The cerebellum comprises two major portions, the cerebellar cortex and the cerebellar nuclei, the latter being conventionally given various terms (deep nuclei, central nuclei or intracerebellar nuclei). A number of anatomists have been making particular efforts to analyze the unique structure of the cerebellar cortex by means of classical histological techniques and by electron microscopy. Extensive physiological invetigations have also greatly contributed to elucidating the neuronal functions of the cerebellar cortex and provided an effective model to reveal the basic mechanisms of the brain function. Ito and his collaborators made an epochmaking discovery that the Purkinje cell in the cerebellar cortex is inhibitory in nature. This has become a breakthrough against the stalemated studies on the cerebellar anatomy and has drawn our attention to the significance of the excitatory input to cells of the cerebellar nuclei, which are under inhibitory control by the Purkinje cells. Our anatomical studies have been devoted to elucidating the origin of the excitatory afferents and analyzing the neuronal organization of the cerebellar nuclei. In this article recent advances have been reviewed primarily from the anatomical aspects.
Projections to the cerebellar nuclei from the inferior olive, the lateral reticular nucleus and the spinal cord were established by experimental anatomical methods at the light and partly at the electron microscope levels. Additional projections have been reported to originate from the red nucleus, external cuneate nucleus and vestibular organ. Correspondingly, Golgi observations show that there is a terminal pattern specific to the afferents of extrinsic origin in the cerebellar nuclei. These fibers issue many coilaterals passing through the nuclei whereas the Purkinje cell axons terminate within a confined area with dense ramifications. Electron microscope studies by Chan-Palay suggest that the terminals of Purkinje cell axons have elliptical synaptic vesicles and make axosomatic synapses while those of extrinsic origin have round vesicles, making axodendritic synapses.
Two types of neuronal element were identified in the nuclei, one is a large projection neuron and the other a small interneuron. The axon of the former type gives off recurrent collaterals, with which interneurons are connected. The interneurons project, in turn, onto the projection neurons and the other interneurons, presumably to establish a negative feedback circuit.
At present it seems premature to systematize our knowledge since all the information available is still incomplete in many respects. For example, the origin of the excitatory afferents to the cerebellar nuclei is not fully disclosed, and the identification of axon terminals is not yet verified experimentally. However, it is expected that many difficulties will be surmounted by the recent technical innovations in the field of neuroanatomy, the methods which take advantage of anterograde and retrograde axonal transport.

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Recently, increasing evidence points to the inhibitory effect of dextran sulfate (abbreviated to DS) on the fibrosis of experimental animals. However, the literature dealing with the exact mechanism responsible for this phenomenon is scarce. The aim of the present study was to obtain further information on this problem.
In the first experiment, the author has evaluated the inhibitory effect of DS on granulation tissue by measuring its effect upon collagen elaboration in a subcutaneously implanted polyvinyl formal sponge (PVF) in rats. The groups which received intraperitoneal injections of DS for 2 weeks showed a decrease in tissue ingrowth and collagen formation in the PVF sponge implants as compared to controls.
Following this study, to evaluate the influence of DS on the formation of pneumoconiosis of rats by the intratracheal injection of a suspended selite solution or fiberous tissue formation in the lung of rabbits induced by the serial i. v. injection of bleomycine, comparative studies between the treated and control groups were made histochemically. From the results of these experiments, it can be shown that the formation of collagen in the lungs of experimental animals was markedly inhibited by the i. p. or i. v. injection of DS.
To obtain further information about the effect of DS on the collagen synthesis of fibroblasts, the following experiments were performed on monolayer and suspension cultures of chick embryo fibroblasts. The addition of DS in concentrations from 10 to 1000 μg/ml to the medium of fibroblasts cultures causes a reduction in cell numbers. It was also shown that the incorporation of ³H-deoxyadenosine into DNA synthesized by fibroblast cultures is depressed by the addition of DS.
To clarify the lysosomal enzymatic response of cultured fibroblasts to DS treatment, the following histochemical and fluorescencemicroscopic studies were perfomed. When fluorescencemicroscopy is used, the increased lysosomal granules in cultured fibroblasts were demonstrated one hour after the addition of DS. The increased acid phosphatase activities in cultured fibroblasts under treatment with DS was also histochemically demonstrated. Biochemical studies on acid phosphatase and cathepsin D activities show that these enzyme activities were significantly increased at 1 hour after the DS treatment, and then returned to the pretreatment level within 2 hours. The histochemical and biochemical results support the possibilities that the collagenolytic enzyme activity of lysosomal origin may be also induced by DS treatment. From the investigation of the effect of DS on the collagen synthesis of fibroblasts in tissue culture, it was shown that collagen synthesis during DS treatment is significantly inhibited. From the results obtained it can be concluded that inhibition of fibrogenesis in in vivo and in vitro experiments caused by DS can be explained by a reduction in DNA synthesis or by a depression of collagen synthesis. In addition, the increased activity of the lysosomal enzyme induced by DS treatment may also play a role in depression of the intracellular metabolism of fibroblasts.

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In order to elucidate the functional significance of the spike and wave produced by electrical stimulation of VA and RET, electrophysiological study was carried out in rabbits and the following results were obtained.
1. On the arousal reaction, evoked muscular discharge of the fore and hind limbs, recruiting response, spike and wave caused by RET stimulation, barbiturate and chlorpromazine showed an inhibitory effect, cardiazol a facilitatory effect and morphine an intermediate effect of the two.
2. On the evoked muscular discharge observed in the fore and hind limbs by the stimulation of the cerebral cortex or hippocampus, all of the simultaneous stimulations at 3Hz,8Hz and 100Hz of RET showed an inhibitory effect, while in the case of VA, some showed a facilitatory effect, though some showed an inhibitory effect.
3. A parallelism was noted between the drug action on the effect of stimulation of VA and RET on the evoked muscular discharge produced by the stimulation of the cerebral cortex or hippocampus and that on the spike and wave.
4. In the experiment of the effect of stimulation at 3Hz on the average evoked potential noted in the cerebral cortex and brain stem reticular formation by the sciatic nerve stimulation, VA stimulation showed an inhibitory effect and RET stimulation a facilitatory effect on the early components of N₁and N₂.
5. On the H wave and M wave observed in the m. gastrocnemius tibialis by the tibial nerve stimulation, VA stimulation showed an inhibitory effect, but RET stimulation showed a facilitatory effect. On the nociceptive evoked muscular discharge observed in the tibialis anterior muscle by the tibial nerve stimulation, however, both VA and RET stimulations showed an inhibitory effect.
6. On the intestinal movement, VA stimulation at all frequencies of 3Hz,8Hz and 100Hz showed an inhibitory effect, while RET stimulation at 100Hz showed an inhibitory effect, though the stimulation at 3Hz showed a facilitatory effect.
It was concluded from the results obtained in the present study that the inhibitory effect from RET is shown on the efferent pathway, while that from VA is shown on the afferent pathway, proprioceptive reflex and intestinal movement and that which is involved in the manifestation of petit mal is VA.

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The autonomic nerve fibers distributed in the walls of blood vessels maintain an adequate blood distribution and supply to the whole body. The growth of malignant tumors is also considered to be influenced by the degree of tumor vasculature, including nerve fiber distribution. When the tumor growth lacks adrenergic innervation, then it is assumed that such a state enhances the tumor growth. It is of great value to determine the relationship between tumor vasculature and the degree of innervation in order that the appropriate chemotherapy and angiography can be utilized and applied to patients with cancer.
To our knowledge, the work reported here is the first designed to determine whether or not there actually is an adrenergic innervation involved in tumor vasculature.
The tumors used in these experiments were Walker Carcinosarcoma 256, Yoshida sarcoma, AH 130, NG-induced stomach cancer and DMBA-induced mammary cancer in rats, and Sarcoma 180, Myeloma (MOPC 104 Tumor) in mice. Stomach, mammary and rectal cancer as well as Wilmus tumor were also examined as clinical materials. The fluorescent histochemical technique of Falck was employed for the detection of noradrenergic fluorescemce. For detection of the nerve endings along the tumor vasculature, Seto's modification of Bielschowskys' silver impregnation method was used. For the histochemical technique of determining monoamine oxidase activity and the chemical assay of catecholamine, Anton's method was employed.
The vasculature in the transplants of each tumor was demonstrated to be sinusoidal vessels in which noradrenergic fluorescence was absent. In the adjacent areas, however, where invasion of the tumor had not occurred, fluorescent fibers were demonstrated in the blood vessels. Catecholamines were not detected in the tumor tissues; and the nerve component around the tumor vasculature was absent. Thus it was evident that the adrenergic innervation in the sinusoidal vessels of experimental transplantable tumor, NGinduced stomach cancer and DMBA-induced mammary cancer is lacking. In the study of actual clinical cases, noradrenergic fluorescence in the vessels of stomach, rectal and mammary cancer tumors could not be demonstrated. Noradrenaline fluorescence tended to disappear in the normal appearing vasculature of the invaded area in cases of infiltration by NG-induced stomach cancer. MAO activities in both experimental and clinical tumors showed no clear cut tendency. The absence of vascular smooth muscle, the effector apparatus of adrenergic vasoconstriction may explain the lack of adrenergic innervation of the sinusoidal vasculatures. The results seen with the MAO activities cannot, however, explain the disappearance of adrenergic innervation of the vasculature of the invading tissue. Nerve destruction as a result of the tumor invasion has to be considered here.
Further studies are in progress concerning the lack of adrenergic innervation in the blood vessels in tumors.

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In 1957 congenitally diabetic KK strain mice were found and they have been experimentally used in perusing the nature and pathogenesis of diabetes mellitus and diabetic retinopathy. Many biochemical and histological studies on various organs of this mice have been reported. But as to the eye pathology, no typical diabetic retinopathy such as microaneurysms, bleeding and exudates often seen in human diabetes has ever been seen, though there have been a few papers reporting subclinical retinal angiopathy using a trypsin digestion method and electron-microscope. From the electro-physiological standpoint none of study has ever been reported on this mice.
On the other hand, it is a well known fact that even at the earliest stage of human diabetic retinopathy, electroretinograms especially their oscillatory potentials are frequently deteriorated characteristically. So it seems worthy to study the KK mice eyes electroretinographically.
This study was designed first to observe ERGs of untreated KK mice comparing with those of nondiabetic DDY mice, and second to study how diabetogenic influence of ovine growth hormene administration could be manifested in KK mice ERGs and in DDY mice ERGs and if there were any difference in susceptibility to the growth hormone between the two strains:

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In this communication, the authors have reported the calculation procedure of autocorrelation coefficients and power spectra in studying electroencephalogram, and its application to a clinical experiment on electrophysiological effects induced by so-called vasodilators on the market. ATAC 501-20 and FACOM 230-30 were used for on-line and off-line processings of EEG recorded on magnetic tape. In the latter case, the authors have adopted the flow chart published by Southworth and the continuous sliding method prepared for this experiment.
150mg of Cyclandelate and 15mg of 8-isoxsuprine hydrochloride, having been diluted with 20% glucose solution up to 20cc, were intravenously administered over four minutes in six subjects; two normal volunteers, two arteriosclerotic and two unilaterally brain damaged patients. A control experiment was also made in the same subjects using placebo solution before the drug experiment. Vital signs such as blood pressure, body temperature, pulse and respiration rate were continuously monitored and automatically plotted by CMS 100. EEG were derived from central and occipital regions in the first four subjects while from frontal or temporal regions in the other two patients with localized damages by surgical operation, Neither in frequency nor in power of the predominant rhythm, any significant change was found even after the administrations of two vasodilators. It was however noted that by Cyclandelate the abnormally increased power decreased at the damaged regions and it became almost equal to that of corresponding regions in the intact hemisphere in the two patients with brain damage (.10>P>.05), and that by Isoxsuprine the proportion of power of predominant rhythm to that of back ground activity augmented in the majority of studied cases (.10>P>.05). According to Stosseck, ganglion cell metabolism is of greater importance than blood flow to cerebral functions mainly because the brain cortex possesses a large functional reserve which protects it even when its oxygen supply fluctuates to extremes. In the present study, the authors have convinced the presence of a protective mechanism such as Stosseck presumed. On the other hand, the authors noted the differences in power between intact and damaged regions and also their improvement by the administration of Cyclandelate. It must be an expression of circulatory improvement as well as functional and metabolic improvements at the damaged region in the brain cortex.
Vital signs plotted on chart clearly presented the differences between two substances studied. Cycladelate provoked nothing particular either subjectively or objectively, while Isoxsuprine produced reddened, heat and heavy sensations lasting 2 to 12 hours subjectively and significant increases of pulse rate and pressure without exception objectively. It indicates that Cyclandelate works at muscular tissue of arterial wall and Isoxsuprine at α- and β- receptors in the wall. The authors have accordingly been impressed that Isoxsuprine would produce vasodilation of extracerebral arteries more intensively than that of intracerebral ones.

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Effects of the low temperature and of the electrical square wave stimulation on spontaneous contractions of isolated guinea-pig atria and the influence of thiamine tetrahydrofurfuryldisulfide (TTFD) on these effects were investigated and the following results were obtained:
1) Atrial spontaneous contractions were arrested within 15 minutes by the change of temperature in the medium from 30 to 20°C. When TTFD was added to the medium at concentrations higher than 10^-5g/ml one hour before the temperature change, the contractions were not arrested even at 30 minutes after the change of the temperature.
2) The arrhythmic contractions were induced on the rhythmic contractions of isolated atria by the electrical square wave stimulation given at a duration of 5 msec., at 120 cycles per minute, and at several critical intensities. When TTFD was added to the medium at concentration of 10^-4g/ml one hour before the stimulation, the critical intensity to induce the arrhythmic contractions was increased by the presence of the drug.
3) The influences of TTFD on the responses of atrial tissue against these two kinds of extrinsic physical stimulations were seen even at 30 minutes after the drug was washed out from the bath fluid, when the isolated atria had been pre-incubated with the drug at the same concentration for one hour before the temperature change of the medium or the stimulation by the electrical square wave.
From these results, it was assumed that TTFD might reveal these effects through the stabilization of the tissue membrane.

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Lipofuscin of the neurones of the rat brain was studied by the autofluorescent method. The validity and specificity of the autofluorescent method for lipofuscin were investigated in the present studies. In comparison to the ordinary histochemical methods, the autofluorescent method for lipofuscin was advantageous for investigating the fine distribution of pigment in the cytoplasm of the neurones, because the bright, yellowish gold autofluorescence was easy to recognize against the dark background. Autofluorescent granules were distributed mainly in the cytoplam of the neurones and neuropil. In the neurones, the types of distribution of the lipofuscin are classified as follows: 1) a coarse granular distribution with clump formation near the nucleus (clump type); 2) a fine granular structure, distributed diffusely in the cytoplasm (diffuse); 3) intermediate type of the 1) and 2). In young and infant rats, lipofuscin is distributed diffusely in the cytoplam in fine granules. As the ageing process advances, the clump type of lipofuscin distribution is more and more frequently noted.
The autofluorescent granules were first seen in the neuropil, particularly in the neurophil existing in the surroundings of the spinal cord, in the 1-month old rats. The granules appeared in an indefinite and variable form having a variety of different sizes and, being very fine, developed a green-yellow autofluorescence. In the 3-months old rats, lipofuscin was noted as fine granules having an orange-yellow fluorescence in the cytoplasm of the anterior column, which was diffused but not yet clumping. In this stage, lipofuscin was rarely found in the dorsal root of ganglion or in the thalamus, and, if found, was not in the cytoplasm. In the 6-month old animals, lipofuscin granules increased in number and were found in the neurones of the cerebral cortex, hippocampus, caudate nucleus, thalamus, brain stem and spinal cord.
In the animals 12-months old, lipofuscin accumulation was much more advanced and distributed densely in the cytoplams of the neurones of the cerebral cortex, hippocampus, basal ganglia, thalamus, brain stem and spinal cord. Dorsal ganglia also showed a marked lipofuscin content in the cytoplasms of the neurones. The distribution of the lipofuscin in the fluorescent studies corresponded well to the findings of the ordinary histochemical methods, such as the PAS and Sudan III stainings.
The decrease of the lipofuscin content in the neurones of the spinal cord, cerebral cortex, cerebellar cortex and dorsal ganglia in the centrophenoxine administered rats was well demonstrated by the present fluo rescent methods.
The validity and specificity of the autofluorescent method for lipofuscin were discussed briefly in the present paper.

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The ultrastructure of lipofuscin in rat brain was investigated electromicroscopically in the present studies. Lipofuscin structures of various regions of the brains of young and old animals were studied. According to the aging process, lipofuscin structures varied remarkably, i. e. from small, round or oval, lysosomal structure with fine dense granules to more complicated structures, characterized by an internal lamellar or granular structure with or without vacuoles. Electromicroscopically, lipofuscin first appeared in one-month-old rats in the neurons of the cerebral cortex, spinal cord and thalamus. Lipofuscin in this stage was characterized by small, oval and homogeneous structures with fine granules. However, even in young animals (three month old rats), lipofuscin in the cerebral cortical neurons was exceptionally irregular in its shape and contained remarkably large vacuoles in its structure.
In aged rats, topograhphpical differences of the lipofuscin structures were more remarkable. In the neurons of the cerebral cortex, lipofuscin was large and irregular in shape, containing many coarse granules. Large and irregularly shaped vacuoles were also noted. On the other hand, lipofuscin in the thalamus appeared homogeneous with fine granules. Few vacuolar structures were found in these cells. Intermediate types of the lipofuscin were noted in the neurons of the cerebellar cortex and ventral horn of the spinal cord. Essentially, lipofuscin of these regions was similar to that of the cerebral cortex, although vacuoles of the lipofuscin structures appeared more small and showed oval or round contours in these areas. Neurons of the dorsal ganglia contained a characteristic type of lipofuscin, i. e. invariably oval or round in shape and contained one or two relatively large vacuoles. Lamellar structures were occasionally found in the dense portions of the lipofuscin. The dense and vacuolated bodies of the lipofuscin types were also noted in the perikarya of the satellite cells of the dorsal ganglia.
In the animals treated with centrophenoxine, the most remarkable findings of the lipofuscin changes were noted in the neurons and satellite cells of the dorsal ganglia.
Although a decrease in the amount of lipofuscin was not well demonstrated in the present experiments, the size of the vacuoles of the lipofuscin became remarkably large in the neurones, and the vacuolization of the dense bodies was noted in the satellite cells of the dorsal ganglia. The present findings of the lipofuscin changes induced by centrophenoxine administration corresponded well to the reduction of the lipofuscin pigment as demonstrated in the light and fluorescent microscopic investigations by Tani (1975).

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In his previous paper the author reported the result of an electron microscopic study on morphological changes of the hyalocytes caused by photocoagulation. On the 3 rd-5 th day after mild photocoagulation the hyalocytes increased in number and numerous cytoplasmic granules appeared in the cytoplasm of the hyalocytes. The author suggested that these numerous cytoplasmic glanules might be mucopolysaccharide granules and products of hyalocytes. In the present study an attempt was made to identify the nature of cytoplasmic granules by histochemical procedure. Eyes of Albino rabbits were photoco agulated using xenon-arc photo coagulator and were enucleated 1 - 5 days after coagulation. Histologic sections were made and HE, PAS-, PAS-alcian blue, Toluidin blue-, Cresyl violet-, Sudan III-, Sudan black B stain was performed. From the result obtained by the histochemical study, the author presume that the cytoplasmic granules in hyalocytes are precursory substance of hyaluronic acid which includes mainly neutral-mucopolysacchride or glucoprotein, and partially glycogen or lipoprotein.

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