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Mice were trained in an avoidance learning task. The incorporation of 3H-leucine into the hippocampal regions of trained mice was higher than that of control mice. When mice were injected with cycloheximide, a strong inhibitor of protein synthesis, impairment was evident in acquisition of learning. Cycloheximide produced morphological changes in mitochondria and microtubules of some brain axons. It is suggested that the cycloheximide-induced learning impairment may be due to the blocking of the synthesis of the specific protein necessary of neutral conductivity.

The relationship between immune insulitis and glucose tolerance was investigated in three groups of mice following active immunization with different components of bovine pancreatic hormone. An abnormal blood glucose level was observed in the three groups ranging from 33.3% to 87.5% of sensitized mice. A relationship was not present between the glucose tolerance response and the presence of insulitis or anti-insulin antibody in the blood of sensitized mice. However, all sensitized mice with a marked decrease in glucose tolerance were found to have insulitis. In animals without established insulitis and with no demonstrable anti-insulin antibody, abnormal glucose tolerance was noted. This latter condition occurred more frequently with recrystallized insulin than with a-component and did not occur with monocomponent insulin. These findings seemed to indicate that two distinct processes involving some circulating antibodies with anti-insulin antibody and insulitis might be involved in the development of the observed glucose tolerance abnormality.

Cell-mediated immunity was studied in 23 cases of advanced gastrointestinal cancer. The patients received levamisole at 150 mg/day for three consecutive days each week for four weeks. In cases at the terminal stage of gastrointestinal cancer, the blastformation rate of peripheral blood lymphocytes against phytohemagglutinin (PHA) after the administration of levamisole showed a slight increase, but cases with blastformation rates over 40% increased markedly three or four weeks after the initial administration of levamisole. The peripheral blood lymphocyte count showed little change in these cases.

Plasma postheparin lipolytic activity (PHLA) was measured on 50 patients with systemic lupus erythematosus (SLE). Plasma PHLA was significantly decreased in SLE patients. This decrease was most striking in the acute phase of the disease. There was a close relationship between decreased PHLA and immunologic factors indicative of the acute phase of SLE. These immunologic factors included shaggy antinuclear antibody pattern, low serum complement titer, high DNA antibody titer, mixed cryoglobulin and lumpy glomerular pattern by immunofluorescent staining.

The microfilaria of Brugia pahangi obtained from an experimentally infected dog were observed with the electron microscope. The sheath was composed of small granules and was covered with electron-dense particles on the outer surface and with small granules on the inner surface. The cuticle was composed of an outermost layer, a trilaminate membrane and an inner layer. The hypodermis was composed of four components as in the adult stage (two small ones on the lateral sides, two large ones on the dorsal and ventral sides). The muscle cells comprised a single layer under the hypodermis on the dorsal and ventral sides. On each side, two muscle cells usually appeared in a transverse section. The thick myofilament was surrounded with 8 to 12 thin myofilaments. Dense bodies were present around the cephalic space. In the cells of the nuclei column, the cytoplasm was very narrow, and the electron-dense nucleus close to each other. The cuticular central canal was connected to the buccal cavity and to the inner body. A sponge-like structure was seen at the junctional part of the canal and the inner body. The inner body showed a homogeneous granular appearance. Eight cephalic papillae were observed at the head tip. Two amphids, each having more than eight cilium-like structures, were connected with the nerve elements and open in the head part. Two phasmids, each having one ciliumlike structure, opened in the caudal part. Two types of neurosecretory granules were observed in the nerve ring and the dorsal and ventral longitudinal nerves were clear except in the anterior and the posterior part of the worm. The excretory and the anal vesicles had contacts with thin and thick cytoplasmic processes respectively, and these vesicles opened to the exterior. The nuclei of the G cell and R cells showed similar electron-density. Lamellate structures were present in the muscle and the hypodermis.

The precipitation reaction of bovine serum albumin coupled with p-azophenylleucine with homologous antibody was inhibited by several structurally related haptens. The isobutyl group substituent on alpha-carbon atom of the leucine residue contributed more than -5.8 Kcal/mol to the free energy of binding. This value was consistent with the free energy change expected from the transfer of n-butane from an aqueous environment to liquid n-butane. The observed contribution was explained, in terms of the hydrophobic interaction of the isobutyl group with the antigen binding site of the antibody molecule. These results were also compared with other hapten-antibody systems.

With the electron microscopic and the negative staining method, the glomerular basement membrane of human and bovine kidneys was shown to have a definite fine meshwork structure. The pores of the meshwork of bovine glomerular basement membrane appeared to be pentagonal or hexagonal in shape. Strands of the meshwork branched three-dimensionally and made up the whole basement membrane. The portion of the sgrand between two neighboring branches was presumed to be a structural unit of the basement membrane. Glomerular basement membrane in man showed a structure similar to that seen in cattle, although the pore size of the meshwork was smaller in man than in cattle.

Gastrointestinal cancer patients were followed up for up to 30 months postoperatively and their clinical status related to a parameter of nonspecific immunity, the blastformation rate of peripheral blood lymphocytes against phytohemagglutinin. By the fourth postoperative week, the blastformation rate had recovered from the effect of the operation. In patients who had undergone curative resection, the postoperative level rose to exceed the preoperative level, whereas whereas in those in whom resection had not been possible, the blastformation rate failed to show this rise by the fourth week, and continued at the decreased immediate postoperative level. Results for long-term follow-up (30 months postoperatively) showed that the blastformation rate continued at high levels (almost all over 40%) in cases of curative resection without recurrence, but remained low (under 40%) in those in which the tumor could not be removed. The 40% level of the blastformation rate test thus correlated well with the prognosis. The blastformation rate, therefore, proved a very good parameter for following the pre-and post-operative clinical course of gastrointestinal cancer patients.

In vitro and in vivo testosterone metabolism was studied using rat skin. The in vitro stoichiometric studies strongly suggested the existence in the skin of 5a-reductase and other enzymes involved in testosterone metabolism. The predominant metabolites were 5adihydrotestosterone, androstandiol and 6.4-androstenedione. The rate of testosterone metabolism in vitro was higher in preputial skin than in dorsal skin. The main metabolites were androstandiol and 6 4-androstenedione in vivo whereas dihydrotestosterone and androstandiol were predominant in vitro. .6.4-Pathway is considered to be more active in vivo in adults than in newborns. The difference in the in vivo uptake increase of testosterone-3H after castration suggests the possible existence in the organs and skin areas of androgen pools of different sizes. The in vivo uptake and metabolism of testosterone were examined in the nuclei of newborn rats. Dihydrotestosterone and androstandiol detected in the nuclei of preputial skin, dorsal skin and liver were 42.8%, 24.3% and 27.8%, of total radioactivity incorporated into the respective organs. The liver incorporated only a small amount of radioactivity compared with the skin.

The surface of Gross virus-induced murine lymphoblasts and C-type virus particles budding from these cells were investigated under the scanning electron microscope (SEM). The cells appeared spindle-shaped or roughly-rounded with extensive surface features consisting of microvilli, blebs and ruffled membranes. C-type virus particles were detected on the cell membrane as small spherical particles, distinguishable from the microvilli. Clustered virions were observed in some cases. However, the distribution of virions appeared to be random. The surface of the virion was smooth and had no globular units at high magnification. These morphological observations were confirmed in ultrathin sections.

The intracellular localization of the avian myeloblastosis virus (AMV) genome was studied. Nuclear and mitochondrial DNAs from myeloblasts were examined by hybridization with 32P labeled AMV-RNA of high molecular weight for the presence of virus specific DNA sequences. Nuclear DNA (nDNA) from myeloblasts specifically hybridized with viral RNA, whereas purified closed circular mitochondrial DNA (mtDNA) did not hybridize with viral RNA. It was therefore concluded that viral genome was present in nuclear DNA and not in mitochondrial DNA. Likewise, in normal chick cells, nDNA but not mtDNA hybridized with viral RNA.

Deoxyuridine suppression tests have been performed by two different methods of six normoblastic and eight megaloblastic marrows. A good correlation was obtained between the results by the modified and the original methods. The simplified method was found to be applicable for a clinical purpose to diagnose megaloblastosis in the marrow. Uptake of 3H-deoxyuridine into DNA and effect of various concentrations of thymidine was studied on five normoblastic and six megaloblastic marrows. In megaloblastic marrows, a greater amount of thymidine was required to obtain the same rate of suppression of 3H-deoxyuridine incorporation into DNA than in normoblastic marrows. Impairment of thymidine incorporation into DNA in megaloblastic marrows was not revealed. Therefore, lower rate of suppression of 3H-deoxyuridine by thymidine in megaloblastic marrows may be due to impairment of the incorporation of deoxyuridine before the addition of thymidine.

Rat kidney endothelial cell morphology was examined after introducing iron colloid particles of positive or negative charge to investigate the relationship between the electric charge and permeation through the glomerular capillary. The kidneys were first perfused with Hanks' solution through the renal arteries and then with iron colloid particles of positive or negative charge. The iron colloid particles of positive charge were prepared with ferric chloride and cacodylate solutions, and the negative particles were prepared with iron chondroitin sulfate colloid particles. The iron colloid particles of positive charge adhered to the surface of endothelial cells of the glomerular capillaries, as well as the arterioles, capillaries and venules. Some particles were taken up by pinocytosis, accumulated in the glomerular basement membrane and appeared in the urinary spaces passing through the filtration slits of podocytes. Iron colloid particles of negative charge neither adhered to the endothelial cells nor were taken by the cells. They did not permeate into the urinary spaces. Permeation into the tubular lumen through the peritubular venules was not observed with particles of positive or negative charge.

Mitochondrial RNA (mtRNA) was synthesized from purine and pyrimidine nucleosides in coupling with oxidative phosphorylation using isolated mitochondria. The in vivo synthesized mtRNA was adenine-uracil rich and sedimented at about 20 S by sucrose density gradient centrifugation. A major part of the newly synthesized mtRNA was shown to be poly (A)-containing RNA by the resistance to the digestion with pancreatic RNase and RNase T1 and the affinity to poly (U)-Sepharose columns or Millipore filters.

Operative treatment of fractures of the neck and trochanter of the femur does not always produce a satisfactory result. This is usually due to biomechanical problems with the available internal fixation methods. We studied the anatomy of the neck of the femur by roentgenograms and sectional specimens from 70 cadavers. In addition, various nail-plates were subjected to buckling tests and, by simultaneously attaching a strain-gauge, stress distribution was calculated. The results of these preliminary studies were then used to design a new nail-plate better than those available at present. Testing of this new nail-plate confirmed that it had a strength equal to that of the Holt nail-plate (the strongest of the available nail-plates).

Salmonella typhimurium was invariably isolated from our J strain murine leukosis. Immunization of D103 mice with either inactivated Salmonella typhimurium or the cell-free extract of leukosis inhibited the transplantation of leukosis. The adoptive immunization of D103 mice with spleen cells of Strong A mice immunized with either Salmonella or the cell-free extract of leukosis inhibited the transplantation of leukosis. The addition of either Salmonella or the cell-free extract of leukosis inhibited the migration of macrophages of leukosis spleen in tissue culture. Strong A mice is non-susceptible to J strain leukosis. However, inoculation of neonatal Strong A mice with the cell-free extract of leukosis produced a susceptibility to the transplantation of leukosis. These results suggest that both a filtrable agent and Salmonella typhimurium are present in cells of this leukosis and might be etiologically related to the leukosis.

Factors influencing the prognosis in gastric cancer treated by curative resection include lymph node metastasis and the extent of invasion of the gastric wall. Lymph node metastasis can be removed surgically, but the extent of invasion is not amenable to external measures. Of these two factors, the extent of wall invasion has the greatest influence on prognosis in cases undergoing curative resection. With lymph node removal of equal extent the prognosis worsens in proportion to the depth of invasion. Further, lymph node metastasis increases with increasing depth of invasion. Metastasis was seen in Group 2 and 3 nodes in more than 60% of cancer with invasion beyond the Tunica muscularis propria (pm), indicating that wide lymph node removal is essential in cancers with deep invasion of the wall. The effects of extended radical operation on the host as illustrated by the indices of total serum protein and albumin levels were no different from those of less extensive resections. It was confirmed that extensive radical resection did not delay postoperative recovery.

Twenty-five cases of paraplegia due to fracture-dislocations of the thoracic and lumbar vertebrae were treated using the halo-pelvic apparatus. Thirteen of them only needed the apparatus, two underwent laminectomy, and ten had posterior spinal fusion in addition. The advantages of this method are that gentle reduction can be achieved without severe complications, and that posterior spinal fusion can be performed with this apparatus on, thus enabling an early start to the subsequent exercise program and minimal absence from work.

Isolated hepatic cells from adult rats were prepared by perfusing the livers with trypsin. The highest yield of viable cells was obtained by perfusing the liver with 0.1% trypsin, pH 7.0, at 37 degrees C for 30 min. Following this treatment about 70% of cells excluded trypan blue. The isolated cells contained many binucleate cells. Between 60 and 70% of DNA present originally in the liver was recovered from the isolated hepatic cells, which had higher glucose 6-phosphatase activity than the liver. Thus the resulting cell population seems to be rich in hepatocytes. The isolated hepatic cells, however, lost some of their cellular proteins such as alanine and tyrosine amino-transferases. It was suggested that the membranes of isolated hepatic cells might be damaged by both enzymatic digestion and mechanical destruction.