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The ferric nitrilotriacetate-induced carcinogenesis model is unique in that reactive oxygen species-free radicals are involved in the carcinogenic process. But the effects of iron-withdrawal in the progression of renal cell carcinoma are not well understood. We performed repeated phlebotomies on animals that had been administered ferric nitrilotriacetate in the initiation stage of renal cell carcinoma (phlebotomy group), and compared the development of renal tumors with those not receiving repeated phlebotomies (non-phlebotomy group). Ferric nitrilotriacetate-treated male Wistar rats were randomly divided into 2 groups: a phlebotomy group (21 rats) and a non-phlebotomy group (17 rats). Ten age-adjusted normal rats were also observed as a normal group. Hematocrit was maintained under 25% in the phlebotomy group. Hematocrit levels in the normal group and in the non-phlebotomy group were not significantly different. As a result, the incidence of renal cell carcinoma was not significantly different between phlebotomy and non-phlebotomy animals. However, the total weight of the renal cell carcinoma was significantly heavier in the animals from non-phlebotomy group than in those from the phlebotomy group (23.64 g +/- 18.54 vs. 54.40 g +/- 42.40, P < 0.05). The present study demonstrated that phlebotomy after the administration of ferric nitrilotriacetate did not reduce the incidence of renal cell carcinoma. In addition, we showed that iron withdrawal at the promotion stage of carcinogenesis will retard tumor growth.

We have previously developed an enzyme-linked immunosorbent assay (ELISA) to measure stool decay-accelerating factor (DAF) and found that stool DAF concentrations were significantly elevated in patients with colorectal cancer, suggesting that the measurement of stool DAF may be valuable for the detection of colorectal cancer. In order to refine the assay for the measurement of stool DAF, we investigated 1) effects of centrifugation of stool samples, 2) effects of detergents, and 3) adequate combination of various anti-DAF monoclonal antibodies for the ELISA system using only monoclonal antibodies. We found that high-speed centrifugation could be omitted and that only the removal of large undigested food residues by centrifugation of short duration in a low-speed benchtop microcentrifuge sufficed to adequately prepare the stool samples. Addition of 2 detergents, octyl beta-glucoside and sodium deoxycholate, known to solubilize glycosyl-phosphatidylinositol-anchored proteins such as DAF, did not influence stool DAF values. By using 2 mouse anti-DAF monoclonal antibodies (clone 4F11 and 1C6), we were able to achieve a stable ELISA for the measurement of stool DAF using a uniform source of antibodies. The results should allow us to consistently apply the DAF assay for routine use in the detection of colorectal cancer.

The preS2 region of the hepatitis B virus (HBV) has been reported to have human polymerized albumin receptor (PAR) activity, which correlates with viral replication. Here, we studied the genomic sequence of the preS region from rare patients lacking PAR activity, despite active viral replication. PAR and DNA polymerase activity was identified in 178 HBe antigen-positive HBV carriers, and a significant correlation between 2 markers was shown, except in 2 hepatitis patients lacking PAR activity. Nucleotide sequences of the preS region of HBV from both patients were examined by direct sequencing of PCR products. In one patient, a 45-base deletion was found to overlap half of the putative polymerized human albumin binding site in the preS2 region. In the other patient, a point mutation at the first nucleotide of the start codon of the preS2 region of HBV was found. There was no such genomic change in the 3 control HBV sequences. These results indicate that the preS2 region is necessary for binding of polymerized human albumin, and this is the first report of naturally existing mutant virus with no or low PAR activity.

We developed a monoclonal antibody (MoAb) (clone 5E8) against an antigen on the bile canalicular membrane of rat hepatocyte. By immunoblotting, MoAb 5E8 detected a band of 110 kD. In this study, we used the phage display technique to identify the target antigen recognized by MoAb 5E8. We screened a random phage display library expressing 12-mer peptide sequences and identified a peptide sequence, FHFNPYTGHPLT, as an epitope. We compared this peptide sequence with those of dipeptidyl peptidase IV (DPP IV, E.C.3.4.14.5) and Cell-CAM105, which proteins were located by a database search based on the information of tissue localization and approximate molecular weight of the MoAb 5E8 antigen, and sequence similarity with a region in DPP IV (amino acids 225-233) but not with Cell-CAM105 was found. In addition, we immunohistochemically stained various tissues (liver, small intestine, and kidney) of Japanese Fischer 344 rats, known to be deficient for DPP IV, with MoAb 5E8 and showed that the expression of MoAb 5E8 antigen was negligible or weak. In contrast, tissues sampled from the same organs of Sprague-Dawley rats, known to express DPP IV, were positively stained. These findings suggest that the antigen recognized by MoAb 5E8 is DDPIV and its major epitope is located in amino acids at positions 225-233.

To compare morphological changes in the umbilical cords from chronic hypertensive and preeclamptic patients having normal or pathological umbilical artery Doppler ultrasonographic results. Umbilical cords from 34 normotensive, 31 chronic hypertensive and 70 preeclamptic women with normal and abnormal Doppler flow velocity waveforms (FVW) at 35-40 gestational weeks were studied. Morphological changes in the umbilical cords were examined on formalin-fixed, paraffin-embedded sections. The total umbilical cord area, total vessel area, and wall thickness of umbilical vessels were measured in systematic random samples using unbiased stereology methods. An ANOVA test was used for statistical analysis. In the chronic hypertensive and preeclamptic groups with normal Doppler FVW, the thickness of the umbilical cord vessels remained nearly constant, whereas both the total area and the lumen area were reduced. These changes correlate with the histopathological findings, suggesting a mainly vasoconstrictive effect. By contrast, analysis of the preeclamptic group with pathologic Doppler FVW showed a comparable reduction of all parameters of the umbilical cord. Histopathological findings were related to smaller, contracted smooth muscle cells of the vessel wall, which is suggestive of a predominant hypoplastic mechanism. As a result of reduced uteroplacental perfusion, fetal hypoxia and intrauterine growth retardation become unavoidable in preeclampsia. The histopathological changes in the umbilical cord between the chronic hypertensive and preeclamptic patients depend on the Doppler results. In conclusion, the umbilical artery Doppler FVW indices provide good values for predicting intrauterine growth retardation in preeclamptic patients.

Dynamin is a protein essential to endocytosis. Dynamin 2, a dynamin isoform, is expressed most intensely in testicular tissue; however, precise localization has never been studied. Therefore, we investigated the expression of dynamin 2 in rat testicular tissue using immunohistochemical methods, and discuss here the physiological function of this protein. Testicular tissues were obtained from Wistar rats at 10, 21 and 63 days of age. Immunohistochemistrical examination and Western blot analysis were conducted using dynamin 2 specific antibody. Western blot analysis showed that expression in 21- and 63-day-old rats was more intense than that in 10-day-old rats. Dynamin 2 expression was observed using immunohistochemical method in the seminiferous tubules of all rats. In the 63-day-old rats, the expression was intense, especially in spermatids in the earlier maturation stages and in spermatocytes, and was observed in Sertoli cells. However, in spermatids, the expression gradually declined as spermatids matured to spermatozoa. In the 21-day-old rats, the expression was evident in spermatocytes and Sertoli cells, but that in the 10-day-old rats was weak. Intense expression of dynamin 2 during spermatogenesis suggests that this protein plays an important role in this process.

We have designed to apply 2-pyridine aldoxime methiodide(PAM), considered to be a cholinesterase reactivator in vitro, both to the laboratory rabbits poisoned by parathion and to the patients of parathion poisoning, and obtained the following results: 1. With administration of PAM, a prompt and complete dispersion of symptoms of the poisoning can be realized. 2. Cholinesterase activity of red blood cell has instantly and completely recovered, and that of serum transiently. 3. The amount of serum mucoprotein and the activity of active protein-SH-radical of serum varied in direct proportion to the activity of serum cholinesterase. 4. Generally, an intravenous injection of 1g. PAM is sufficient even in the severe case and it may be increased when necessary. 5. The ill effect has not been encountered in the PAM administration. 6. PAM exerts no influence on the cholinesterase activity of normal blood. 7. PAM is expected to play an important role as a prophylactic agent of alkylphosphate poisoning. From these results it seems clear that PAM is a specific and effective antidote against alkylphosphate intoxication.

To reveal the relationship between the morphologic structure and the functioning of cells it is of great importance to know the molecular arrangement in cytoplasm. For this purpose the observation by polarization microscope is one of the most exellent methods. There are several excellent works on nerve fibre done using polarized lightl,2,3,4 but there is no report concerning the nerve cell itself. It is the purpose of this paper to show our data obtained on ganglion cells and nerve fibres with the deduced speculation on the structural arrangement of lipoprotein in the protoplasm of nerve cells and fibres.

The existence of autonomic adjustment functions of eye pressure was demonstrated in various ways, both clinically and experimentally. It is possible to consider that in normal condition, I.O.P. is controlled autonomically like cardiac or respiratory rate irrespective of the internal or external influences of the body. The auther calls such a phenomenon "autonomic eye pressure adjustment function". The mechanism of this physiological function will be reported on in articles to follow.

1. The shell of the ova of Enterobius vermicularis is composed of two chitinous layers, a compact outer layer and a looser inner layer. Both surfaces of the two layers have a dense border. 2. The outer layer has innumerable tubules about 0.2 micron in diameter, and only those tubules found in the thinner part of the layer open to the outside and inside. 3. The outer layer of mature eggs is about 0.45 micron and the inner layer about 2 to 6 microns, in thickness. 4. The chitinous microfibrils in both layers form a rcticular structure which contains very fine granules in the mesh.

In 1955 SANO found mitochondria by the supravital stain with Janus green B in the basophilic stippled cells from the circulating blood of the lead intoxicated rabbitsl , and in 1956 by means of electronmicroscope VALLEJO-FREIRE, BRUNNER et al. found mitochondria in the reticulocytes2,3, and later at the end of 1956 BRAUNSTEINER et al. also succeeded in revealing mitochondria and the vesicular structure by electron microscope in the ultra thin section of young red cells4. We also have found the mitochondria and the endoplasmic reticulum in young red cells. It has been discussed long whether the reticulum of reticulocytes is a preexistent structure or an artifact. The fact that the mitochondria exist in the reticulocyte seems to support strongly the preexistence theory of the reticulum, substantia reticulo filamentosa. However, the fact that the reticulum has several characteristics different from the general mitochondria5,6 can not be ignored. In this paper we should like to demonstrate the photos of mitochondria and the endoplasmic reticulum in the denucleated red cells revealed by electron microscope comparing to the picture of reticuluocyte appeared by supravital stain.

The evaluations of the basal metabolism before the operation, at the completion, and at the follow-up examinations, have been conducted on the patients with cervical carcinoma, all under the age of 50 years, and operated on in the Clinics of Obstetrics and Gynecology, Okayama University Medical School and the following results are obtained: 1. The basal metabolism of the patients with cervical carcinoma of either stage I or stage II as compared with that of the normal women is more accelerated; while the basal metabolism of the cervical carcinoma of stage II. is more augmented than that of the cervical carcinoma stage I. 2. The basal metabolism at the completion of operation is markedly lower than that before the operation. 3. In those who received the autotransplantation of the ovary concomitantly with operation, the basal metabolism once increases at the 4th month after the operation and after that it maintains a low stable state. 4. The basal metabolism of those who received the operative castration continues increasing up to the 8th month after the operation and thereafter it returns to a rather balanced state. 5. From the aspects of the fluctuations of the basal metabolism, it has been recognized that the autotransplantation as compared with the castration exerts less influences on the somatic system and for a shorter period of time, and also the endocrine system of the former returns to the balanced condition earlier.

1. Adversive movements were induced by electrical stimulation and metrazol injection on area 4c of the cerebral cortex. 2. The adversive movement from area 4c does not pass through the thalamus, nucleus caudatus, nucleus lenticularis or superior collicuIus, but through direct efferent pathways in the internal capsule. 3. The adversive movement from area 4c passes through the pyramidal tract.

1. The rates of histamine release from the liver, skin and muscle by four kinds of histamine-releasing substances, sinomenine, compound 48/80, tween 20 and polyvinylpyrrolidone (PVP), were compared by intravenous injection in dogs, each in a dosage to cause a fall of approximately 80 per cent in the arterial blood pressure. 2. By compound 48/80, the rates were especially marked from the liver and muscle and only slight from the skin, while those by sinomenine, tween 20 and PVP were largest from the skin, followed by those from the liver and muscle, in that order. The rate of histamine release from the skin by PVP was characteristic in that it was far larger than that by other releasers. 3. On direct application of the drug solutions to the excised tissues of the liver and skin the rates of release of histamine differed only slightly by the tissue in any of these releasers 4. Some considerations were given on the reason for the different ratios by the organ of in vivo histamine release though as yet no definite conclusion could be drawn.

From the results of the various tests thus far mentioned, it may be said that of the patients with primary glaucoma, be it. inflammatory or simple, the majority point to the functional disturbances and unbalanced conditions of the diencephalo-hypophyseal system as well as of the autonomic system, and that their autonomic adjustment functions of the eye pressure as compared with those of the normal are considerably disturbed and are in unbalanced state.

The purpose of the present study is to reveal the precise mechanism of nervous and humoral regulations of lipid and carbohydrate metabolisms in the adipose tissues. Histochemical and biochemical observations were made on the innervated and denervated interscapular brown adipose tissues and partly on the liver and adrenal cortex of male mice during starvation with or without carbohydrate introduction with special consideration to the changes of the lipid and glycogen contents and to the activities of several important enzymes as well as to pH values in the tissues. In a state of absolute starvation, the animals died in a few days showing a gradual discharge of stored lipids from the innervated brown adipose tissues, while in the denervated tissues the stored lipids increased gradually even in a state of slight or moderate starvation as well as in the cases of normally fed animals. The increase of lipids continued before the stage of severe starvation and the stored lipids being rapidly discharged became nil at the terminal stage of life. Introduction of glucose into starved animals caused also a more marked deposition of glycogen in the denervated than in the innervated tissues in proportion to the degree of starvation, although it did not cause the deposition in both tissues at the terminal stage of life. These facts represent that the nervous regulation is essential for the mobilization of lipids and carbohydrates from this tissue. Adrenalectomy also caused the death of animals within a few days with a gradual decrease of depot lipids. In this case denervation likewise caused a marked depositon of lipids in the brown adipose tissues, showing a sudden escape of lipids at the end of life. Experiments on transplanted adipose tissues taken from the animals at the terminal stage of starvation, proved that the tissue cells retain the ability to deposit lipids until the end of life. Chemical estimation elucidated that the serum glucose and lipids fall markedly at the terminal stage of life. The innervated tissues showed increased activities of succinic dehydrogenase, alkaline phosphatase, ATPase and lipase during starvation with a gradual discharge of lipids. Glucose injection increased the degree of the activities of all these enzymes, though in the terminal stage of starvation the ATPase activity declined again. The activity of total cholinesterase declined slightly in severe starvation. The pH value fell gradually with the progress of starvation. On the other hand, in the denervated tissues the activity of succinic dehydrogenase fell with an increased deposition of lipids, though in the final stage of starvation the activity rose with the discharge of lipids; while the activities of phosphatase, ATPase and lipase rose during starvation and total, unspecific and specific cholinesterase activities declined slightly. The pH value in the denervated tissues rose slightly during mild starvation and fell markedly in severe starvation. Observations proved that the activities Df these enzymes and pH, which are under the control of the autonomic nervous system, have close relationships to the deposition and the discharge of lipids and glycogen from the adipose tissues, and that the rapid discharge of lipids from the denervated tissue at the terminal stage of life is an expression of the onesided progress of oxidative process which may mean a complete loss of regulation of metabolism.

1) Cerebellar convulsion was identical with the cerebral cortical epileptic convulsion and the number of cases in which the march of spasm was observed were quite the same as that of cases in which convulsion occurred at the same time on the whole body. 2) No convulsion occurred by stimulation of the vermis cerebellaris and also convulsions occurred very rarely by that of the cerebellar nuclei. 3) In cases having the march of spasm caused by stimulation of the lobus lunatus anterior, spasm began in the fore limb, while by stimulation of the lobus lunatus inferior and lobus semilunaris spasm started mainly in the hind limb on the side of stimulation. 4) In the case of stimulation of cerebellum, the pathway of the impulse to the opposite side was considered to be the communication between both cerebellar hemispheres and both thalami and thus the march of spasm spread from one side of the body to the other side. 5) No march of cerebellar epileptic convulsion occurred without the cerebral motor cortex. 6) After the removal of both sides of the cerebral motor cortex no march occurred, but the general convulsion occurred. 7) No convulsion occurred by stimulation of the cerebellar hemisphere after the removal of both thalami or both nuclei lenticulares. 8) The march of convulsion occurs by close cooperation of the pyramidal and extrapyramidal tracts. It seems that for the impulse of the convulsion the extrapyramidal tract plays an important role, while for the start of the convulsion, that is, march of spasm pyramidal tract plays the main role.

The analgesic effects of morphine and some related compounds, such as meperidine, observed by the conventional method, are supplemented by the release of epinephrine from the adrenal medulla. It is assumed that this action of epinephrine is not due to an additive synergy in the analgesic effect but to the face that the action of epinephrine on a definite higher center or centers effects synergistically in the reflex depressant action of these analgesic agants. This assumption is based on the following evidences. Prolongation of reaction time in mice by morphine and meperidine (but not by ohton), determined by the hot-plate method, was significantly reduced by adrenalectomy and this reduction was normalized by the concurrent use of epinephrine, in a small dose which in itself cannot prolong the reaction time. No such action was found in cortisone and DOCA. The effects of morphine and meperidine in prolonging the reaction time were reduced by priscol and dibenamine, as well as by tetraethylammonium salt. A large dose of pyrazolone derivatives causes, not the prolongation of reaction time but a jumping reflex response in the early stages, indicating central excitation, in part of the mice. The ratio of mice exhibiting such an early reflex increases with adrenalectomy or the administration of dibenamine, and is markedly decreased by epinephrine, insufficient to show any analgesic response by itself, and by cortisone. This action of cortisone indicates some difference in the natures of central excitation by pyrazolones and by morphine. Judging from the work of SCHAYER18, the distribution in the brain of epinephrine injected in the dose to normalize the reduced effect of morphine in the adrenalectomized mice, may also be anticipated by the epinephrine which might be released from the adrenal medulla by morphine in an amount much smaller than the "near·lethal doses9 ".

1) The contents of sialic acid in patients of various diseases sera were determined and increases of it were noticed in several diseases. 2) Sialic acid contents ranged between 50 and 100 mg./dl. in the normal serum. 3) But in the pathological serum, it ranged between 90 and 170 mg./dl. in cancer patients, between 80 and 110 mg./dl. in peptic ulcer, between 75 and 135 mg./dl. in arachnoiditis, and between 90 and 120 mg./dl. in epilepsy. 4) In other several diseases, sialic acid contents were determined.