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.     

Viral antibodies in oligoclonal and polyclonal IgG synthesized within the central nervous system over the course of mumps meningitis

The occurrence of viral antibodies in relation to IgG separated by thin-layer polyacrylamide gel isoelectric focusing was studied in CSF and serum from 24 patients with mumps meningitis by immunofixation with viral antigens and autoradiography. Eleven of the patients displayed on the autoradiograms evidence of locally in the central nervous system synthesized mumps virus antibodies which were related to oligoclonal IgG bands in all 5 patients who displayed this CSF abnormality, otherwise to polyclonal IgG bands. Local synthesis of mumps virus antibodies was detectable in 43% of specimens obtained 1–13 days after onset, and in 75% obtained 27–47 days after onset. Only one patient displayed local synthesis of antibodies to other viruses (measles and herpes simplex) which could then be traced to polyclonal IgG bands.     

Cerebrospinal fluid specific proteins in multiinfarct and senile dementia

Cerebrospinal fluid (CSF) from patients suffering from senile dementia (SD) and multiinfarct dementia (MID) was fractionated into CSF-specific and antigenically serum-like proteins, using affinity chromatography with antihuman serum antibodies. The samples were isoelectric focused. Protein patterns were compared to similarly treated CSF from patients suffering from transient ischemic attacks (TIA), or normal volunteers. Characteristic changes were found in the CSF-specific protein pattern from SD patients.     

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.     

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.     

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.     

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.     

IgM and IgG responses during chronic relapsing experimental allergic encephalomyelitis (r-EAE)

During chronic relapsing experimental allergic encephalomyelitis (r-EAE) in guinea pigs, serum IgM and IgG concentrations increased markedly early in disease. Serum IgM and IgG increased similarly in control animals immunized with Freund's incomplete adjuvant (FIA) and Mycobacterium tuberculosis (MT). In the chronic phase of r-EAE but not in control animals, elevated IgM was also found in central nervous system (CNS) extracts, suggesting intrathecal IgM synthesis. IgG antibodies against myelin and myelin basic protein (MBP) were regularly detected in r-EAE sera from day 21 post inoculation (p.i.), reaching maximum levels in the early chronic phase. IgG antibodies against galactocerebroside (GC) and galactose appeared in some r-EAE sera. Oligoclonal IgG bands were demonstrated in all r-EAE guinea pig sera 21-26 days p.i. The bands in serum decreased in number and strength in the chronic phase. They could be traced to antibodies against MT in 4 of 10 animals, but not to antibodies against myelin, MBP, GC or galactose. Oligoclonal IgG bands were also regularly visualized in r-EAE CNS 124 days p.i., suggesting persistent intrathecal IgG synthesis. They varied in number and migration between different regions of individual CNS. Oligoclonal CNS IgG was related to antibodies against MT in only one of 7 animals, and in no case to antibodies against myelin.     

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.     

Histochemical fibre-type profile in the human masseter muscle

A histochemical characterization of the masseter muscle was performed on biopsy samples of dentate subjects with normal occlusion. There was a continuum of ranges of oxidative and glycolytic capacities of the masseter muscle fibres. Besides the lightly-stained type I and the darkly-stained type II fibres, fibres with intermediate staining reactions for standard ATPase at pH 9.4, IM fibres, were seen in all biopsy samples. IM fibres had some staining characteristics in common with type I, i.e. the reaction for NADH-TR and for ATPase after preincubation at pH 4.6 and 4.2. Like type II fibres they showed strong reaction for menadione-linked alpha-glycerophosphate dehydrogenase and for phosphorylase. The ATPase reaction after preincubation at pH 4.6 did not generally reveal subtypes of type II. It is concluded that the masseter muscle in normal human subjects has a very special fibre composition, with ATPase-IM fibres being a part of the normal fibre population.     

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.     

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.     

Hereditary optic atrophy with probable association with a specific HLA haplotype.

A family with hereditary optic atrophy in 4 members of 3 generations is described. The clinical findings differ from those previously observed in hereditary optic atrophy and in Leber's disease, indicating that the hereditary optic atrophy described in this report represents a new disease entity, which is inherited in an autosomal, dominant way with incomplete penetrance. Analyses of the cerebrospinal fluid and serum did not reveal signs of immunoglobulin synthesis within the central nervous system, i.e. findings encountered in a considerable proportion of patients with optic neuritis. An association was found between the family members affected by the disease and the major histocompatibility system haplotype A2 B8. A linkage thus occurred between the disease and the HLA region on human chromosome No. 6.     

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.     

Sexuality in a 70-year-old urban population

Aspects of sexuality in 70-yr-old men and women were investigated as part of a population study in Gothenburg, Sweden. Seventy-six out of 166 men (46%), and 36 out of 266 women (16%) reported that they still had sexual intercourse. For married men the corresponding figure was 66 out of 128 (52%), and for married women 33 out of 91 (36%). The associations between continued sexual intercourse and marital factors, sexual factors, physical health, personality, mental health and some environmental factors were studied in married subjects and the results were as follows. Men who continued to have sexual intercourse had seldom suffered early parental death, seldom woke up during the night, had better mental health according to a global rating, and had a more positive attitude towards sexual activity among the aged. Women who continued to have sexual intercourse had comparatively young husbands, had no increase in emotional lability during recent years, had low levels of anxiety, had better mental health according to a global rating, had a general feeling of being healthy, judged their marriage to be happy and had positive experience of sexual intercourse and a positive attitude towards sexual activity among the aged.     

Weekly monitoring of dexamethasone suppression response in depression: its relationship to change of body weight and psychopathology

Weekly dexamethasone suppression tests (DST) were performed in 19 hospitalized patients with major depressive disorder, endogenous subtype, and who had an abnormal DST at admission. Depression scores (Hamilton Rating Scale) and weight changes were collected by investigators who were blind to the test results. Major findings were: (1) the DST gradually normalized 3-4 weeks prior to full resolution of clinical symptomatology; (2) weight loss was an important patient variable which may have contributed to false positive DST results; however, the positive correlation between changes in DST results and changes in depression scores in all our patients with or without weight loss suggests that psychopathological factors other than weight change participate in the development of dexamethasone resistance in depression; (3) the low dose (1 mg) version of the test requires careful control of minor medical disturbances, which can make the test result ambiguous. The data suggest that after resolution of some methodological issues the DST may serve as a valuable laboratory test to monitor clinical progress during drug treatment.     

A new type of hereditary distal myopathy with characteristic sarcoplasmic bodies and intermediate (skeletin) filaments

A family with a hitherto unrecognized type of distal myopathy is described. The disorder appears to be of late onset and to be inherited through a dominant autosome. It has a more malignant course than the distal myopathies described earlier, from which it can be differentiated clinically by an early involvement of thenar muscles and hand flexors. The key to the correct diagnosis is provided by the morphological and immunohistological investigation of muscle biopsies, which show typical sarcoplasmic bodies and an abundance of intermediate-sized (skeletin) filaments.     

ACTH and multisteroid responses to corticotropin-releasing factor in depressive illness: relationship to multisteroid responses after ACTH stimulation and dexamethasone suppression

One hundred micrograms of ovine-corticotropin releasing factor (o-CRF) was administered intravenously to eight unmedicated patients with severe endogenous depression. Responses of immunoreactive (ir)-ACTH and the adrenal glucocorticosteroids corticosterone (B), 11-deoxycortisol (S), cortisol (F) and cortisone (E) were measured and compared with those following synthetic corticotropin stimulation and dexamethasone suppression. A comparative evaluation of the three pituitary--adrenal function tests suggests that hypersecretion of ir-ACTH and adrenal corticosteroids (B, S, F, and E) in depression reflects a central dysfunction rather than an altered responsiveness of the pituitary or adrenal glands. The data illustrate that the o-CRF paradigm is a valuable instrument to further support the hypothesis that a limbic--hypothalamic overdrive is the basic mechanism underlying exaggerated adrenocortical output in the endogenous subgroup of depressed patients.