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The ultrastructural and biochemical changes in the brain tissue of 20 mice were studied. The mice, separated into acute and chronic groups, were injected with phorbol myristate acetate (PMA) to trigger the release of free radicals. Malondialdehyde measurement and electron microscopic examination were applied for the evaluation of the effects of the free radicals. The level of lipid peroxide in the chronic PMA group was found to be significantly higher than it was in the acute PMA group (P < 0.005). An electron microscopic examination of the acute group revealed disruption of the mitochondrial cristae and dilatation of the endoplasmic reticulum in the neurons. Myelin sheaths of the nerve fibers exhibited focal structural changes. Neurons and neuroglial cells in the chronic group, however, exhibited distinct ultrastructural alterations. The ultrastructural and biochemical findings showed that free radicals lead to brain damage.

Thomsen-Friedenreich antigen (T antigen) has been supposed to be a cancer-specific carbohydrate antigen. We have previously shown that one third of the Japanese population normally expressed T antigen in gastric surface epithelia and the other two thirds expressed fucosyl-T antigen. Their sialylation and blocked-synthesis were associated with diseased conditions. In the present study, we studied gastric surface epithelial expression of monosaccharide antigen Tn, i.e., a precursor of T antigen, and sialyl-Tn. Normal fundic and pyloric epithelia, respectively, expressed Tn supranucleally and cytoplasmically, but did not express sialyl-Tn. In the intestinal metaplasias and intestinal-type adenomas, goblet cells expressed sialyl-Tn in their vacuoles, and absorptive cells expressed Tn apically. In gastric-type adenomas, Tn, but not sialyl-Tn, was detected. Intestinal-type cancers expressed Tn and sialyl-Tn more often than the diffuse-type cancers. Five cancers did not express Tn, sialyl-Tn, or the T-related antigens. In these, four were diffuse-type cancers. We concluded that: a) normal gastric epithelial cells express Tn; b) metaplastic differentiation is associated with sialylation of Tn and c) expression of Tn and sialyl-Tn is depressed in the gastric cancers.

Origins and distribution of the human inferior phrenic arteries were studied by dissecting 68 Japanese adult cadavers. The inferior phrenic arteries were usually observed as paired (left and right) vessels. Their origins were summarized as follows: a) the aorta itself (85/138 cases, 61.6%), b) the ventro-visceral arteries (celiaco-mesenteric system of the aorta) including the celiac trunk (39/138 cases, 28.2%) and the left gastric artery (4/138 cases, 2.9%), and c) the latero-visceral arteries (adreno-renal system of the aorta) including the middle adrenal artery (4/138 cases, 2.9%) and the renal artery (6/138 cases, 4.3%). The left and right arteries occasionally originated in common trunk from the aorta, celiaco-mesenteric system or adreno-renal system (22/138 cases, 15.9%). A typological diagram explaining these variations is given. The inferior phrenic arteries, especially the left ones, sometimes issued visceral or esophageal branches. This fact indicates that the inferior phrenic arteries are homologous with the celiac trunk and mesenteric arteries. It is further discussed that the celiac trunk and mesenteric arteries are originally paired vessels, through introduction of our previous typological diagram of the abdominal arteries.

Recent data suggested that platelet-activating factor (PAF) could play a pathophysiologically important role in the progression of hypoxic-ischemic brain injury. We investigated brain tissue PAF concentration in the hypoxic-ischemic brain of immature rats. Endogenous PAF concentration in brain tissue showed a marked increase in hypoxic-ischemic pups (Group 1, 85.6 +/- 15.5 pg/mg protein) when compared to that of the control (9.1 +/- 3.1 pg/mg protein). In addition, we studied the effects of pretreatment with L-carnitine (5 days and 2 h before the hypoxia) on endogenous PAF concentration in the hypoxic-ischemic brain. Endogenous PAF concentration in the short-term pretreatment group (Group 2, 81.6 +/- 9.7 pg/mg protein) was not different than in Group 1 rat pups. However, a significantly decreased PAF concentration was found in the group of pups that received carnitine pretreatment for 5 days (Group 3, 30.5 +/- 11.0 pg/mg protein). These results indicate that PAF is an important mediator in the immature rat model of cerebral hypoxic-ischemic injury. The suppressor effect of L-carnitine on PAF production may give new insight into the treatment of hypoxic-ischemic brain injury.

We studied the association of fatty liver with subcutaneous and visceral obesity in 46 male and 36 female patients with body mass index (BMI) over 22 kg/m2. The correlation coefficient between the ratio of the visceral adipose tissue to the subcutaneous adipose tissue (V/S) and the computed tomography (CT) number of the liver was -0.299 (P < 0.05) and that between the V/S ratio and the ratio of the CT number of the liver to that of the spleen (CT-L/CT-S) was -0.335 (P < 0.05) in the males. Partial correlation analysis after making correction for BMI showed an increased correlation coefficient of -0.485 (P < 0.05) between the V/S ratio and the CT-L/CT-S ratio in the males. The odds ratio in the males for CT-L/CT-S below 1.0 and V/S above 1.0 was 3.25 with a 95% confidence interval of 1.02 to 9.39. No such association between the V/S ratio and the CT-L/CT-S ratio was present in the female patients. Multiple regression analysis with serum level of alanine aminotransferase, a marker of fatty liver, as an independent variable revealed a partial regression coefficient of -17.7 for CT-L/CT-S (P < 0.05) in the males and -21.7 (P < 0.05) in the females, validating the CT-L/CT-S ratio as an index of fatty liver. The results indicate the association of fatty liver as determined by the CT-L/CT-S ratio with visceral obesity in males.

We studied the magnetic resonance imaging (MRI) of 120 knees in 86 rheumatoid arthritis (RA) patients and of 14 unaffected knees in 12 control cases. We also developed a scoring system as a quantitative analysis method. We divided the MRI into 10 items, and classified the severity of the symptoms into 4 grades (score 0 to 3). The average total score increased according to the radiographic grade. Soft tissue lesions were clearly detected, even in the early stages of RA. Items such as synovial proliferation showed a high score even in the early stages, suggesting that it was the initial symptom of RA. The score also showed a correlation with the inflammatory signs. These results suggest that this scoring system is very sensitive and yields a good reflection of RA activity. We demonstrated that this system is simple and convenient for routine diagnostic use. We further demonstrated that it is useful for following the advancement of RA and for evaluating the response to treatment.

Thirteen patients exhibited a communicating hydrocephalus following subarachnoid hemorrhage secondary to ruptured intracranial aneurysms and were treated with shunt procedures. The interval between subarachnoid hemorrhage and surgery averaged 9 weeks. Seven of the patients showed improvement. The prognostic value for surgical management was evaluated on the basis of three different diagnostic examinations (computed tomography(CT), cisternography and constant infusion test). A correct diagnosis was obtained in 78 per cent in cisternography, and 63 per cent in infusion test and CT. All patients responding to surgery showed a typical pattern in cisternography, consisting of ventricular retention of radiopharmaceutical tracer for 48 h or longer in association with no radioactivity over the cerebral hemispheres. The constant infusion test correlated well with typical cisternographic patterns. CT is useful in demonstrating pathophysiological changes in hydrocephalus. Periventricular hypodensity was visible in patients with normal or slightly elevated intracranial pressure, accompanied by fairly rapid deterioration. All of them responded well to shunting. In most cases which benefited from the shunt, the postoperative CT showed not only normal-sized ventricles but also marked regression of the hypodensity over a short period.

Chromosome studies were conducted on two patients with adult T-cell leukemia. In both patients, a marker chromosome 14q+ and a structural change involving chromosome 1 with trisomy of the q arm were found in peripheral blood leukocytes. The 14q+ marker chromosome had resulted from translocation from #5p in one patient and #5q in the other patient. The present and previous studies suggest that the donor chromosomes involved in the 14q+ translocation are variable. This indicates that the 14q+ marker chromosome rather than the donor chromosome is intimately related with adult T-cell leukemia.

The effect of cytochalasin B (CB) on the surface structure of Ehrlich ascites tumor cells was investigated using the scanning electron microscope. The effect occurs in two steps: formation of zeiotic knobs on the cell surface and subsequent grouping of the knobs at one pole of the cell. The early step of zeiotic knob formation occurs at low concentrations of CB (0.5-1 microgram/ml) at 37 degrees C and at high concentrations of the drug (5-10 microgram/ml) at low temperature but within 1 min at 37 degrees C. This step is only partially inhibited by 5 x 10(-3) M sodium azide. The subsequent grouping of zeiotic knobs lasts for more than 2 min at 37 degrees C and occurs only in the case of high concentrations of CB. It is inhibited by sodium azide and is often associated with grouping of the microvilli, which are then lost from all of the cell surface except the area of knob-grouping.

125I-labeled insulin binding to peripheral human erythrocytes was studied in patients with chronic liver disease. The maximum specific 125I-labeled insulin binding was 12.10 +/- 1.13 %/4 x 10(9) cells (mean +/- SD, n = 10) in normal subjects, and significantly higher in cirrhotic patients (15.32 +/- 1.73 %, n = 11, P less than 0.01) but not in patients with acute and chronic hepatitis (11.44 +/- 2.10 %, n = 3 and 13.2 +/- 1.87 %, n = 7 respectively). The complication of diabetes mellitus significantly increased (P less than 0.05) the maximum insulin binding in chronic hepatitis. Scatchard analysis and average affinity analysis of the binding data suggest that increased insulin binding in cirrhotic patients is due to an increase in the number of insulin binding sites per erythrocytes. The complication of diabetes in chronic liver diseases results in an increase in affinity of insulin binding sites.

3-(3-methyl-3-butenyl)-1,2,3,4,5,6-hexahydro-6, 11-dimethyl-8-hydroxy-2,6-methano-3-benzazocine (KF-1820) is a derivative of benzomorphan and is different from pentazocine only in the site of the double bond. KF-1820 showed potent analgesic activity in all tests performed. KF-1820 was 6 to 12 times and 30 to 40 times more potent than morphine and pentazocine, respectively, when administered subcutaneously. KF-1820 had little or no narcotic antagonist property. Physical dependence liability tests indicated that KF-1820 may be a little less, or as liable as, pentazocine to produce physical dependence. ID50 values of KF-1820, pentazocine and morphine for depression of contractions of isolated guinea pig ileum to coaxial stimulation correlated well with their analgesic activities in the rodent. The dissociation equilibrium constant of KP-1820 confirmed the in vivo finding that KF-1820 had little or no narcotic antagonist property.

In rats anesthetized with urethane, the effects of distention of the stomach upon cecal motility and neural mechanisms which generate this effect were studied. Cecal motility was inhibited which generate this effect were studied. Cecal motility was inhibited when the pars glandularis of the stomach was distended by pressure ranging from 25 to 30 cm H2O. This inhibitory reflex was not affected by bilateral cervical vagotomy, but completely abolished following bilateral severance of the greater splanchnic nerves or after intravenous administration of guanethidine. After transection of the spinal cord at the level of the 5th thoracic segment the inhibitory reflex remained intact, but was abolished following pithing of the 6th thoracic segment and below. It may be concluded that the afferent and efferent path of the gastrocecal inhibitory reflex mainly pass through the greater splanchnic nerves and the reflex center is located in thoracic segments caudal to the 6th thoracic segment.

Drug effects were studied on anaphylactic histamine release from rat mast cells sensitized in vitro with mouse IgE antibody. When histamine release was elicited by adding Ca-++ at various times after antigen-stimulation of sensitized cells in Ca++-free medium, the drugs to be tested were added shortly before each Ca++ addition. Quercetin was effective only when added before or immediately after antigen. Theophylline and disodium cromoglycate (DSCG) were active irrespective of the time interval between antigen and Ca++ addition. Verapamil was more effective when added before or simultaneously with antigen than when added later. When tested in the two-stage experiments, quercetin showed inhibition only in Stage 1 and verapamil was inhibitive primarily in Stage 1, while theophylline and DSCG wee only inhibitive in Stage 2. It seems that quercetin selectively and verapamil primarily act to block calcium-gate opening resulting from antigen-antibody interaction on the mast cell membrane, while theophylline and DSCG selectively inhibit the passage of calcium through open calcium channels.

<p>A cytogenetic study was performed on 74 children with at least three major or minor congenital malformations and mental retardation, and whose phenotypes did not fit any well-defined syndrome. The chromosomes were examined routinely using banding techniques. A total of 11 patients (14.9%) was found to have a major chromosome abnormality: one patient had a sex chromosome structural abnormality and 10 patients had an autosomal structural abnormality, including 4 patients with partial trisomies, 4 patients with partial monosomies, and 2 patients with tertiary trisomies. Two of them had probable intrachromosomal duplication which would not have been identified by conventional staining alone. Familial transmission was ascertained in 5 of 10 cases in which both parents were studied. In addition, 5 patients (6.8%) were noted to have the following chromosome heteromorphisms: partial inv 1qh, inv 9qh, 9qh+, and Yqh+. These results show that chromosome abnormalities contribute much to the etiology of unclassifiable multiple malformations associated with mental retardation. Furthermore, the demonstration of subtle chromosome rearrangements by means of banding techniques provides important implications in medical practice for the diagnosis of affected patients as well as for the genetic counseling of the families.</p>

The antimycotic action of 1, 4-bis-(m, m'-amidinophenoxymethyl)-cyclohexane dilactate (MAC), a synthetic diamidine compound, on Candida albicans was studied. The minimum inhibitory concentration (MIC) ranged from 3.31 to 6.25 micrograms/ml against both standard and clinically isolated strains. MAC was fungistatic at MIC and weakly fungicidal at the concentration of 100 micrograms/ml. MAC did not affect the cell wall or cause cell lysis. Intracellular constituents, such as 260 nm and 280 nm absorbing materials, were released from the cells by treatment with MAC indicating that MAC affected membrane permeability. The release of 260 nm absorbing material was inhibited by the presence of Ca2+ and Mg2+. Acidic phospholipids such as cardiolipin and phosphatidylglycerol inhibited the anti-Candida activity of MAC, but sterols and lecithin were not inhibitory, indicating that MAC interacted with acidic phospholipids of the cell membrane. Freeze-fracture electron microscopy showed that MAC caused aggregation of membrane particles and patch formation on the P face, which may indicate that MAC is a membrane disrupting agent. It appeared that MAC affected C. albicans at the cell membrane by interacting with acidic phospholipids and caused disorganization of the membrane structure resulting in the release of intracellular constituents without lysis.

Masugi nephritis was induced in rats by a single intravenous injection of rabbit anti-rat kidney serum, and studied with a scanning electron microscope. A characteristic finding was the presence of white cells, probably polymorphonuclear leukocytes, with many microspikes which penetrated through degenerated glomerular endothelial cells to be in direct contact with the glomerular basement membrane. This finding confirms the pathogenic role of leukocytes in glomerulonephritis induced by anti-glomerular basement membrane antibody.

Insulin and human erythrocyte cell membrane interactions were studied with respect to binding and dissociation. The per cent of specific binding of 125I-labeled insulin to erythrocytes was directly proportional to the cell concentration. The optimum pH for binding was 8.1. The initial binding rate was directly proportional to, and the steady state insulin binding was reversely proportional to, the incubation temperature. The per cent of specific binding of 125I-labeled insulin was 12.10 +/- 1.13 per cent (mean +/- SD)/4 X 10(9) cells (n = 10) at 0.8 ng/ml insulin. Native insulin competed with 125I-labeled insulin for binding and showed almost complete inhibition at 10(4) ng/ml. The Scatchard plots were upward concave. Maximum binding capacity was 230 binding sites per cell. The average affinity constant decreased as the per cent of fractional occupancy increased. Affinity constants for the empty and filled sites were 1.49 and 0.16 X 10(8) M-1 respectively. Bound insulin was displaced by native insulin. The dissociation rate by "dilution + native insulin" was higher than that by "dilution only". The dissociation rate was accelerated even by the physiological concentration of insulin and maximum at 100 ng/ml. It is concluded that human erythrocytes have insulin binding sites which are indistinguishable from insulin receptors on the target tissues for insulin.

A permeable cell system has been developed by treatment with saponin for studying in vitro replication of DNA and chromatin. DNA replication of simian virus 40 nucleoprotein complexes (SV40 chromatin) in saponin-treated permeable cells was found to be more efficient than that in digitonin-treated permeable cells. Autoradiography of the agarose-gel revealed that [alpha-32P]dCTP was incorporated into SV40 DNA I, II and replicating intermediates. The time course of the incorporation indicated complete replication of SV40 DNA and chromatin with a full number of nucleosomes. The saponin-treated permeable cell system will serve as a useful system for studying in vitro replication of DNA and chromatin in eukaryotic cells.

Using a direct immunofluorescent method, histological locations of immunoglobulins (IgG, IgM, IgA and IgD of heavy chain, and kappa and lambda of light chain) and complement components (C3 and C4) were studied in 78 brain tumors, which included 24 astrocytomas, 6 metastatic tumors, 5 medulloblastomas, 4 malignant lymphomas, 15 meningiomas, 8 schwannomas, 8 pituitary adenomas, and 8 other miscellaneous brain tumors. IgG-positive cells were observed in the perivascular regions of astrocytomas, but were more marked in those of high grade, metastatic tumors and meningiomas. Malignant lymphomas demonstrated IgG and IgM-positive cells accompanied by either kappa of lambda light chains. C3 and C4 were much less evident in these tumors. Pituitary adenomas showed slight positive stains for both immunoglobulins and complement components on the blood vessel walls, Immune reactions against brain tumors were discussed including the clinical application of autologous lymphocyte infusion in malignant gliomas and combination chemotherapy in intracranial malignant lymphomas.

<p>The kinetics in tumor cells and various factors affecting the tumor accumulation of 67Ga-citrate and 201Tl-chloride were studied in vitro. 67Ga was taken up gradually by tumor cells and its excretion from the cells decreased with time. 201Tl was taken up rapidly by tumor cells. Its excretion was very rapid, indicating that the two nuclides had entirely different kinetics in tumor cells. The uptake of 201Tl by culture cells correlated with that of 42KCl and was inhibited by Ouabain. 201Tl was hardly taken up by nonviable tumor cells. These facts indicate that active transport involving Na-K ATPase is involved in the tumor accumulation of 201Tl. The uptake of 67Ga and 201Tl by tumor cells was not affected by the administration of anticancer agents. The uptake of 67Ga by tumor cells was dependent upon the concentration of transferrin in the medium, which apparently plays a role as one of the pathways of tumor accumulation of 67Ga.</p>