It is reported that GABA (γ-amino butyric acid) & GABOB (γ-amino β-hydroxy butyric acid)have an inhibitory action to the central nervous system. Recently, S-GABA (γ-amino β-sulfonyl butyric acid) & P-GABA (γ-amino β-phenyl butyric acid)have been composed from GABOB, and reported that they also have an inhibitoryaction to the convulsive seizure. In the experiments in dogs, P-GABA, S-GABA & GABOB solutions were applied on the cerebral at rest and after discharge caused by electrical stimulation of motor cortex were recorded to examine the anti-convulsive action of these solutions. In the experiments in cats, cortical evoked potentials caused by electrical stimulation of thalamus were recorded to examine the action of GABOB by mearns of computer technique. Furthermore, the application of GABOB & S-GABA solution on the epileptogenic cortical focus of human epileptic was performed and the corticogram was recorded with reference to spikes and after-discharges to examine the anti-convulsive actions of these solutions. The results are following: 1) Application of S-GABA solution on the cerebral cortex caused low voltage activity and spiking activity in corticogram. 2) P-GABA caused spiking activity, developing to the generalized convulsive seizure pattern. 3) These spiking activity caused by S-GABA and P-GABA was inhibited by GABOB solution. 4) S-GABA did not inhibit the after discharge or spiking activity on the epileptogenic cortical focus of human epileptic. GABOB, however, showed a strong inhibitry action to after discharge & spiking activity. 5) Application of GABOB on the cerebral cortex reversed the cortical evoked potentials caused by electrical stimulation of thalamus. From these findings, it is concluded that GABOB has an inhibitory action on the cerebral cortex, but S-GABA & P-GABA have no inhibitory action.
In the experiments in the Part I, it has been clarified that GABOB has an inhibitory action to the cerebral cortex and may apply directly on the cerebral cortex without side effect. In this Part II, a clinical study has been performed on administration of GABOB into the cerebro-spinal fluid cavity. One is the application of GABOB to the intradural cavity during craniotomy of brain tumor to prevent the postoperative convulsions, and the other is the intrathecal and intraventricular administration of GABOB when postoperative convulsions occur. For the purpose of preventing the postoperative convulsions after craniotomy, 100mg of GABOB was applied on the cerebral surface during craniotomy in 293 cases of brain tumor. Except for operative deaths, a comparison of the postoperative convulsions was made between the GABOB group and the control group. 1) The occurrence of postoperative convulsions was decreased in the GABOB group. 2) In the GABOB group, the onset of postoperative convulsions was later than that of the control group. 3) Frequency of postoperative convulsions was decreased in the GABOB group, and majority of the cases showed only one seizure. 4) Administration of GABOB into the intradural cavity showed no side effect. There were 14 cases of postoperative convulsive state. Application of GABOB into the intraventricular or intrathecal cavity was effective to inhibit convulsive state in all cases without any side effect. From the these results, it is recognized that application of GABOB into the cerebro-spinal fluid cavity is most effective method to the prevention and treatment of the postoperative convulsions.
(1) Approximately 20 kinds of amino acids were found in pleural fluid or ascites of patients with malignant tumor in the terminal stage. Among those, found were increased amount of essential amino acids such as Leu, Ileu, Thr, Val, Arg and Lys, a few unidentified ninhydrin-positive spots, and a spot suggestive of β-amino-isobutyric acid. From the fact that, those are important amino acids which constitute body protein, an increased amount of the amino acids in the pleural fluid and ascites are though to indicate the leak of the inversingly destructed body proteins in the terminal stage of malignancy. (2) Pro, Glu, Lys, and Orn were increased and Met decreased in the gastric juice of patients with stomach cancer. These supposedly resulted from qualitative abnormality of glandular epiterial cells terminating to malignant proliferation. (3) Fractionation of bone marrow cells. Concertration of amino acids was increased in acute leukemia, whether lymphatic or myelogenous. Amino acids which constitute nucleas were different in acute and chronic leukemia. If these result reflect the pathogenesis of leukemia, it follows, interestingly enough, that acute and chronic leukemia have different cause.
(1) An unidentified peak found in the serum of hypoplastic anemia is thought to be L-sarcosine, L-homocitrulline or α-amino-n-butyric acid. The pattern, however, varies from case to case as shown in the data of thin-layer-chromatography. It suggests a deversity of cause or pathogenesis of this disorder. (2) A peak indicative of Asparagine, Glutamine and X (some unidentified substance) was found in the urine of hypoplastic anemia. (3) Some abnormality in amino acid was found in the mitchondrial fraction of the bone marrow aspirate of hypoplastic anemia. The result is interesting as compared with the abnormality of nuclear found in acute leukemia.
The changes of rat muscle fiber structure, fiber types and the distribution after the reunification of the nerve and cross-innervation between the nerve to M. soleus (SOL) and M. extensor digitorum longus (EDL) were cytologically studied and the following results were obtained: (1) In cross-innervation experiments, changes of the fiber types occured, namely, the white fibers distinctly appeared, in the SOL normally composed of the red and intermediate fibers, as if the SOL converted to EDL which was ordinarily consisted of three types of muscle fibers. This result was ascertained by an electron-microscopic study, and the white fibers, found in cross-innervated SOL, had the motor endplates and sarcoplasmic reticulum as in the original white muscle fibers. (2) In the reunification study of the nerve to SOL and EDL, the muscle fibers, fallen in denervation-atrophy stage, were regenerated to almost normal in constructure. The distribution of the muscle fibers, however, was changed; a tendency to be grouping a single fiber type was noticed in the muscle fibers. (3) These results suggested that the distribution of muscle fibers were greatly influenced by the peripheral nerve control.
The changes in muscle fibers after the crush injuries of the peripheral nerve were studied by using rat sciatic nerves, and the following results were obtained. (1) A parallel relationship was observed between the recovery of the muscular function and the histochemical features of the muscle fibers. (2) After severe crush injuries, a tendency to be grouping a single fiber type was observed, although that scarcely occured after slight injuries. (3) Both the muscular function and structure recovered better after crush injuries of the nerve than after the reunification.
Atrophy of rat muscle fibers by a tenotomy of the achilles tendon and a gips-fixation of the whole hind limbs were histochemically studied, and the following results were obtained. (1) Gips-fixation and tenotomy experiments, the red and intermediate muscle fibers were markedly fallen in atrophic stages. (2) After the tenotomy, denervated red and intermediate muscle fibers were scattered partially in the M. soleus. (3) By the tenotomy, the white muscle fibers kept almost normal in comparison with the red ones. (4) The atrophy of the muscle fiberss was more remarkable in the gips-fixation than in the tenotomy. This tendency was more marked in the M. soleus than the other muscles. (5) Mitochondria were more destroyed in quality than in quantity in atrophied muscle fibers.
The report describes the findings on the infectivity of DNA partially purified from SV 40 propagated in the monkey kidney cells (BSC 1) in vitro and importance of nucleic acids on their oncogenic properties, particularly induction of tumor by DNA in newborn hamsters. At 30 days post inoculation, the most remarkable changes occurred in the liver, lungs and subcutaneous tissues. Cellular responses of vascular cells were predominant when injected with DNA extracted from SV 40 viral particles, and these findings were distributed in the inter-stitial cells of the portal spaces of livers and lungs. High incidence of liver cirrhosis in primates were observed in hamsters. From the experiment the findings of oncogenic capacity of DNA has attracted a considerable attention for the approach to resolve the course of cancer from the view of the infectious DNA.
Cellular responses to DNA of SV40 virus were more accentuated by inoculation of cell free filtrates of BSC-1 cells infected with DNA than of DNA alone. Essential histologic findings induced by DNA developing viral agents were similar to the cell responses to DNA. 39 of 128 hamsters (about 30 per cent) developed tumors within about 200 days post-inoculation of these DNA developing viral particles. Sarcomas were common and they were confined to the subcutaneous area inoculated the agents. From the experiment the findings of oncogenic capacity of DNA developing viral particles has attracted a considerable attention for the approach to resolve the course of cancer from the view of the infectious DNA.
For the purpose to clarify whether the adsorption of materials on the cell surface is the necessary requirement for phagocytosis, the phagocytosis of iron colloid particles by ascites macrophage was examined. The iron colloid particles were adsorbed on the cell surface of macrophage and taken up into vacuoles in cytoplasm. By the pretreatment of macrophage with papain, bromelin or Nagarse, macrophages failed to adsorb colloid particles on their surface and decreased in their phagocytic activity. Papain pretreatment would liberate some substance (s) responsible for adsorption of iron colloid particles from cell surface of macrophage. Ca, Mg-free medium, and pretreatment with EDTA, heparin, saponin, trypsin, chymotrypsin, neuraminidase, hyaluronidase and lysozyme had no such effects. From these results it was concluded that adsorption of material on cell surface is necessary prerequisite for phagocytosis. This requisite was discussed in respect to the mechanism of recognition of “not-self” by the cell.
In acatalasemia we often encounter specific oral gangrene called Takahara's disease. With the purpose to elucidate the causative factor of this gangrene, ducks having only a trace amount of catalase in their blood or plalate tissue were used as experimental animals. Diplococcus pneumoniae (Type II) is known to generate hydrogen peroxide and contains little or no catalatic substance in itself. By suspending this Diplococcus pneumoniae in isotonic saline solution of 0.75% glucose, this suspension was in ected under the mucous membrane of the duck palate. Then histo-pathological investigations and macroscopical observations were carried out at certain intervals after the injection. The results obtained were as follows. 1) Macroscopically, 24 hours after injection there appeared whitish coat and slight reddening and swelling surrounding the coat, and 72 hours after injection gangrene resembling the one observable in acatalasemia cases appeared. 2) Experimental histopathological study showed marked changes in blood vessel wall, In contrast, pathological changes of muscles and glands were hardly observed. Now we hold such hypotheses proposed by Kaziro or Takahara that dysfunction of the so-called respiratory enzyme group or oxygen deficiency due to methemoglobin-formation are the causative factors of this disease. From these results, it is assumed that the macroscopical and histopathological changes in duck palate resembling the findings observed in acatalasemia cases were caused by the oxidative action of deposit of hydrogen peroxide generated by Diplococcus pneumoniae (Type II). The action mechanism of hydrogen peroxide is not definitively clarified from these results. But it is certain that the circulatory disturbances brought about by the marked changes in blood vessel wall, especially the wall of arteries, seem to evoke definitively oral gangrene.
As described in Part 1, by injecting Diplococcus pneumoniae which generates hydrogen peroxide under the mucous membrane of the palate of duck, there appeared pathological changes in duck palate resembling macroscopically and microscopically the findings observed in acatalasemia cases. Being without definite conclusion on the point of action mechanism of hydrogen peroxide, it was assumed that the changes in duck palate were caused by hydrogen peroxide generated by the cocci. To illustrate the point of action mechanism of hydrogen peroxide and the etiology of Takahara's disease the degradation of oxyhemoglobin and the methemoglobin-formation in culture of these cocci supplemented with duck blood, rabbit blood, acatalasemic blood or normal human blood were investigated by the following methods in each chapter.