the difference being most evident in the 2B fibres. In the protein-deprived rats the 2B fibres atrophied while the type 1 and type 2A fibres simply failed to grow. Histochemical and ultrastructural examination revealed a marked reduction of the subsarcolemmal mitochondria after prolonged protein deprivation; normally large accumulations of mitochondria are seen preferentially in type 2A fibres.     

Clinical data and the identification of special forms of multiple sclerosis in 1271 cases studied with a standardized documentation system

In a multicenter study the clinical data of 1271 patients with multiple sclerosis (MS) were recorded in a standardized manner and analysed by a computer program.

Some of the retrospective data are compared with previous reports. The frequency of optic nerve involvement in the present series was close to the Japanese figures.

The development of signs and symptoms during the course of MS was given for the 1271 patients and differences in the reversibility of symptoms are presented.

In this study, one of the chief purposes was the selection of groups of MS patients with particular symptomatology and course of the disease for prospective, detailed study.

The following groups were selected and are under further investigation: 109 patients with an exclusively spinal symptomatology throughout the course of their disease; 441 patients with optic neuritis as initial symptom; 110 patients with early brain-stem involvement; 64 benign cases (duration of the disease more than 14 years and disability not more than 3 according to Kurtzke); 35 malignant cases (duration of the disease under 5 years and disability grade of 7 or more); 83 families with more than one member with MS; 289 females with a history of pregnancy, childbirth and/or use of oral contraceptives.

In 339 patients a lumbar puncture was performed at the present examination. The parameters determined constitute a pathognomonic pattern highly indicative of the diagnosis of MS.     

Immunoglobulin-producing cells in CSF and blood from patients with multiple sclerosis and other inflammatory neurological diseases enumerated by Protein-A plaque assay

Using the Protein-A plaque assay, numbers of IgG + IgA + IgM producing cells determined in patients with multiple sclerosis (MS) were 0.1–5% in CSF and 0.1–0.7% in peripheral blood; interestingly, 7 of 11 MS patients had IgM producing cells in CSF. In patients with aseptic meningitis (AM), the corresponding values were 0.04–7.5% in CSF and 0.4–2.4% in peripheral blood. There were more Ig producing cells in peripheral blood from patients with AM and MS than in healthy subjects. cocorrelation between numbers of IgG producing cells in CSF and the concentrations of intrathecally produced IgG (CSF IgG index) was registered in patients with AM: the same was true for IgA. The Protein-A plaque method, adopted for 20 × 10³ lymphocytes, makes possible enumeration of Ig-producing cells in CSF and discrimination among cells secreting different Ig classes, thereby being a powerful tool for studying immune reactions in the CNS-CSF compartment.     

Biofeedback treatment for muscle pain associated with the temporomandibular joint

Biofeedback treatment for muscle pain is discussed. Polygraph recordings taken before and during treatment were evaluated, and improvement in ability to control muscle tension clearly observed. The case history given is only a typical example. As the individual is able to gain control over muscle activity there is concomitant reduction of pain. It is concluded that where muscle spasm or tension results in pain, biofeedback can be an effective treatment.     

Imaging of [C]-labelled RO 15-1788 binding to benzodiazepine receptors in the human brain by positron emission tomography

The benzodiazepine antagonist Ro 15-1788 was labelled with [¹¹C] and examined for possible use as ligand for PET scan studies on benzodiazepine receptors in the brain of cynomolgus monkeys and human subjects. [¹¹C] Ro 15-1788 allowed the in vivo visualization of benzodiazepine receptor binding in cerebral and cerebellar cortical areas as well as in basal brain nuclei in PET scan images. [¹¹C] Ro 15-1788 exhibited a high ratio of specific benzodiazepine receptor binding (cerebral cortex) to non-specific binding (pons) and the kinetics of binding should be satisfactory for quantitative clinical PET scan studies using [¹¹C]. The in vivo binding of [¹¹C] Ro 15-1788 in the cerebral cortex of cynomolgus monkeys and healthy human subjects was reduced by approximately 90% within 10 min after the intravenous injection of a high dose of unlabelled Ro 15-1788 (0.5 mg/kg i.v.). Different areas of the healthy human brain showed an approximately 10-fold variation in maximal [¹¹C] Ro 15-1788 binding that corresponded to the previously known distribution of benzodiazepine receptors in these regions. The highest degree of binding was obtained in the medial occipital cerebral cortex followed by frontal cortex, cerebellum, thalamus, striatum and pons. Two psychiatric patients with anxiety syndromes who had been treated for a long time with high doses of benzodiazepines had roughly the same degree of maximal [¹¹C] Ro 15-1788 binding in brain regions as the healthy subjects but the rate of decline of [¹¹C] Ro 15-1788 in the brain was higher. This indicates that there is measurable competition between [¹¹C] Ro 15-1788 binding and clinical benzodiazepine concentrations in the body fluids of psychiatric patients. The results demonstrate that [¹¹C] Ro 15-1788 should be a valuable tool for quantitative analyses of benzodiazepine receptor characteristics and receptor occupancy in the brain of patients with neuropsychiatric disorders.     

Latent herpes simplex virus trigeminal ganglionic infection in mice and demyelination in the central nervous system.

Mice were inoculated with herpes simplex virus (HSV) type 1 by gently scraping the skin of the nose with a fine needle. About 80% of the animals developed latent inapparent HSV infections in trigeminal ganglia. Virus was demonstrable for at least 6 months post inoculation (p.i.) by cocultivation of ganglionic tissue with GMK cells. Histologically, trigeminal ganglia revealed infiltrations of inflammatory cells even 6 months p.i. In addition, lesions occurred in the brainstem corresponding to the entry of trigeminal roots, trigeminal tracts and nuclei. Inflammatory cell infiltration, disruption of myelin sheaths and macrophages laden with myelin degradation products were observed 7 days p.i. Fourteen to 30 days p.i. electron microscopy demonstrated completely naked axons. In the transitional region of the trigeminal root denuded axons occurred in the central part of the region while the peripheral myelin, bordering the demyelinated central segments, was intact. Small areas of demyelination were still detectable 3 and 6 months p.i. but there were then also signs of remyelination. Possible mechanisms causing the demyelinations are discussed.     

Psychosocial outcome one year after a first myocardial infarction

Psychosocial outcome in terms of mental state, health preoccupation, leisure activity, avoidance behaviour, sexual activity and attitude towards life and the future one year after a myocardial infarction (MI) was studied in 177 consecutive male, able-bodied patients below 61 yr of age with a first MI. Questionnaires and a brief interview covered the psychological and social data while the somatic variables were recorded in a standardized medical examination. Emotional distress, self-reported symptoms, avoidance behaviour, overprotection, pessimism and a diminished sexual activity were frequent, indicating a poor adaptation. These disturbances were apparent two months after the MI and remained stable. Psychological factors were stronger determinants of maladjustment than smoking, angina pectoris and recorded somatic illness. Neither severity of the infarction nor social and demographic factors determined maladjustment. Intervention must take place early and be directed to psychological factors as well as to the cardiac condition.     

Different types of antibrain antibodies in multiple sclerosis: Studies employing myelin-deficient mutants of mice

The presence of complement fixing IgG class antibrain antibodies is a distinctive feature of multiple sclerosis (MS). Only two of the several specificities of these antibodies are yet identified. Testing a number of MS sera and CSF samples against homogenates of brain from two myelin-deficient mouse mutants, Jimpy and Quaking, and their littermate controls confirmed the occurrence of antibrain antibodies directed against both myelin-associated and non-myelin antigens.     

Sarcoplasmic bodies in distal myopathy compared with nemaline rods

Sarcoplasmic bodies in a late onset distal myopathy and rods in nemaline myopathy have been investigated by electron probe X-ray microanalysis correlated to light microscopy. Sarcoplasmic bodies were glassy, drop-shaped structures up to 10 microns of length and easily distinguished in the scanning mode of electron microscopy performed on thick freeze-dried cryosections. They were found to be source of X-ray spectra characterized by a high sulfur peak. On semithin epoxy sections the sarcoplasmic bodies were observed in the scanning transmission mode as electron-dense structures which, according to X-ray microanalysis, exhibited a high sulphur and osmium content, possibly indicating the presence of sulphydryl groups. The nemaline rods were of 3 different types as judged by their light-microscopical appearance. They were, however, not visible in the scanning mode of electron microscopy performed on freeze-dried unstained cryosections. There were small differences in the elemental composition between different rods within the same biopsy but these were not systematically related to the differences in morphological appearance.     

Measles antibodies and histocompatibility types in multiple sclerosis

Measles antibody titres and HLA antigens were determined in 71 White and 11 Coloured multiple sclerosis (MS) patients and 71 White and 11 Coloured age and sex-matched controls. Measles antibody titres were determined by the hemagglutination inhibition test and HLA antigens were determined serologically by a micro-lymphocytotoxicity test. Measles antibody titres were significantly higher in MS than in control cases and this was true for both female and male patients. No association was observed between the HLA antigens, especially HLA-A3 or HLA-B7 and measles antibody titres in the sera of MS patients or controls.     

Cerebrospinal fluid lymphocytes from patients with multiple sclerosis and aseptic meningo-encephalitis respond in mixed lymphocyte culture

Proliferative responses of cerebrospinal fluid lymphocytes (CSF-L) and peripheral blood lymphocytes (PBL) from patients with multiple sclerosis (MS) and aseptic meningo-encephalitis (AM) were tested in allogeneic mixed lymphocyte culture (MLC). PBL from various sources (MS, AM, healthy subjects) were used as stimulator cells. CSF-L from 10 of 13 patients with MS and all 15 patients with AM were MLC-reactive to an extent not significantly different from that of PBL. No consistent differences in mixed lymphocyte reaction (MLR) patterns were registered in MS when clinical (exacerbation, age at onset, duration of disease, disability) and CSF variables (mononuclear cell count, CSF IgG index) or presence of HLA Dw2 were considered. The MLC response of PBL obtained from MS and AM patients did not differ significantly from that of healthy individuals. The results contrast with our previous observation of low proliferative response of MS CSF-L to mitogens. Clonal expansion of alloreactive CSF-L offers the possibility of further studies of their characteristics.     

Antibodies to viral and non-viral antigens in subacute sclerosing panencephalitis and multiple sclerosis demonstrated by thin-layer polyacrylamide gel isoelectric focusing,antigen immunofixation and autoradiography

Antibody activity in IgG zones separated by thin-layer polyacrylamide gel isoelectric focusing (PAGIEF) was determined in 3 patients with subacute sclerosing panencephalitis (SSPE), 4 patients with multiple sclerosis (MS) and 4 subjects with psychosomatic disorders, using antigen immunofixation and autoradiography. Viral (measles, herpes simplex type 1, mumps) and non-viral (purified bovine myelin, bovine myelin basic protein, bovine oligodendrocytes, MS and normal human brain extract) were used as antigens. All oligoclonal and some of the polyclonal CSF IgG zones in the patients with SSPE contained measles virus antibodies, as did some of the oligoclonal and polyclonal CSF IgG zones in 3 of the patients with MS. No antibodies were detectable in CSF or serum IgG zones against any of the non-viral antigens tested.     

The distribution of intermediate filament protein (skeletin) in normal and diseased human skeletal muscle: An immunohistochemical and electron-microscopic study

The presence of intermediate filaments in various mature and immature eukaryotic cells is well documented. By using antibodies against the intermediate (skeletin) filaments of cow heart Purkinje fibres, we have in the present work analyzed the distribution of skeletin in normal and diseased skeletal muscle fibres. Antiskeletin proved to be a useful tool for the identification of regenerating fibres in Duchenne muscular dystrophy. In mature muscle fibres with well-preserved myofibrils, skeletin had an intermyofibrillar localization at the Z-disk level where intermediate filaments were demonstrated. The presence of skeletin was also demonstrated around the rods of muscle fibres in nemaline myopathy biopsies, but the rods themselves did not show any cross-reactivity. This report exemplifies the usefulness of antibodies in muscle pathology.     

A longitudinal study of immunological parameters in multiple sclerosis. Cytotoxic antibodies.

Complement-dependent gliotoxic antibody activity was determined in 22 patients with multiple sclerosis (MS) and 19 normal control persons. Peripheral blood serum was collected from MS patients at about 4-week intervals for one year, and the results of cytotoxicity tests correlated with the course of disease. For 10 MS patients with stable disease, complement-dependent cytotoxic antibodies directed against a noncytocidally infected mouse glial cell line (an as yet unidentified virus) were found in significantly higher than normal titer. For 12 MS patients with fluctuating clinical course, the gliotoxic antibody titer remained relatively constant before relapse. During relapse, the titer remained constant or dropped. With remission initially low titers increased appreciably.     

Plasma prolactin and testosterone during the luteal phase in women with premenstrual tension syndrome

(1) Plasma prolactin and testosterone concentrations were measured during the luteal phase in 15 women suffering from premenstrual tension syndrome (PMS). The concentrations of these hormones were compared to those measured in 17 women without PMS. (2) There were no differences between mean prolactin or testosterone levels in the patient group compared to those of the controls. (3) Plasma testosterone — estradiol binding globulin was significantly higher in the patient group.