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Several pedigrees of which some members showed a clinical syndrome consisting of mental changes, choreatic involuntary movements, limb muscles atrophy, and acanthocytosis have been reported in the United States and the United Kingdom. Such a case and some of the family members who had such abnormalities as acanthocytosis, hypo-beta-lipoproteinemia, convulsions, and confusion was observed. Results of biochemical analysis of catecholamines and their metabolites in CSF and urine showed an elevated value of norepinephrine in CSF and increased urinary secretion of DOPAC. The authors propose to designate this syndrome an amyotrophic chorea with acanthocytosis.

The authors studied the distribution of met-enkephalin, α-endorphin, β-endorphin and LHRH within the central nervous system of rats by the indirect immunofluorescent technique, and observed α-endorphin-like immuoreactivity in the median eminence adjoining the portal vein as nerve terminals of dot-like immunofluorescence. This finding deserves special attention since α-endorphin has been considered physiologically inactive. Nerve terminals of α-endorphin-, β-endorphin- and met-enkephalin-like immunoreactivities were immunohistochemically confirmed in the medial hypothalamus. These results positively suggested that this area was playing comprehensive roles in physiological functions of the hypothalamo-pituitary system.To visualize neuropeptide-containing nerve cell bodies, we applied the immunofluorescent technique on various neuropeptides to intraventricularly colchicine injected rats. Some LHRH and met-enkephalin containing nerve cell bodies were observed without colchicine, though. All of substance P-, LHRH- and met-nekephalin-positive nerve cell bodies were visualized in the ventromedial hypothalamic nucleus, substance P- and β-endorphin positive nerve cell bodies in the arcuate nucleus, substance P-positive ones in the posterior hypothalamic nucleus and met-enkephalin-positive ones in the dorsomedial hypothalamic nucleus. Besides, substance P-containing and metenkephalin-containing nerve cell bodies were coexisting in the mesencephalic central gray matter. α-Endorphin-containing nerve cell bodies were also noticed in the caudate nucleus.In addition, calcitonin-like immunoreactive cell bodies were observed in the anterior lobe of the pituitary body.

We performed light and electron microscopic autoradiography of GABA and opiate receptors using 3H-muscimol and 3H-DAMA.Light microscopically, distribution of muscimol and DAMA binding sites was demonstrated by means of Texture Analysing System (Leitz).For electron microscopic autoradiography, selection of development method is important. The authors obtained silver grains in a pattern precisely localized to the cytoplasmic membrane, i.e, the receptor site by means of EAA development.We observed 3H-muscimol binding site in the neuropiles of the cerebellar molecular layer and the substantia nigra ultrastructurally. Receptor sites labeled with silver grains were located not only on the synaptic regions but also on the plasma membranes of the dendrites and axons not corresponding to synaptic sites. 3H-DAMA binding sites in the caudate nucleus and the amygdaloid nucleus were noted on the plasma membranes of the axons, dendrites and nerve cell somas, some corresponding to synapses, others not. Autoradiographical observation of neurotransmitter receptors has still problems to be solved. Nevertheless, this technique is very important to observe the morphological relationship between transmitters and their receptor sites.

The binding properties of the calcium channel antagonist, [3H]nitrendipine, were investigated in homogenates of the rat cerebral cortex, heart and ileum. The specific component of [3H]nitrendipine binding was consistent with mass-action behavior and was characterized by a high affinity dissociation constant in the range of 0.1-0.3 nM. A variety of other calcium channel antagonists inhibited the binding of [3H]nitrendipine with Ki's that agree generally with the ability of these drugs to block contractions of cardiac and smooth muscle. The inhibition of [3H]nitrendipine binding by other dihydropyridines was consistent with competitive antagonism whereas the inhibition caused by verapamil and D600 resembled negative heterotropic cooperativity. Consistent with this latter postulate was the observation that the kinetics of [3H]nitrendipine binding are altered by verapamil, with both the association rate and the dissociation rate being increased. La+3 and several divalent cations caused an inhibition of [3H]nitrendipine with the rank order of potency being Cd+2 greater than La+3 greater than Ni+2 greater than Co+2 = Mn+2 greater than Mg+2 = Ba+2 greater than Ca+2.

The authors observed substance P-, somatostatin- and β-endorphin-like immunoreactivities ultrastructurally in the perikarya of the primary sensory ganglion cells by means of Nakane's enzyme-labeled antibody technique. As the results, the immunoreactivities of the neuropeptides were observed as irregularly shaped masses always encapsulated with membrane-bound contours of which diameters were 200nm to 2μm. Such neuropeptide-containing immunoreactive masses encapsulated by the membrane were usually seen in the vicinity of the Golgi apparatus. These immunoreactivities of the neuropeptides were more often observed in smaller nerve cells, though they were sometimes observed in the larger ones, too.The authors also observed substance P- and somatostatin-like immunoreactivities in the Rexed's lamina II in the posterior horn of the spinal cord as nerve terminals. Substance P- and somatostatin-containing nerve terminals were often stained diffusely by positive immunoreactivity and within them there were denser immunoreactive vesicles uniform in size. These electron dense vesicles with positive immunoreactivity were noted along the nerve axon to the terminal.

The authors radioimmunoassayed cyclic nucleotide concentrations in plasma and biopsied muscles of muscular dystrophy and muscles of chicken embryo. c-AMP concentrations in plasma were significantly lowered in Duchenne-type muscular dystrophy and this lowered degree was correlated with the stage of progression. Plasma c-GMP levels were also depressed in Duchenne-type dystrophy. In biopsied muscles, c-AMP concentrations per milligram of non-collagen protein were within normal limits. Therefore, the decrease of plasma c-AMP concentrations might be an expression of total metabolic changes rather than a pathologic process of the muscle itself. As for the dystrophic chicken embryo, both c-AMP and GMP concentrations were decreasing in the pectoral muscles in parallel with the advancement of hatching stages.

The binding properties of the calcium antagonist, [3H]nitrendipine, were investigated in homogenates of the rat cerebral cortex and myocardium. The specific component of [3H]nitrendipine binding was consistent with mass action behavior and was described by a high affinity dissociation constant in the range of 0.1 – 0.3 nM. [3H]nitrendipine binding was sensitive to inhibition by other calcium antagonists and by the cations Ca+2 and La+3. The inhibition of [3H]nitrendipine binding by verapamil was not of the simple competitive type but resembled allosteric inhibition, suggesting that there are at least two binding sites for calcium antagonists.

Genetic studies were made in 120 males and 92 females of 408 constituents of 22 pedigrees of familial amyloid polyneuropathy (FAP) originated from Ogawa Village area, Japan. The results were as follows. 1) The ages at the onset ranged from 20 to 68, and the mean age was 35.38 in males and 37.88 in females. 2) The cumulative morbid risk ratio was high as 0.8 and above. 3) The penetrance was very high,i.e. 100% when calculated from parents' side and 99.29% from children's side. No skipping of generations was noticed except a case in which the determination of “affected” or “non affected” was impossible. 4) The segregation ratios were 34.67±27.50% as calculated by a single selection and 45.80±2.86% by a complete selection. 5) The transmission mode of FAP originated from Ogawa Village, Japan was autosomaly dominant.

Nakane's enzyme-labeled antibody technique revealed that cells containing neurotensin-like immunoreactivity were widely distributed in the anterior lobe of the pituitary body. Immunohistochemical studies on serial sections showed that a part of neurotensin positive anterior lobe cells contained beta-endorphin-like peptide simultaneously. The results show that beta-endorphin and neurotensin occur together in certain pituitary cells and this is an evidence of coexistence of more than one peptide within one anterior pituitary cell.

A newly discovered large concentration of familial amyloid polyneuropathy (FAP) in Japan is clinically outlined. The importance of the urinary secretion of IgA in these cases is stressed. Dimethyl sulfoxide administration to these patients induced clinical improvements accompanied by increased excretion of low molecular weight proteins. Amino acid composition of amyloid protein of the Ogawa village-type FAP cases was similar to that of primary amyloidosis.

DMSO was therapeutically administered to patients with FAP and in about half of the patients there was some clinical improvement. Urinary proteins were analyzed biochemically and immunochemically before and after DMSO administration in seven cases of amyloidosis. As the results, increased excretion of various proteins of different molecular weights in the urine was observed depending on cases and examined organs. The in vitro effects of DMSO on amyloid proteins were examined. DMSO-degraded amyloid proteins showed void-volume materials and lower molecular weight components on Sephadex G column elution profiles as did guanidine-degraded amyloid protein. Among various denaturating or reducing agents, DMSO is the least potent in dissolving amyloid fibrils into prealbumin-related proteins.

Thyrotropin releasing hormone (TRH) directly influences central nervous system (CNS) function, independent of its pituitary action. Although these CNS effects have been behaviorally characterized, information is not yet available on the precise regional distribution of its receptor. TRH receptor binding was examined in the monkey CNS by the radioreceptor assay for clarifying the site of TRH action. TRH was bound to brain tissue membranes via high-affinity (Kd = 5.9 × 10−9M) and low-affinity (Kd = 11.2 × 10−8M) components. TRH receptor binding varied dramatically throughout the monkey brain, with more than a 40-fold variation. The limbic system contained the greatest amount of binding. The next highest areas were the cerebral cortex, hypothalamus, interpeduncular nucleus and periaqueductal gray matter of the midbrain. Receptor binding was very low or not detectable in the medial thalamus, cerebellum, brain stem, spinal cord and white matter. These data suggest that TRH has an effect on the CNS via limbic system, cerebral cortex and midbrain.

These days, much progress has been achieved on biochemical studies of amyloidogenesis and the relationship between clinical types and amyloid-proteins has been well documented.

Ca ion channel antagonists have been attracting much attention as therapeutic drugs for cardiovascular disorders such as angina pectoris and hypertension, especially from the viewpoint of pharmacological mechanism. Recently, through Ehlert and Itoga’s experiments, the Ca ion channel antagonist was confirmed to bind specifically, not only to vascular smooth muscle but also to gastrointestinal smooth muscle and even to the neuron itself (1). This broke new ground in the study of the pharmacological action of Ca ion channel antagonists.

Some of the calcium antagonists with diverse structures are considered to specifically block voltage dependant calcium ion channels of excitatory membranes. Each drug acts on a specific site of the calcium ion channel. Receptor binding experiments with use of tritiated Ca antagonist make it possible to examine the functional sites of these drugs. In this paper, we performed binding experiments and autoradiographic studies Ca ion channel antagonist binding sites using tritiated nitrendipine(NTD) in the rat brain. Brain P2 fraction was prepared, and saturation analysis and kinetic studies at the temperature of 0°C, 25°C and 37°C were performed. In addition, competitive studies by various Ca antagonists were done. The in vitro autoradiographic study was done as follows: After cryostat sections of the rat brain were incubated with 2nM 3H-NTD, a tritium sensitive film was apposed on the slides in the dark and stored for 4 weeks at 4°C. As control, experiments were done with sections to which 10#x2212;5 M nifedipine was added at the same time. As preliminary experiments of autoradiography, saturation analysis on cryostat sections at 0°C was done, with results showing a Kd value of 60pM. Autoradiographic studies of 3H-NTD revealed that specific binding sites were diffusely distributed in the neuronal elements with dominancy in the superior colliculus, hippocampus and interpeduncular nucleus.