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Hematological changes occurring during use of left ventricular assist devices (LVADs) were evaluated in 3 patients suffering from postcardiotomy cardiogenic shock. LVAD treatment ranged from 6 to 9 days. During the procedure, no anticoagulants were used in the first two cases, while in the third case, a protease-inhibiting agent, nafamostat mesilate (FUT-175), was used. In the first two cases without any anticoagulants, fibrinopeptide A (FPA) and thrombin-antithrombin III complex (TAT) increased markedly over the course of LVAD treatment, suggesting the excessive activation of the coagulatory system. The fibrinolytic system also became activated during LVAD treatment as was indicated by a marked increase in FDP-D-dimer and alpha 2 plasmin inhibitor-plasmin complex (PIC). Continual decreases observed in Factor XII and prekallikrein indicate that the coagulofibrinolytic activation occurring during LVAD treatment is presumably the result of contact activation of these factors due to interaction of blood with the internal surface of the LVAD. In the third case with FUT-175, both coagulation and fibrinolysis were successfully maintained at minimum levels as was demonstrated by the extremely low levels of these molecular markers. There was also no significant consumption of any contact factors. FUT-175 looks promising as an anticoagulant during the use of cardiac assist devices.

A human monoclonal antibody (MCA), CLN-IgG, showed cytotoxic effect in vitro against the cervical carcinoma cell line, ME-180, by antibody dependent cell-mediated cytotoxicity (ADCC). To determine which fractions of cells in peripheral blood lymphocyte (PBL) mediate ADCC, PBL were separated with nylon wool column and sheep red blood cells (SRBC). Both adherent cells (monocyte) and non-T, non-B cells showed cytotoxicity by ADCC. Human non-T, non-B cells showed higher cytotoxic activity against ME-180 cells than monocytes. Furthermore murine effector cells were less effective in ADCC than human effector cells with human MCA.

A 59-year-old man was admitted to our hospital because of compression fracture of the lumbar spine and pubic bone fracture following fall from a ladder. On admission the only a little left pleural effusion in the thorax was noted. Two days later, x-ray film of the chest revealed massive left pleural effusion. Under the diagnosis of left hemothorax, left thoracotomy was performed. Then we found incidentally that the left pericardium had ruptured longitudinally over the length. Herniation of the heart was not developed. The ruptured pericardium was repaired using Teflon mesh.

Treatment of postpneumonectomy pyothorax due to bronchopleural fistula (BPF) is troublesome, especially with methicillin-resistant staphylococcus aureus (MRSA) infection. Moreover, in a bypass-grafting case, the management becomes more complicated. We reported a successful treated case of MRSA pyothorax due to BPF after grafting and pneumonectomy. In a 48-year-old woman performed grafting and pneumonectomy for traumatic aneurysm of the thoracic aorta, MRSA pyothorax due to BPF occurred. BPF was successfully closed by fibrin-glueing under bronchofiberscopy. However pyothorax was not improved by thoracic irrigation for a month. Therefore, open pleural drainage underwent. At the same time, bronchial stump and graft surface was covered with the omental pedicle flap. The open wound had become sterile in two months, and the thoracic window was closed three months after the open drainage.

We analyzed the outcome for 18 patients with prosthetic valve endocarditis (PVE) treated between 1965 and 1990, 17 of whom had undergone valve replacement with mechanical prosthetic valves and one of whom had a bioprosthesis. Two patients developed infection within 60 days after surgery, and 16 thereafter. Fifteen patients received combined medical and surgical therapy and three medical therapy. In 14 patients, surgery had been performed during active infection. Mortality rate of those who had received combined medical and surgical therapy was 27%, and that of those who had received medical therapy was 67%. At operation, para-annular abscess was around the mitral prosthesis was found in three patients and around the aortic prosthesis in eight. Seven patients required reoperation for postoperative paravalvular leakage, in six, para-annular abscess had been found at the operation for PVE, and in one para-annular abscess had been noted. One patient who had undergone reoperation had developed reinfection after the first surgery and died due to multiple organ failure after the second operation (Danielson's translocation technique). In one patient who had complete loss of supporting tissue because of severe para-annular abscess, we had performed aortic valve replacement by implanting the aortic valve prosthesis into the left ventricle with Dacron felt-supported sutures placed in the mitral annulus and the muscles of the left ventricular outflow tract. This patient showed no postoperative infection or no paravalvular leakage.(ABSTRACT TRUNCATED AT 250 WORDS)

Between January 1983 and June 1990, there were 48 patients who underwent surgery for mitral regurgitation due to degenerative diseases. Among these, 20 patients received mitral valve repair. Overall operative mortality was 5% for patients who underwent valve repair, and 7.1% for those who underwent valve replacement. We standardized a maneuver for valve repair in August 1988 in an attempt to expand its indications. There were 35 patients who underwent surgery prior to that date (group 1), and 13 patients after that date (group 2). There were nine patients (25.7%) in group 1 and 2 patients (84.6%) in group 2 who underwent valve repair. Among these, one patient (11%) in group 1 died within 30 days after the operation, but there were no surgical deaths for any patients in group 2. In addition, one patient (11%) in group 1 and one (9%) in group 2 required another operation for valve replacement. Doppler echocardiographic studies performed postoperatively in 18 patients who had undergone valve repair showed that 13 (72.2%) had no regurgitation, 4 (22.2%) had trivial regurgitation, and 1 (5.6%) had mild regurgitation. Postoperative valve area as determined by continuous-wave Doppler echocardiography was 3.7 +/- 1.1 cm2 (mean +/- SD) for patients who had undergone reconstruction and 3.1 +/- 0.7 cm2 for those who had undergone replacement.

Ten cases of central airway obstruction mainly caused by extrinsic compression due to the growth of extratracheal malignant tumors or longitudinal extension of tracheal adenoid cystic carcinomas, underwent palliative intubation subsequent to endoscopic Nd-YAG laser treatment. Mean length of the severe stenosis in these cases was 4.4 cm (3-7 cm). Sole application of endoscopic Nd-YAG laser to the stenosis failed relief of the symptom and an immediate palliative intubation was recommended. Mean time of the temporary intubation was 7 days (4-11 days). Airway was maintained by this intubation and also retained enough after extubation. Therefore, it seemed that, in a palliative treatment of the central airway severe stenosis, usefulness of the combination management of Nd-YAG laser with following temporary intubation was revealed. However, in order to maintain the airway for recurrence of the obstruction, use of indwelling airway stents seemed a better application. The longest period of follow-up in the cases treated by indwelling airway stents was 6 months and one of the cases is a now in comfortable state.

Postoperative pulmonary complications cause the decrease of the flow of remaining pulmonary circulation. We examined the effects of the difference of resected lobes on the postoperative course and remaining pulmonary circulation of the lobectomized lung cancer patients using a pulmonary digital subtraction angiography. In all cases with preoperative pulmonary complications, circulatory flow of the remaining lung on the operated side significantly decreased. In the cases without preoperative pulmonary complications, only the cases performed left upper lobectomy developed the decrease of the circulatory flow on the operated side. This seemed to be chiefly caused by a postoperative continual atelectasis of the remaining lower lobe due to kinking of the bronchus. On the other hand, the postoperative decrease of the residual pulmonary circulatory flow on the operated side was not developed in the cases undergoing a segmentectomy, even with pulmonary complications. Therefore, for any case requiring a left upper lobectomy or the case with an impaired lung requiring any type of lobectomy, contralateral pulmonary function should be exactly evaluated preoperatively.

A He-Ne laser flowmeter (wavelength: 632.8 nm, power: 2 mW) has already been used to measure blood flow in skin, muscle, and mucosa. However, the application of this flowmeter for the beating heart has been left undeveloped due to its difficulty. For the purpose of establishment of the laser measurement of myocardial blood flow, we redesigned a flow probe to be small and light and used a connecting paste to support the subepicardial flow probe. After resolving many obstacles, the noninvasive and real-time blood flow measurement of the beating heart was made possible. The flow volume in subendocardial myocardium was greater than the volume in subepicardial myocardium, and the average ratio of subendocardial flow to subepicardial flow was 1.62 +/- 0.21.

We studied surgical results of 14 cases of ischemic mitral regurgitation. There was no surgical death in 10 cases with left ventricular aneurysm, and their clinical symptoms improved except 3 with the combined operation of left ventricular aneurysmectomy, mitral annuloplasty and bypass grafting. The range of the abnormal contracting segment significantly decreased after surgery except in 3 cases in whom clinical status was not improved. Three of 4 cases which underwent bypass grafting and mitral annulo-valvuloplasty survived, but one of them died of graft-versus-host disease. In the three survived cases, severe mitral regurgitation disappeared. We have concluded as follows: In cases of left ventricular aneurysm, a sufficient aneurysmal resection is very important to control the mitral regurgitation, and the additional procedures of mitral annuloplasty and bypass grafting are essential. The mitral valve replacement is recommended in case of the complete disruption of the papillary muscle. Mitral valvuloplasty combined with annuloplasty is suitable to control the regurgitation in the regional mitral prolapse due to the torn chordae.

Bronchial mucosal blood flow (BMBF) was measured with a laser-Doppler flowmeter in a canine model (n = 20), and the measurement was evaluated to see if it was a useful method for diagnosing allografted lung rejection. The ratio of the value of BMBF at the level of the donor second carina against that at the level of carina (the L/C ratio, an index of BMBF of donor bronchus) decreased in accordance with the extent of lung rejection, and it increased and entered the normal range with the reversal of lung rejection. Compared with the L/C ratio and the rejection grade by histologic changes in open-lung biopsy, the L/C ratio at grade 0 (latent phase) was 0.91 +/- 0.07; at grade Ia (early vascular phase), 0.86 +/- 0.05; at grade Ib (late vascular phase), 0.68 +/- 0.10; at grade II (early alveolar phase), 0.60 +/- 0.14; and at grade III (late alveolar phase), 0.50 +/- 0.15. A significant difference was noted between grades Ia and Ib (p less than 0.01) and between grades Ib and III (p less than 0.01). The sensitivity and the specificity in the detection of early rejection before grade Ib were 96% and 92%, with only one false-negative and two false-positives resulting from 51 measurements of BMBF. In three cases of serious lung infections, the L/C ratio did not fall, and the rejection could be distinguished from infection. These results suggest that measurement of the BMBF is useful for detecting the early rejection of transplanted lungs.

We investigated the relationship between the rejection of lung allografts and the bronchial mucosal blood flow with a laser flowmeter. Nineteen mongrel dogs underwent left lung allotransplantation and were given daily oral immunosuppressive therapy with azathioprine and cyclosporine. The bronchial mucosal blood flow at the carina and the bifurcation of left upper and lower bronchi were measured on days 14, 21, and 28 after left lung transplantation. The bronchial mucosal blood flow of the transplanted lungs was expressed as the ratio of bronchial mucosal blood flow at the bifurcation of left upper and lower bronchi to the bronchial mucosal blood flow at the carina (L/C ratio) instead of the absolute value because bronchial mucosal blood flow was affected by the depth of anesthesia of the dogs. We classified the histologic appearance of the transplanted lung tissue into one of five grades: 0, 1a, 1b, 2, and 3. No rejection was in grade 0, and as the rejection process progressed the higher grades were used in order. The mean L/C ratios for grades 0, 1a, 1b, 2, and 3 were 0.95 +/- 0.03, 0.82 +/- 0.05, 0.68 +/- 0.04, 0.58 +/- 0.07, and 0.30 +/- 0.07, respectively. Thus the L/C ratio decreased as the rejection process progressed. The histologic changes of the donor main bronchus in each rejection grade were investigated. Mononuclear cell infiltration and edema around the small vessels was seen in early rejection. These same histologic changes appeared in muscular arteries as rejection progressed, and the damage to the small vessels and muscular arteries was more severe in late rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

The hemostatic effect of nafamostat mesilate (FUT-175) was evaluated in patients undergoing cardiopulmonary bypass (CPB) surgery. Thirty patients undergoing aortocoronary bypass grafting were divided into two groups. In the control group, anticoagulation was achieved with an initial dose of heparin (3 mg/kg). In the FUT-175-treated group, in addition to the ordinary treatment with heparin, FUT-175 was infused continuously into the circuit throughout the procedure at a rate of 100 mg/hr. Thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA), and fibrin degradation products (FDP-D) dimer increased in both groups as CPB proceeded. In the FUT-175-treated group, these parameters remained lower and decreased more rapidly after the end of CPB. Alpha 2 plasmin inhibitor/plasmin complex (PIC) increased progressively during CPB in the control group; no such significant increases were seen in the FUT-175-treated group. Postoperative blood loss was significantly lower in the FUT-175-treated group than in the control group. It was concluded that FUT-175 reduces postoperative blood loss by inhibiting both coagulation and fibrinolysis during CPB.

A study was undertaken to evaluate hemolysis and subsequent renal damage in 14 patients undergoing cardiopulmonary bypass (CPB) surgery. In all patients, free haptoglobin disappeared completely 30 to 90 minutes into CPB, while free hemoglobin (Hb) levels increased progressively. The NAG index and alpha 1M index also increased progressively, indicating renal tubular injury due to hemolysis (Study 1). An additional 20 patients were monitored intraoperatively for plasma free Hb levels by a newly developed colorimetric method using a haptoglobin coated strip. Free Hb levels during CPB exceeded 30 mg/dl in 14 patients, who were immediately given haptoglobin. This treatment eliminated plasma free Hb within 30 minutes, and effectively prevented hemoglobinuria. Haptoglobin treatment brought significant decreases in the NAG index and alpha 1M index, suggesting a protective effect on renal function (Study 2).

Melanoma is a valuable model to study phenotypic traits that are regulated during cell differentiation and malignant transformation. Melanoma cells display extensive phenotypic and antigenic heterogeneity. Studies of this attribute have provided insight into events that take place during normal melanocyte differentiation and give clues to traits that contribute to malignancy. It is possible that the phenotypic and genotypic heterogeneity present among melanoma cells within a single lesion includes a subset of cells with traits that favor tumor progression and metastasis. This review discusses the identification and characterization of antigens expressed by melanoma cells and their potential contribution to melanocyte differentiation and malignant transformation.

In this study, we investigated the dependency of estramustine binding protein (EMBP) from rat prostate on endogenous androgen. The EMBP content of the dorsolateral prostate markedly decreased 14 days after castration and increased again after the cessation of the weekly subcutaneous administration of 2 mg of Estradiol-17 beta valerate, in accordance with the recovery of prostate weight and serum testosterone concentration. This result clearly demonstrated that EMBP, which was present in very small quantities in the dorsolateral prostate, had a dependency on endogenous androgen as well as on the ventral prostate EMBP. We investigated the changes in prostate weights, EMBP concentration and serum testosterone level throughout life. The ventral prostate weight began to increase rapidly at 7 weeks of age and showed a broad peak from 11 to 14 weeks of age and then gradually decreased. On the other hand, the dorsolateral prostate weight began to increase rapidly at 7 weeks of age and continued to increase very gradually even after 10 weeks of age. There was a remarkable difference in the changes in EMBP concentration between the ventral prostate and the dorsolateral prostate. In the ventral prostate, EMBP concentration increased markedly from 4 to 9 week of age. Thereafter it continued to increase very gradually. On the other hand, in the case of the dorsolateral prostate, EMBP demonstrated higher and fluctuating concentration from 4 to 15 weeks of age. After 16 weeks of age, EMBP showed lower and stable concentration, although the weight of dorsolateral prostate showed gradual increase. These results suggested that there exist, beside androgens, some factors that participated in the regulation of growth and functional metabolism in the dorsolateral prostate after 16 weeks of age.

Amorphous copoly(L-lactide)/glycolide, 70/30 mol%) with weight average molecular weights of 16,900-41,300 were synthesized by ring-opening polymerization in the presence of catalysts using a molecular weight moderator lauryl alcohol. The in vivo degradation profiles of the copolyesters, which were evaluated by implanting them subcutaneously in the back of rats, showed a typical S-type degradation pattern. A luteinizing hormone-releasing hormone agonist (LH-RH agonist), des-Gly10-[Leu6]-LH-RH ethylamide monoacetate, was incorporated into the small cylinders of copoly (L-lactide/glycolide) with a weight average molecular weight of 24,000. The cumulative amount of drug released in vivo from the cylinders showed an S-type profile in analogy with the in vivo degradation pattern. This was demonstrated from data such as serum drug level and pharmacological influence on rat prostates.

The angiographic findings of Takayasu's arteritis in a series of 113 patients were reviewed. Predominant findings were stenotic or occlusive changes, but fusiform or saccular aneurysms were also found in 36 patients (31.9%) in the various sites of aorta and its major branches. Multiple aneurysms were found in 15 patients. The most common site of aneurysms was the ascending aorta (16 patients); in 7 of the patients these were complicated by aortic regurgitation. Aneurysms developed in the aortic arch in 3 patients, in the descending aorta in 11, in the abdominal aorta in 7, and in the major branches of the aortic arch in 9 patients. In 2 patients, follow-up angiograms showed enlargement of the aneurysms, and rupture of the aneurysm occurred in 1 patient. Aneurysms were found even in young patients. A fifteen-year-old female showed a huge aneurysm in the ascending aorta as the initial manifestation of this disease. Thickening of the walls of aneurysms was common and characteristic. This study revealed the moderately high incidence of aneurysms of various sites of arteries in patients with Takayasu's arteritis. The authors conclude that aneurysm, as well as occlusive changes, can be a primary lesion.

New thermo-responsive hydrogels were synthesized by copolymerizing acryloyl-L-proline methyl ester (A-ProOMe) with minor amounts of 2-hydroxypropyl methacrylate (HPMA) or polyethylene glycol 600 dimethacrylate (14G), using gamma-rays from a 60Co source. In water, extensive swelling of the hydrogels occurred at 10 degrees C, but there was marked deswelling as the temperature was raised to 37 degrees C. The poly(A-ProOMe-co-HPMA) hydrogel was characterized by an initial rapid shrinkage at the surface in the deswollen state; this shrinkage arose because of the formation of a rigid membrane barrier devoid of micropores. The system is therefore 'surface regulated'. In contrast, no such a barrier formed in the deswollen poly(A-ProOMe-co-14G) hydrogel. The whole matrix shrunk without the disappearance of micropores, and it is therefore a 'matrix pumping' system. Testosterone was incorporated into both these types of hydrogels, and the drug-loaded hydrogels were implanted subcutaneously into the backs of castrated rats. The daily dose of testosterone released in vivo from the poly(A-ProOMe-co-HPMA) hydrogel was constant at approximately 30 micrograms/day throughout an experimental period of 54 weeks. In contrast, drug release from the poly(A-ProOME-co-14G) hydrogel reached a maximum after one week and then decreased linearly with time down to the 7th week, when it was undetectable. These conclusions were supported by the changes in weight of the ventral prostates and right-side seminal vesicles of the rats, which were restored to normal when delivery of the testosterone was sustained.

Relatively low-molecular-weight copolyesters of glycolic acid (GA) with lactones such as gamma-butyrolactone (BL), delta-valerolactone (VL), and epsilon-caprolactone (CL) were synthesized by copolycondensation without catalysts. The resulting copolyesters are intended as carriers for drug delivery systems. Copolyesters with approximately 85 mol% GA (number-average molecular weight (Mn): 2900 +/- 100) are crystalline and solid and show a parabolic-type in vivo degradation pattern. The in vivo degradation of amorphous-pasty poly (GA/CL) (approximately 50/50 mol%) changed from parabolic-type to linear-type to S-type pattern as their molecular weight increased. A luteinizing hormone-releasing hormone agonist, [D-Leu6, des-Gly10]-LHRH ethylamide monoacetate (LHRH agonist), was incorporated into small cylinders with these copolyesters. An initial burst of LHRH agonist was observed for cylinders prepared with parabolic-type degrading copolyesters, in contrast to a marked delay in LHRH agonist release for cylinders prepared with S-type degrading copolyesters. The resulting daily dose of drug was maintained an approximately constant, though decreasing stepwise with time. For example, the daily amount of LHRH agonist released in vivo from a cylinder prepared with poly(GA/CL) (50/50 mol%; Mn = 4500) was 61 +/- 39 micrograms/day throughout an experimental period of 10 weeks with a corresponding pharmacological effect on the rat prostate.

The hemostatic alterations in two adult patients who were supported by left ventricular assist devices (LVADs) because of postcardiotomy heart failure were evaluated. In both patients, fibrinopeptide A and thrombin-antithrombin III complex increased markedly during the first several days, and thereafter decreased moderately but remained above normal over the entire procedure. Furthermore, fibrinopeptide B beta 15-42 and alpha 2 plasmin inhibitor-plasmin complex were also markedly increased over the entire course of LVAD treatment. These data show that the LVAD system strongly activates both the coagulation and the fibrinolytic system, even when thromboembolic or bleeding complications are not clinically evident. Furthermore, the decrease in physiological coagulation inhibitors, especially protein C, indicates that these factors are activated and consumed during LVAD treatment. Because protein C is important in regulating the coagulation cascade during LVAD treatment, exhaustion of this system might result in thromboembolic complications during LVAD treatment.

1. Five perchloric acid-soluble fractions (PASFs) obtained from ascitic fluids of three patients with primary hepatocellular carcinoma (HCC), a patient with liver metastatic carcinoma (LUC) from ureteral carcinoma and human normal serum (NS) were subjected to DEAE-cellulose column chromatography to separate seven glycoprotein fractions, respectively. 2. In this chromatography, two HCC-PASFs gave a Thomsen-Friedenreich (T)-active glycoprotein, respectively. 3. Other HCC-PASF gave a T-active glycoprotein, two blood group N antigen precursor glycoproteins and an N antigen precursor glycoprotein with T activity. 4. LUC-PASF gave two T-active glycoproteins and an N antigen precursor glycoprotein with T activity. 5. NS-PASF did not give these serologically active glycoproteins.

The authors report four cases of familial pituitary adenomas from two unrelated families. No clinical or biochemical evidence of multiple endocrine neoplasia, type I (MEN-I) was demonstrated. Detailed study of the family trees disclosed no other family members affected by MEN-I. Familial occurrence of pituitary adenomas unassociated with MEN-I is rare.

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.

The effect of alpha-globulin, the dominant binding protein for fractionated 3H-heparin, on the hepatic uptake of 3H-heparin was studied by liver perfusion experiments in rats. Fractionated 3H-heparin concentration in the recirculated perfusate decline one-exponentially with time for each of six initial concentration levels of alpha-globulin. The hepatic uptake clearance of fractionated 3H-heparin was 0.154 ml/min/g liver in the absence of alpha-globulin, and it decreased with increasing alpha-globulin concentrations. This result indicates that the hepatic uptake rate of alpha-globulin-bound fractionated 3H-heparin is lower than that of unbound fractionated 3H-heparin. On the other hand, it was indicated that almost all fractionated 3H-heparin binds to alpha-globulin at 8 mg/ml of alpha-globulin in in vitro study. However, the hepatic uptake clearance of the heparin at the concentration was of a certain value that could not be ignored. It was suggested that alpha-globulin-bound fractionated 3H-heparin also contributed to the hepatic uptake of fractionated 3H-heparin. Therefore, a protein-mediated transport system, which has been reported for some low molecular weight drugs, may also exist in the hepatic uptake of such a high molecular weight compound as fractionated 3H-heparin.

"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.

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.

Sequential polydepsipeptides containing both peptide and ester bonds, poly[(L-alanyl)n-gamma-ethyl L-glutamyl-L-lactyl] (n = 0, 1, 2, and 3) (poly[(Ala)n-Glu(OEt)-Lac]), were prepared for application as biodegradable carriers for drug delivery systems. The in vivo degradation of these polymers was evaluated by subcutaneous implantation in the backs of male rats, and was strongly influenced by the number (n) of Ala units in poly[(Ala)n-Glu(OEt)-Lac]. The resulting poly(Ala-Ala-Glu(OEt)-Lac) gave the highest degradability, in which 100% degradation was observed 24 weeks from the start of implantation. A luteinizing-hormone-releasing hormone agonist des-Gly10-[D-Leu6]-LH-RH ethylamide (LH-RH agonist), was incorporated into a sequential poly(Ala-Ala-Glu(OEt)-Lac) carrier by the melt-pressing technique, which gave fine cylindrical polymer formulations with different structures of drug dispersion, e.g., blend-type and sandwich-type formulations. The rate of in vivo release of LH-RH agonist from a blend-type formulation showed a linear decrease with time until its release was finished after 6 weeks' implantation. In contrast, in a sandwich-type formulation, the in vivo release rate was apparently maintained constant over a period of 16 weeks (24 +/- 14 micrograms/day).

R24, a mouse IgG3 mAb against GD3 ganglioside, was shown to bind to itself in a homophilic manner. This was demonstrated by augmented binding of 125I-labeled R24 to the cell surface of GD3+ cells by unlabeled R24 and by direct binding of biotinylated R24 to R24 adsorbed on solid phase. Although homophilic binding was evident when R24 was bound to solid phase, R24-R24 aggregates could not be detected in solution under otherwise identical conditions. R24 bound to four other mAb (two IgG3, one IgG2a, one IgM) directed against GD3 but did not bind to a panel of 21 other mAb including other IgG3 mAb and mAb directed against non-GD3 ganglioside. Evidence implicating the GD3-binding site of R24 in homophilic binding included the following observations: 1) F(ab')2 fragments of R24 could bind to R24, 2) an antiidiotypic mAb against the GD3-binding site of R24 inhibited R24 homophilic binding, 3) an IgM anti-GD3 mAb also demonstrated homophilic binding to R24, and 4) homophilic binding was a function of immunoreactivity and avidity for GD3. R24 variants with 40-fold lower avidity for GD3 demonstrated a similar decrease in homophilic binding. Inasmuch as R24 bound to R24 F(ab')2 fragments and specifically to anti-GD3 mAb, it appeared that the target for homophilic binding was an epitope within the V region of anti-GD3 mAb. It is likely that homophilic interactions result in increased affinity of R24 for GD3 through increased effective valency of antibody-Ag complexes.

Low molecular weight and amorphous copolyesters composed of 70 mol% L-lactic acid and 30 mol% DL-hydroxy acids such as DL-lactic acid, DL-alpha-hydroxy-n-butyric acid, DL-alpha-hydroxyisovaleric acid and DL-alpha-hydroxyisocaproic acid were synthesized by direct copolycondensation in the absence of catalysts, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. For this purpose, the copolyester was moulded into a small cylindrical specimen under melt-pressing technique and implanted subcutaneously in the back of male adult rats. The in vivo degradation pattern can be subdivided into three types: the formations of parabolic type (L-LA/DL-HBA copolymer), linear type (L-LA/DL-LA copolymer) and S type (L-LA/DL-HIVA and L-LA/DL-HICA copolymers). A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide monoacetate (LH-RH agonist), was incorporated into the small cylinders of copolyester formulations, of which the strongest pharmacological influence was observed in a copoly(L-LA/DL-HICA) formulation system, resulting in the maintenance of effective pharmacological influence throughout an experimental period of 15 wk, at which the in vivo release rate of LH-RH agonist was held constant at approximately 45 micrograms/d.

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.

The spontaneously epileptic rat (SER), a mutant homozygous for both zitter and tremor genes, exhibits absence-like seizures and tonic convulsions without external stimulation from 7 to 8 weeks of age. Histopathological studies of the central nervous system revealed the following abnormalities. The 35-day-old SERs which exhibit body tremor, and which have never shown seizures, had marked vacuolation and hypomyelination in the brainstem and cerebellum. The vacuoles were produced by splitting of the myelin sheaths and swelling of the dendrites and were related to primary swelling of the astrocytes. The 2- to 3-month-old SERs with staggering gait and seizures showed focal axonal swelling ('torpedo') and advanced vacuolation in the granular cell layer of the cerebellum in addition to the abnormalities observed at 35 days of age. Degenerative neurons and spheroidal bodies were observed in the substantia nigra and ventral tegmental nucleus. These brain areas are known to be related to tonic convulsions in the several experimental models. The SER is believed to be a useful tool for the investigation of the relationship between the structure and function of the central nervous system in epilepsy. It is probable that the more severe changes in the cerebellum are responsible for the staggering gait.

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 purpose of this study is to compare the results of TR repair by using doppler echocardiography. 52 patients who underwent tricuspid repair surgery from 1980 to 1987 were studied. 30 patients received Kay's annuloplasty (K-A group) while 16 patients were repaired with Carpentier's ring annuloplasty (C-E group). A new classification of TRs according to the direction and the area of the regurgitant flow on doppler echocardiogram was applied to the preoperative TRs. In addition to grading the severity of the regurgitations on a four-point scale, the TRs were subdivided into three types according to the direction of the regurgitant flow toward, the interatrial septum (type a), the center of the atrium (type b), and the lateral side of the right atrium (type c). Regurgitation covering more than two of the three areas was recognized as massive TR. In the K-A group, 5 cases showed massive TR and 11 cases showed localized TR preoperatively. Localized TR cases were well controlled in all cases but 4 out of 5 massive TR cases remained third grade and type b postoperatively. In the C-E group, 9 cases showed massive TR and 7 cases showed localized TR. All cases were displayed good control of the regurgitation postoperatively. Postoperative pressure half time of the tricuspid valve orifice treated with the two types of annuloplasty were 108 +/- 25 msec in the C-E group versus 151 +/- 43 msec in the K-A group (p less than 0.001), which indicates the tendency of the K-A group to produce narrowed tricuspid orifice.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to establish the best manufacturing conditions for preparation by the direct compression method of tablets which contain microcapsules having a minimal destruction rate of the coating wall, show the same dissolution pattern as microcapsules, and have enough mechanical strength for practical use, and to elucidate the internal structure of the tablets under the best manufacturing conditions. Degree of destruction of the microcapsule wall was evaluated by the dissolution rate of the medicine in the microcapsules. To learn the mechanical strength of tablets, the crushing strength and friability were measured; their internal structure was analyzed by the porosity and pore size distribution. The best manufacturing conditions for the tablets were thus determined, and it was clarified by analysis of the internal structure that these conditions are markedly affected by the flowability of prescribed powders and the packing state at compression.

It was very difficult to measure myocardial blood flow in clinical cases. Recently, a He-Ne laser doppler flowmeter was developed, and we made it possible to measure the pre-and post-operative myocardial blood flow in cases of coronary artery bypass grafting (CABG). We applied a laser flowmeter to 30 cases of bypass grafting to the left anterior descending coronary artery (18 cases with IMAG and 12 cases with SVG). The preoperative myocardial blood flow at the right ventricular anterior wall was 77 +/- 15 ml/min/100 gr, and the postoperative flow at the same point was 81 +/- 12 ml/min/100 gr. There was no significant change between the pre-operative value and the postoperative one. Myocardial blood flow at the left ventricular anterior wall in SVG group significantly increased from the preoperative value of 58 +/- 11 ml/min/100 gr to the postoperative value of 86 +/- 9 ml/min/100 gr (p less than 0.001). In IMAG group, myocardial blood flow at the left ventricular anterior wall similarly increased from 73 +/- 14 ml/min/100 gr to 83 +/- 15 ml/min/100 gr (p less than 0.01). The postoperative value of IMAG group was almost equal to the value of SVG group. The increased rate of myocardial blood flow at the left ventricular anterior wall was 52 +/- 32% in SVG group and 18 +/- 12% in IMAG group. These rates were obviously distinguished from the increased rate at the right ventricular anterior wall.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

We have studied the effects of extracorporeally induced systemic hyperthermia on cell-mediated immunity in 12 patients. Also, the effect of heating and anti-cancer drugs on ADCC activity 3 Plaque forming method and 51Cr release method) and NK activity (51Cr release method. target: K-562 cells) of normal human lymphocytes was studied in vitro. The following results were obtained: Lymphocytes, T-cells and IgGFcR+ T-cells counts slightly decreased during the hyperthermotherapy in patients. During initiation of the hyperthermotherapy (Rectal temp. 41.6-41.8 degrees), ADCC activity, PHA, and Con-A induced lymphocyte blastogenesis were slightly depressed, while NK activity was slightly enhanced. At the end of the hyperthermia, ADCC activity, lymphocyte blastogenesis and NK activity were extremely depressed. In vitro, 1 hour of heating at more than 40 degrees C extremely depressed ADCC activity. By heating at 42 degrees C, ADCC activity was depressed depending on heating time, while NK activity was slightly enhanced for the first 10 minutes and then depressed depending on heating time. The administration of anti-cancer drugs (MMC, 5-FU, ADM) did not affect NK activity at all during the heating at 42 degrees C. From these results, it is highly suggested that immunopotentiators should be used during extracorporeally induced systemic hyperthermia in order to make up for the depressed cell-mediated immunity.

Two distinct antigen systems (L26 and L27) specifically expressed in human B lymphocytes were identified using TB2-2B3 (2B3) and T3-5B3 (5B3) monoclonal antibodies, respectively. Whereas L26 antigen defined by 2B3 were rarely expressed on the surface of B cells but abundant in the cytoplasm, 127 antigens detected by 5B3 was clearly expressed on the cell surface. These two antigens appeared to be restricted in their expression to B cells, as they were found in most B cells but not other cell types including thymocytes, T cells, monocytes and granulocytes. Functional studies demonstrated that L27 was more easily lost from B cells after activation with pokeweed mitogen than was L26. Likewise, plasma cell myeloma, as well as normal plasma cells, was devoid of both L26 and L27, whereas immunoblastic sarcoma of B cell type expressed L26 but not L27. These two antigens co-existed in the same B cell lines including Epstein-Barr virus transformed B cell lines, B cell type acute lymphatic leukaemia (B-ALL) cell line, Burkitt's lymphoma cell lines and myeloma cell lines, but pre-B and common ALL cell lines were entirely negative for both L26 and L27. Immunoprecipitation studies showed that L26 consisted of at least two polypeptide chains with molecular weights of 30K and 33K daltons, which were clearly distinct from HLA-DR antigens. The antigen L27 is presently under study.