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We measured plasma levels of tissue factor (TF), total tissue factor pathway inhibitor (TFPI) and free TFPI antigen in patients with diabetes mellitus (DM), hyperlipidemia and disseminated intravascular coagulation (DIC). The mean TF, total TFPI and free TFPI antigen concentrations were significantly higher in patients with DM than in controls and the plasma TF concentration was significantly higher in patients with retinopathy or nephropathy than in DM with no complications. The mean TF, total TFPI and free TFPI antigen concentrations were significantly higher in patients with hyperlipidemia than in controls. There was a significant positive correlation between levels of total TFPI and total cholesterol. In patients with hyperlipidemia, the level of total TFPI was significantly decreased compared to base line level by cholesterol lowering drug, however, free TFPI concentration did not change by cholesterol lowering drug. The TF and total TFPI concentrations were significantly higher in patients with DIC than in controls.

The aim of this work was to conduct a histopathological study of the different pathways of colorectal tumorigenesis by using Ki-67 and p53 immunoreactive stains. Between 1987 and 1993, 14,023 patients were investigated by colonoscopy at Akita Red Cross Hospital and several affiliated hospitals. Five hundred and sixty-five cases of early colorectal neoplasms identified in this population were used in the present study. Specimens were cut in half: one half was cut along the vertical axis, the other half along the horizontal axis to analyze the structure of glands which opened to the surface. They were stained with hematoxylin-eosin, Ki-67 and p53 immunoreactive stains. macroscopically, early colorectal neoplasms were classified into two types: protruding type and depressed type. The protruding type was mainly composed of branching glands. In contrast, the depressed type was almost completely composed of straight glands which opened to the surface. The Ki-67 positive ratio was almost equal. However, the p53 positive ratio was significantly different in the protruding type and the depressed type. The results suggest the existence of at least two pathways of colorectal tumorigenesis: one with the process of branching structure and one without the process of branching structure. Furthermore, there were clinical and immunohistochemical indications that the depressed type invades into deeper layers more rapidly than does the protruding type.

Ulcerative colitis (UC) is a disease of acute on chronic at the active stage when lymphocytes, plasma cells as well as neutrophils and eosinophils infiltrate in the colonic mucosa. Molecular pathoimmunology of UC was discussed in this article from the viewpoint of disease susceptibility gene, immune activation gene of immunocompetent cells, molecular biology of cytokines, and molecular biology of colonic epithelial cells. HLA-DR2, DRB1* 1502, is the most susceptive gene for development and intractability of Japanese UC, and HLA-BW52 which was most frequently associated with Japanese UC and HLA-B35 which was also associated with Jewish UC were reported to have a common origin. Expression of IL-2 receptor and HLA-DR protein used as immune activation genes of lymphocytes was accelerated in UC. Overexpression of proinflammatory cytokines such as IL-1, IL-6 and IL-8 was found in the colonic mononuclear cells of UC, but IL-2 mRNA expression was not accelerated in UC. Therefore, immunological imbalance in the colonic mucosa may play an important role in the pathophysiology of UC.

Measurements of protein-to-creatinine ratios (Up/Cr) in simple voided urine samples were compared with 24-hour urinary protein excretions in order to quantify [correction of guantify] proteinuria in inpatients and outpatients. A highly significant linear correlation (r = 0.73), was observed between the two variables. A closer correlation was found in the urine samples obtained from outpatients with non-nephrotic syndrome and normal renal function. Furthermore, in the investigation of urine samples from inpatients, there was a significant correlation between the two variables in urine obtained during the morning, but neither in the early morning nor at night. However, there was no significant correlation between males and females. The results of our study indicate that Up/Cr in urine samples obtained during the morning provides an accurate quantitative estimate of protein excretion. Furthermore, in clinical practice, this is a suitable method of quantifying proteinuria in patients with renal diseases, particularly, non-nephrotic syndrome and normal renal function.

To clarify the mechanism of action of immunoglobulin (IgG) in intravenous immunoglobulin therapy for ulcerative colitis (UC) patients, we studied the effect of IgG on the dynamics of immunocompetent cells in the colonic mucosa of experimental colitis induced by dextran sulfate sodium (DSS) in rats. The administration of the same species' IgG suppressed the mucosal infiltration of immunocompetent cells (activated T cells, macrophages and neutrophils), although the different species' IgG didn't. We have already shown that the same species' IgG, suppressed the production of inflammatory cytokines (TNF alpha, IL-1 alpha and IL-8) in the colonic mucosa of experimental colitis induced by DSS. In the present report, we demonstrated the different species' IgG, as well as same species' IgG, suppressed the production of inflammatory cytokines (TNF alpha and IL-1 alpha) from lamina propria mononuclear cells of rat large intestine in vitro. Therefore, it was considered that the suppression of cytokine production was a consequence of the decreased immunocompetent cells in colitis mucosa. Furthermore, we demonstrated that the DSS-treated antigen presenting cells (APCs) activated antigen-specific T cells as a possible mechanism underlying the colitis induced by DSS and the same species' IgG inhibited this activation of T cells.

We investigated the lymphocyte-activation antigens and the expression of cytokine genes in the mucosa of ulcerative colitis (UC). Fresh colonic mucosal biopsy specimens from patients with UC and controls were fixed for the immunohistochemical study of CD4, HLA-DR, and CD25, and other specimens were prepared for the RNA analysis of cytokines. Gene expression was evaluated by the reverse transcription-polymerase chain reaction, and the radioactivity of dot-blotted amplified cDNA was standardized by co-amplified beta-actin cDNA. The inflamed mucosa of active UC showed increased CD4+DR+ and CD25+ cells in comparison with control subjects. Active UC showed significantly increased mRNA expression of IL-1 beta, IL-2R alpha, IL-6, IL-8, and TNF alpha compared with the controls. We found no significant difference in the mRNA expression for IL-2, IL-4, IL-10, and IFN-gamma between active UC and controls. Increased CD4+DR+ and CD25+ cells in active UC mucosa indicate mucosal CD4(+) T cell activation in the lamina propria, but we did not clarify Th1 or Th2 specific T cell activation from our study of cytokine mRNA expression. The increased mRNA expression for IL-1 beta, IL-6, and TNF alpha in the mucosal lesions of UC indicates that these inflammatory cytokines may play important roles in the pathogenesis of UC.

Disseminated intravascular coagulation (DIC) is characterized by extreme activation of intravascular coagulation, and clinical manifestations such as bleeding and/or multiple organ failure is sometimes observed in advanced cases of DIC. The balance of coagulation and fibrinolysis activation varies according to the underlying diseases of DIC. DIC cases are classified as the type with predominant coagulation activation and the type with predominant fibrinolysis activation in former type plasma levels of thrombin-antithrombin III complex (TAT) are greatly increased, and those of plasmin-alpha 2 plasmin inhibitor complex (PIC) are slightly increased. In addition plasma levels of plasminogen activator inhibitor 1 (PA1) are greatly increased, multiple organ failure is a major clinical manifestation in advanced cases and sepsis is a representative underlying disease. In the second type both plasma levels of TAT and PIC are greatly increased, plasma levels of PA1 are almost within normal limits. Bleeding is a major clinical manifestation in advanced cases and acute promyelocytic leukemia (APL) is a representative underlying disease. The classification of DIC should be considered when choosing treatment with DIC. Diagnosis of pre-DIC status is based on gradually decreasing platelets counts in sepsis and on mild elevation of FDP and D dimer in APL, leukemia and cancer.

Adenosine is released by the placenta into the fetal circulation and has potent antilipolytic properties in vitro. Nonshivering thermogenesis cannot be demonstrated by cooling fetal sheep in utero but can be induced by supplemental oxygenation and umbilical cord occlusion; this suggests the presence of inhibitor(s) of placental origin. To test whether circulating adenosine could be such an inhibitor, a series of experiments was carried out in nine fetal sheep at 136–145 d gestation. Birth was simulated in utero by sequentially cooling the fetus 2.49 ± 0.23°C with no change in the low levels of plasma FFA or glycerol; ventilating with O2 via an exteriorized tracheostomy tube and umbilical cord occlusion. Thermogenic indices rose markedly, and plasma FFA and glycerol concentrations peaked at 725 ± 88 µEq/L (p < 0.01) and 771 ± 154 µmol/L, (p < 0.001), respectively, O2 consumption rose to 20 ± 2 mL/min/kg, and temperature increased 1.99 ± 0.35°C. The long-acting adenosine analog N6-(L-2-phenylisopropyl)-adenosine (PIA) was then infused (90 µg/kg bolus, then 300 µg/kg/h for 30 min); plasma FFA and glycerol decreased to 265 ± 56 µEq/L (p < 0.003) and 477 ± 102 µmol/L (p < 0.04), respectively; O2 consumption fell rapidly to 4.5 ± 0.3 mL/min/kg (p < 0.01); temperature decreased 1.89 ± 0.39°C (p < 0.001); and fetal arterial BP decreased to 38 ± 5 mm Hg (p < 0.004) in 30 min. A stepped dose-response study was performed in three fetal sheep. Birth was simulated in utero and then PIA was administered in escalating doses for five sequential 30-min periods with 60-min intervals in between, starting at 0.08 µg/kg bolus. The fetal arterial blood pressure was not affected by any of the relatively low doses of PIA used; however, all of the doses of PIA inhibited nonshivering thermogenesis in a dose-dependent manner. These results are consistent with adenosine suppression of brown adipose tissue thermogenesis in utero and suggest that adenosine may be an inhibitor of placental origin.

This study was performed to clarify the relationship between activated (HLA-DR-expressing) CD4+ and CD8+ cells in the colonic lamina propria of ulcerative colitis and other immunological factors, i.e., epithelial DR expression, serum soluble CD25 levels, and colonic mucosal CD25+ cells. The frequency of epithelial DR expression was positively correlated with the numbers of CD4+ and CD8+ cells. The percentages activated CD4+/CD4+ cells were higher in mucosae with DR- epithelium than in mucosae with DR+ epithelium. The serum soluble CD25 levels were increased in ulcerative colitis, and there was an inverse correlation between these levels and the relative number of activated CD4+ cells in untreated active disease. These results suggest that interactions among mucosal CD4+ cells, colonic epithelium, and serum soluble CD25 might play an important role in the pathogenesis of ulcerative colitis.

To clarify the mechanisms of action of immunoglobulin (IgG) in intravenous immunoglobulin therapy for the ulcerative colitis (UC) patients, we studied the therapeutic effect of IgG on experimental rat colitis induced by dextran sulfate sodium and on the production of inflammatory cytokines such as TNF alpha, IL-1 alpha and IL-8. The administration of rat IgG demonstrated to suppress the development of blood stool and the induction of the ulcerative lesion in large intestine. The levels of TNF alpha, IL-1 alpha and IL-8 were increased in blood and mucosa of the large intestine in this model. Rat IgG showed a tendency to decrease the levels of the cytokines in colonic mucosa. This result seems to provide a piece of explanation of how massive administration of IgG shows an improvement in the ulcerative lesion of UC patients.

Intracranial hemorrhage in a full-term infant is uncommon, is usually subarachnoid in type, and is usually associated with operative vaginal delivery or asphyxia.A 15-year-old primigravid woman at 37 weeks' gestation developed a prolonged second stage of labor associated with persistent occiput posterior position. With the onset of pushing, baseline fetal heart rate (FHR) decreased and variability increased. Thirty minutes before vaginal delivery, sudden fetal tachycardia (up to 210 beats per minute) was observed, with absent variability and minimal decelerations. At birth, the infant was apneic and hypotonic, but lacked biochemical evidence of acidemia or asphyxia; seizures developed in the early neonatal period. Subarachnoid hemorrhage was demonstrated by computed tomography of the head.The occiput posterior position, marked molding, and prolonged labor with compulsive pushing may be associated with an increased risk of adverse outcome, even unrelated to the details of delivery. The change in FHR pattern, to a lowered baseline rate and increased variability, suggests increased intracranial pressure. The sudden change to fetal tachycardia with absent variability before delivery suggests intracranial hemorrhage or injury.

Some chromosomal or subchromosomal deletions observed in a variety of cancer cells may be related with metastatic properties of the tumor cells. Thus, relationship between allelic losses and metastatic ability is here investigated of ten in vitro clones obtained from 505 cells that are derived from a fibrosarcoma induced in a F1 mouse between C3H and C57BL strains. Allelic loss was examined using 61 microsatellite markers spanning all autosomes and deletions of various loci were observed in all of the clones. One clone showed a metastatic ability higher than the parental 505 cells and the other clones. This particular clone specifically lost a chromosome 16 derived from C57BL, suggesting an association of this chromosome deletion with the metastatic ability. Consistently, examination of metastatic nodules derived from 505 cells and one in vitro clone showed that the cells with deletion of the C57BL chromosome increased in number during metastasis. These results suggest that mouse chromosome 16 may harbor a gene(s) involved in metastasis.

We previously reported that primary biliary cirrhosis (PBC)-like hepatic lesions were induced in (bm12xB6)F1 mice undergoing graft-versus-host reaction with major histocompatibility complex class II disparity. In this paper, we report on a new experimental system, enabling establishment of more progressed stages of PBC-like lesions and clarification of the role of CD8+ cells in the development of the lesions.Recipient (bm12xbm1)F1 mice were thymectomized and administered anti-Lyt-2 monoclonal antibodies intraperitoneally to deplete host CD8+ cells as completely as possible. The treatment was necessary to induce autoimmune hepatic lesions in this type of F1 mice. Recipients were divided into five groups: group 1 received B6 CD4+ cells on day 0 and 2 weeks later, B6 CD8+ cells; group 2, only B6 CD4+ cells on day 0; group 3, only B6 CD8+ cells on day 14; group 4, B6 CD4+ on day 0 plus F1 CD8+ cells 14 days later. Cell transfer was not done in group 5. All of the mice were killed on day 28 for examination by light and electron microscopy and also by immunohistochemistry.PBC-like hepatic lesions without tissue destruction were induced in the mice of group 2, as was previously reported. In addition to similar lesions to group 2, destruction of hepatocytes and bile duct epithelia was induced in the mice of group 1. Weak lymphocytic infiltration and periductal concentric fibrosis were observed in the mice of group 3. PBC-like hepatic lesions without tissue destruction were induced in mice of group 4 as were those of group 2. However, the cellular infiltration was much weaker.For the animal model of PBC, we have devised a new experimental system in which the role of donor or host type CD8+ cells is assessable. Tissue-destructive lesions were induced only in mice that received donor CD4+ cells followed by CD8+ cells. The PBC-like lesions were suppressed by host type CD8+ cells. These results suggest that destructive hepatic lesions of PBC might progress through CD8+ cells in cooperation with CD4+ cells, and that host type CD8+ cells could act as "regulatory" T cells for the progression of the lesions.

To see hemodynamic changes induced by exercise in pregnant women, we performed blood flow velocimetry with an ultrasonic pulsed Doppler in femoral (FA), external carotid (CA), uterine (UA) and umbilical arteries (Umb A) of pregnant women before and after aerobic dancing at an intensity of approximately 65% maximal heart rates. The subjects were 21 volunteer pregnant women at from 34 to 40 weeks of gestation without obstetrical problems. The velocimetry was done at intervals of five minutes for only one artery of the four arteries. The measurement was repeated 4 times. The following results were obtained: (1) Both pulse rates and blood pressure (BP) increased significantly five minutes after the onset of exercise (p0.05) and tachycardia continued for 20 minutes. The intensity of exercise was equivalent to 68.8 +/- 1.1% of the maximal heart rates (mean +/- S.E.). (2) Systolic peak velocity in the FA of the pregnant women increased by 130%, flow volume per minute jumped by 337% (p0.05), and the pulsatility index (PI) decreased by 80% (p0.05). (3) Neither the systolic peak velocity nor the PI of CA and UA changed significantly. (4) The FHR became tachycardic due to exercise from 142.2 +/- 2.5 bpm to 161.1 +/- 3.8 bpm, associated with the increase in maternal pulse rates. (5) The PI of Umb A was decreased from 0.95 +/- 0.04 to 0.80 +/- 0.03 by exercise. The PI showed a negative correlation (r = -0.37, p0.05) with the FHR, not different from a correlation shown without exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

This paper will study the possibility of a He II refrigerator made up of three cold compressors by making use of helium-3 characteristics. This system is compact enough to fit inside a small cold box, so it can be easily connected with an existing helium-4 refrigerator. We designed the compressors, calculated the He II cooling capacity, 4.4 K refrigeration load, required inventory of helium-3, and Carnot efficiency. Though helium-3 is expensive, the required inventory of helium-3 to be filled inside this He II refrigerator was calculated to be small enough to prove practicality of constructing this refrigerator.

We have developed a completely oil-free compressor used for the highly reliable helium refrigeration system for a superconducting generator and carried out performance tests under actual condition.

A wet type helium turbo-expander with expected adiabatic efficiency of 70 % at inlet pressure, temperature, and outlet pressure of 1.3 MPa, 6.0 K, and 0.2 MPa, respectively, has been developed. An alternator is adopted as a brake where a permanent magnet is held in the turbine shaft. And a self-acting gas bearing is used at thrust and journal bearings. An electromagnet supports thrust bearing to lift up the thrust disk when initiating operation. Design mass flow rate of the turbine is determined to be 60 g/s, corresponding to the JT mass flow rate in the existing helium liquefier/refrigerator. In the cryogenic performance test, the turbine had increased helium liquefaction rate by four times larger than the liquefaction rate without turbine operation.

269 Background: We examined the prognostic factors for recurrence after TURBT using molecular markers as well as the scoring system of the EAU. Methods: Eighty-eight patients with primary or recurrent bladder tumors who underwent TURBT followed by the single postoperative immediate instillation of pirarubicin and no further instillations were enrolled between 2003 and 2006; the median follow-up period was 46 months. The time to first recurrence was the primary end point of this study. Patients were divided into EAU recurrence risk groups as follows: low-risk group (total score, 0), intermediate-risk group (total score, 1-9) and high-risk group (total score, 9-17). The intermediate-risk group patients were subdivided into a total score of 1-4 and a total score of 5-9. Immunostaining using Ki-67, pHH3, CK18 and Survivin were performed on the TURBT specimens. Results: According to the risk stratification, 5, 82, and 1 were assigned to the low-, intermediate-, and high-risk recurrence groups, respectively. During the follow-up, recurrences were observed in 0% of the low-risk group, 45% (37 out of 82) in the intermediate-risk group and 100% in the high-risk group. We evaluated various predictors of a recurrence-free outcome among the 82 intermediate-risk patients. In univariate analyses, EAU score (1-4, 32.1% vs 5-9, 62.1%; p = 0.0011), high CK18 expression (negative, 31.4% vs positive 88.8%; p < 0.0001), high Ki-67 index (< 5%, 35.4% vs > 5%, 52.5%; p = 0.017) and high Survivin nuclear staining (< 5%, 35.9% vs > 5%, 62.5%; p = 0.004) were associated with recurrence. In a multivariate analysis, EAU score (HR 2.95, p = 0.003) and a high CK18 immunostaining (HR 6.70, p < 0.0001) were independent predictors of disease recurrence. Conclusions: A single immediate chemotherapy instillation is, by itself, insufficient for the treatment of patients in the intermediate- or high-risk recurrence groups defined by the EAU guidelines. Strong immunohistochemical expression of CK18 and the EAU scoring system appeared to be independent predictors of clinical outcome among patients with urothelial carcinoma of the bladder. No significant financial relationships to disclose.

Sjögren's syndrome (SS) is characterized by lymphocytic infiltration into, and destruction of exocrine glands, resulting in dryness of the mouth and eyes. The disease is considered to have an autoimmune etiology, however, its etiopathogenesis remains largely unknown. Recently, retrovirus is suggested to participate in the pathogenesis of SS, because SS-like lesions are reported in HIV infection or in human T cell leukemia virus type I infection. Moreover, human intracisternal A-type retroviral particles are reported to be detected in SS patients. During the course of our study on the histopathology of mice infected with a murine retrovirus, we happened to find SS-like exocrinopathy in those mice.Four-week-old C57BL/6 (B6) mice were injected intraperitoneally with LP-BM5 murine leukemia virus. This virus is known to induce splenomegaly, lymphadenopathy followed by lymphoid malignancy, and profound immunodeficiency in sensitive strains of mice. From 4 to 16 weeks after the virus inoculation, the infected mice were sacrificed and their submandibular and lacrimal glands were analyzed light and electron microscopically and immunohistochemically. The existence of the virus in the lesion in situ was also analyzed by the same method, and additionally by a polymerase chain reaction method.Periductal lymphocytic infiltration into the submandibular and lacrimal glands was observed in all the virus-infected mice at 4 weeks after the infection and progressed with time. Extraglandular lymphocytic infiltration was also observed in liver, kidney, lung, and pancreas. Immunohistochemical examination revealed that most infiltrating cells into the glands were composed of CD3+ T cells (CD4-dominant), Mac-1+ cells, and B220+ cells. The virus genome was detected in submandibular glands by immunohistochemistry or by polymerase chain reaction. In addition, retroviral particles were secreted into the lumen of exocrine ducts of submandibular glands.This might be an SS animal model that is induced by a certain defined retrovirus. This experimental system might provide us with valuable information for analyzing the mechanisms of how a retrovirus could induce SS.

We have recently reported that simultaneous determination of the fucosylation and glucosaminylation of alpha-fetoprotein (AFP) was useful in the differential diagnosis of various liver diseases. Here, we measured these indices in germ cell tumor and compared them with those in various diseases to reveal the characteristic feature of the carbohydrate moiety of AFP in this tumor.Fucosylation and glucosaminylation indices of AFP were determined for 743 serum samples from 10 patients with germ cell tumor, 437 with hepatocellular carcinoma (HCC), 241 with benign liver diseases (24 patients with acute viral hepatitis, 99 with chronic hepatitis, and 118 with hepatic cirrhosis), and 55 with carcinoma metastatic to the liver from digestive organs (41 from stomach, 10 from gallbladder, 2 from pancreas, and 2 from colon) by crossed immunoaffinoelectrophesis in the presence of concanavalin A and Lens culinaris agglutinin.The fucosylation index of AFP in germ cell tumors (99% +/- 2%, mean +/- SD) was higher than those in HCC (39% +/- 31%), carcinoma metastatic to the liver (76% +/- 27%), and benign liver diseases (4% +/- 7%); the differences were statistically significant (P0.001). The glucosaminylation index of AFP in germ cell tumor (45% +/- 20%) also was significantly higher than those in HCC (4% +/- 4%) and in benign liver diseases (1% +/- 4%) (P0.001). The difference in mean percentage of the glucosaminylation index, however, was not significant between germ cell tumors (45% +/- 20%) and carcinoma metastatic to the liver (39% +/- 23%).The current study indicates that the most characteristic feature of glycosylation of AFP in germ cell tumors is fucosylation rather than glucosaminylation.

We report here on three patients with cirrhosis for whom an early recognition of hepatocellular carcinoma was made possible by the measurement of the degree of fucosylation (fucosylation index) of alpha-fetoprotein. Increased levels of this index associated with a moderate increment of serum concentration of alpha-fetoprotein were observed in three patients with cirrhosis who showed no indication of hepatocellular carcinoma by several imaging modalities. Four years after the onset of an increase in the fucosylation index, small hepatocellular carcinoma with a tumor diameter less than 2 cm was revealed in case 1. In cases 2 and 3, small hepatocellular carcinomas were detected 24 mo and 9 mo, respectively, after the first sign of the increase in the index. However, the development to hepatocellular carcinoma was not detected in five patients with cirrhosis in whom continuous increments of serum concentration of alpha-fetoprotein with low levels of fucosylation index were observed during the prospective follow-up from 3 to 9 yr. These findings indicated that the fucosylation index of alpha-fetoprotein can be used as an aid in an early recognition of hepatocellular carcinoma, especially in patients with cirrhosis during the follow-up process in which the moderate increment of serum concentration of alpha-fetoprotein is noted.

A congenitally dysfunctional form of prothrombin, Prothrombin Himi, shows reduced fibrinogen clotting activity, although it retains full hydrolytic activity toward synthetic substrates. To elucidate the structural abnormality of the variant prothrombin, we first performed genetic analysis of dysprothrombin. Polymerase chain reaction amplification of the exons 8 through 14 of the proband and her family members' prothrombin genes, which code the thrombin moiety, followed by single-strand conformation polymorphism analysis, identified two variant conformers in exon 10 specific to this family. One variant allele detected in the father was inherited by the proband and one of her sisters, and the other detected in the mother was also inherited by them. This result indicates that the proband has two different base pair changes in the gene. Sequencing showed two novel point mutations in the proband's gene. One is a T to C transition at position 8751, resulting in the substitution of threonine for methionine at codon 337 (Thrombin Himi I). The other is a G to A transition at 8904, resulting in the substitution of histidine for arginine at codon 388 (Thrombin Himi II). By sequencing analysis of her parents, it was determined that Thrombin Himi I was inherited from the father and Thrombin Himi II from the mother. These results confirm that Prothrombin Himi is compound heterozygous for two dysfunctional prothrombin molecules.

The world’s largest centrifugal cryogenic helium pump has been developed, which can circulate the supercritical helium at 4 K and 0.9 MPa of the mass flow rate of 350 g/s with the pump head of more than 0.15 MPa at the design condition. The induction motor is adopted as the pump driving system and the pump impeller is made of aluminum precision casting. The bearing system adopts the self-acting gas bearing, which can be free from the shaft seal mechanism and maintenance for long term. Reducing the heat leak from the motor part to the impeller part, the motor system is cooled at 80-K region by liquid nitrogen. And the pump adiabatic efficiency has been attained to be 86% at the rated design condition.

A centrifugal compressor for a completely lubricant free helium refrigeration system is now being developed using magnetic bearings. The compressor has four compression stages and each stage is independently driven by a 25-kW built-in motor at the speed of 100, 000 rpm. The inlet of the compressor is maintained at a temperature of 80 K during operation by liquid nitrogen, and the motors are also maintained at the same temperature. Since the rotor of the motor has been fabricated from dissimilar materials to have a one piece construction using the hot isostatic press (HIP) technique, it is expected that it will deform when exposed to cryogenic temperature. The peripheral speed of the motor rotor will reach 340 m/s during operation. The peripheral speed of the impeller at the first stage will reach 568 m/s. This report summarizes the investigation results when the system was operated at 100, 000 rpm using dummy impellers.

Congenital dysfibrinogenaemia was found in a 39-year-old female and her two children. The proposita, apparently heterozygous for this abnormality, had no episode of bleeding or thrombosis. The abnormal fibrinogen showed normal release of fibrinopeptides A and B but impaired polymerization of the fibrin monomer. Amino acid sequence analysis of the whole A alpha-chain isolated from fibrinogen Kanazawa showed a substitution of Leu for Pro at position 18 in the A alpha-chain. This substitution was corroborated by the analysis of the amino acid sequence which demonstrated the lysyl endopeptidase peptides derived from the A alpha-chain of fibrinogen Kanazawa. The minimal genetic exchange responsible for this substitution was a C----T transition in the middle position of the Pro codon. We conclude that Pro-18 in the A alpha-chain is crucial for the polymerization of the fibrin monomer.

Seventy eight patients with ulcerative colitis were treated by thymectomy combined with conventional therapy. An interim analysis was made after a median follow-up of 40 months in the thymectomized group and after 25 months in 173 from a non-thymectomized group. The percentage of remission periods in the thymectomized group was significantly higher than that in the non-thymectomized group as estimated by the "patient-month" method. Histological examination of the excised thymus revealed hyperplasia of the thymic epithelial cells and/or the formation of lymphoid follicles. Anticolon antibody activity of the serum from the thymectomized patients decreased gradually and disappeared in 5 years or more. "Thymectomy via the suprasternal notch with parasternal incision" which was applied in this study, is simple and not invasive. Therefore, it is recommended that thymectomy should be considered as one of the treatment for patients who are resistant to conventional therapy.

The sera from patients with various liver diseases were investigated for the antibody against calmodulin (CaM) extracted from bovine brain by the enzyme linked immunosorbent assay. The specificity and purity of CaM were confirmed by the Western blot technique using anti-CaM antibody (anti-CaM) positive sera. IgA class antibody was frequently detected in patients with hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH) and chronic active hepatitis (CAH). On the other hand, IgG class antibody was very often present in patients liver cirrhosis, AIH and acute viral hepatitis (AVH). Sixty seven percent of patients with AVH in the acute phase were positive for IgM class anti-CaM and 33% of patients with AVH in the convalescent phase positive respectively. In AVH, the titer of anti-CaM reached its peak on 26.3 days after the onset. The titer of anti-CaM in fulminant hepatitis was higher than that in AVH. Seventy percent of type A hepatitis patients were positive for IgM class anti-CaM, 33% of type B and 33% of type non-A non-B. These results suggest that the frequency and titer of anti-CaM may depend upon the type of hepatitis and the degree of liver cell injury.