Okayama University Medical School

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.

Viral nucleoprotein complexes were extracted from nuclei of permissive cells (CV-1) infected with simian virus 40 (SV40) and examined by electron microscopy. SV40 nucleoprotein complexes (SV40 chromatin) showed nucleosomes in linear bead-like arrangements along the extended closed circular DNA. The contour length of the SV40 chromatin was only 1.0-1.8 times shorter than that of viral DNA obtained after deproteinization. The data suggest that the circular DNA in SV40 chromatin can be extended to nearly its full length without detachment of the histone complexes.

A case of uterine adenomatoid tumor in a 47-year-old female was studied with both light and electron microscopes. The tumor was circumscribed, 2.5 cm in diameter, and located in the posterior wall of the uterus. In light microscopy, tumor cells showing "signet-ring" appearance arranged in cords or tubules. Hyaluronidase-sensitive acid mucopolysaccharide was present in the cells and luminal surfaces. Mucicarmine stain was negative and periodic acid-Schiff reaction was faintly positive. In electron microscopy, the tumor showed basal laminae, well-developed desmosomes and numerous microvilli. Intercellular spaces were present between adjacent cells. Small intercellular spaces were separated from the large lumens by desmosomes and tight junctions, while large spaces communicated with the tubular lumens. Forty-four reported cases of adenomatoid tumor in females were briefly reviewed.

The rate of blastformation of peripheral blood lymphocytes in response to stimulation by phytohemagglutinin (PHA) was assessed preoperatively in 393 patients with gastrointestinal cancer. The series consisted of 291 cases of gastric cancer and 102 cases of colon cancer, all patients being under 70 years of age. The blastformation rate was related to the stage of cancer ground at operation. Preoperative blastformation rates for both colon cancer and gastric cancer decreased as the cancer progressed. With Stage I gastric cancer 81.4% of those that underwent curative resection had preoperative blastformation rates greater than 40%. However, the number of those with blastformation rates over 40% decreased markedly in the curative cases of gastric cancer Stage II to stage IV. Eighty three percent of cases that underwent curative resection with colon cancer, including advanced cancer, had preoperative blastformation rates of over 40%. These results indicated that the correlation of the preoperative blastformation rate with success of curative resection better for colon cancer than for gastric cancer.

With the recent advances in the immunological surveillance system, an understanding of the role of host immunity has become essential to the management of carcinogenesis, tumor proliferation, recurrence and metastasis. Although it is important to continue chemical and surgical treatment of cancer, support of the anti-tumor immune system of the host should also be considered. Long term remission has been reported in leukemia by treating with BCG after chemotherapy whereas surgical treatment is usually more effective in preventing cancer recurrence in digestive organ cancer. The first step is extirpating the tumor as thoroughly as possible and the second step is chemo-immunotherapy. Cancer immunity, however weak, constitutes the basis for other treatments in selectively attacking cancer cells remaining after surgery, chemotherapy or irradiation. Immunotherapy should thus not replace chemotherapy or radiotherapy, but these methods should be employed in combination to attain more favorable results.

Using the method for the determination of the lipoyl dehydrogenase activity in intact erythrocytes described by Seet and Lee (1975), it was demonstrated that in patients with Spielmeyer-Vogt-Batten's disease, this activity was around the lower limit of normal. In these patients, the enzymatic activity is significantly reduced to such an extent that it may affect the function and metabolism of the erythrocytes.

Human KC cell monolayer inoculated with concentraten Mason-Pfizer monkey virus (MPMV) showed syncytia formation within an hour. The cell fusion was blocked by the treatment of the MPMV with neutralizing antiserum. Treatment of the MPVM with beta-propiolactone resulted in the loss of infectivity although KC cell fusion ability of the virus still remained. KC cells inoculated with unconcentrated MPMV showed no cell fusion even after several transfers, although a chronic MPMV infection was established. The virus-producing KC cells were refractory to fusion by MPMV. Human embryonic lung cells (HEL) were infected by serially diluted MPMV harvested from virus-producing culture, transferred twice, then cultivated together with KC cells for syncytia formation to examine the end point dilution titer of the virus. HEL infected by 10(-4)-diluted MPMV still induced syncytia formation by cocultivation with KC cells.

An improved direct colorimetric method for determining the concentration of urinary hippuric acid as an index of toluene exposure was described. One tenth ml of urine was diluted with 0.4 ml 0.01 M phosphate buffer H 6.9 and mixed with 0.5 ml pyridine. The mixture was layered on 0.2 ml benzenesulfonyl chloride. The reaction was started by mixing for one min with a mechanical shaker. The colored solution was allowed to stand for 30 min, diluted with 5 ml ethanol, and absorbance measured at 410 nm within 30 min after the dilution. The coefficient of variation of this method was 6% and the recovery 103% when urine contains about 0.2-0.5 mg hippuric acid per ml of urine. The concentration was linear up to 2.0 mg per ml hippuric acid in a specimen.

The chemotactic activity of granulocytes obtained by the Terumo Filtration Leucapheresis System (F.L.) was examined by the method of Boyden's chamber. The number of cells migrating through the Millipore filter was expressed as the chemotactic activity. The mean values were 117 for the F.L. and 122 in a control, in which cells were collected from the same donor blood using dextran sedimentation. The results suggested that the in vitro chemotactic function of granulocytes obtained by F.L. was within normal limits.

To investigate the role of folic acid deficiency in the pathogenesis of anemia in the elderly, hematological examinationa and assays of serum iron, vitamin B12 and folate were carried out on the 86 elderly patients admitted to a home for the aged. Means of red blood cell counts, hemoglobin levels and hematocrit were 385.3 x 10(4)/mm3, 12g/dl and 36%, respectively. These levels were lower than any other report in Japan. Anemia was detected in 23 out of 86 patients. Judging from mean corposcular volume and mean corposcular hemoglobin, most of them were normocytic and normochromic. Although low serum levels of iron and folate were rather frequently observed, the results on hematological examinations suggest that deficiency of these factors alone is not the cause of the anemia in the elderly patients. Rapid clearance of 5-methyl-tetrahydrofolic acid and increased excretion of formiminoglutamic acid after histidine loading were revealed in some of those who had subnormal serum folate levels. Therefore, supplementation of folic acid is recommended to those who had poor dietary intake.

 To determine whether the predominant infiltration with memory CD4⁺T cells in joints is specific to the local immune and inflammatory response in rheumatoid arthritis (RA), the proportions of CD45RA⁺ or CD45RO⁺ cells in the CD4⁺T cell populations in three different compartments (i.e., peripheral blood, synovial fluid, and synovial tissue) from patients with RA and osteoarthritis (OA) were compared by two-color flow-cytometric analysis. In the CD4⁺T cell population of peripheral blood, the number of CD45RO⁺ cells was relatively higher than CD45RA⁺ cells in both RA and OA patients, but their percentages did not differ from those found in healthy individuals. However, the great majority of CD4⁺T cells present in synovial fluid and synovial tissue were CD45RO-positive and CD45RA-negative in both patient groups; although CD4⁺T cells infiltrating both the disease compartments were markedly greater in RA joints, their mean percentages of CD45RO⁺ cells were not significantly different from those in OA joints. These data indicate that an accumulation of CD45RO⁺ memory CD4+T cells is a generalized phenomenon during local inflammatory responses in both RA and OA joints, and may be due mainly to the propensity of these cells to preferentially transmigrate into the inflamed joint via adhesion molecules as compared with CD45RA⁺ naive CD4⁺T cells.

To determine the extent to which recent advances in biomechanical technology have been implemented and to evaluate these new technologies, 84 unilateral above knee (A/K) amputees and their prostheses were surveyed in the Chugoku-Shikoku district of Japan, especially in regard to the types, sockets and components of A/K prostheses currently in use. Background factors such as age and sex of the A/K amputees and the period after amputation were also surveyed. Of the 84 amputees surveyed, 74 (88.1%) were over 40 years old and 40 (47.6%) were over 60 years old. There were 10 women (11.9%) and 74 men (88.1%). The period after amputation was under 25 years in 58 (69.0%) cases. Regarding the type of A/K prostheses, one-third of the prostheses was of the exoskeletal type and two-thirds were of the endoskeletal type. Although the endoskeletal type is becoming more popular recently, elderly A/K amputees tend to use the exoskeletal type. Thirty-one (36.9%) had plug-fit sockets which are preferable for those who follow the Japanese practice of sitting on the floor, especially for elderly amputees. Thirty-seven (44.0%) had a lock-knee, 27 (73.0%) of which were used by amputees over 60 years old. Seventy-three (86.9%) had a single-axis ankle which is generally considered to be the most stable ankle. Thus, the most common combination of prosthetic components for elderly A/K amputees was the plug-fit socket, lock-knee joint and single-axis ankle.

Our aim was to clarify the effect of a somatostatin analogue (octreotide) on glucose flux in conscious dogs. We monitored the effects with catheters in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery before and after oral glucose administration. A significant increase of portal vein plasma flow after oral glucose was completely suppressed by both 4 and 1 μg/kg octreotide. All doses of octreotide (4, 1 and 0.1 μg/kg) suppressed the glucose-induced increment of arterial glucose by dose response. Only 4 μg/kg of octreotide slightly but significantly suppressed hepatic glucose output. Marked suppression and delayed glucose absorption by the intestine was observed after 4 μg/kg of octreotide. One and 0.1 μg/kg octreotide also suppressed glucose absorption without delayed absorption. Total amounts of absorbed glucose during 3h after oral glucose were 24 ± 11% with 4 μg/kg of octreotide, 37 ± 16% with 1 μg/kg of octreotide, and 48 ± 8% with 0.1 μg/ kg of octreotide, all of which were significantly less than that of the control (73 ± 8%). Using 4 μg/kg of octreotide treatment, the liver took up only 5 ± 4% of the absorbed glucose, while the liver took up 35 ± 6% and 43 ± 9% of the absorbed glucose with 1 and 0.1 μg/kg of octreotide. These latter values were similar to that of the control value of 34 ± 4%. In conclusion, we found that octreotide administered before oral glucose had a remarkable stabilizing effect on postprandial glycemic surges. Both the direct inhibitory effect of octreotide on portal vein plasma flow and impaired glucose absorption would contribute to this decreased postprandial hyperglycemia, while its suppressive effect on other hormones, such as insulin and glucagon, did not seem to influence the reduction of hyperglycemia.

 This study was conducted to evaluate the frequency of DNA transfection into human cells following X-ray irradiation. We transfected plasmid DNA (pSV2neo) into human cells, HeLa and PA-1, by either calcium phosphate precipitation or the lipofection method immediately after irradiating the cells with various doses of X-rays. The transfection frequency was evaluated by counting the number of G418-resistant colonies. When circular plasmid DNA was used, irradiation up to a dose of 2 Gy dose-dependently increased the transfection frequency, which reached a maximum of 5 to 10-fold that of the control unirradiated cells. When linear plasmid DNA was used, the transfection frequency was 2 times higher than that of circular DNA. All five of the clones that were randomly chosen expressed the transfected neo gene. In addition, the pSV2neo gene was randomly integrated into the genomic DNA of each clone. These findings indicate that X-ray treatment can facilitate foreign DNA transfer into human cells and that radiation-induced DNA breaks may promote the insertion of foreign DNA into host DNA. The enhancement of DNA transfection with X-rays may be instrumental in practicing gene therapy.

The effect of various non-depolarizing neuromuscular blocking agents (gallamine, pancuronium, vecuronium, d-tubocurarine, metocurine, atracurium and pipecuronium) on [³H] acetylcholine release in the response to field electrical stimulation was investigated in vitro in preparations of the guinea pig right atrium. In this preparation, atropine enhanced and oxotremorine, a muscarinic agonist, reduced the release of [³H] acetylcholine. Atropine reversed the inhibitory effect of oxotremorine in a concentration dependent manner, indicating that there is negative feedback modulation of acetylcholine release from the vagal nerve. While pancuronium, gallamine and atracurium enhanced the release of [³H] acetylcholine, d-tubocurarine, metocurine, vecuronium and pipecuronium did not affect it. Pancuronium and gallamine also reduced the inhibitory effect of oxotremorine and the K_d value of pancuronium for muscarinic receptors located on cholinergic nerve terminals was 2.31 μM. These findings indicate that pancuronium and gallamine enhanced the release of acetylcholine from the atrial parasympathetic nerve, probably by inhibiting presynaptic muscarinic receptors.

We report a method of endoscopic retrograde sphincterotomy in patients in whom the optimal viewing of the papilla of Vater is hardly obtained. Percutaneous transhepatic cholangiodrainage (PTCD)-tube is placed under ultrasonographic guidance. PTCD-tube coming out of the papilla of Vater is observed by the endoscope and the guide wire inside the shpincterotome is inserted into the PTCD-tube. Sphincterotome is advanced into the common bile duct by the guidance of the guide wire and PTCD-tube. Sphincterotomy is performed in a usual fashion. Two patients with previous history of gastrectomy underwent this procedure with successful results. This method should be tried when usual method of EST is difficult and unsuccessful.

The axial length of the eye, the radius of the anterior corneal surface, and the diameter of the cornea were measured on 40 eyes of 20 New Zealand White rabbits. The ultrasonographic measurements of the axial length of the eye showed a mean value of 15.12 ± 0.51mm (15.33 ± 0.50mm in males, 14.96 ± 0.46mm in females). The mean corneal radius was 7.26 ± 0.26mm (7.18 ± 0.9mm in males, 7.32 ± 0.33 mm in females); the mean value of the difference in corneal curvature between two principle meridians was 0.21 ± 0.12mm; and the mean horizontal and vertical diameters of the cornea were 13.41 ± 0.34mm and 13.02 ± 0.30mm, respectively. Although the diameter of the cornea of rabbits was bigger than that of humans (average, horizontal 11.75mm, vertical 10.55mm), the axial length of the eye was 0.7 times that of humans (23-24mm), and the radius of corneal curvature was relatively smaller than that in humans (7.7-7.8mm).

We studied deformity of the proximal end of the femur following open reduction using the wide exposure method for developmental dislocation of the hip. We reviewed radiographs of 22 children with unilateral dislocation of the hip who had undergone open reduction between one and three years of age. Ages at final examination ranged from 14 to 21 years. None of the patients in this study had undergone any additional surgery. Avascular necrosis of the femoral head was not observed in any patients. Radiographic measurements were observed when the children were 3, 6, 9, and 12 years old, and at the final examination. Coxa magna and valga were the factors associated with poor results. Coxa valga had occurred at 6 to 12 years of age, but rapidly improved thereafter. Throughout the course of treatment the epiphysis-femoral neck angle was within the normal range. The fusion of the epiphyseal growth plates on both sides occurred simultaneously. The coxa valga was due to valgus of the femoral neck, and not to valgus head tilt. These results suggest that, provided the mechanics of the joint have been properly corrected as in our operation, the biomechanics of the hip will improve until growth ceases, but that it may take more than ten years to attain normality.