It is recognized that injury to vascular endothelial cells and enhanced platelet aggregating activity are important in the onset and development of atherosclerosis. The present experiment was conducted to investigate whether oxidized low density lipoprotein (LDL) is a predisposing factor of atherosclerotic lesions. LDL fractions collected from rabbit plasma were treated with cupric chloride (CuCl₂) to form oxidized LDL. This was intravenously administered to rabbits, and adenosine diphosphate (ADP) -induced platelet aggregation and the circulating endothelial cell count were measured as an index of vascular endothelial cell injury. The following results were obtained. 1) As the concentration of CuCl₂ was increased, the lipid peroxide (LPO) level in the oxidized LDL increased. 2) When 25 or 50μmol CuCl₂ acted on LDL fractions, platelet aggregation was significantly enhanced (p<0.05) . 3) When 10, 25 or 50μmol CuCl₂ acted on these fractions, the circulating endothelial cell count was significantly increased (p<0.05) . From the above results it was assumed that oxidized LDL enhanced platelet aggregation and injured vascular endothelial cells, and thus contributed to the onset and development of atherosclerosis.

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Only 17% of mice inoculated with lethal doses of Escherichia coli survived for 5 days after the challenge. Significant antibacterial activity of PSK, a protein-bound polysaccharide, was induced when the mice were pretreated with 40 mg/kg of PSK by an intraperitoneal, subcutaneous or intramuscular route, but not by an intravenous route, 48 hr before the E. coli inoculation. Repeated oral administration of PSK for 2 weeks (20 mg/kg, 3 times per week) before E. coli inoculation was also effective. Intraperitoneal administration of PSK was most potent, inducing significant polymorphonuclear cell accumulation and generation of luminol-dependent chemiluminescence by peritoneal exudate cells, with a peak 24 hr after administration of the PSK.

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Intraperitoneal administration of lignin-related pine cone antitumor substance (Fr. VI) induced factor (s) that stimulated chemiluminescence generation and NBT-reducing activity in human promyelocytic leukemic HL-60 cells. The production of the stimulating f actor (s) reached a maximum level 2 hrs after Fr. VI administration, and declined thereafter. The stimulation of chemiluminescence generation by the peritoneal factor (s) was synergistically enhanced by simultaneous addition of tumor necrosis f actor-α (TNF-α), but not by addition of granulocyte colony stimulation factor (G-CSF) . Incubation with both of the antisera raised against these cytokines almost completely eliminated the stimulation effect of peritoneal fluids. This suggests a significant role for G-CSF in Fr. VI induction of various immunopotentiating activities we have previously reported.

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The clinical problems of gastric adenoma are its differentiation from carcinoma and its coexistence with carcinoma. We challenged these problems with a magnifying endscope in the elevated lesions of the stomach including adenoma and IIa-type early gastric carcinoma. The subjects included hyperplastic polyps (15 cases), adenomas (15 cases), ha-type early cancers (7 cases), IIa+IIc-type early cancer (1 case), well-differentiated early cancers of excavated type (17 cases) and Borrmann's type I advanced cancers (4 cases) . The tissue samples taken from these subjects during surgery were also observed with a stereo-microscope to compare the findings with those obtained with the endoscope. The adenoma surfaces showed several different patterns, i.e., dotty, sulciolar, gyrus-like, nodular and mixed pattern. Positive correlation was present between the endoscopic findings and the degree of the histological atypia in adenoma. Namely, the dotty pattern, the sulciolar pattern and the gyrus-like and nodular pattern were frequently associated with mild, moderate, and severe cell atypia. On the other hand, the findings of magnifying endoscopy in the cases of the gastric carcinoma were characterized by the lesions of an irregularly nodular or destructive pattern, which were clearly differentiated from those of adenoma. The above results suggest that the follow up of gastric adenoma with a magnifying endoscopy is as useful as a biopsy.

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The effects of trimethadione (TMO) and its metabolite, dimethadione (DMO), on human liver microsomal debrisoquine 4-hydroxylase (cytochrome P-450_db1) activity were studied. Inhibition curves showed that there is no significant decrease in the activity of debrisoquine 4-hydroxylase by TMO or DMO (0.1μM to 10mM) . These data suggest that debrisoquine 4-hydroxylase in human liver is not responsible for N-demethylation of TMO, nor are TMO or DMO bound to its active site.

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Acid resistance of the surface enamel in human deciduous and permanent teeth after etching with 30% phosphoric acid was investigated by atomic absorption spectrometry, electron probe microanalysis, scanning electron microscopy, and Knoop microhardness tests. The surface enamel containing a higher Ca concentration did not show a lower acid dissolution, but that with less dissolved Ca occupied wider areas of the ‘prismless’ structures. Surface ‘prismless’ enamel, therefore, tended to have stronger resistance to phosphoric acid than surface prismatic enamel, but the acid-influenced layer that contained ‘prismless’ structures was weak against physical forces. The results suggest that the surface ‘prismless’ layer forms a barrier against enamel caries and acid etching. With acid etching and bonding techniques, the ‘prismless’ layer which interrupts adhesive penetration of resin to the underlying prismatic enamel will be apt not only to adhere poorly to the resin, but also to break away with the resin.

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This investigation was undertaken to demonstrate the cytogenesis of cardiac ganglia in prenatal rats from day 14 to days 16, 18, 20, and 21 of gestation (D14-16, D18, D20-21) . Special attention was given to the relationship between the differentiation and the maturation of organelles in the developing ganglion cells. In the cardiac ganglion of the prenatal rat, the undifferentiated cells differentiated into neuroblasts, which can be subdivided into apolar, early bipolar, intermediate bipolar, and late bipolar neuroblasts. The immature neuron, derived from the late bipolar neuroblasts, can be further divided into early and late immature neurons. This coincides with the differentiation and maturation of the ganglion cells. Well-developed Golgi complex, rough endoplasmic reticulum, and mitochondria, increased predominantly. During the developmental stage of the neuroblast, only part of its cell body was surrounded by satellite cells. However, the cell bodies of immature neurons and their afferent axon terminals were completely ensheathed by satellite cells. It is concluded that the number and maturity of organelles of the ganglion cell increase concomitant with its differentiation and maturation.

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Ultrastructural changes of chondrocyte mitochondria in strontiuminduced rachitic tibia epiphysis were revealed by transmission and scanning electron microscope. After per os administration of a strontium diet for 2 weeks, the following rachitic changes occurred in the tibial epiphyseal growth plates: The growth plates in the rats fed the strontium diet (strontium group), in particular, the hypertrophic zone, became thicker than those fed the control diet. X-ray microanalysis of the deep hypertrophic zone in the strontium group revealed the presence of abundant cations such as calcium, phosphorus and strontium, probably indicating interference with progressive ordinary mineralization. The hypertrophic chondrocytes in the strontium group had many longitudinally elongated, bent or bifurcated mitochondria. The mineralization disturbance and arrest of terminal differentiation of chondrocyte by the rachitic condition may be responsible for the morphological alteration of the chondrocyte mitochondria. These findings indicate that chondrocyte mitochondria correlate with their surrounding mineral phase and are ultrastructuarlly affected by disturbance of the correlation.

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Effects of zinc N- (3-aminopropionyl) -L-histidine (Z-103) on DNA synthesis in primary cultured rat hepatocytes were studied. Male adult rat hepatocytes were isolated by perfusing the liver with collagenase in situ and cultured as monolayers in Williams' E medium. DNA synthesis was monitored by measuring incorporation of [³H] -thymidine into DNA with or without aphidicolin. Z-103 in a concentration range of 10^-7 to 10^-5 M stimulated DNA synthesis in cultured hepatocytes. L-carnosine or ZnSO₄⋅7H₂O also had similar stimulative effects, but to a lesser degree than Z-103. This result indicates that Z-103 remarkably stimulates DNA synthesis of primary cultured adult rat hepatocytes, and that the stimulative effects can be ascribed to both L-carnosine and zinc moieties.

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The primitive cardiac loop in the stage 14 (Hamburger and Hamilton) chick embryo was subjected to brief vibratory stimulation that resulted in a broad spectrum of cardiovascular malformations. We also describe a method for quantitative analysis of shape development in chick embryo heart before and after applying the vibratory stimulation to the primitive cardiac loop, using the neural tube of the embryo to establish a coordinate system for objective evaluation of the positional changes of the different parts of the developing hearts. The device used to apply mechanical vibration to the cardiac loop was constructed of a variable frequency generator, an electromagnet, and a digital frequency meter. We observed several types of malformations: straddling AV valves, variable sizes of VSD, and DORY. The most frequent and striking cardiac malformations in our experiments were positional anomalies, isolated dextrocardia with straddling AV valves. In morphometric changes after the vibratory stimulation, the right ventricular and bulbar borders were prominent and held position longer than those of the left ventricular development. The right ventricular border deviated far to the right in the developmental process. The bulbar border was shifted less than the right ventricular border. This might indicate that the myofibrillar network extended to the right side of the cardiac loop simultaneously with abnormal polarity.

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The ultimate therapy for open fractures is yet to be developed. From 1978, we treated 20 cases of diaphysial open tibial and femoral fractures by a combination of Intramedullary nail and local continuous perfusion. According to Gustilo's classification (J. Bone Joint Surg. 58-A: 453-458), 6, 8, and 6 patients were classified into types I, II, and III, respectively. To allow the perfusion solution to flow smoothly through the bone marrow while performing thorough brushing and debridement, the bone was internally fixed using a Kuntscher nail with pore holes at 3.0 centimeter intervals. A Salem tube was then inserted into this nail for local continuous perfusion. In this way, the affected bone was internally fixed securely and antibiotics could be effectively administered. So far, no case of osteomyelitis or broken nail has been observed after this therapy.

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We used electron microscopy to examine the catecholaminergic innervation of neurons containing luteinizing hormone releasing hormone (LHRH) in the medial preoptic area of the rat. Double immunolabeling was used with the antisera of LHRH and tyrosine hydroxylase (TH) or phenylethanolamine-N-methyltransferase (PNMT), which are biosynthetic catecholamine enzymes. In simple LHRH-immunolabeled sections, immunonegative terminals making synaptic contacts with LHRH-like immunoreactive (LHRH-LI) nerve cell bodies and processes were sometimes found. In double immunolabeled sections, catecholaminergic axon terminals labeled with TH were found making synapses with LHRH-LI nerve cell bodies and processes. PNMT immunoreactive terminals, but fewer than TH-immunoreactive terminals, were also found making axo-somatic and probably axo-dendritic synapses with LHRH-LI neurons. LHRH-LI terminals were occasionally found making synapse-like contacts with LHRH-LI cell bodies or processes. It thus appears that in the medial preoptic area of the rat, catecholaminergic neurons, at least those containing adrenaline, innervate neurons containing LHRH and regulate their secretory activity or other functions through synapses.

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