Studies were made on the changes of peripheral lymphocyte count and those of some immunoreactivities observed in 21 patients with advanced cancer following the chemoimmunotherapy including OK-432.
The res ults obtained were as follows:
1) Peripheral lymphocyte count incr eased in 15 of 21 cases (71.4%) following immunostimulants administration; i. e. in 6 of 11 cases (54.5%) treated with OK-432 only, and in 9of 10 cases (90%) treated with both OK-432 and PSK (Krestin) as immunostimulants.
That is to say, in the cases treated with OK-432 combined with PS K, peripheral lymphocyte count increased more frequently than in those treated with OK-432 alone.
These increment occurred 2 to 4 weeks after administration of t hese immunostimulants was begun.
Besides, in 2 of 4 cases examined, the proportion of T lymphocytes in peripheral lymphocytes was found to be increased.
2) In some cases, seral γ-globulinl evels increased following the therapy including immunostimulants. In one of the cases, all of IgA, G, M, E increased, and in another, only IgG increased.
3) The reactivity against skin tests using PPD or PHA was intensified in 4 of 6 cases (66.7%) and in 2 of 3 cases respectively, following the treatment with immunostimulants.
In a large majority of these cases, the augmented reactivity was accom panied by increased peripheral lymphocyte count.
4) In all of the ca ses which had shown positive reaction to PPD before the treatment, the increment of peripheral lymphocyte count was seen following immunostimulants administration. On the other hand, the latter was detected only in one half of the cases which had shown negative reaction.
5) F urther, the incidence of peripheral lymphocyte increase was compared among the patients groups, each treated with different administrative schedule respectively: The immunostimulant therapy antecedent to the combination of chemotherapy caused increment of peripheral lymphocyte count in all of 5 cases (100%), while chemotherapy followed by immunostimulants induced the increment in only 4 of 7 cases (57.1%). Simultaneous combination therapy caused it in 5 of 7 cases (71.4%).
6) Among the cases show ing reactive fever against OK-432, the increment of peripheral lymphocyte count was more frequent than among the cases without the fever.
7) Among 9 cases which had shown high level of carcinoembryonic antigen, only 3 showed lowering of its level following the chemoimmunotherapies, although in 8 of these cases (88.9%) peripheral lymphocyte counts were increased following the therapies, i. e. wide discrepancy was observed between these two parameters.

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The purpose of present experiments was to investigate feasibility of Sclero-Uveoretinectomy for an resection of intraocular tumor, intraocular biopsy and extraction of nonmagnetic intraocular foreign bodiy.
Presen t experiments were performed in two different procedure. One is a so-called trephine method and the other a scleral flap method.
A trephine method was performed to investigate an area and limitation for Sclero-Uveoretinectomy.
A surgical procedure of the trephine method was as follows:
Three week prior to resection, a rabbit eye was treated by diathermy, photocoagulation or cryotherapy. After a chorioretinal scar was developed, a scleral supporting ring was sutured in the episclera and eye wall resected by trephine 8mm in diameter. A resected area was transplantated with a scleral homograft.
A surgical procedure of a scleral flap method was as follows:
After a scleral supporting ring was sutured, a scleral flap w as made, diathermy was appplied in around an area to be resected. under a sclaral flap After diathermy was applied, sclero-chorioretinectom y was performed and the scleral flap was sutured.
A procedure for biopsy of the choroid and the retina was as follows.
A scleral supporting ring was sutured and a scleral flap (7×7mm) was made in equator region. After scleral flap was formed, diathermy and wet-field coagulation or cryotherapy was made in an area to be resected under a sclaral flap and partial screo-chorioretinectomy was performed beneath the scleral flap. The scleral flap was sutured.
The result were as follow:
1. Eye balls tolerated aga i nst these kinds of operations.
2. Complications which occurred in eye wall resection were bleeding from choroidal vessels, vitreous loss, vitreous hemorrhage, postoperative inflammation, retinal detachment, infection and phthisis bulbi.
3. Diathe rmy coagulation was effective to prevent bleeding from the choroidal vessels during entire procedure and postoperative complication.
4. Eyes which were resected 180°in the anterior segment developed in phthisis bulbi.
5. Eyes resected an horizontal meridian of the globe including the long posterior c iliary artery met severe vitreous hemorrhage and showed an inevitable poor prognosis.
6. Eyes resected in a vertical meridian of the globe excluding the long posterior ciliar artery met a few complications and took a good prognosis.
7. Biopsy specimen could, be removed by application of diathermy and cryotherapy without destruction of histological structure, but structure of biopsy specimen which was removed by wet-field coagulation was greatly destroyed. Comparing these kinds of proce dures, we could demonstrated a posibility of partial eye wall resection or biopsy of the retino-chroidal tissue. A scleral flap method using a scleral supporting ring was made with a few complications. Application of diathermy and cryotherapy under a scleral flap were necessary to prevent from choroidal bleeding.

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With the purpose to clarify the immunological disturbances being behind the several pulmonary diseases, studies were made on autoantibodies (RA test, LE phenomenon, LE test, ANA, DNA test and others) and hypergammaglobulinemia found in 55 cases (one of acute bronchitis,8 of chronic bronchitis,16 of pneumonia,2 of interstitial pneumonitis,6 of pulmonary fibrosis,4 of pneumoconiosis,15 of pulmonary tuberculosis, and 3 of pulmonary emphysema) which had been treated in our department during the last 8 years.
Several autoantibodies and hypergammaglobulinem ia were found not only in chronic pulmonary diseases as reported in several literatures, but also in acute pulmonary diseases such as pneumonia; i. e. RA test 37.5%, DNA test 1/16, ANA (2) */16 (* titers were low, lox) and hypergammaglobulinemia 30.8%.
Above mentioned findings seem to suggest that further studies on immunological disturbances would be necessary not only in chronic pulmonary diseases such as chronic bronchitis and pulmonary fibrosis, but also in acute pulmonary diseases such as pneumonia.

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To ascertain the effect of fat-content in diet on the development of breast cancer, the semisynthetic diets containing corn oil (polyunsaturated fatty acids; more than 80%) in the weight percentages of 0,8 or 40 were prepared and 141 young adult Sprague-Dawley females were used for the following experimental designs. In the first group, the uptake and clearance of labeled DMBA within the mammary fatty pads of 20 rats administered by fat-free and 40%corn oil diets, respectively, at the ages of 45-87 days were observed in 3 days after the intravenous injection of carcinogen. In the second group,90 rats (a-subgroup) were intubated by 10mg of DMBA twice on the ages of 56 and 59 days, and 31 rats (b-subgroup) never received DMBA. The animals of b-subgroup were fed on fat-free,8% corn oil and 40% corn oil diets, respectively, at the ages of 70-100 or -115 days, and they were finally sacrificed either for the determination of serum prolactin and estrogens or for the analysis of fatty acid compositions within the mammary fatty pads. The effective number of rats in a-subgroup were fed on 3kinds of the above-mentioned semisynthetic diets, respectively, at the ages of 90-150 days, and they were applied to the observations on the developments of mammary cancers, endocrinologic states of these cancer-bearers and fatty acid compositions of these mammary tumor phospholipids.
In group II a, the averages of caloric intake were 52.4,52.2 and 50.3 Cal/rat/day, respectively, in the fat-free,8% corn oil and 40% corn oil diet groups, and the curves of average body weight were not different from each other diet group. However, both the average number of cancer per a rat (3.2±2.2,6.5±2.5) and average weight of cancer per a rat (654.0±498.7mg,690.5±477.3mg) were much higher in the 8% and 40% corn oil diet groups, wit h compared from the fat-free diet group (1.6±0.9,331.6±226.5mg). These figures were statistically different from each other diet group (p<0.01). The endocrinologic states (serum prolactin, serum estrogens, prolactin/estrogens at the same sexual cycle and weight of the endocrine organs) of the hosts were similar in each diet groups. In the mammary tumor phospholipids, linoleic acid increased and arachidonic acid decreased in the 40% corn oil diet group, in comparison of the fat-free diet group. These deviations were statistically significant (p<0.01). In group 11b, the hormonal balances of animals seemed to be not disturbed by these semisynthetic diets, and linoleic acid within the mammary fatty pads decreased profoundly in the fat-free diet group, where any disorders from essential fatty acid deficiency could not be detected yet. In group II, the uptake and clearance of tritiated DMBA within the mammary fatty pads of the 40% corn oil diet group were not significantly different from those of the other diet groups.
In conclusion, the extremely high corn oil diet enhanced prominently the devel opment of DMBA-induced mammary cancers, especially number of cancer per an animal, without any endocrinologic and caloric alterations in these cancer-bearers. Such an enhancement might be introduced by the increased amounts of polyunsaturated fatty acids within the mammary fatty pads of the hosts and by some alterations of fatty acid composition of the tumor phospholipids.

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The incidence, gastric juice secretion, serum gastrin level and conversion to intractable peptic ulcer in patients of peptic ulcers complicated with liver diseases were surveyed. Numbers of cases with liver diseases were 579 out of 30480 clinical ones during January 1971 through December 1977 at the departments of internal medicine and 178 out of 2354 autopsied ones in the past 26 years at the department of pathology of Kansai Medical University.
The complication incidences of peptic ulcers with liver diseases in clinical cases were 12.1%in inactive chronic hepatitis,10.0% in decompensatory liver cirrhosis and 10.0% in primary liver carcinoma. Those in autopsy cases were 11.2% in liver cirrhosis and 14.0% in primary liver carcinoma. The complication frequency of peptic ulcers was higher in portal liver cirrhosis than in post necrotic liver cirrhosis, not related with the presence or absence of primary liver carcinoma.
Serum gastrin levels at fasted resting state were high in decompensatory liver cirrhosis and gastric cancer although it was in the normal range in most of the other diseases. Its level in liver cirrhosis was higher in cases with esophageal varices than those without them.
The recurrence of intractable peptic ulcers accompanied with liver dise ases was always observed and it was not related with the decline of liver function. Moreover, no specific findings were observed either with the time interval of the recurrence, nor with the site, size or type of peptic ulcers.

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Some purified esterases for lipids, e. g. mould lipase, snake venom phospholipase A², cholesterol esterase from microorganism, were applied for the analysis of smaller fat granules in ultrastructure. The enzymes were purchased from Böhringer-Mannheim Co., and another mould lipase was donated from Drs. Tsujisaka and Iwai of Osaka Municipal Technical Research Institute. Some organs containing various amounts of lipids in rats, e. g. early and recovery stages of the Ethionine-induced fatty liver in females, the liver of fasting females, the Gentamicininjured renal cortex, the lactating mammary gland and the adrenal cortex of resting males, were perfused with a heparin-containing saline for 2 min and subsequently with 1/2 Karnovsky fixative for 3 min. Both tissue blocks, sized 0.5-1cm³, from the perfused organs and the atheromatous focus of human aorta were incubated in cold Karnovsky fixative for 1-2 hr, washed in cold cacodylate buffer with sucrose overnight, cut to 40μ-thick sections by Vibratom. The free-floating sections were treated in the following digestion media, respectively, at 37°C for 1/22 hr, while the medium was usually shaken rhythmically on the machine. The digestion medium was composed of 4m1 of 0.05 Tris buffer,1 ml of 2% calcium chloride and an enzyme. The enzyme was added as follows; 0.075 ml of lipase of Drs. Tsujisaka and Iwai at pH 7.2 for triglycerides detection,0.5 ml of snake venom phospholipase A2 of Böhringer at pH 7.5 for phospholipidsdetection, or 0.21 ml of cholesterol esterase of Böhringer at pH 7.6 for cholesterol esters detection. Duplicate control sections were treated in the reaction medium without enzyme. After treatment the sections were washed in cold distilled water, immersed in 0.1% lead nitrate for 15 min, washed again thoroughly in distilled water, post fixed in cold osmium buffer for 1.5 hr, dehydrated in cold graded ethanols according to Idelman's procedure, and finally embedded in epoxy resin. The ultrathin sections with or without metal staining were observed under an electron microscope. Derived fatty acids after the digestion with a specific enzyme were detected as lead soaps which had not been seen in the duplicate control section. These reaction products should indicate the location of the substrate lipid. Derived fatty acids could be also observed by means of Holczinger's method for fatty acids under a light microscope, when both pretreatments of removal of fatty acids and calcium in tissues should be done.
Many co arse reaction products for triglycerides could be seen on newly appearing and disappearing fine lipid materials within the hepatic cells. Those for phospholipids revealed in some cytosegresomes of renal cortex, milk fat globule membranes, and biomembrane system of the examined cells, More trials are requested for ultrastructural detections of cholesterol esters, but the reaction products after cholesterol esterase digestion could be seen in adrenal cortical cells and macrophages in atheromatous foci. Both utility in histochemical analysis for the mixed phase of lipid spheres and limitation depending on the size of lipid particles were discussed on the ultracytochemical observations by this enzymic digestive method.

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The surgical indication of the cerebral AVM is usually decided by its clinical symptoms and circulatory pattern as well as its size and location. The objects of this study are to enable to resect various kinds of the cerebral AVM whenever indicated and/or to develop a new operative procedure. For these purposes, the author investigates fine anatomical structure and hemodynamics of the AVM, using plastic casts obtained from surgical and autopsied specimens, fluorescein angiography during operation, and sequential subtraction angiography technique. The results obtained from this study show the findings described as follows:
1) The parent artery, so-called feeding artery of the AVM, suppl ies not only the nidus of the AVM but the brain parenchym adjacent to the AVM.
2) The circulation of the cortical surface surround ing the AVM is found to be delayed comparing with that of the AVM.
3) The parent artery gives several abnormal shaped branches on its course to the peripheral part. Here, the author designates these abnormal tributaries as proper feeder, which also form important part of the nidus.
4) The connecting vessel which has the possibility to develop into the feeder as hemodynamic change occurs, is observed between the AVM and the normal cortical artery.
5) Abnormal vascular channels within the nidus, including both the p roper feeder and the drainer in the nidus, have a complicated anatomical relationship among them, showing an appearance of diverging and connecting each other in an obtuse angle.
6) Coil-like vessel and aneurysmal dilatation are observed in r elatively fine vessels within the AVM. There is a tendency that the larger the size of the AVM is, the larger the diameter of abnormal vessel becomes.
7) It is indica ted that the ordinary circulatory pattern in the nidus of the AVM is originating from its external zone and running toward the drainer in the nidus of the AVM. In large AVMs, delayed circulation at the adjacent part of the drainer in the nidus is seen.
8) Reserve nidus or preangiomatous area is not revealed on angiogram and lo c ated in the peripheral zone of the AVM, where no main stream of AV shunt is produced. It is suspected that the peculiar circulatory pattern in these areas is the cause of failure in angiographical demonstration.
9) Large drainer in the nidus forms the centrally situated core of the nidus and drains exclusively from the AVM.
10) Superficial draining vein of the AVM receives blood both from the AVM and the adjacent normal cortex, so that the congestion and disturbance of venous return in the neighboring normal cortex can be produced by increased venous pressure.

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Internal Medicine, Saiseikai Izuo Hospital, Osaka, Japan Collagen diseases, especially systemic lupus erythematosus (SLE), are often accompanied by psychoneurological disorders. But, it is a rare instance that these disorders appear prior to the physical symptoms. In such cases, as to the correlation between the collagen diseases and the antecedent psychoneurological disorders, several possibilities should be considered, although definite conclusion may not always be obtained.
We have recently experienced such fo ur cases as follows:
Case 1: T. Y.,40 y. o., female. (Table 1)
The patient was diagnosed as thrombocytope nic purpura, and also as epilepsy eight and six years ago respectively. After six years administration with phenobalbital alone, leucopenia, thrombocytopenia and seral anti-DNA antibody (×160) have been detected.
In this case, a possibility that the prior epilepsy (grand mal) and the status suspicious of collagen disease, especially SLE, have developed relatedly should be preferred to other possibilities.
Case 2: N. E.,50 y. o., male. (Table 2)
After treatment with diphenylhydantoin and phenobalbital under the diagnosis of epilepsy (grand mal) for thirty-four years, the patient obtained complains of fever, polyarthralgia and butterfly erythema. Laboratory examinations revealed ANA (×320), Anti-DNA antibody (×80), BFP (+), while CHSO being normal.
In this case, diphenylhydantoin ind uced SLE should be most preferable as the diagnosis.
Case 3: T. T.,44 y. o., female (Table 3)
The patient has been showing schizophren ia-like psychopathy since 24 to 25 years of age, i. e.7 to 8 years antecedent to the diagnosis of SLE, which was established on the basis of symptoms and signs, i. e. fever, butterfly erythema, positive LE phenomenon, ANA (×648), Anti-DNA antibody ( x 160), low CHSO, anemia, leucopenia, thrombocytopenia, and proteinuria. Corticoid therapy resulted improvement of her physical laboratory findings except for psychopathy. In spite of her psychopathic disposition (her grandmother: mental disease), the possibility of SLE initiating with antecedent symptomatic psychopathy should be most preferable as the diagnosis.
Case 4: M. T.,54 y. o., female. (Table 4)
A depressive psychopathic state appeared, accompanied by fever and skin eruption. Her laboratory findings such as anemia, leucopenia, ANA (×640), Anti-DNA antibody (×29), RA BFP (+), low CHSO, Microsome test ×6400, and Thyroid test ×400 suggested SL E. Thereafter, her psychopathic state fluctuated concomitantly with her physical and laboratory abnormalities. Corticoid administration resulted subsequent improvement of all of the abnormal findings including the psychopathic disorder. In this case, the psychopathy ma y seemed to be a symptomatic psychosis, while her psychopathic disposition was suggested by her family history, i. e. her sister had schizophrenia.

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Nineteen patients with cancer of colon or of rectum treated in our department in the past 16years (1965-1980) were studied on the factors possibly related to the occurrence of these cancers directly or indirectly. In one case, derm atomyositis was seen concomitantly with the rectal cancer.
In other two cases, uterine or gastric cancer were recognized antecedently or subsequently to the colon cancer respectively. And also, carcinomatous diathesis was found in the family history of 2 cases; in one of which, his father had similarly suffered from colon cancer.
Moreover, antecedent diabetes mellitus were complicated in 3 (15.8%) among the 19 colon cancer cases, the frequency being higher than that in the population of the country: the relationship between the diabetes mellitus and the occurrence of colon cancer should be further investigated.
Although the number of the cases examined was limited, these findings seem to suggest that autoimtnune diseases such as dermatomyositis, antecedent cancers, hereditary loading of carci nomatous diathesis, and also diabetes mellitus may affect the incidence of colon or rectal cancer.

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In 1972, Brunner and coworkers suggested that patients with normal and high renin essential hypertension were at an increased risk of stroke or myocardial infarction as compared with patients with low renin. High PRA level appears to be a risk factor for cardiovascular complications in essential hypertension. But there are many controversies regarding that report.
Several authors reported that urinary or plasma noradrenaline level elevated and correlated slightly positively to PRA level in patients with essential hypertension. It seems that renin-angiotensin system and the sympathetic nervous system may play important roles in maintaining high blood pressure at least in a part of essential hypertension. However, there is no definite evidence that these factors are involved in the pathogenesis of essential hypertension.
In order to investigate interrelations among the renin-angiotensin system, the sympathetic nervous system and the grade of cardiovascular damage in essential hypertension, PRA and severity index were estimated in 105 patients with essential hypertension and urinary noradrenaline was measured in 36 out of 105 patients and in 11 normal subjects. The subjects were either untreated or withheld from any antihypertensive drug for at least one week before the study. Dietary sodium was unristricted.
In the morning under a fasting condition, urine was voided completely at 8: 00 a. m. and blood sample for PRA was taken at 9: 00 a. m. after a one hour rest. Then the subjects took 80 mg of furosemide orally and a second blood sample was taken at 12: 00 a. m. after three hours of ambulation. Urine specimens were collected from 8: 00 a. m. to 9: 00 a. m. and from 9: 00 a. m. to 12: 00 a. m. to estimate the noradrenaline excretion rate at rest and during provocation, respectively.
PRA was measure d by radioimmunoassay and urinary noradrenaline was determined by the trihydroxyindole method. The severity of essential hypertension was estimated according to the severity scoring proposed by three Departments of Internal Medicine of Tokyo University.
The hypertensive subjects were classified into low, normal and high renin g roups depending on their renin responses to the provocation (furosemide plus ambulation) taking into account patients' age. The res ults were as follows:
1) Sixty-six percent of low renin hypertensive subjects was female. Fifty six percent of all hypertensive women belonged to the low renin group.
2) PRA level correlated positively with blood pressure at rest in all essential hypertensives and in the high renin group. However, no correlation was found in low and normal renin groups.
3) There was no significant differnce in the total severity index between low and normal renin groups. The mean value of the index in the high renin group was high as compared with the other groups.
4) There wa s no correlation between age and urinary noradrenaline excretion rate in normal subjects and in all hypertensive patients. Moreover, the urinary noradrenaline excretion rate did not significantly correlate with blood pressure and PRA level in all patients and in each renin subgroup.
5) The urinary noradrenaline excretion rate during provocation in about 25% of essential hypertensive subjects was elevated above Mean+ 2SD of that in normal subjects.
6) There was no marked difference in urinary noradrenaline excretio n rate at rest among renin subgroups. The change in noradrenaline excretion rate by provocation in the low renin group was low as compared with the other groups.
7) The urinary noradrenaline excretion rat e during provocation in the mild essential hypertension (less than 6 point of total severity index) was significantly higher than that in the moderate essential hypertension (from 7 to 10 point).

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