Systemic injection of high doses of antigen into a preimmunized animal results in transient unresponsiveness of cell-mediated immune responses. This phenomenon is known as desensitization. Serum interleukin 2 (IL-2) activity was found transiently in desensitized mice 3 hr after the antigen challenge. These mice did not reveal antigen-nonspecific delayed-type hypersensitivity (DTH) 1 day after the challenge. Spesific suppression of DTH was observed in later stages. Sera from 3 hr-desensitized mice had suppressive effects on DTH in preimmunized mice. Administration of recombinant IL-2 into preimmunized mice led to the failure of development of DTH to antigens. These observations indicate that IL-2 play is important in a suppressive environment.

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Ultrasound color Doppler flow mapping image (CFMI) equipment, SSA-270A (Toshiba Co.) was used to quantitatively measure liver tumor blood flow. Its clinical utility was evaluated in 89 patients with liver tumors, including 28 hepatocellular carcinomas (HCCs), 39 metastatic liver tumors, 20 hepatic hemangiomas and 2 cholangiocellular carcinomas. Blood flow inside the tumor was detected by CFMI and analyzed by pulsed Doppler method. Tumor blood flow was detected in 71.4% of HCCs, 59.0% of metastatic liver tumors, 5.0% of hepatic hemangiomas and 100% of cholangiocellular carcinomas. There were no differences between the Doppler signal waveform patterns of the HCC and metastatic liver tumors, but in tumors over 5 cm in diameter, the maximum blood flow velocity of metastatic liver tumors was higher than that in HCCs', or any tumor less than 5 cm in diameter. The resistance index of HCCs was lower than that of metastatic liver tumors. We concluded that CFMI and analysis by pulsed Doppler method are useful in differential diagnosis of liver tumors.

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Blood flow of brachial artery, radial artery, cephalic vein (shunting vein) and ulnar artery was measured by a real time ultrasonic duplex system and clinically evaluated in 71 hemodialyzed patients. Volume blood flow (VBF) of the shunt side was greater than that of the normal side. Mean VBF in the shunt side of the brachial artery was 737.3m1/min and that of the radial artery was 570.8m1/min. VBF in the group with side-to-side anastomosis was greater than VBF in the group with side-to-end or end-to-end anastomosis. Mean shunting vein VBF in the group with side-to-side, side-to-end and end-to-end anastomosis was 916.2m1/min, 554.2ml/min, and 430.4m1/min, respectively. At the ulnar artery, VBF in the group with end-to-end anastomosis was less than that of the groups with side-to-side or side-to-end anastomosis. In the groups with side-to-side or side-to-end anastomosis, the direction of blood flow through the radial artery was reversed and toward the anastomosis at the peripheral site. This fact indicates that additional blood flow through the palmar arches contributes to increased shunt flow through both the side-to-side and the side-to-end anastomoses. In comparison with pathogenesis of chronic renal failure, diameters of radial artery and shunting vein in the group with diabetic nephropathy were less than those of the group with chronic nephritis, but there was no significant difference in VBF. Shunt flows ranged from 100 to 1000m1/min for the patients with no shunt complications. High output heart failure developed in two cases with a side-to-side anastomosis and, the shunt flows proved to be above 2000m1/min. Flow measurement by the ultrasonic duplex system is non-invasive, easy to handle and useful for long term follow up of hemodialyzed patients.

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Serum CA19-9 was studied clinicopathologicaly and tissue CA19-9 was immunohistologically by the enzyme antibody method in 271 (241 resected) patients with primary and solitary gastric cancer. In 67 serum CA19-9 positive cases (47 resection cases), the positive rate and measurement value increased with advance in the stage of the disease. Compared to with CA19-9 negative cases, the positive cases included fewer curative resection cases. Immunohistological staining revealed tissue positive rate of 70.2% in CA19-9 positive cases, with significant difference. The poorly differentiated type and cytoplasmic types were predominant in CA19-9 positive cases, and the positive rate increased with increase in invasion depth into the gastric wall, the degree of vascular invasion, lymphnode metastasis, and clinical stage. The 5-year survival rate in the serum and tissue CA19-9 positive cases was lower than that in negative cases. There was a tendency toward a low 5-year survival rate in cytoplasmic type cancers. The findings suggest that measurement of serum and tissue CA19-9 is useful and clinically meaningful to indicate the degree of advance and malignancy of gastric cancer, decision making for intensive treatment, and prognosis.

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Nucleolar organizer regions (NORs) are loops of DNA that transcribe to ribosomal RNA. AgNORs are argyrophilic intra-nuclear dots stained by a silver staining technique for NORs associated non-histone protein. The amount of AgNORs was investigated with reference to histological factors, which may indicate cell proliferation, in 40 cases of gastric cancer. We investigated the value of BrdU L.I. (Bromodeoxyuridine labeling index) and DNA ploidy pattern in the same cases. Significant differences were found in the numbers of AgNORs and BrdU L.I. among the histological types (well, mod<por<muc), INF (INF α<β<r), stroma (middle type<scirrhous type) and “growth pattern” (superficial type<middle type<pen type) . There was also significant difference between the depths of invasion (ps (-) <ps (+) ) . However, there was no significant difference in DNA ploidy patterns among these histological factors. These results indicate the value of determining the number of AgNORs and BrdU L.I. relative to cell proliferation in gastric cancer, and that the AgNORs score may give a more accurate estimation of the biological character in gastric cancer, similar to BrdU L.I.

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The liver tissue pH was measured for the purpose of evaluate on of the viability of transplanted liver easily and early. [Materials and Methods] Male W istar strain rats weight 250g were used. The liver was removed by Kamada's method with necessary modifications. (Experiment 1) The tissue pH was measured at perfusion rates of: Group I, 0.05; Group II, 0.5; and Group III, 16 (ml/h/BWg) . (Experiment 2) The tissue pH preservated at 4°C and normal room temperature and ΔpH×preservation time were measured to calculate the 7-day survival rate. (Experiment 3) The tissue pH was measured in relation to various solutions for preservation-Group H: Hartman D solution, UW solution and Group UW, Group HP: Prostaglandin E1 (hereafter referrd to as PG) -added Hartman D solution (1μg/ml), and the 7-day survival rate after preserving for 6 hours was calculated. (Result) (Experiment 1) The fall in the tissue pH tended to be high in the order of Group II, III and I. (Experiment 2) Changes in the pH were hardly evident at normal room temperature. Normal room temperature pH reflected the survival rate and correlated with the value expressed in ΔpH×preservation time (min) . On the basis of this finding, the preservation time enabling 80% survival in Experiment 1 was estimated at Group I 150 minutes, Group II 540 minutes and Group III 135 minutes, showing the time in Group II to be the best preservation time to enable preservation for many hours. (Experiment 3) A sharp fall in pH to the minus side was seen from the beginning in Group H, while in Group UW a sharp increase in pH to the plus side followed by a slow decrese was noted, but the decrease did not reach the minus side. Group HP showed changes similar to those in Group UW. (Conclusion) Measuring the liver tissue pH over time in the simple immersion preservation of the liver was of use for evaluating viability easily and early, the survival rate could be predicted by the tissue pH×preservation time (min), and the value calculated by the 80 % survival rate was 4.86. The most suitable condition of preservation was perfusion rate of 0.5 ml/h/BWg, temperature at 4°C and the UW solution. It was conjectured that addition of PG to solution protected the liver.

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To investigate the role of AgNORs for evaluation of chemotherapy, change of AgNORs was observed before and after chemotherapy. A comparative review was also made by histological evalution of chemotherapy for stomach cancer. Twenty-three patients with stomach cancer were treated by chemotherapy ; 17 with 5'-DFUR, and 5 with CDDP. The mean number of AgNORs was 5.75±1.02 before treatement and 3.83±0.97 after treatment. There was a significant difference between groups (p<0.01) . In classification of the nucleus form: A type had a large solitary round argyrophil structure, with a significant increase of AgNORs (0.24±0.23 before and 1.21±0.59 after chemotherapy, p<0.01) . A significant decrease of AgNORs was found in both B type (several small dots as 1.51±0.80 before and 0.33±0.4 after chemotherapy) ; and D type small black dots (3.79±1.41 before and 2.25±0.94 after chemotherapy, p<0.01) . Depth invasion revealed significant decrease in AgNORs in both PS (-) and PS (+) groups. The number of AgNORs in the PS (-) group was 5.95±1.13 before and 3.43±0.97 on the mucosal surface, 3.83±0.38 at the tip part after chemotherapy. In the PS (+) group it was 5.63±0.91 before and 4.14±0.84 on the mucosal surface, 3.69±0.53 at the tip part after chemotherapy. In the decreasing rate, the PS (-) group was greatly reduced on the mucosal surface (p<0.05) . Both differentiated type and undifferentiated cancer types showed significant decrease of AgNORs (p<0.01), and the decreasing rate was only slightly affected by the differentiation. In the histological evaluation of chemotherapy for stomach cancer, grade 0, I a, I b, and II were adapted in 7, 8, 4, and 4 patients respectively. Even in patients with grade 0, the AgNORs number was 6.28±1.04 before and 3.32±0.90 on the mucosal surface, 3.66±0.50 at the tip after chemotherapy. Thus, a significant decrease was obtained (p<0.05) and the decreasing rate was significant on the mucosal surface. Even in patients with grade I a or more, the AgNORs was 5.54±0.96 before and 4.05±0.94 on the mucosal surface, 3.66±0.50 at the tip part after chemotherapy. Thus, a significant decrease was observed (p<0.01) and the decrease rate was high at the tip part. In the histological evaluation of chemotherapy, 7 patient of the 5'-DFUR group showed grade 0, and 10 patients showed grade I a or more. In the CDDP group, 6 patients in all showed grade I a or more. In the change of AgNORs, 5'-DFUR showed a higher decreasing rate on the mucosal surface after chemotherapy, whereas CDDP showed a higher decreasing rate at the tip part. Thus, the effect-appearing positions were different by the type of agent and method of administration. Accordingly, it was suggested that, the change of AgNORs in preoperative chemotherapy was reflected with morphological change by chemotherapy even in patient with no histological change. Thus, the present method might become an auxiliary means for judging the effect.

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To explore the involvement of oxidative stress in diabetic nephropathy, we examined serum ascorbic acid (AsA) and lipoperoxide (LPO) levels in patients with diabetes mellitus (DM, n=81) in relation to nephropathy assessed by various clinical parameters such as proteinuria, creatinine and albumin in serum, fasting blood glucose, and glycohemoglobin (HbAic) . Age-matched non-diabetics (n=15) were examined as controls. W e measured total, reduced and oxidized (dehydro-) forms of AsA. Diabetics were classified as normo-, micro-, macro-albuminuria and nephrotics. Diabetic patients with normoalbuminuria showed significantly lower AsA than non-diabetics (P<0.05) . Significant decrease of AsA was also found in diabetics with micro-, macro-albuminuria and nephrosis (p<0.001) . Although no significant difference in dehydro-AsA (DAsA) was seen among diabetics, the ratio of DAsA/ total AsA was tended to increase in relation to the protein content in urine, and this was significant in diabetic nephrosis (p<0.05) . AsA levels correlated with albumin concentration in sera of total diabetics (p<0.01), and the ratio of DAsA/TAsA was correlated with serum creatinine levels (p<0.05) . In contrast, we observed no significant relation between AsA and HbAIC. Our results suggest that serum AsA decreases in diabetics regardless of management of blood glucose and that AsA was decreased in association with severity of nephropathy. This may be due to oxidative stress. LPO in diabetics was elevated and the increment was associated with severity of nephropathy. W e could not, however, find a significant relation between AsA and LPO. Thus, serum AsA may not directly reflect the oxidative stress of lipoproteins.

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For the purpose of establishing a selective heating method for tumors located deep, ferromagnetic substance was selectively incorporated into the tumor, and high frequency electromagnetic waves were need to induce heat. Magnetic iron oxide (tri-iron tetraoxide) particles, 150Å mean particle size, were coated with liposomes having no immunogenicity or toxicity, and bonded with hematoporphyrin, a substance with affinity to the tumor, to prepare the liposomal ferromagnetic particles (HP-LM) . In heating tests on rabbits, after tumor grafting (VX-2) into the lower thigh, HP-LM was inoculated at 100 mg/kg into the femoral artery. The following groups, A, B and C, were heated for 20 minutes each, by a high frequency inductive heater, once a week, 3 times in all. Group A received one does ; group B received two doses ; and group C were the control group. Significant differences temperature elevation and tumor retraction were noted in the respective group. Arterial injection accumulated HP-LM in the tumor tissue, and intermittent heating by high frequency electomagnetic waves retracted the tumor. This method is suggested for benefisial heating effects.

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To establish a method of selective hyperthermia for deep tumors, hematoporphyrine liposomal magnetite (HP-LM) was prepared, and administered through intra-arterial catheter connected to a subcutaneous infusion port in a rabbit previously transplanted with VX-2 tumor in the thigh. Effective methods of HP-LM administration and tumor heating in high-frequency inductive heating are discussed. The results of our study showed that by using an intraarterial infusion port, HP-LM could be administered without damaging the tumor feeding vessels. Bi-weekly administration of HP-LM result in gradual washout of HP-LM and only transient anti-tumor effect could be achieved by heating once per week. Heating at least twice per week was thought to be necessary obtain long term anti tumor effects. To enhance the anti-tumor effect, concentration of HP-LM in the tumor must be conserved against the washout caused by blood flow. Frequent administration of HP-LM through the infusion port may by necessary. Optimal antitumor effect could be achieved by heating the tumor immediately after administration of HP-LM and heating intermittently.

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The intentions of surgery for the cleft palate patient include both closure of the cleft, and acquisition of favorable velopharyngeal function, that is normal speech. As an index for evaluating normal speech, we examine the velopharyngeal function, but use hypernasality which is highly correlated for clinical judgment. There has already been much research into speech disorder of patients with cleft lip and palate, but, there has been no report regarding the influence of confounding factors. In this research, stratified analyses have been made regarding postoperative hypernasality and confounding factors in 155 cases. The following factors are listed in the clinical records : patients attributes (sex, birth weight, degree of palate dehiscence, age at surgery), surgical technique and findings of postoperative causes, (size of fistula, degree of push back, movement of soft palate) . No significant relation was observed between hypernasality and sex, birth weight, or size of fistula. Significant relations were observed between nasality and the degree of palate dehiscence, age at surgery, surgical technique, degree of push back and movement of soft palate. The factors with significant relation to hypernasality were further analyzed to identify the most confounding factor. As a result, it was concluded that age at surgery is related most closely and directly to the presence or absence of hypernasality, even if all of the various factors are considered.

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Ultrastructural changes of endothelial cells of cardiac microvasculature during ischemia and reperfusion were observed and compared to those of mycardial cells in isolated rat hearts, to find clues to the mechanism of reperfusion injury. The hearts were perfused for 15 minutes in the Langendorff mode and then made ischemic by occluding coronary flow on the following schedules : non-ischemic, 15, 30 and 60 minutes normothermic ischemic groups (n=5 each) . It was noted that after gloval ischemia the degree of cellular damage in myocardial cells and microvasculature became progressively worse. The most remarkable changes of the endothelial cells were loss of pinocytotic vesicles in the cytoplasm and appearance of many cytoplasmic protrusions into the lumen. The mean count of pinocytotic vesicles (per 1μm²of cytoplasm) decreased significantly to 34.2, 22.07, and 10.36 in proportion to ischemic time. As ischemia progressed, the mean value of the number of cytoplasmic protrusions into the lumen (per cell membrane 10pm long) increased significantly to 1.28, 3.00 and 6.18. In 60 min ischemia group they could not be counted because the endothelial cells were extremely damaged.

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A clinico-pathological study of the advanced lung cancer less than 30mm in size was performed. We treated 158 primary lung cancer patients from January 1, 1987 to December 31, 1992. In 28 cT1 NO MO non-small cell lung cancer patients, there were 8 cases with pT1 N2 MO (p-Stage IIIA) or pT1 anyN M1 (p-Stage IV) advanced lung cancer. However, these cases were not assessed preoperatively. The age range was 46-82 (average 64.3 years) ; 4 were male. Of these 8 patients, 5 were detected in mass surveys for lung cancer, 3 were detected by complaints. In these cases, the range of lung tumor diameters was 15-30 mm (average 20mm) and the levels of serum CEA were below 5ng/dl. The histological types were adenocarcinoma in all of 8 patients. Histopathologically, lymphatic invasion was observed in 8 of these cases, and mediastinal lymph node metastasis in 4. W e conclude that constructive mediastinal lymph node dissection, adjuvant therapy and reliable preoperative diagnosis are important to small sized advanced lung cancer.

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For surgery of the hand, we reported case studies of internal fixation with titanium miniscrews and miniplates. We have seen 64 cases (Herbert screw, 44; Leibinger-System, 13; Champy-System, 7) . The ages ranged from 15 to 55 yr, 34±6 (mean±S. D.) . It is advantageousl that this internal fixation can fix small fractures rigidly, and permit early exercises of the finger joints.

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A 75-year-old man was found to have a mass in the right scrotum durings examination for gastric cancer, and was admitted to our department. Under diagnosis of a right testicular tumor, right high orchiectomy was performed. Histological examination of the tumor indicated an epidermoid cyst of the testis. 116 cases of testicular epidermoid cyst have been reported in the Japanese literature, and are briefly reviewed here.

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A case of spontaneous fractures of the bilateral femoral neck in a patient with rheumatoid arthritis is reported. A 67 year old female visited our hospital with a chief complaint of the right coxalgia, and because of gait disturbance, was hospitalized. In a roentgenogram, a bone fracture overlooked in the first test was observed in the second diagnosis as a fracture of Garden type III. An artificial head replacement was performed, but left coxalgia, similar to the right coxalgia, developed thereafter. Since a Garden type III fracture was observed in the second rentgenogram, an artificial head replacement was performed in the left side also. As is often the case, the diagnosis of spontaneous fracture was difficult. However, since early treatment is important when a patient with a heavy bone atrophy complains of pain, treatment should be performed with this disease in mind, even if the roentgenogram shows no apparent change.

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