Tissue polyamines were examined in 111 cases of breast cancer and 15 cases of benign breast tumor. Three common polyamines, i.e., putrescine, spermidine and spermine were found in all the tissue samples analyzed. The levels of the three polyamines were 5 to 7 times higher in breast cancer tissue than in normal breast tissue, and 2 to 4 times higher in cancer tissue than in benign breast tumors. Moreover, N¹-acetylspermidine was detected in 89.2% of cancer tissue, 20.0% of benign tumor tissue and in only 2.0% of normal breast tissue.
There was no significant difference in the polyamine levels of ER (estrogen receptor) -negative carcinomas and ER-positive carcinomas. The N¹-Acetylspermidine levels of ER-negative tumors were higher than those of ER-positive tumors. Similar findings were found with respect to the PgR (Progesterone receptor) status of tumors. Putrescine levels of breast cancer tissue were significantly higher in pre-menopausal women than in the post-menopausal group. The spermidine levels of normal breast tissue were significantly higher in the pre-menopausal group than in the post-menopausal group.
Besides the above three polyamines, two minor unknown polyamines, X-1 and X-2, were detected in about 9% of breast cancer tissue. The retention time of X-1 corresponded to that of homospermidine and the retention time of X-2 corresponded to that of aminopropylhomospermidine or canavalmine. The fraction containing X-1 was incubated with either putrescine oxidase or polyamine oxidase and the oxidation products were analyzed. Product analysis showed that X-1 was indeed identical to homospermidine.

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The proliferative kinetics of blasts of the granulocytic series was investigated in 10 patients with Di Guglielmo syndrome (G group) and the results were compared with those of our previous study in patients with RAEB, RAEBt, and acute leukemia without marked erythroblast dysplastic changes (non-G group). The results obtained were as follows :
(1) The G group consisted of 3 cases in the RAEB phase, 3 cases in the M6 phase and 4 cases in the leukemic phase (M2 or Ml) according to the FAB's new criteria. Except for the MI of the RAEB phase, the mean values for the TLI and MI of blasts in each phase were significantly lower than in normal subjects. In TLI, the mean value was significantly higher in the RAEB phase than in either the M6 or the leukemic phase, while no difference was observed between the means of the latter two phases. A similar tendency was observed in MI. Among all patients in the G group, both TLI and MI were significantly correlated with blast counts of bone marrow smears. These results are similar to those obtained in the non-G group and thus it seems that in the G group RAEB phase can be classified the preleukemic phase and the M6 phase as the leukemic phase, providing evidence of the adequacy of FAB's new diagnostic criteria for M6.
(2) In the RAEB phase of the G group, there was a tendency toward prolonged blast DNA synthesis time and an increased number of small blasts not labeled with ³H-TdR. This tendency was more distinct in M6 and leukemic phases, supporting our view that the RAEB phase should be regarded as the preleukemic phase in the G group.
(3) Marrow GM-CFU colony formation was observed in the RAEB phase but not in the M6 or the leukemic phases.
(4) The TLIs of erythroblasts in the G group were compared with those in the non-G group. It appeared from the results obtained that the target of the neoplastic transformation in the G group might be the pluripotent hematopoietic stem cells.

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Serum levels of tumor markers CA19-9 and CA50 were examined in 115 cases of gastric cancer and immunohistochemical staining was carried out. The relationship between CA19-9, CA50, clinical histopathological findings and prognosis was analyzed. The results were an follows.
1) Serum levels of CA19-9 and CA50 were higher than in healthy controls, and paralleled tumor stage. The positive rate for serum CA50 was a little higher than for serum CA19-9, but serum CA50 was elevated in few cases of cholecystitis control.
2) The higher the serum levels of CA19-9 and CA50, the more advanced the severity of histopathological findings.
3) Serum levels of CA19-9 were significantly correlated with CA50 levels in gastric cancer (r=0.928).
4) The positive rate for serum levels was greatly increased by the combined assay for CA19-9, CA50 and CEA compared with single assay.
5) Immunohistochemical staining for CA19-9, CA50 showed localization to the apical border and intraluminal space in well differentiated cancer as apposed to the cytoplasm in poorly differentiated cancer.
6) The higher the positive rate in for tissue CA19-9 and CA50, the more advanced stage and the histopathological findings.
7) The prognosis was worse in the serum and tissue CA19-9 and CA50 positive group than in the negative group.
All of the above results suggests that the measurement of CA19-9 and CA50 in serum and tissue reflects biological behavior and histopathological malignancy in gastric cancer and facilitates the determination of appropriate therapy for gastric cancer patients as well as the assessment of preoperative stages and prognosis.

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We studied 61 patients with primary intracranial germ cell tumors treated between 1954 and 1988 and reviewed previous reports. Our patient series included 48 males and 13 females with an age range of 5 to 41 years (mean, 15 years). Thirty-six tumors arose in the pineal region, 14 were suprasellar, and 11 in the basal ganglia and thalamus. There were 42 germinomas, 5 teratomas, and 14 malignant germ cell tumors (MGT) (8 embryonal carcinomas, 3 yolk sac carcinomas, and 3 choriocarcinomas). The diagnosis was histologically verified in 43 cases (29 operations, 12 autopsies, 2 cytological studies); the remaining 18 tumors were diagnosed on the basis of characteristic clinical and radiological features, tumor markers, and response to radiotherapy.
We evaluated these patients' clinical symptoms, radiological images, and tumor markersexisting in both serum and cerebrospinal fluid (CSF) -revealed by immunohistochemistry. These markers included alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PALP). The levels cf tumor markers reflected tumor state and were well correlated with the histological diagnosis ; i.e., yolk sac carcinoma produced AFP ; choriocarcinoma, HCG ; embryonal carcinoma, AFP and HCG; teratoma, CEA ; and germinoma, PALP.
The enzyme activity of PALP in CSF was measured by enzyme antigen immuno-assay (EAIA) in 14 patients in our laboratory. In 4 out of 6 germinoma patients, pre-treatment PALP in CSF exceeded 7 ng/ml and marked reductions occurred with radiation, while pre-and post-treatment PALP in patients with other germ cell tumors lower than 5 ng/ml. These results with EAIA suggested that measurement of PALP levels would be useful in the management of patients with germ cell tumors, particularly germinomas.
The therapeutic regimens included surgery, irradiation, and chemotherapy. Germinomas were curable by radiation therapy. Teratomas were cured by microsurgery alone. Patients with radioresistant MGT and distant metastases had a poorer prognosis. Chemotherapy appeared to be a promising approach to treat MGT. Compared to radiation therapy alone, the theoretical advantages of chemotherapy include : 1) tumor specificity ; 2) control of occult distant metastases ; 3) a possible synergistic effect with radiation therapy ; and 4) reduction of the radiation dose and thereby lessening of the potential for late radiation-induced damage to the central nervous system.
During the last 3 decades, dramatic improvement in the management and outcome of intracranial germ cell tumors has been accomplished by : 1) the introduction of high-resolution CT and magnetic resonance imaging ; 2) pre- and post-treatment assessment of tumor markers in serum and CSF ; 3) advances in microsurgical and stereotactic surgical techniques ; and 4) new chemotherapeutic agents and regimens. Questions and controversies remain, however. For example, should all pineal germinomas be biopsied or should radiation therapy be initiated without biopsy? How heavily can we rely on the histologic specificity of tumor markers? Is prophylactic spinal irradiation indicated in all cases of germinoma? What chemotherapy regimens are most effective against various types of MGT? Which is preferable as initial treatment of MGT, radiotherapy or chemotherapy? For further improvements in the treatment of primary intracranial germ cell tumors, more extensive investigation of their clinical and biological characteristics is necessary.

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Neuronal survival and neurite elongation in tissue culture are usually evaluated by counting the number of nerve cells and measuring neurite length on photographs, respectively. Because this is very time-consuming and not free of some artificial aberration, more reliable and simpler methods are needed. In this report, enzyme immunoassay (EIA) for quantitation of neurofilament protein is demonstrated to be an excellent method for evaluating neurite outgrowth and the number of surviving neurons in tissue culture. EIA is applied to the evaluation of nerve growth factor (NGF) -dependent neurite regeneration capacity in aged animals and to a study of the cytotoxic effects of dopa and dopamine on cultured nerve cells.
Dorsal root ganglion (DRG) neurons were obtained from 10-week-old (Group Y), 72-week-old (Group M) and 114-week-old (Group O) male mice. Dissociated neuronal cells from each group were cultured for 4 days in chemically defined serum-free medium including various levels of NGF up to 160 ng/ml. Then EIA was performed using rabbit anti-neurofilament protein (NF) serum as the first antibody. NF content was expressed as optical density.
EIA revealed less neurite outgrowth in Group M than in Group Y, but acceleration after the addition of a large amount of NGF. Neurite elongation capacity in Group O was moderately reduced at all levels of NGF when compared with the other groups. At the same time, however, significant NGF-dependent neurite regeneration capacity was preserved in aged animals. In Group Y and M, maximum length (ML : length of the longest neurite of an individual neuron) and total length (TL : sum of the length of all neurites of the neuron) were also quantified by tracing the distance on photographs. Optical densities were well correlated with ML in both groups and TL in Group Y. There was no correlation between optical densities and TL in Group M because of considerable fluctuation in TL.
EIA optical density, i.e., NF content, was determined to be a reliable index for evaluating the number of surviving neurons in tissue culture. DRG neurons were obtained from 5-week-old mice and were seeded at various densities. The number of neurons counted and EIA optical density were significantly correlated. Using this method the effects of dopa and dopamine on the DRG neurons were tested. Neurons were destroyed by exposure to 0.5 mM dopa or 1.0 mM dopamine with or without superoxide dismutase and catalase, but they were spared by pretreatment with 1.0 mM deferoxamine mesylate. These results indicate that dopa and dopamine cause neuronal cell death in the presence of a small amount of iron in the culture with little or no participation by reactive oxygen species. As reported elsewhere, formation of malondialdehyde is also observed in the reaction between dopa and dissociated cerebral cortical neurons only when iron is present, which suggests that the complex of dopa (or dopamine) and iron initiates cell membrane lipid peroxidation leading to the neuronal destruction. In Parkinson's disease the mechanism of cytotoxicity may involve neuronal degeneration in the substantia nigra, which has an abundance of both iron and dopaminergic neurons. Further study is required to elucidate what triggers iron and dopa (dopamine) -mediated lipoxigenation of cell membranes in human brain in the presence of protective factors such as iron-transporters, tocopherols, phosphates, etc.

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The present study was attempted in order to investigate the effectiveness of propranolol in limiting of myocardial infarct size following ligation of the left coronary artery in Wistar rats. The non-infarcted ischemic zone, the border zone, was significantly larger in the rats sacrificed 3 hours after the ligation (25.6±4.9% LV) than in those sacrificed 6 hours after ligation (10.7±6.6%LV). No border zone was demonstrated when the rats were sacrificed 12 hours after the ligation. Nor were any differences in the size of the area at risk found among the above 3 groups. The size of the infarcted area was significantly smaller than in the control group (46. 0±5.5%LV) when propranolol was administered intraperitoneally before (25.3±4.6%LV), immediately after (35.0±4.1%LV) or 3 hours after ligation (36.6±4.7%LV). However, propranolol could not reduce infarct size when administered 6 hours (44.1±8.5%LV) or 12 hours (46.2±3.6%LV) after ligation of the coronary artery.
The present study clearly demonstrates the presence of a non-infarcted ischemic zone, a border zone, until at least 6 hours after the ligation of the coronary artery and reduction of the infarcted area by propranolol when administered until at least 3 hours after the ligation. Thus, the author postulated the usefulness of beta-blocking agents in the early phase of acute myocardial infarction.

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Methamphetamine (MAP), ephedrine (EPH) and cocaine (COC) are frequently abused and sometimes result in psychotoxic effects in human. The present study was undertaken to examine the effects of single and repeated administration of MAP (1.25-10mg/kg s.c.), EPH (20-80mg/kg i.p.) and COC (10-40mg/kg i.p.) on stereotyped behavior, such as sniffing (SN), head-bobbing (HB), licking (LI), head-weaving (HW), turning (TU), back-pedalling (BP) and gnawing (GN) in rats, as animal models of psychotoxic symptoms. Moreover, in order to investigate the neurochemical basis for such changes, the brain levels of dopamine, noradrenaline and their metabolites were determined in the striatum.
Among these drugs, MAP produced the most dynamic and diverse behavioral changes in the following order : locomotion-and rearing-increase→SN→HB→LI and HW→TU, BP and GN. The behavioral effects of EPH resembled those of MAP, though the activities v, ere low. However, COC failed to produce LI, HW, TU, BP or GN even in the subconvulsive dose of 40mg/kg i.p. Of these stereotyped behaviors, SN and HB were found to be strongly dose-dependent in all cases of administration of the three drugs. When the drugs were repeatedly administered, the SN-and HB-producing effects markedly enhanced showing the reverse tolerance, but no reverse tolerance to the other stereotypy-producing effects. Once reverse tolerance was established, it was maintained for 1 month after the drug was discontinued.
The neurochemical studies demonstrated that dopaminergic neurons play an important role in the development of reverse tolerance to the SN-and HB-producing effects in all cases in which the three drugs were administered. It was also suggested that noradrenergic neurons are involved in the case of COC administration.

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Asymptomatic myocardial infarction (MI) was found in 8 (3%) of the 274 patients with MI who underwent coronary angiography, and half of them were diabetics. They represented only 7% of all diabetics however. Twenty-four (9%) had new onset angina within 2 weeks before MI. Among them, 9 (38%) were diabetics and they represented 15% of all diabetics. In terms of the incidence of MI with or without angina, except for the new onset group, there was no significant difference between diabetics and non-diabetics. The severity of coronary atherosclerosis was independent of the presence of angina prior to MI. Our results indicated that the incidence of asymptomatic MI in diabetics is not as high as previously believed.

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Most people are aware that leukocytes are reduced as a result of radiation therapy, and many chemical protectors are given to prevent leukopenia in radiation clinics.
We studied the peripheral leukocyte counts of 100 patients treated with radiation from 1986 to 1988. Leukocytes were reduced during radiation therapy, but the decrease was not significant, the leukocyte counts fell below 3000/μl in only 6 patients. In only 1 patient was the leukocyte counts reduced to below 2000/μl by radiation. The results of this study indicate that adequate criteria for estimation of the effects of chemical protectors are needed in radiation therapy.

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Out of 97 cases with curative resection for gastric cancer who were treated at the Gunma University Hospital, 7 (7.2%) had skipped metastasis (SM) in the regional lymphnodes (LN). Each SM except for one case was hard to know in advance at the time of laparotomy. They are currently alive and disease free. The SM was observed in the group of relatively elderly patients. Most of the tumors were Borrmann type III macroscopically, while histopathologic evaluation revealed an infiltrating type with lymph vessel invasion of the cancer cells and scarce lymphoid reaction of the host. The histologic reaction in the regional LN of the patients with SM was evaluated in terms of sinus histiocytosis (SH) and follicular hyperplasia (FH). Both of these parameters were graded into three categories : (-), (+) and (+ +). The LN with positive metastasis were classified into SH (-) and SH (+), 80% and 20%, respectively, and that with negative metastasis into SH (-), SH (+) and SH (+ +), 68%, 29% and 3 %, respectively, suggesting that regional LN of the patients with SM is histologically inert. Thus, immigrating cancer cells will pass through these LN barriers more easily than the hyper-reactive one. The results in the present study lend further support to the notion that radical extended LN dissection should be needed in improving the outcome of gastric cancer surgery.

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Changes in blood glucose and plasma lipids were studied in 15 mice after inoculation with encephalomyocarditis-virus-M-variant. Glucose levels were significantly elevated 1 week after infection, and remained elevated for the duration of the experiment. Serum total cholesterol and triglyceride levels were elevated and reached their maximums 2 weeks after infection, whereas HDL-cholesterol levels had decreased 1 week after infection and reached its maximum at 4 weeks after infection. Histologic examination revealed insulitis and myocarditis. A delay in the elevation of HDL-cholesterol was noted in this study.

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Myocardial T1-201 Washout rates (WORs) after exercise stress were measured in 15 normal subjects and 67 patients with coronary artery disease (CAD) or chest pain syndrome and the usefulness of WOR for the detection of CAD was studied.
Myocardial tomograms were obtained both immediately after exercise and 3 hours later using a rotating gamma camera in 15 normal subjects and 67 patients. After low-pass filtering, images were reconstructed into short-axis, horizontal long-axis and vertical long-axis tomograms and visually interpreted. By using short-axis tomograms, left ventricle WORs were expressed as circumferential profile curves at the apex, center and base of the ventricle. Lower normal limits of the WOR were set at 2 SDs from the mean of the normal subjects. The combination of visual interpretation of SPECT with WOR increased the sensitivity of detection of CAD from 8.3% to 66.7% in patients with three-vessel CAD without losing specificity.
WOR after exercise stress is believed to be a useful method of detecting multivessel CAD.

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