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Effects of oral administration of NaCl on salivary and systemic clearance of Li+ were investigated following bolus intravenous administration of LiCl in male beagle dogs. Fifty ml of NaCl solution (100 meq/l) was administered orally 7 times at 1 h intervals. Gustatory stimulation of salivation was continued for 390 min using citric acid solution. Saliva was collected by means of permanent fistulae for parotid and mandibular-sublingual glands. Salivary clearance of Li+ was markedly increased by continuous stimulation of salivation, and was enhanced further after oral administration of NaCl solution. Renal clearance of Li+ showed a decreasing tendency under continuous salivation compared with the condition without gustatory stimulation; however, this decreasing tendency disappeared after oral administration of NaCl solution. Consequently, systemic clearance of Li+ was increased due to the contribution of increased salivary clearance. Enhancement of salivary Li+ clearance after administration of NaCl suggests the salivary excretion mechanism of Li+ may include a reabsorption process, like its renal excretion. Administration of NaCl solution had similar effects on salivary and systemic clearances of K+ to those on Li+ clearances, and a significant correlation was observed between Li+ and K+ clearances of both salivary gland and kidney.

Although various methods for keeping long term good pulmonary function have so far been studied, no reliable method for heart-lung preservation has been established yet. Recently, we aimed at heart-lung preservation using the autoperfusion method and mainly examined pulmonary function after transplantation. After preserving heart-lung organ blocks extracted from mongrel dogs by autoperfusion method, 10 left lungs (preserved for 6.8 +/- 0.8 h) were orthotopically transplanted and combined heart-lung transplantation was performed under extracorporeal circulation using 5 heart-lung grafts (preserved for 7.5 +/- 0.5 h). All of lung-transplanted dogs were alive; preserved lungs showed good gas exchange power from immediately after transplantation. Left lungs on the 3rd day showed normal histological findings and chest X-P also revealed good pneumatization of transplanted lungs. The heart-lung transplantation enabled 4 cases to be free from extracorporeal circulation and arterial blood gas analysis also revealed good results [PO2 396.5 +/- 34.7 mmHg, PCO2 35.5 +/- 6.9 mmHg (FiO2 1.0)]. Lung tissue findings after 6 hours from the above freedom showed slight edema alone. The above results suggested the effectiveness of the autoperfusion method for heart-lung preservation.

"Postoperative erythroderma", the pathogenesis of this disease have solved as graft-versus-host disease (GVHD) due to blood transfusion, is fatal and impossible to cure for the time being. Therefore the prevention against the disease is very important. One woman and three men who underwent an operation and blood transfusion at our department died of this disease. They fell into high fever on 11-13 days, erythroderma on 12-16 days, liver dysfunction on 14 days, and leukocytopenia on 17-19 days, after surgery and transfusion. Eventually, they all suffered from thrombocytopenia, diarrhea, renal dysfunction, and sepsis which led to death. The clinical course, macroscopic and microscopic findings of them coincided with those of GVHD. Since 1989, we have tried following methods for prevention of postoperative erythroderma: Reducing blood transfusion, especially fresh blood and fresh thrombocyte plasma, by using predeposited autologous blood, autologous washed erythrocytes collected from the operative area before and after extracorporeal circulation (ECC), concentrated residual blood from the ECC using a hemoconcentrater, and 1,500 rad of cobalt-irradiation of fresh blood, fresh thrombocyte plasma, and blood collected within 7 days prior to the transfusion. Postoperative erythroderma has not been experienced by introduction of these methods since 1989.

We have reported intrathoracic heart-lung transplantation in rats could be made easily by using Internal Shunt Method as described elsewhere. In this study, we examined the rejection of intrathoracic heart-lung allografts in this model to determine whether acute pulmonary rejection precedes cardiac rejection following heart-lung transplantation or not. Ten heart-lung allografts (no immunosuppressive agent was given) and four isografts were examined pathologically. There was no pathologic change except perivascular or peribronchiolar edema in isografts, which was attributed to operative damage. Acute pulmonary rejection apparent pathologically 3 days after transplantation and lung allografts lost its function 6 days after transplantation. Otherwise, acute cardiac rejection first became apparent pathologically 5 days after transplantation. And their pulsation appeared well 6 days after it. It is concluded that pulmonary rejection precedes cardiac rejection following heart-lung transplantation.

Twenty-four patients with aneurysm of Valsalva sinus were surgically repaired over a 23 year period (1965-1988). These patients were ranged 2 to 54 years of age and eleven of them were male. Rupture of aneurysm of Valsalva sinus was combined with aneurysm in 20 cases, ventricular septal defect in 12 cases and aortic regurgitation in 6 cases. At present, our routine operative procedure for ruptured aneurysm is direct closure of the defect with patch closure of aneurysm after resection of the aneurysm, but when the diameter of aneurysm is smaller than 7 mm, direct closure of the defect of the aneurysm was used. Only one patient after patch closure of ruptured sinus of Valsalva (Konno type I) required reoperation for penetration into left ventricle. This case might be avoided if patch was sutured to annulus of aortic valve. There were two operative death and one late death. The former died of cerebral infarction and low output syndrome, the latter died of sepsis. The mean follow-up period (+/- standard deviation) was 8.2 +/- 6.0 years. All patients that were followed were thirteen and found to be in New York Heart Association class I.

From 1977 to 1988, 390 cases of lung cancer were resected in our hospital. In 12 patients (3.1%) a postoperative bronchopleural fistula developed. This complication occurred more commonly after right pulmonary resection than left and most common after right pneumonectomy. Moreover, that had occurred following right pneumonectomy was most fatal. After right middle and lower lobectomy, this complication occurred at the same rate as after pneumonectomy and also caused a fatal result. On the other hand, after the resection of single lobe, the rate of the occurrence of a bronchopleural fistula was lower. And, even if it had developed, the fistula sometimes could be healed by a conservative treatment only. In one of our cases the fistula was successfully treated by intra-bronchial gluing through a bronchofiberscope.

The purification of 45 KDa EMBP and the production of monospecific anti-serum is described. 45 KDa EMBP was purified by relatively simple methods using ion exchange HPLC (TSK-GEL DEAE-5PW column) and size exclusion HPLC (TSK-GEL G3000SW column). The results clearly demonstrated the speed and simplicity of the method using these columns, compared to previously-described methods for purification of 45 KDa EMBP.

The surgical treatment of pulmonary adenocarcinoma was studied on the basis of the postoperative long-term results in 211 cases. The overall five-year survival rate was 42% for adenocarcinoma and 48% for squamous cell carcinoma, and there was no significant difference. In stage I, as the degree of differentiation became lower, the prognosis became poorer. In stage III, the five-year survival rate was 50% for the alveolar cell type and 32% for the well differentiated type. The prognosis was better than in the moderately or poorly differentiated types. The prognosis of T1N0 cases was 79% in T1, but it was significantly lower 39% for T2 cases. Among T3 or T4 cases other than N2, the two-year survival rate was 15%, and the longest survival recorded was 32 months. The results were also poor in 9 cases undergoing extensive surgery, with the two-year survival rate being only 10%. Of the N2 cases undergoing extensive surgery all died within a year, except for one case surviving two years following panpleuro-pneumonectomy. In N2, the prognosis was significantly worse if there were two or more foci of mediastinal lymph node metastasis or if subcarinal lymph node metastasis was present. In the long surviving cases, cancer-bearing survivors were about twice as common as with squamous cell carcinoma. Recurrence was usually by distant metastasis (mainly to the brain), being twice as common as local recurrence. Therefore, in adenocarcinoma the significance of postoperative adjuvant therapy was considered to be greater than in squamous cell carcinoma.

Machado-Joseph disease (MJD), one of the most common types of hereditary spinocerebellar degeneration caused by abnormal expansion of the CAG repeat in the MJD1 gene, presents atrophy of the infratentorial structures neuropathologically and neuroradiologically. Although a significant positive correlation has been reported between infratentorial atrophy and the number of expanded CAG repeat units, the exact changing course of brainstem size in the individual case remains to be resolved. We investigated seven cases of genetically confirmed MJD longitudinally by magnetic resonance imaging with observation periods of 4.5-10.6 years. Measurement of the midsagittal areas of infratentorial structures disclosed progressive atrophy of the pontine base and cerebellum, which correlated significantly with age, whilst midbrain and pontine tegmentum showed atrophy with no significant progression, suggesting it was better identified as 'small size' and might have mostly been completed before the initial symptoms. Such differences between regions in atrophy progression must be caused by a difference in the neuropathological course.

Epitaxial growth of the Mn-containing novel ternary compound MnGeP2 has been investigated. Prior to the growth experiments, theoretical studies using an ab initio calculation were carried out, on the basis of which the stable existence of MnGeP2 with a chalcopyrite structure was predicted. Growth experiments of Mn-Ge-P were performed on GaAs(001) and InP(001) substrates using a molecular beam epitaxy (MBE) technique, in which Mn and Ge were supplied from solid sources and P from a tertiary butyl phosphine (TBP) gas source. The optimum growth condition has been estimated on the basis of X-ray diffraction studies. Oriented overgrowth of MnGeP2 was confirmed from a reciprocal lattice mapping (RLM) on X-ray diffraction (XRD) analyses, and lattice constants have been determined to be a=0.569 nm and c=1.13 nm based on the assumption that the material has a tetragonal crystal structure.

In this article, the clinical experience with a cardiopulmonary bypass (CPB) using a newly developed hollow fiber oxygenator with an ultra-thin layer of silicone is reported. A comparative study of biocompatibility between the new oxygenator and a heparin coated oxygenator is also described. The CPB was performed with a silicone coated oxygenator, Mera Excelung Binding Prim HPO 15 H-C (Group I, n = 6) or Binding Prim HPO 25 H-C (Group II, n = 10) (Senko Medical Instrument Mfg., Tokyo, Japan). Air could be vented through the silicone coated hollow fibers, and it was easy to prime the circuits. The CPB duration was 101 +/- 37 min and 170 +/- 64 min for Groups I and II, respectively. There were no deaths and no complications from CPB. Partial arterial pressure of O2 levels 60 minutes after the start of CPB were 529 +/- 28 mm Hg and 529 +/- 28 mmHg for Group I and II, respectively. Partial arterial pressure of CO2 levels 60 min after the start of CPB were 36.4 +/- 4.6 mmHg and 39.4 +/- 4.4 mmHg, respectively. Plasma free hemoglobin at 60 min was 33.5 +/- 17.2 mg/ dL and 46.7 +/- 26.1 mg/dL for Groups I and II, respectively. As an evaluation of biocompatibility, the effects of the new oxygenator on platelet activation (GP Ib, IIb/IIIa), coagulation (TAT), fibrinolysis (PIC), and inflammatory response (C3a, granulocyte elastase) were investigated during CPB and comparing to those of the heparin coated oxygenator. There were no significant differences in GP Ib, GP IIb/IIa, TAT, PIC, and granulocyte elastase between the two oxygenators. However, 60 min after the start of CPB, the C3a was significantly lower for the new oxygenator group than for the heparin coated oxygenator group (p < 0.03). The new oxygenator showed good gas transfer, low hemolysis, and good biocompatibility. Because of its durability and good biocompatibility, the new oxygenator was determined to be suitable for prolonged extra corporeal circulation.

An 8-month-old female infant with a primary carcinoma of the choroid plexus developed a rhabdomyosarcoma in the anterior chest wall at the age of 1 year and 2 months. Her mother had developed a liposarcoma in her left thigh at the age of 17 years. One of the patient's siblings had a rhabdomyosarcoma of the epipharynx at the age of 1 year. This is the fourth reported case of a choroid plexus carcinoma occurring in Li-Fraumeni syndrome.

Three novel antigen systems (L22, L23, and L24) expressed on human B cell subpopulations were identified by using TB1-2C3, TB1-2B3, and TB1-3C1 monoclonal antibodies, respectively. L22 was expressed on a minor subpopulation of B cells in human lymphoid tissues and in the peripheral blood. These B cells associated with L22 were resting small B cells mainly located in the mantle zone of lymphoid follicles, most of which also expressed IgM and IgD on their cell membrane. This antigen was absent from all cultured hemopoietic cell lines including B cell-derived cell lines as well as from all human B cell malignancies, except for B cell-type chronic lymphocytic leukemia and hairy cell leukemia. L23 and L24, on the other hand, existed on approximately two-third of B cells in blood and lymphoid tissues. These L23 and L24 antigens were expressed largely on small lymphocytes located in the mantle zone of lymphoid follicles and to a lesser extent on large blastic cells within lymphoid germinal centers. L23 and L24, like L22, seem to disappear from B cells during their differentiation into antibody-secreting cells, because they were not expressed on normal and neo-plastic plasma cells. This is additionally confirmed by the observation that L23 and L24 were expressed little or not at all on pokeweed mitogen-activated and Epstein-Barr virus-transformed B cells, and were absent from some of B cell malignancies that have been thought to correspond to the later stages of B cell development. Although L23, but not L22 and L24, was faintly expressed on mature granulocytes and monocytes, none of L22, L23, or L24 existed on human thymus and T cells. Immunoprecipitation studies showed that L23 and L24 were different molecular species consisting of a single glycoprotein with m.w. of 205,000 and 145,000, respectively. L22 antigen is presently under study.

Spleen cells obtained from Lewis rats were cultured with 4 micrograms/ml Con A for 96 hr, and activated cells were fused with BW5147 mouse T lymphoma cells. Seven clones obtained by fusion expressed rat IL 2R. The expression of rat IL 2R on those hybrid cells could be up-regulated by IL 2 itself, ATL-derived factor, and TPA and CA++ ionophore. Those IL 2R could be down-regulated by murine MoAb ART-18 that detects rat IL 2R. All hybrid clones produced IL 2 constitutively. IL 2 produced by hybrid cells bound to its receptor and promoted the proliferation of hybrid cells in some clones. Incubation of cells with exogenous IL 2 resulted in the proliferation of hybrid cells, whereas the proliferation of some clones was inhibited by exogenous IL 2, indicating that IL 2 had bifunctional properties on cell growth. Rat IL 2R from 6H2-F9 hybrid cells was studied by both one- and two-dimensional SDS-PAGE with ART-18. The IL 2R derived from 6H2-F9 cells had 72,000 to 77,000 and 40,000 to 48,000 m.w. major components under nonreducing conditions, and had 50,000 to 56,000 m.w. major and 35,000 to 38,000 m.w. minor components under reducing conditions. The 110,000 m.w. component, the third component of IL 2R, was constantly observed in 6H2-F9 hybrid cells.

Rat T lymphocyte antigens were defined by using two distinct monoclonal antibodies (R1-3B3 and R1-10B5). R1-3B3 antibody, when tested for its reactivity with rat lymphoid cells by immunofluorescence, stained almost all of thymus and T cells but not the majority of B cells and bone marrow cells. The antigen defined by R1-3B3 existed more abundantly on medullary thymocytes and peripheral T cells than on cortical thymocytes. Immunochemical data showed that R1-3B3 antibody recognized a single glycoprotein with a m.w. of 67,000, showing marked electric charge heterogeneity with isoelectric points ranging from 5.4 to 7.3. R1-10B5 antibody, on the other hand, had more restricted reactivity with rat T cells and labeled approximately 85% of thymus cells and 30% of the peripheral T cells but neither B cells nor bone marrow cells. These T cells positive for R1-10B5 appeared to be negative for W3/25 antigen, which has been shown to be the marker for the rat T cell subset associated with helper function. R1-10B5 antibody detected a basic glycoprotein complex consisting of sulfhydryl-linked subunits with 30,000 and 34,000 m.w. Although the antigen defined by R1-3B3 was resistant to trypsin digestion, the one detected by R1-10B5 was much more sensitive to trypsin cleavage. All of these data obtained with either R1-3B3 or R1-10B5 are quite comparable to those reported for mouse Lyt-1 or Lyt-2,3 antigens, and thus suggest that the antigens defined by R1-3B3 and R1-10B5 antibodies represent rat homologues of Lyt-1 and Lyt-2,3 antigens in the murine system, respectively.

Con A-activated rat thymocytes were used to immunize mice, and immune spleen cells were fused with NS/1 myeloma cells. One clone, designated 5C6-F4, reacted strongly with Con A-activated rat thymocytes and some LPS-activated rat spleen cells but not with normal thymocytes, spleen cells, or bone marrow cells of rat origin. The 5C6-F4 did not react with Con A-activated thymocytes of mouse origin. Immunoprecipitation of 5C6-F4 antigen from surface-iodinated Con A-activated rat thymocytes or LPS-activated rat spleen cells revealed its m.w. to be approximately 100,000. The kinetic studies of the expression of 5C6-F4 antigen revealed that 5C6-F4 antigen was detectable at 6 hr after Con A stimulation of rat spleen cells, whereas IL 2 receptor (IL 2R) was detectable at 12 hr. The appearance of 5C6-F4 antigen and IL 2R precede the onset of DNA synthesis of Con A-activated spleen cells. Thus, 5C6-F4 antigen is classified as early activation antigen. The 5C6-F4 inhibits the lymphocyte proliferation induced by mitogen and the IL 2-driven rat T cell proliferation. Sequential immunoprecipitation study as well as binding inhibition study indicated that the 5C6-F4 antigen is distinct from IL 2R molecule. The 5C6-F4 antigen appears to be a novel rat lymphocyte activation antigen that exhibits immunoregulatory function and also may serve as a useful marker of T cell activation.

Cell-surface gangliosides are presumed to play a role in cell growth and differentiation. With the use of monoclonal antibodies directed against GD3, a disialoganglioside expressed predominantly by cells of neuroectodermal origin, we have found that GD3 is expressed by a subpopulation of cells of the immune system including: 1) fetal thymocytes in subcortical regions and near vessels, 2) lymph node lymphocytes in interfollicular areas and near vessels, and 3) a small subset of T cells in the peripheral blood. Mouse monoclonal antibodies (two IgGs, one IgM, and F(ab')2 fragments) reacting with GD3 were found to stimulate proliferation of T cells derived from peripheral blood. Proliferation of T cells was observed even in cultures depleted of macrophages, suggesting that activation by anti-GD3 was not dependent on the presence of accessory cells. T cell proliferation was maximum between days 5 and 7 of stimulation and was preceded by expression of interleukin 2 receptors. No stimulation was observed with control antibodies of the identical isotype or with monoclonal antibodies recognizing the gangliosides GD2 or GM2. During stimulation by anti-GD3 monoclonal antibodies, there was an expansion of the GD3+ pool of T cells, but depletion of GD3+ T cells prior to stimulation abrogated the response. Proliferation induced by binding to GD3 could be augmented by exogenous interleukin 2 and phytohemagglutinin. Anti-CD3 (T3) monoclonal antibodies had little or no effect. These results demonstrate that binding to GD3 on the surface of T cells can elicit signals for T cell proliferation.

To investigate whether a different type of neurons has a different susceptibility to a drug in producing epileptiform activity, we compared penicillin induced epileptiform activities of the two types of neurons in the hippocampal formation of guinea pigs, i.e. the CA 3 pyramidal cells in the hippocampus proper and the granule cells in the dentate gyrus, using slice preparations. The thin slice of 0.4 mm thickness was cut nearly perpendicularly to the longitudinal axis of the hippocampus and was transferred to a nylon mesh in an observation chamber which was perfused with the oxygenated and warmed medium at a rate of 2 ml/min. Under tenfold magnification stimuli were delivered to the nerve fiber layer through bipolar electrodes and evoked field potentials were recorded from the cell body layer with glass micropipettes of 10 mu tip diameter filled with normal medium. In both cell body layers no epileptiform field potentials could be induced during perfusion of normal medium even if stimulus strength was increased. The CA 3 pyramidal cell body layer showed a delayed multipeaked field potential in response to threshold stimulus applied to the mossy fiber in penicillin-containing medium (Pc concentration = 500, 1000, 2000 I. U./ml). When the strength of stimulation increased, the latency shortened, but the amplitude and the duration of epileptiform activity did not change. The granule cell body layer generated no epileptiform activity in response to weak electrical stimulus applied to the perforant path in penicillin-containing medium (Pc concentration = 500, 1000, 2000 I. U./ml). However, at high penicillin concentrations (1000, 2000 I. U./ml) multiple population spikes having a short latency appeared on intense stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

A retrospective examination was made of eleven patients that developed prosthetic valve endocarditis (PVE) during the period from January 1960 to December 1987. Infection occurred in one patient within 60 days after surgery and in 10 thereafter. Causative organism was found in 6 patients. As organism, Staphylococcus species were noted in 4 patients and Peptstreptococcus was noted in one patient and Aspergyllus was noted in one patient. Three of eleven patients received medical treatment only and the other 8 patients were received surgical treatment. Mortality rate was 67% in medical group and 29% in surgical group. Two patients with medical treatment died of cerebral infarction about 40 days after the onset of PVE. In surgical group one patient died of uncontrollable Aspergillus infection and the other one died of dyspnea. No survivors who was treated surgically have developed reinfection or relapse of infection but four of them developed perivalvular leakage and needed reoperation. Absolute removal and closure of the valve ring abscess and reconstruction of defect should be considered for those needed surgical treatment to prevent reinfection and relapse developing.

It is well known that hemolysis by extracorporeal circulation is major cause of renal failure after open heart surgery. The purpose of this study is to investigate the effects of administration of haptoglobin (Hp) during extracorporeal circulation. The patients were divided into two groups: Group I 10 patients underwent open heart surgery for extracorporeal circulation; Group II 10 patients underwent open heart surgery for extracorporeal circulation with the administration of 4,000 IU of Hp. The serum level of total Hp was elevated in group II during bypass, and reduced at 1st day in both groups more than pre-operative level. The serum level of total Hb was elevated in both groups during bypass, and reduced at 1st day within normal limits. Free serum Hb was found in group I at 30 min after start bypass and increased during bypass and urinary Hb was also found. However, in group II free Hb was not found during and after bypass. Urinary NAG and alpha 1 Mg levels of group I were significantly higher than those of group II. The administration of Hp during extracorporeal circulation prevents the increment of serum free Hb and is effective for protection of renal function.