Histological examinations of the kidney taken from a rat fed on a high 1-tyrosine diet revealed deposition of ochronosis pigment in the lumens of the distal tubuli as well as in the interstitial tissue, however, no gross signs of pigment deposition were found.
To the author's knowledge, the first report that could cause ochronosis pigment to occur in animals by feeding tyrosine in excess, was published by BONDURANT et al. in 1966, and this report seems to be the second one. This indicates that it is very difficult to induce ochronosis in animals, in contrast to that it is comparatively easy to induce alcaptonuria in animals by feeding tyrosine.
Moreover, judging from the degree of decolorization of the alcian blue (below pH 2.0)-positive finding by treatment with a 4-hour,60°C methylation as well as the metachromatic intensive coloration of the cresyl fast violet staining, it seems that sulphatides are present in ochronosis pigment and calcareous casts in the distal tubuli, and that they would take part in the formation of both the above-mentioned two substances.
On the other hand, it has been found that considerable amounts of ceroid coexist with large amounts of hemosiderin in the individual macrophages in the lymph nodes of the rat group with alcaptonuria. These findings are supposed to be caused by phagocytosis of increased amounts of erythrocytic stroma by macrophages in the lymph nodes as a result of enhanced hemolysis attributable to chronic nephrosis due to alcaptonuria.

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In order to know the pharmacological actions of 4-(2-hydroxy-3-isopropylaminopropoxy)-indol (LB-46) in isolated rat heart muscle, the influences of this drug were examined on (a) the spontaneous contraction rate of the right atrium, (b) the contractile tensions of the spontaneously contracting right atrial muscle and of the electrically driven papillary and left atrial muscles, (c) the refractory periods of the papillary and left atrial muscles, and (d) the correspondences of responses to high frequent stimulation in the papillary and left atrial muscles. Methods and Materials
Male adult rats of both sexes weighing 300 to 400g were used. After sacrifice by severing the common carotid arteries, the heart was excised, and tissue preparations of their right and left atria and of papillary muscles were severally suspended in a Magnus' apparatus in a Locke's solution saturated with pure oxygen at 30 to 31°C.
The right atrium was used to examine the drug effects on rate and tension of spontaneous contractions while the papillary and left atrial muscles were used to examine the drug effects on their contractile tensions, refractory periods, and correspondences of responses to high frequency stimulations. When the papillary and left atrial muscle tissues were used, they were driven by electrical stimulations at supramaximal intensities, at duration of 10 and 5 msec, respectively, and 120 cycles per min. The drug applied was added to the medium in which the preparations were contracting, and was expected to act easily on these tissues.
When the refractory periods of the papillary and left atrial muscles were examined, Govier's method was used: basal stimulations were given to the muscles at supramaximal intensities, at durations of 10 and 5 msec, respectively, and at 60,120, and 240 cycles per min;and test stimulations, whose conditions were the same as those of the basal stimulations, were given at from 60 to 480 msec after each corresponding basal stimulation. If the time intervals between the two kinds of stimuli were of shorter durations than the refractory periods proper to the tested muscles, muscular contractile responses corresponding to the test stimulations would hardly appear. When the muscular responses corresponding to the test stimulations began to appear during gradual increase of the time intervals, the estimated time intervals were defined to represent the refractory periods of the muscles tested.

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Dextran sulfate (DS) and urokinase (UK) are being used to enhance the effects of anti-tumor drugs. In the present investigation attempts were made to elucidate the cellular mechanism of the enhancing effects of DS and UK ultracytochemically.
Yoshida ascites sarcoma cells transplanted intraperitoneally into the female Donryu rats weighing approximately 80-100g were used and the ultracytochemical detection of the acid phosphatase (ACPase) activity was made on these cells to observe changes in the lysosomal system. In all experiments the cells collected by centrifugation of ascites 5 to 6 days after an intraperitoneal transplantaion were used. Experiments were investigated under conditions described below.1) Effects of DS and/or UK. DS (60mg/kg. b. w. in saline), UK (400units/kg. b. w. in saline), DS+UK (DS 60mg+UK 400 units/kg), control (saline alone)2) Effects of puromycin or acinomycin D.3) Effects of DS and UK concomitant treatment with mitomycin C (MMC). In control groups, the ACPase activity was observed mainly in lysosomes and occasionally in the Golgi apparatus. The number of lysosomes was rather scarce. In experimental groups treated with DS and/or UK, the smooth tubules in the centrosphere area showed the marked ACPase activity in addition to the lysosomes and the Golgi apparatus. The enzymatic activity of the Golgi apparatus was higher in these

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There have been reports concerning an application of hyperthermia for the treatment of malignant tumors. To raise the local temperature of a tumor, microwave irradiation was used for its local heat effect in deeper structure.
Yoshida sarcoma cells were transplanted subcutaneously into bilateral hind limbs of rats. Tumors on the left side were heated to 42°C for 30 min, by exposure to 2450 MHz microwave, while body temperture was kept below 37°C throughout the treatment. Immediately after microwave irradiation,3H-thymidine was given intraperitonealy to rats. Tumors on the right side were served as a control without microwave irradiation and 48 hrs. later animals were sacrificed. Samples were oxidized by Tri-Carb. autosample oxidizer and radioactivity was measured by a liquid scintillation counter. In irradiated group, the percent ratio of disintegration per minute per mg weight of the irradiated tumor versus that of the non-treated was 48.1±18.1, i. e., an uptake of 3H-thymidine was markedly suppressed by microwave irradiation. In the non-treated group, there was no significant difference in 3H-thymidine uptake between the tumors on the right side and these on the left. However, microwave irradiation did not apper to affect significantly the size and weight of tumors. Histologically, it seemed that there was more prominent necrosis in the treated tumor than in the non-treated, which may be a histological manifestation of the decreased thymidine uptake.
Further studies using experimental brain tumors in rabbits were performed. VX-2 carcinoma was transplanted into the right frontal lobe, and on the 5th and 7th days tumors were heated to 42°C for 2hrs, by exposure to microwave. During microwave irradiation, local temperature was monitored by an epidural thermister needle. Evans' blue solution was intravenously given immediately after microwave irradiation and rabbits were sacrificed on the 3rd or 7th day after treatment with microwave. These animals showed clinical evidence of tumor ghowth;increasing irritability, loss of appetite, and even lethargy, and these signs were remarkably slight in the microwave irradiated group. Macroscopic examination revealed that the size of tumor was much larger in the non-irradiated group than in the irradiated. Tumors of the non-irradiated group were stained uniformly with Evans' blue on the 10th day, and small dark brown spots were scattered on the 14th day. In the irradiated group dark brown areas, which were confirmed to be necrosis microscopically, occupied most part of the tumor and occasional blue stain was noted around those areas as early as on the 10th day. On the 14th day there was a small tumor mass growing next to the necrotic area. Histologically, the tumor was densely cellular with small foci of necrosis on the 10th day and the areas of necrosis became large and abundant and various stages of degenerative changes were noted in the cells surrounding the foci of necrosis on the 14th day in the nonirradiated group. In the irradiated group, much larger areas of necrosis were noted and tumors were entirely necrotic in one third of the irradiated on the 10th day after transplantation. In addition to a large extent of necrosis, the pattern of various stages of cell degeneration surrounding the necrosis was not seen, which were typically recognized in the non-irradiated tumor. Edematous changes of the surrounding brain tissue were marked in the irradiated group, and even disappearance of adjacent nerve cells was noted in some cases. However, microwave irradiation of normal brain tissue has no such effect.

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A study was made in unanesthetized rabbits of the changes in intestinal movement due to electric stimulation on the limbic system in reference to electrical activities of the central nervous system.
1. Following 3 Hz stimulation given to the amygdaloid nucleus, the development of spike and wave in EEG of the cerebral cortex and hippocampus was accompanied by a facilitated intestinal movement.
2. When the frequency of stimulation was increased from 3 to 8 Hz, recruiting response began to appear, followed by either facilitation or inhibition of intestinal movement.
3. With 100Hz stimulation given to the amygdaloid nucleus, the arousal pattern appeared in EEG, followed by a marked inhibition of intestinal movement, being accompanied by tonic type or tonic phasic type evoked muscular discharges in the fore and hind limbs,
4. The area for the intestinal inhibition only tended to be located centered on the central nucleus, while the area for both facilitation and inhibition located diffusely in the amygdaloid nucleus.
5. It was demonstrated that the facilitatory impulse due to stimulation of the amygdaloid nucleus passed through the vagus nerve while the inhibitory one passed through the splanchnic nerve.
6. Stimulation (3,8,100Hz) of the hippocampus resulted in no marked changes in intestinal movement.
7. Studies on the effects of various drugs on EEG and inhibition of intestinal movement revealed that the regulation of amygdaloid nucleus for intestinal movement was carried out through the lower center.
8. The amygdaloid nucleus influenced intestinal movement most markedly, followed by the septal nucleus and midbrain reticular formation in order.
9. The inhibitory effect due to stimulation of the amygdaloid nucleus was abolished by a destruction of the hypothalamus (DMH), unlike the case with the inhibitory effect due to stimulation of the reticular formation.

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The pharmacological actions of 1-(7-indenyloxy)-3-isopropylaminopropan-2-ol hydrochloride (YB-2) in isolated rat heart muscles were examined on (a) the spontaneous contraction rate and tension of the right atrium, (b) the effect on arrhythmic contractions of the right atrium induced by the electrical stimulation, (c) the contractile tensions of the electrically driven papillary and left atrial muscles, (d) the refractory periods of the papillary and left atrial muscles, and (e) the correspondences of responses to high frequency stimulation in the papillary and left atrial muscles.
Materials and Methods
Adult rats of both sexes weighing 300 to 400g were used. After sacrifice by severing the common carotid arteries, the heart was excised. The right and papillary muscles were prepared and severally suspended in a Magnus' apparatus in a Locke's solution saturated with pure oxygen at 30 to 31°C.
The right atrium was used to examine the drug effects on rate and tension of spontaneous contractions and on their electrically induced arrhythmic contraction, while the papillary and left atrial muscles were used to examine the drug effects on their contractile tensions, refractory periods, and correspondences of responses to high frequency stimulations. When the papillary and left atrial muscle tissue were used, they were driven by electrical stimulations at supramaximal intensities, at durations of 10 and 5 msec, respectively, and 120 cycles per min. The drug applied was added to the medium in which the preparations were contracting 30 min before the estimation of each drug effect, and was expected to act easily on these tissues. When the drug effect on the arrhythmic contraction of the right atrial spontaneous contractions induced by electrical stimulation was examined, the stimulations were given to the preparation at critical intensities, at a duration of 5 msec, and at 120 cycles per min, and, then, it was examined whether the electrically induced arrhythmic contractions could be prevented by the drug or could not.
When the refractory periods of the papillary and left atrial muscles were examined, Govier's method was used: basal stimulations were given to the muscles at supramaximal intensities, at durations of 10 and 5 msec, respectively, and at 60,120, and 240 cycles per min;and test stimulations, whose conditions were the same as those of the basal stimulation. If the time intervals between the two kinds of stimuli were of shorter durations than the refractory periods proper to the tested muscles, muscular contractile responses corresponding to the test stimulations would hardly appear. When the muscular responses corresponding to the test stimulation began to appear during gradual increase of the time intervals, the estimated time intervals were, defined to represent the refractory periods of the muscle tested.

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