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The percentages and absolute numbers of gamma delta T cells per CD3 positive cells (T cells) in four different compartments, namely peripheral blood, synovial fluid, synovial membrane and lungs from patients with rheumatoid arthritis (RA) and in peripheral blood from healthy controls were studied by two color flow-cytometric analysis. The percentages (mean +/- SEM = 6.3 +/- 0.8%, n = 22) and absolute numbers (70 +/- 11/microliters, n = 22) of gamma delta T cells in peripheral blood from RA patients were not different from those of 22 age-matched healthy controls (7.5 +/- 0.9%, 81 +/- 17/microliters, respectively). The gamma delta T cells in peripheral blood from 50 RA patients were, however, significantly decreased in negative correlation with the value of CRP as a marker for inflammation, although they had no correlation with the titer of rheumatoid factor as an autoantibody. The percentages of gamma delta T cells in synovial fluid from 10 patients (3.3 +/- 0.5%, n = 10) or in synovial membrane from 5 patients (4.2 +/- 1.9%, n = 5) and in bronchoalveolar lavage fluid from 6 patients (3.6 +/- 0.8%, n = 6) were not different from those in peripheral blood from the same patients. Thus, gamma delta T cells are not the dominant infiltrating T cell subset in the inflammatory sites of RA patients.

The present study was undertaken to determine whether a biventricular bypass system operated in an independent variable rate (VR) mode can maintain the entire circulation. Two pusher-plate pumps which incorporated the Hall effect position sensors were used to bypass the right and left ventricles in 10 sheep under fibrillation. The flow distributions of the pump output to the carotid and renal arteries were investigated every 6 h using ultrasonic blood flow meters for 24 h in 5 animals, and the controllability of the VR mode was evaluated in 5 long-term experiments. The carotid artery flow ratio to the pump output decreased significantly from 4.7 +/- 0.8% before the bypass to 2.7 +/- 0.9% after 24 h. However, the renal artery flow ratio did not change throughout the experiments. In the long-term experiments, the animals were kept alive from 3 to 48 days (mean 15.6 days). The mean pump output had been maintained at more than 90 ml/min/kg for the first 7 days. After the surgery, the pump driving conditions were not readjusted in any experiment. The results indicate that the biventricular bypass system operated in the independent VR mode automatically maintains the entire circulation at a satisfactory level.

We measured hepatitis C virus antibody titers in 13 patients with chronic hepatitis C to determine whether titration of hepatitis C virus antibody was useful or not, to predict and evaluate the efficacy of interferon (IFN) treatment. During administration of IFN, hepatitis C virus titers declined in all patients. Antibody titers performed before treatment as well as just at the end of treatment did not correlate with change of the alanine aminotransferase levels during administration of IFN. Antibody titers declined continuously after treatment in 5 patients with normal alanine amino-transferase levels for over 6 months after discontinuation of IFN. Antibody titers rose again in 6 patients whose alanine aminotransferase levels fluctuated after treatment. An exceptional pattern of change occurred in 2 patients whose antibody titers declined continuously although their alanine aminotransferase levels fluctuated after treatment. Repeated titration of hepatitis C virus antibody appears to be useful for evaluating the long-term efficacy of IFN treatment.

The proliferative activity of various parts of normal and malignant endometrium was evaluated using an immunohistochemical approach and flow cytometry (FCM). The two monoclonal antibodies, Ki-67 and anti-DNA polymerase alpha antibody (anti-poly alpha antibody) were used to detect the proliferative activity of cells, and the percentage of the Ki-67 and anti-poly alpha positive cells were measured. Proliferative indices (PI; percentage of S and G2M phase) and DNA ploidy were measured by FCM. Normal endometrial specimens from 29 patients with benign diseases were used and three different parts (fundus, middle, and low part of the uterus) were examined. In the proliferative phase of normal endometrium, there was no significant difference in the proliferative activity in the three parts. In 20 patients with endometrial carcinomas with myometrial invasion, tissues were taken from the myometrial invasive site and the central part of the tumor tissue. In the cases of endometrial carcinoma, the myometrial invasive site had a higher proliferative activity than central part of the tissue. The proliferative activity measured by the immunohistochemistry was correlated with the histological grade of malignancy, but it was not consistent with PI by FCM. This suggests that the proliferative activity measured by the immunohistochemistry is independent of flow cytometric PI.

A new model of status epilepticus (SE), which was induced by intermittent electrical stimulation (20 Hz for 20 sec every min for 180 min) of the deep prepyriform cortex, has been developed in the conscious rat. SE was induced in 9 of 16 rats in the drug-free group. The number of stimulation trains required to induce SE in this status subgroup was 125.6 +/- 12.7 (mean +/- SEM) and the mean duration of self-sustained seizure activity (SSSA) occurring after cessation of the stimulation session was 295.4 +/- 111.4 min. Some animals showed secondary generalized seizures. Significant cell loss was observed in the hippocampal CA3 pyramidal cell layer ipsilateral to the stimulation site and bilateral CA1 areas in the status subgroup compared with the group subjected to sham operation. In addition, there was a significant negative correlation between the duration of SSSA subsequent to the stimulation session and the total number of intact pyramidal neurons observed in the bilateral CA1 and ipsilateral CA3 subfields of the status subgroup. There were significant differences between the status and non-status subgroups with respect to the number of afterdischarges (ADs) and the total AD duration during the stimulation session. Pretreatment with phenobarbital (30 mg/kg) prevented the development of SE and hippocampal cell loss completely. Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist (0.25 or 1 mg/kg), also prevented hippocampal cell loss, although it did not block SE generation completely, which suggests dissociation of the mechanisms underlying the development of SE and hippocampal damage. These results indicate that prolonged SSSA actually causes hippocampal damage and it is critically dependent upon NMDA receptor participation.

Indocyanine green (ICG) was injected into rat liver nodules induced by 2-acetylaminofluorene (2-AAF) via portal vein. The relationship between ICG staining and cell atypism of liver nodules was examined by means of histology and DNA flow cytometry. After 2-AAF administration, many small nodules appeared on the liver surface. All hyperplastic nodules were ICG stained until 10 weeks after the administration, but some nodules were not stained after 14 weeks. ICG-stained nodules histologically consisted of benign tissues and borderline lesions, and many of them showed "diploidy" in DNA cytometry. ICG-unstained nodules consisted of hepatocellular carcinoma (HCCs) and borderline lesions, and many of them showed "aneuploidy". In this way, it has been suggested that HCC could derive from hyperplastic nodules and that they might lose an ability to take up ICG in the process of hepatocarcinogenesis. Immunohistochemical staining for glutathione-S-transferase alpha (GST-alpha), a carrier protein of ICG in hepatocytes, was well correlated with ICG staining in the nodules, suggesting that the loss of ICG uptake in HCC was partly due to the decrease of GST-alpha. Moreover, the appearance of ICG unstained and aneuploid nodules was significantly inhibited in rats which were fed on diet containing Syosaiko-to after the administration of 2-AAF. Chemopreventive effect of Syo-saiko-to on hepatocarcinogenesis was identified.

We determined plasma human atrial natriuretic peptide (hANP) levels in normal pregnancy and pregnancy induced hypertension (PIH). The plasma hANP levels slightly decreased in the first trimester of normal pregnancy and tended to recover as pregnancy advanced, although these changes were slight. However, the plasma hANP level in puerperium was higher than that in the third trimester of normal pregnancy. The plasma hANP level in mild PIH was not significantly higher than that in the third trimester of normal pregnancy. In contrast, the plasma hANP level in three cases of severe PIH was approximately 200% higher than those in the normal third trimester and mild PIH.

Since December 1988, a centrifugal ventricular assist device (VAD) was used to support the circulation in 5 patients who could not be weaned from cardiopulmonary bypass (CPB) or developed cardiogenic shock after removal from CPB. Three patients required a left VAD, one needed a right VAD. One patient had biventricular support using a centrifugal left VAD and a diaphragm type right VAD. The duration of the centrifugal VAD support ranged from 6 to 136 (mean 72)h. All patients were weaned from the VAD, but only 2 patients were discharged from the hospital. Two patients died of multiple organ failure, and one died of cardiogenic shock caused by intractable arrhythmia. Infection occurred in all non-survivors, and 2 of them developed renal failure. We conclude that the centrifugal VAD is effective to recover a failing ventricle. The factors related to the unsuccessful recovery were delayed start of the VAD support and major complications such as infection as infection and renal failure.

We compared gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced T1-weighted images (T1-Gd) with the histopathological findings in 13 patients with bone or soft tissue sarcomas. Signal intensity of the viable tumor tissue was increased in T1-Gd in 92% of the patients. The necrotic or cystic areas in the tumor were not enhanced, rendering them distinctly. The degree of enhancement of the edematous area around the tumor was similar to or more marked than that of the tumor in 54% of the patients. Area showing inflammatory cells infiltration and edematous areas in the tumor tissue were also enhanced. Thus, the effect of preoperative chemotherapy in tumor tissues other than necrotic and cystic areas tended to be underestimated in T1-Gd. Its effect should be comprehensively evaluated based on not only T1-Gd but also T2-weighted images and findings of other imaging techniques.

Simultaneous radiohyperthermotherapy (SRH) is a combined hyperthermia-radiation therapy in which irradiation is given during heating. Mutual interference between the high energy radiotherapy system (Toshiba LMR-15A) and the 13.56 MHz capacitive heating system (Omron HEH-500C) was tested with phantom materials prior to a clinical trial with SRH. The energy and flatness of irradiation were not affected by the heating system within the range of clinical use. The high energy radiotherapy system did not affect the increase or distribution of temperature during simultaneous treatment. The results of this phantom study indicated that these apparatuses would not produce clinically significant mutual interference during SRH. A clinical trial was performed on a 57-year-old woman with postoperative recurrence of rectal cancer. This is the first reported clinical case treated with true SRH in which external irradiation was administered during mid capacitive heating. Twelve SRH treatments were performed on the recurrent lesion at a frequency of twice a week for six weeks using the apparatuses described above. There was a significant reduction in pain after treatment. The tumor marker carcinoembryonic antigen (CEA) level decreased after treatment. On CT images taken after treatment, the tumor site became a low density area which indicated necrosis. There were no side effects. These results suggest that further clinical study of SRH should be performed to clarify its advantages.

Southern blot hybridization was used to detect the rearrangement and amplification of five proto-oncogenes (bcl-2, bcl-1, c-myc, c-myb and c-Ha-ras) and one tumor suppressor gene (RB-1) in 55 Japanese patients with non-Hodgkin's lymphoma; 16 with T-cell lymphomas and 39 with B-cell lymphomas (7 follicular and 32 diffuse lymphomas). Genetic abnormalities of the proto-oncogenes were detected in 7 of the 55 (13%). Genetic abnormalities of bcl-2 plus other genes were detected in 5 of 7 cases of follicular lymphoma (71%), rearrangements of bcl-2 and c-myc, rearrangement of bcl-2 and amplification of c-myb. Genetic abnormalities were observed in only three cases of diffuse lymphoma. In each of 3 cases of B-cell lymphoma, one of the genes, blc-2 mbr, bcl-2 mcr and c-myc, was rearranged respectively. The incidence of genetic abnormalities in diffuse lymphomas (6.3%) was lower than that in follicular lymphomas. None of diffuse lymphomas had double oncogene abnormality. No abnormalities were found in RB-1, bcl-1, and Ha-ras. These findings suggest that follicular lymphomas are associated with some abnormalities of oncogenes not restricted to bcl-2 that facilitate growth which may be associated with their clinical features.

Acute superior mesenteric artery syndrome (SMAS) following a major surgical procedure is extremely rare, and represents an iatrogenic cause of postoperative upper gastrointestinal obstruction. In this report, the first documented case of acute SMAS following a left hemicolectomy is presented in an obese patient. Upper gastrointestinal roentgenographic series and conservative management remain to be the first line diagnostic and therapeutic modalities and were successful in our patient. Up to date no patient with SMAS reported to be obese but apparently obesity per se, can not be considered as an insurance. A postoperative acute SMAS is impossible to predict depending on the previous history, predisposing factors and the physique of the patient. Therefore, the surgeon should be aware of the SMAS and it is his task to secure all the precautions in order to preclude excessive traction on the mesenteric vasculature and vascular compression of the duodenum during surgery. In cases in which SMAS is suspected during extended colonic resections with lymph node dissection, duodenal mobilization seems to be selectively justifiable.

In the present study, 14 cases of Kimura's disease were clinicopathologically studied. The disease occurred at ages ranging from 5 to 75 years. The average age was 37.8 years. Sexes were about equally affected. The most common sites were the subcutis of head and neck, and parotid gland. Simultaneous involvement of lymph nodes occurred in 5 cases. Laboratory findings revealed eosinophilia in almost all the patients, but serum IgE levels were not elevated in 2 patients. Lesions were surgically removed and the clinical course thereafter was favorable for all but one case. Histologically, lesions were characterized by lymphoid follicles, granulation tissue with infiltration by many eosinophils, lymphocytes, plasma cells, mast cells and histiocytes, proliferation of blood vessels and fibrosis. Immunohistochemically, IgE reacted strongly in germinal centers, showing a reticular pattern. IgG-, IgA- and lysozyme-positive cells were scattered mainly in interfollicular granulomatous areas. Pathogenesis of this disease is briefly discussed.

Twenty patients with cholelithiasis associated with valvular heart disease were studied to assess the need and the optimal time for cholecystectomy. Twelve patients (11 symptomatic and 1 asymptomatic patients) underwent cholecystectomy. The remaining patients were asymptomatic. The levels of the total bilirubin in 9 patients, and of LDH in 15, were higher than normal. In most of the patients, the serum transaminase levels were higher than normal, but in few cases, the levels were higher than 200 IU/l. These abnormal values, however, were not consistently observed in these patients. No clear association between the type and form of valvular heart disease was demonstrated. The type of prostheses used for valve replacement in these patients were ball, tilting disc and leaflet. No significant differences in efficacy were observed among different types of prostheses. The incidence of silent stones is high in patients with valvular heart disease and heart surgery often causes deterioration in patients with cholelithiasis. The recovery of the patients who underwent cholecystectomy before valve replacement were better than those who underwent cholecystectomy after heart surgery. In conclusion, therefore, patients showing any abnormal results in liver function tests should be assessed in detail by abdominal echography and should receive surgical treatment of biliary tract before heart surgery if necessary.

Since detection of hepatitis C virus RNA by the polymerase chain reaction (PCR) showed that there existed anti-C100-3 (anti-HCV) antibody negative patients infected with HCV, we attempted to find out whether there were any clinical or viral genomic differences between the anti-HCV antibody positive and negative groups. One hundred and fifty-nine patients with chronic liver diseases with hepatitis C virus RNA in their sera were selected. Anti-HCV antibody was tested for anti-C100-3 antibody by an enzyme linked immunosorbent assay. The incidence of anti-HCV antibody was 129/159. The concentration of serum gamma-globulin, the titier of ZTT, and the positive rate of the PCR with the primers of the NS3/4 region (NS3/4PCR) were significantly higher in the anti-HCV antibody positive group than in the negative group. However, the other data such as alanine aminotransferase activity or past history were not significantly different. Nucleotide sequence of the cDNA fragments of NS3/4 region amplified by the PCR did not differ significantly between isolates from anti-HCV antibody positive and negative sera. The sequences observed in the present study did not differ significantly from those reported previously. Although there remains the possibility that the variation of viral genomic sequences may cause the absence of anti-HCV antibody, these results suggested that the individual clinical backgrounds or immunoreactivity of the patients might influence the antibody development.

A cell line of human lung large cell carcinoma (LCC) was established directly from the metastatic skin tumor tissue. The clinical course of the patient who carried this carcinoma was peculiar; generalized lymphadenopathy, histologically resembling Hodgkin's disease, was found as the first clinical symptom. The lung tumor was not discovered until the time of autopsy. This cell line (KaMi) grew adherent to culture vessels with the population doubling time of 20.6h, formed colonies in soft agars with efficiency of 22.6%, and formed tumors in athymic nude mice. The authenticity of KaMi was confirmed by chromosomal analysis and isoenzyme patterns. KaMi cells bore a strong resemblance to the original tumor cells which were composed of small spindle cells, large polygonal cells, and multinucleated giant cells. Immunohistochemically, KaMi cells showed a weak tendency to differentiate to squamous cells, and these immunohistochemical reactivities were almost compatible to those of the original tumor cells, but ultrastructurally, KaMi cells were more immature than the original ones. Treatment with several reagents could not augment a differentiation of KaMi cells. Cytokeratin profiles showed a tendency of squamous cell differentiation. KaMi cells may aid in elucidating the pathogenesis and biology of LCC and its relationship to other lung tumors.

We performed pulmonary artery angioplasty in 19 patients with lung cancer. The procedure consists of segmental or wedge resrection of the infiltrated pulmonary artery stem followed by reconstruction to avoid pneumonectomy and preserve pulmonary function. Among these cases "double sleeve resection" was performed in 10 cases. The 5-year survival of the angioplasty patients was poor at a rate of 11％, but not significantly different from the survival rates for those patients who underwent bronchoplasy alone or pneumonectomy. A promising prognosis may be expected in cases with N0 and N1 lymph node metastasis. However, this procedure may not replace pneumonectmy in patients with intact pulmonary function.

1. When chicken sarcoma virus is serially inoculated on the mouse brain, it loses its carcinogenecity, but when it is inoculated on young chicken, granuloma develops in the liver and lung. When this granuloma is transplanted on adult chicken, a transplantable fibrosarcoma is obtained. 2. According to literature, the originaltumor of the Brown-Pearce cancer is a basal cell cancer, but that imported to Japan in 1953 presented a histological picture of carcinosarcoma. The metastasized tumor of the eye presents a purely cancer tissue, but when this is inoculated on the testis, carcinosarcoma is reproduced. It is therefore considered that the mother cell of the sarcoma is of host origin. 3. MY sarcoma is not a sarcoma, but is a spindle cell cancer. It might be a sarcoma which transformed into a cancer during serial transplantation, but perhaps it was originally a cancer but had been erroneously diagnosed as sarcoma. 4. The tumors we obtained by means of the feeding tests of Yoshida tumor all developed at organs other than those of the digestive tract. They are chiefly reticulo-sarcoma, but others which develop are malignant granuloma in the liver and lung, malignant adenoma in the kidney, papilloma of pelvis, and ependymoma in the cerebral ventricle. Since the discovery of the Yoshida tumor in 1943, serial transplantation has been conducted for 19 years with this tumor not only in Japan but also in foreign countries, but there has been no report to this date that a transformed strain has developed by cell transplantation. It therefore must be considered that the carcinogenesis observed in our feeding tests is a carcinogenesis due to a mechanism completely unlike that of cell transplantation. It has been confirmed by electron microscopy that in the early stage of transplantation of this tumor into the abdominal cavity there was an additional tumor growth due to the anaplastic proliferation of serous cells. 5. During the serial transplantation of viral tumors and/or virus dependent tumors, the tumor sometimes undergoes a morphological change. Though the cause of this is not yet sufficiently elucidated, it is suspected that there is some relationship with virus in the wide sense.

1. Addition of nicotinamide (l0-2M) into the culture medium brings about an increase of the NAD content and the inhibition of the growth of L cells in culture. This rise of NAD brought about by nicotinamide lasts for 2 to 3 days, and thereafter gradually subsiding, it returns to normal level. 2. When L cells are cultured for several days in the same medium without addition of nicotinamide, there occurs a slow-down of mitosis with lapse of cultivation time but it has been found that this is in no way connected with the intracellular content of NAD. 3. By the addition of isonicotinic acid hydrazide (l0-2M) into the culture medium, there can be recognized a decrease of NAD content in L cell and the inhibition of cell growth. 4. In the case when 3-acetylpyridine (l0-2M) is added, a decrease of intracellular content of NAD in L cells and a marked inhibition of the cell growth can be observed. In the groups cultured in the media, containing 3-AP at the concentration of l0-3M or l0-4M can be seen neither inhibition nor acceleration of the cell growth. The oxygen uptake of the cells cultured in the medium containing 3-AP (l0-2M) hardly differs from that of the control group cultured in the medium not containing 3-AP. 5. On the basis of these results discussion has been made on the relation ship between mitosis and NAD content in the cell.

1. Rat liver mitochondria are swollen by inorganic phosphate in the medium of slightly hypotonic sucrose solution containing respiratory substrate and the mitochondrial swelling is inhibited or turned to shrink by ADP, respiratory inhibitor, anaerobiosis and uncoupler of oxidative phosphorylation. This mitochondrial swelling is not inhibited by the inhibitor of phosphorylating respiration such as oligomycin and tributyltin chloride. 2. Rat liver mitochondria are swollen by ATP in the presence of antimycin A, inorganic phosphate and 0.1 mM of CaCl2 and such a swelling is inhibited by oligomycin. 3. Accumulation of a small amont of P³² in acid soluble Pi fraction of rat liver mitochondria proceeds even in the medium containing neither ATP nor Ca++ but is inhibited by respiratory inhibitor, ATP, ADP and uncoupler of oxidative phosphorylation. The accumulation of P³² in mitochondria, however, is not inhibited by oligomycin. 4. The accumulation of P³² is induced by ATP in the presence of antimycin A and Ca++(O.l mM) and such an accumulation of P³² is inhibited by oligomycin. 5. It is suggested that the Pi-induced swelling of mitochondria is correlated to the accumulation of inorganic phosphate and both of them are tightly coupled to the initial step in the process of oxidative phosphoryaltion.