In order to elucidate the possible influence of smell on living organisms, electrical stimulations were given on the olfactory bulb of rabbit both at high and low frequencies. Following are the effects observed.
1. The threshold of arousal reaction and muscular discharges evoked by the RF (reticular formation) stimulation were elevated significantly. The elevation was more remarkable when stimulated at low frequency.
2. The number of RF unit discharges decreased with the stimulations both at high and low frequencies.
3. The muscular discharges evoked by the stimulation on cerebral cortex were inhibited at low frequency, but at high frequency, they showed no remarkable change.
4. The effect on the muscular discharges evoked by the stimu lation on hippocampus was both facilitatory and inhibitory at either frequency.
5. The effect was facilitatory on both cortical and hippocampal average potentials evoked by the stimulation of sciatic nerve. The facilitatory effect was remarkable on the cortical evoked potentials when stimulated at high frequency, and so was it on the hippocampal evoked potentials at low frequency.
6. The effect was inhibitory on the nociceptive reflex and the M-H wave. It was prominent when stimulated at high frequency.
7. The carotid as well as the femoral blood flow was not affected remarkably.
8. The effect on the intestinal movements was facilitatory at low fr equency, whereas it was an inhibitory one when stimulated at high frequency.
9. The uterine movements were influenc ed in a facilitatory way at high frequency.
10. Barbiturate suppressed all the effects above described.
11. The several kinds of smell samples showe d different effects from each other on the intestinal movements.
12. On the potentials of amygdala evoked by the stimulation, both barbiturate and chlorpromazine showed inhibitory effect while on the contrary, both predonine and TTFD showed facilitatory effect. Morphine, ATP and CDP-choline had no significant effect.
In conclusion, we tried to make it clear using rabbits how the olfactory system can affect the living organism, and also suggested that some chemicals could be of use for the treatment of central dysosmia.

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Human αlactalbumin (LA) was isolated from fresh milk of a lactating woman, and anti-LA serum was obtained from the immunized rabbit. To detect the localization of LA in human mammary tissues, an indirect immunohistological method using this anti-LA serum has been devised. For the observation of LA, the peroxidase anti-peroxidase method was superior to the peroxidaselabelled antibody method on serial sections of the secreting mammary tissue. The immunohistological findings in paraffin section from the routinely formalin-fixed tissue were almost the same as those in paraffin section of the same, Zamboni-fixed tissue. As LA antigen was proved to be relatively stable against the routine histological method, many of clinical samples could be retrospectively applied to the present investigation.
The reaction products of the immunohistological method for LA antigen were detected in functionally active cytoplasma of the mammary parenchymal cells and on secretory materials within the mammary ductules and ducts. They revealed the following staining patterns; reticular, focal, peripheral and membrane-like. LA antigen could never be observed immunohistologically in any other sites than the mammary parenchyms in the present observations on many clinical samples including the placental tissue.
The positivity rates of LA antigen in the present materials were as follows: Resting state of adult normal mammary tissue 0/1, secreting, focally hyperplastic normal mammary glands surrounding the foci, of mammary dysplasia and carcinoma 18/18, mastitis 0/2, gynecomastia 0/2, mammary dysplasia 9/136, mammary fibroadenoma 8/66, and mammary carcinoma 10/113. LA antigen revealed mainly reticular, apical and/or lateral cytoplasmic membranelocated membrane-like staining patterns in the secreting normal mammary glands, but various staining patterns of LA antigen were observed in the malignant mammary tumors, in which the LA-positive tumor cells were spottedly detected, on the cases of mammary carcinoma, there was no definite relationship between the positivity of LA antign and the histological type and grade of differentiation of tumors, although the positivity in the cases of Tnm stage IV orof grade III differentiation appeared to be somewhat higher than the cases of earlier stages or of lesser gradings of differentiation. LA antigen was detected in the metastatic focus of mammary adenocarcinoma in the lymph nodes (1/13). Although the positivity was very low, the positive finding of LA antigen in the metastatic focus may be useful for the evaluation of primary site of malignant tumors.

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Changes of amino acid concentration in plasma during 100g oral glucose load were investigated in patients with liver diseases and healthy controls.
In healthy control the concentration of m any amino acids decreased gradually and attained minimum within 3 hrs after glucose load, recovered to initial level after 6 hrs.
We defined the decrease ratio [D. R.], i.e. the maximum decrease during 3 hrs after glucose load to the initial concentration of amino acid. It was observed that many significant difierences between healthy control and liver diseases, such as liver cirrhosis, hepatoma, chronic hepatitis and acute hepatitis in both the amino acid concentration in fasted state and D. R..
Although the value of total Trp/BCAA + AAA at 3 hrs after load showed signif icantly higher than that of fasted state, in both hepatic diseasses and healthy controls. The value increased in 3 hrs in hepatic diseases more than in healthy control.
The value of BCAA/AAA was kept almost cons tant in control during oral glucose load but decreased in hepatic diseases.

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The orbicularis oculi muscle contracts in response to photic stimulation as a reflexive action. It is called the photopalpebral reflex and is already present during the newborn period. In adults or animals, the photopalpebral reflex shows the function of the midbrain and cerebrum. It is known that hyperosmolality is a cause of intracranial hemorrhage and the dysfunction of the brain in newborns, but the functional damage is not yet clear. So the dysfunction of the brain induced by hyperosmolality can be examined and was in this study using the photopalpebral reflex, There are two ways of recording the palpebral reflex induced by photic stimulation one way utilizes the changes in the electrical potential between the upper eyelid and the ear, which is known as the photopalpebral reflex (PPR), and the other utilizes acceleration changes of eyelid microvibration, and is known as the photo-evoked eyelid microvibration (MV).
The subjects were 9 newborns who had hyperosmolality 4 to 65 hours after birth,107newborns ranging in conceptional age from 25 to 45 weeks, and 5 children (4 to 9 years of age) free of any neurological abnormalities. In both methods, the electrode or pickup was applied to the central part of the upper eyelid with EEG paste and the average of 30 responses was calculated on a digital computer.
The reproducibility of MV and PPR in the same individual was fairly good. PPR responses were observed in the following manner; the early component (PPR_1,2,3 and PPR₄) and the late component (PPRs and PPR₅). The latency in the appearance of MV and PPR shortened with growth, but the amplitude of each reaction was not related to growth.
In active sleep the latency of MV was prolonged and the amplitude was either markedly suppressed or completely lost. But in other sleep states the amplitude of MV was suppressed to about 30% of the responses in the awake state. While the amplitude of the late PPR component was also suppressed during sleep to about 30% of the amplitude in the awake state, the PPR never disappeared during active sleep. The latency of PPR_1,2,3,4 and PPRs was not affected during sleep but the latency of PPR₅ was affected. The latency of the late PPR component is the same as the latency of MV, so it is thought that these reactions have the same reaction pathway. And, because the amplitude of late PPR component and MV were suppressed during sleep, the reaction pathway might include the midbrain reticular formation.
In the case of the early-infantile epileptic encephalopathy with suppression-burst, the late component of PPR and MV were completely lost, so it is suggested that the late PPR component and MV are related to the brainstem Because the early PPR com ponent alone disappeared upon the extraction of the right eye, it is believed that the early component is the ERG. As MV and the late PPR component were observed in the extracted side, the appearance of these reactions is related to the orbicularis oculi muscle and the movement of the eye scarcely affects these reactions.
The latency of MV and PPR s were prolonged and the amplitude of MV and the late PPR component were suppressed with hyperosmolality. But the amplitude of the late PPR component was not directly proportional to the level of plasma osmolality. In newborns, it is believed that the dysfunction of the midbrain reticular formation caused by hyperosmolality can be studied by observing MV.

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1. For the purpose of evaluation of the left ventricu lar function of mitral stenosis in early postoperative period, the left ventricular function of 29 patients (18 cases of pure mitral stenosis (MS),3 cases of MS+ aortic regurgitation (AR), and 8 cases of atrial septal defect (A SD))were evaluated in early postoperative period (6-35 hours after operation) comparing with those of preoperative and late postoperative period (3-8 weeks after operation)
2. In control group (ASD), cardiac index (CI), stroke inde x (SI) and stroke work index (SWI) did not remarkably change, although pulmonary arterial pressure (PAP) and pulm onary arterial resistance (PAR) were decreased in early postoperative period. The arterial pressure (AP) and heart rate (HR) did not show signifcant change.
3. The patients of pure MS were divided in 4 grou ps accordingt o PAP and cardiac rhythmus. In group I, PAP was bellow 25 mmHg with sinus rhythmus, in group II, PAP was bellow 25 mmHg with atrial fibrillation, in group III, PAP was higher than 25 mmHg with sinus rhythmus, in group IV, PAP was higher than 25mmHg with atrial fibrillation. In group I and II, CI, SI, and SWI were remarkably decresed during early postoperative period, but in group III and IV, they were unchangable or little improved in this period. However, in late postoperative period, CI, SI and SWI were improved significantly as compared with those of preoperative period in all four groups.
4. PAP of group III and IV with pulmonary hypertension, fell in early postoperative period. However, in group III, PAP increased again after the short duration of decreased pressure. The decrease of PAP in group I and II was little demonstrated. PAR was tended to increase in early postoperative period in all groups. Particularly, in group III, PAR rose remarkablly, however, in all groups, PAR lowered bellow preoperative value in late postoperative period
5. The right atrial pressure (RAP) was tended to increase in early postoperative period, but the left atrial pressure (LAP) fell in all groups, especially in group III and group IV. The LAP and RAP in MS group were higher than those of ASD group in early postoperative period and the correlation of LAP and RAP in MS group was poor. The estimation of LAP from RAP in early postoperative period of MS group was difficult.
6. The left ventricular function curves with volu me overloading in control group (ASD)located in left upper quadrant but those in MS group located in right lower quadrant in early postoperative period. Particularly the left ventricular function curves of group I located more left upper portion than other groups, and that of group IV located rather right lower portion than other groups. The slopes of left ventricular function curves were gentle except that of group I, which revealed the depletion of left ventricular performance.
7. The value of CI obtained by means of volume load, in early postoperative period (6 hrs after operation) had good correration to the value of CI at rest in late postoperative period.
8. The evaluation of left ventricular function curves obtained in early postoperati ve period was usefull for the postoperative patient management.

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A study was made of the mechanism producing symptoms of the cervical syndrome initiated by electrical stimulation of the great occipital nerve (GON) and the cervical sympathetic nerve (CSN) of rabbits and also an attempt to make clear the mechanism of the action of CDPcholine and Meclofenoxate was undertaken.
Experiment I: The unit disch arge of the reticular formation. The frequency of unit discharges increased through GON and CSN stimulation at 100Hz. It was demonstrated that the above changes were inhibited following the administration of CDP-choline and Meclofenoxate.
Experiment II: The recruiting response due to the stimulation of VA. Its amplitude decreased through GON stimulation at 3Hz, increased through GON stimulation at 100Hz, decreased through CSN stimulation at 3Hz and increased and decreased through CSN stimulation at 100Hz. It was also demonstrated that the increase through GON stimulation at 100Hz was inhibited following the administration of CDP-choline and Meclofenoxate.
Experiment III: The average evoked potential in the cerebral cortex. The amplitude on early component (N1, N2, N3) decreased through GON stimulation at 3Hz, increased through GON stimulation at 100Hz and increased and decreased through CSN stimulation. It was demonstrated that the increase through GUN stimulation at 100Hz was inhibited following the administration of Meclofenoxate.
Experiment IV: The average evoked potential in the hippocampus. The amplitude on late component (HN5, HN6) increased through GON and CSN stimulation at 100Hz. It was also demonstrated that the above changes flattened out following the administration of CDP-choline and Meclofenoxate.
Experiment V: The evoked muscular discharge due to the stimulation of cerebral cortex. The inhibitory effect on forelimbs was noticed through GON stimulation and the facilitatory effect was noticed through CSN stimulation. It was also demonstrated that the above change through CSN stimulation at 100Hz was inhibited following the administration of CDP-choline and Meclofenoxate.
Experiment VI: The evoked muscular discharge due to the stimulation of hippocampus. The inhibitory effect on fore and hindlimbs was noticed through GON stimulation, the inhibitory effect on forelimbs and the facilitatory and inhibitory effect on hindlimbs was noticed through CSN stimulation at 3Hz and the facilitatory and inhibitory effect on fore and hindlimbs was noticed through CSN stimulation at 100Hz. It was also demonstrated that the inhibitory effect through GON stimulation flattened out following the administration of CDP-choline and changed the facilitatory effect following the administration of Meclofenoxate.
Experiment VII: M wave and H wave. The ampuli tude of M wave and H wave decreased through GON and CSN stimulation. It was also demonstrated that the above changes changed the facilitatory effect following the administration of CDP-choline and the change through GON stimulation flattened out following the administration of Meclofenoxate.
Experiment VIII: Gastric movement. Gastric move m ent was inhibited GON and CSN stimulation. It was also demonstrated that the inhibition through GON stimulation changed the facilitatory effect following the administration of CDP-choline.
Experiment IX: The vertebral and carotid blood flow. Their blood flow through GON stimulation remained almost unchanged, but those through CSN stimulation remarkably decreased.

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A patient, a 21 years old woman, had been admitted into our department due to coma with fever. After her admission, she was diagnosed as having viral meningitis based on the nuchal stiffness, flaccid paralysis of her four extremities, abnormal findings of the CSF, i.e. increase of pressure and of mononuclear cell count, and high seral anti-influenza A virus titer. She recovered leaving no trace of psychoneurological disturbance after corticoid therapy. But, thereafter, increased ESR and hypergammaglobulinemia persisted, and besides, antinuclear antibody and anti-DNA antibody as well as Raynaud's phenomenon appeared. Moreover, negative PPD skin reaction and decreased peripheral lymphocyte and active T cell count were observed.
Although, these findings might have been partially induced by the viral infection itself, the course of the patient suggested a preexistent latent SLE with immunodefficiency, particularly that of cell-mediated immunity, and the incidence of the influenza A virus infection might be related to the immunodefficiency antecedent to the probable SLE.
Any reports on the viral meningitis concomitant with SLE can not yet be found in the literature, except for only one reporting a viral meningitis due to herpes virus complicating SLE.

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An autopsy case of primary macroglobulinemia with gastro-duodenal multiple ulcers is reported. The patient was a 68-year-old man who complained of edema of bilateral legs when he was exposed to cold since 65 years old, and after hospitalization he developed multiple skin ulcers of bilateral legs, persistent diarrhea and pathological fracture of the fifth lumbar vertebra.
Serological studies revealed an increase in amount of monoclonal IgM (kappa) up to 5200mg/dl. Cryoglobulin was detected in the serum and C_Iq binding activity amounted to 39%. Urinary Bence-Jones protein was positive. Bone marrow aspiration revealed the proliferation of plasmablastlike cells. The patient died due to pneumonia and gastrointestinal bleeding 3.5 years after the onset of this disease.
Autopsy reveale d gastro-duodenal multiple ulcers. Hepatosplenomegaly and lymph node swelling were not found. The middle lobe of the right lung contained a walnut-sized abscess.
Microscopically plasmocytoid lymphocytes were found to infiltrate into almos t all organs, especially into the bone marrow. Some of these infiltrating cells contained PAS-positive, intranuclear and intracytoplasmic inclusion bodies, and PAS-positive eosinophilic homogeneous material was found to occlude the lumen of some of the submucosal capillaries and lymphatics in almost all organs, especially in the digestive tract.
Gastro-duodenal multiple ulcers seem to have been caused as a result of the occlusion by the same material of submucosal capillaries and lymphatics.
An immunofluorescent study, peroxidase-anti-peroxidase procedure and histochemical analysis revealed that this material is composed of monoclonal IgM (kappa) with an admixture of C₃complement and phospholipid, Persistent diarrh ea of which this patient complained may be due to the occlusion by eosinophilic material of submucosal capillaries and lymphatics of intestine.
Of various factors involved in the formation of this materi al, the deposition of IgM may be a most important one, and in addition, the precipitation of cryoglobulin, C₃ complement and of phospholipid can be enumerated.
It was exceedingly rare in cases of primary macroglobulinemia that IgM-positive materials were deposited, as noted in the present study, in the capillaries and lymphatics throughout the whole body.

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5-fluorocytosine (5-FC), which is currently used against fungal infections with low toxicity, lacks antineoplastic activity in man because of the absence of cytosine deaminase (CDase) in mammalian cells. If enough of 5-FC is delivered to the tumor tissue and CDase in the encapsulated form is implanted in the tumor bed, it is expected that 5-FC would be deaminated to 5-fluorouracil (5-FU) and antineoplastic activity will develop at the local site with minima l systemic toxicity. In the present study, basic experiment of antineoplastic effect induced by combined administration of 5-FC and CDase on the tissue cultured neoplastic cells was reported.
CDase was extracted from cultivated Escherichia coli K-12 strain and purified. Based on the differential absorption of 5-FC at A₂₈₀ and 5-FU at A₂₈₀, CDase activity was measured by spectrophotometric analysis, which substantiated the conversion of 5-FC to 5-FU by CDase. For in vitro studies on its cytotoxicities,2 established cell lines including HeLa and EA-285 glioma cells, and 12 human brain tumor cells in one passage culture (3 glioblastomas,1medulloblastoma,2 astrocytomas,5 meningiomas, and 1 neurinoma) were used, and changes in cellular proliferations and morphological alterations of cultured cells, induced by this combined treatment, were examined.
The results from these studies showed that the combined administration of 5-FC and CDase resulted in significant growth inhibition at higher than 5μg/ml of 5-FC on both HeLa and EA-285 glioma cells although 5-FC or CDase per se had no cytostatic effect. CDase was found to be little inactivated for at least a month in in vitro at 37°C. In cultured human tumor cells, significant growth inhibition was also noted at higher than 25μg/ml of 5-FC. Malignant tumor cells had slightly higher sensitivity to this treatment than benign ones.
The light microscopy revealed cellular damage including loss of cyto p lasmic details, nuclear pyknosis and fragmentation. Changes in the fine structure of the cell surface such as flattening of the surface, decrease and shortening of the cell process, and loss of microvilli were noted by scanning electron microscopy.
The effect of the drugs on the cell cycle traverse of established cells was also studied by a qualitative comparison of the DNA histogram using fluorocytograph. Fluorocytographic study confirmed that the converted 5-FU at higher than 25μg/m1 resulted in an irreversible block in the early S phase with a lethal effect on both established cells.
To know the site of action of the converted 5-FU in the cell cycle, firstly the phase intervals of HeLa cell cycle were determined by evaluating the changes of DNA. histograms of the cells synchronized with the excess thymidine. G1, S, and G2M phase were estimated to be 12,5, and 5 hours respectively. Secondly, analysis of the cell growth and the patterns of the DNA histograms after the drug administration at various phases of the synchronized cells were performed. The site of action of the converted 5-FU was found to be mainly in S phase although the cells in G1 and G2M phases were also influenced.
The author confirmed that 5-FC was converted to 5-FU b y adding CDase and significant antineoplastic activity developed in in vitro. And the author discussed the effects of converted 5-FU on the cell cycle progression as a mechanism of 5-FC and CDase treatment, and a design of capsule containing the enzyme for future clinical application.

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An altered lung volume and electrical resistance of the tissues surrounding the heart can affect vectorcardiographic changes. This study was designed to evaluate whether the altered lung volume by expiratory and inspiratory breath-holding can produce any change of vectorcardiogram. Patients with chronic obstructive pulmonary disease (COPD), but without respiratory failure, were divided into 3 groups according to forced expiratory volume in one second (FEY 1.0 % ): Group 1, consisted of 15 cases with FEV1.0% of 71% or more; Group 2,19 cases of 55% to 70%; Group 3,24 cases of 55% or less. Vectorcardiographic changes, anatomical axis of the heart, diaphragmatic movement determined by chest X-P and gas analysis by exercise testing were investigated in 58 COPD patients and 15 normal men.
1) There was max QRS vector showing backward rotation by deep inspiration in Group 1, Group 3 and normal men. The downward movement changes of max QRS vector by dee p inspiration were seen in Group 1, Group 2 and normal men.
2) The magnitude of max QRS vector by deep inspiration was reduced significantly in Group 2 and normal men and correlated with a decrement of lung triangle area. (Lung triangle area is an area of left side chest X-P; this triangle is formed by three points of bifurcatio trachea, posterior phrenicocostal sinus and a point of intersection of diaphragram and posterior margin of the heart.)
3) The max QRS vector of frontal plane in Group 3 showed greater downward deviation by deep expiration than normal men. The max QRS vector of horizontal plane showed greate r backward deviation by deep expiration than normal men. The magnitude of max QRS vector by deep expiration in Grpup 3 showed significant lower value than normal men. This can be explained adequately on the basis of irreversible inflated lung in patients w ith COPD.
4) Anatomical axis was closely related to electrical axis in normal men in deep expiratory and inspiratory breath-holding, but there was no significant relation in patients with COPD.
5) A decrement of max QRS vector magnitude in frontal plane correlated with a decrement of lung triangle area in Group 2.
6) A good relation was found between movement of diaphragm and FEV1.0%, between an area change of lung triangle and FEV1.0%.
7) PO₂ showed a more significant decrease after Master's 2 steps exercise in patients with poor diaphragramatic movement than in patients with good diaphragmatic movemen t. There was no significant difference in positive rate of Master's 2 steps exercise among the groups. Group 3 showed lower value of PO₂and higher value of PCO2 than normal me n, induced by exercise.
In the light of the evidence, it would seem most probable that the experimental data presented for these supine subjects can most simply be explained on the assumption that the vectorcardiographic changes in COPD, in which max QRS vector become oriented more to the right posterior and inferor direction, are the direct result of excessive lung volume around the heart at the extreme of breath-holding

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Electric potentials from the heart as recorded in the clinical vectorcardiogram may be modified by disease primarily involving the lungs. This report was designed to evaluate vectorcardiographic changes and gas analysis in 10 adults (7 cases with choronic pulmonary obstruction and 3 cases without chronic pulmonary obstruction) during bronchospastic attack and in attackfree state. Vectorcardiographic changes consisted of:
1) Max QRS vector in 8 cases during the episode of bronchospastic attack showed a tendency to shift toward the right posterior and inferior direction. There were 2 exceptions in which direction of max QRS vector in the frontal plane was in the right superior quadrant and max QRS vector in the horizontal plane deviated to the right posterior quadrant. These findings are indicative of respiratory failure and right side overloading due to hyperin flatedlung, hypoxia and hypercapnia.
2) An increase of rightward terminal QRS forces was noted in severe obstructive pulmonary patients. These patients showed the evidence of RV overloading on VCG during bronchospastic attack.
3) A decrement of max QRS vector magnitude in horizontal plane, a decrement of left maximum spatial vector manitude and an increment of rightward terminal QRS forces were closely related to a decrement of PO₂ and an increment of PCO₂. Alternation of max QRS vector magnitude and RV overloading may well reflect hyperinflated lung due to ventilat o ry impairment and respiratory failure due to hypoxia.
4) Deviation of max T vector to left posterior in horizontal plane correlated with an increment of rightward QRS forces and a decrement of PO₂ due to bronchospastic attack. These findings are also regulated in RV overloading due to bronchospastic attack.
5) A decrement of max T vector magnitude was related to a decrement of PO₂ and an increment of PCO₂ due to bronchospastic attack. This primary T change can be explained also on the basis of respiratory insufficiency.
6) Max P vector magnitude was increased significantly during bronchospastic attack. These changes of the QRS loop were reversible and returned to the origin al pattern after relief of bronchospastic attack in all of subjects. Right heart overload was induced temporarily during bronchospastic attack and well reflected VCG changes. These changes of electrical and anatomical condition, induced by bronchospastic attack, around the heart would have a partial influence on these VCG changes.

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