A Tissue-Engineered Artificial Bile Duct Grown to Resemble The Native Bile Duct

The aim of this study was to fabricate an artificial bile duct for the development of a new treatment for biliary diseases. Eighteen hybrid pigs were implanted with a bile duct organoid unit (BDOU) made of a bioabsorbable polymer. Twelve of the transplanted BDOUs had been seeded with autologous bone marrow cells (BMCs) in advance. Six animals, the controls, were grafted with the scaffold alone with no BMCs seeded. The common bile duct was cut, the hepatic cut end of the native common bile duct was anastomosed to the BDOU and the other end was anastomosed to the duodenum. The controls underwent a similar operation. The neo-bile duct was removed at pre-determined time points and investigated histologically. All 18 recipient pigs survived until their sacrifice at 6 weeks, 10 weeks or 6 months. Histological examination revealed incomplete epithelialization of the neo-bile duct at 6 weeks and 10 weeks after transplantation. At 6 months, the organoid exhibited a morphology almost identical to that of the native common bile duct. No differences were found between the controls and BMC-seeded pigs. These results show that the artificial bile duct thus fabricated can serve as a substitute for the native bile duct.     

Effects of cueing on visuospatial processing in unilateral spatial neglect

Patients with typical left unilateral spatial neglect bisected lines after cueing to the left end-point, the fixation point being monitored with an eye camera. They persisted with the point of initial fixation made after cueing and placed the mark there without searching leftwards again. The rightward shift of fixation to the initial point of fixation thus determined the location of the subjective midpoint. We consider that rightward attentional bias increased the amplitude of this shift that was planned on the basis of the perception of the whole line while cueing. This hypothesis may explain smaller but obvious rightward bisection errors found in the cueing condition.     

Clinical study on low body temperature in health subjects

During last year, 931 men aged 51.0 +/- 9.5 years participated in our hospital's 3-day health screening. Their axillary temperature were taken 3 times per day (twice each, at 6:00 a.m., 2:00 p.m. and 6:00 p.m.) during their 3-day stay and the mean axillary temperature was determined for each subject. In 72 among all subjects, the mean axillary temperature was below 36 degrees C. These 72 subjects were classified as low-temperature individuals with normal temperature below 36 degrees C. This study was designed to compare low-temperature subjects with mean axillary temperature, on various factors, such as age, degree of obesity, liver function, renal function, lipids, electrolytes, and biochemical data (blood glucose, serum amylase, and CPK). This study also included seasonal changes in these low-temperature subjects. The following results were obtained. 1) Age was most closely related to low-axillary temperature, and the degree of obesity (modified Broca-Katsura method) had second significant relation. The low-axillary temperature was in common in subjects over 60 years and was also common in obese subjects, regardless of their age. 2) No seasonal effect was observed with low-temperature subjects. 3) Only the age and the degree of obesity (modified Broca-Katsura method) showed negative correlation independently with the mean axillary temperature. (For age, the correlation coefficient was Y = -0.006539X + 36.491, while for obesity it was Y = -0.004536X + 36.203.) Therefore the older and the more obese the subjects, the lower the mean axillary temperature.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinico-pathological study of collagen-related pulmonary lesions in cases of open lung biopsy]

We studied the clinico-pathological correlation of collagen disease-related pulmonary lesions to examine the pathological and radiological features of collagen lung, and the effect of steroid therapy. Ten open lung biopsy cases were examined; 4 male, and 6 female. The mean age was 55 years old. Seven cases developed pulmonary shadows after the diagnosis of collagen disease, and 3 cases showed pulmonary shadow prior to diagnosis. Pathologically, 6 cases proved to be bronchiolitis obliterans organizing pneumonia (BOOP), 3 cases were chronic interstitial pneumonia (UIP), and 1 case was acute interstitial pneumonia. All cases had inflammatory thickening of the interstitium involving the pleura, bronchial wall, and perivascular connective tissue. Half of the cases had bronchiolar inflammatory lesions. Radiologically BOOP cases showed either localized ground glass shadows, or diffuse reticulonodular shadows predominantly in the lower lung fields with shrinkage of affected areas. UIP cases showed reticulonodular shadows, and active UIP cases showed overlapping ground glass shadows. Steroids were administered in cases of BOOP and active UIP, and all cases showed improvement. We consider that open lung biopsy is of use in the diagnosis of some cases and in assessing whether steroid therapy is indicated.     

Immunology: Diversity of the blocking effects of antisperm antibodies on fertilization in human and mouse

The blocking effects of complement-dependent sperm immobilizingantibodies in the sera of infertile women and monoclonal antispermantibodies against humans and mice on fertilization were investigated.The hemizona assay (HZA) and sperm penetration assay (SPA) wereused to study the inhibitory effects of sera from 22 infertilepatients positive for sperm immobilizing antibodies. Use ofthese tests allowed us to differentiate whether the antibodyblocked sperm—zona pellucida tight binding and/or spermpenetration into the ooplasm. The zona pellucida penetrationassay (ZPA) was also used to study the effects of four monoclonalantibodies (mAbs) on human sperm penetration into the zona pellucida.Seven mAbs against murine spermatozoa were tested for theirinhibitory effects on in-vitro fertilization (IVF) and HZA inmice. Of 22 patient sera with sperm immobilizing antibodies,21 (95.5%) inhibited HZA attachment and penetration, whereasthis did not occur in any of 13 patient sera without these antibodies.However, 19 of 22 (86.4%) patient sera with sperm immobilizingantibodies and eight of 13 (61.5%) patient sera without theseantibodies inhibited the SPA. Two (2C6, 1G12) of four mAbs againsthuman spermatozoa showed strong inhibitory effects in all theassays (HZA, ZPA and SPA). One mAb (3B10) did not inhibit HZAbut blocked ZPA and SPA. Another mAb (H6-3C4) seemed to haveno inhibitory effects on fertilization. Two (Vx 5 and Vx 8)of seven mAbs against murine spermatozoa inhibited IVF in micebut did not block mouse HZA. These findings suggest that antispermantibodies block fertilization at specific stages. Some of themmay inhibit sperm capacitation and thus prevent all processesof fertilization that follow. Some other antibodies may notaffect capacitation and sperm binding to zona pellucida butinhibit the acrosome reaction, followed by the blocking of spermpenetration through zona pellucida and ooplasm.     

Clinical significance of reverse redistribution in exercise thallium-201 SPECT after percutaneous transluminal coronary angioplasty

Clinical significance of reverse redistribution on thallium image was evaluated in 54 patients who had undergone PTCA. Thallium SPECT imaging was performed one week and three to six months after PTCA. Reverse redistribution was detected eight of 54 patients one week after PTCA and five of 38 patients three to six months after PTCA. In the segments with reverse redistribution, reduced regional wall motion and lesser degree of coronary stenosis was common features (p less than 0.05) angiography. In conclusion, reverse redistribution had a tendency to appear in the region with mild myocardial injury and relatively high coronary blood flow after PTCA. But in cases with new occurrence and disappearance of reverse redistribution during follow up period, we can not assess the factors to explain these phenomena. In these segments, "coronary flow reserve", "stunned myocardium", "hibernating myocardium" or other factors may be related.     

Clinical usefulness of the measurement of plasma D-dimer levels

To evaluate the clinical usefulness of D-dimer, various effects on the measurement of D-dimer were examined. Although both fibrinolytic and fibrinogenolytic products were detected by the measurement of FDP, only fibrinolytic products were detected by the measurement of D-dimer. In patients with DIC and other thrombo-embolic diseases, plasma D-dimer levels were significantly higher than in normal persons. A significant positive correlation between plasma D-dimer and serum FDP was found in DIC patients. In patients with DIC associated with acute promyelocytic leukemia, which is thought to be an increased fibrinogenolysis state, serum FDP was higher than the plasma D-dimer which suggests that increased fibrinogenolysis affects the result of serum FDP measurement. Plasma D-dimer significantly increased 5 minutes after endoscopic embolization with thrombin in the patients with esophageal varices. However serum FDP increased 30 minutes after the treatment, which suggests that the D-dimer is more useful for rapid detection of coagulo-fibrinolytic change than serum FDP. Plasma D-dimer was significantly higher in patients with cerebral infarction and increased with age. These finding suggest the usefulness of plasma D-dimer measurement for the specific and rapid evaluation of coagulo-fibrinolytic activation and thrombo-embolic state.     

CD8+ T cells from feline immunodeficiency virus (FIV) infected cats suppress exogenous FIV replication of their peripheral blood mononuclear cells in vitro

Summary.  Feline immunodeficiency virus (FIV) isolates from domestic cats have been classified into five subtypes, designated A, B, C, D and E. Although many FIV-infected cats may have frequent contact with multiple strains of FIV, they usually become infected with a single FIV subtype. In the present study, we demonstrate that peripheral blood mononuclear cells (PBMC) of FIV infected cats were resistant to exogenous FIV (second virus) replication in vitro and that the resistance of these PBMC was mediated by CD8⁺ T cells. In cats with a low anti-FIV activity of CD8⁺ T cells, the proviral DNA of the second virus inoculated into PBMC was detected intracellularly, and both the second and the originally infecting strain (original virus) were produced in the culture supernatant. In contrast, in cats with a high anti-FIV activity of CD8⁺ T cells, both the proviral DNA of the second virus and the original virus were detected in PBMC intracellularly, but neither virus was produced in the culture supernatant. However, when PBMCs from these cats were depleted of CD8⁺ T cells, the RNA of both viruses was detected in the culture supernatant. These results suggest that CD8⁺ T cells inhibit the late phase of FIV replication after viral integration. Moreover, the inhibition was also effective against FIV strains of different subtypes from that of the original strain. It appears that the CD8⁺ T cell-mediated immune response plays important roles in the maintenance of an asymptomatic state in FIV-infected cats and their resistance to superinfection. Received December 11, 2001; accepted March 22, 2002 Published online June 21, 2002     

Pituitary Folliculo-Stellate-Like Cells Stimulate Somatotroic Pituitary Tumor Growth in Nude Mice

A new cell line (TtT/GF) established from a murine pituitary thyrotropic tumor having characteristics similar to those of pituitary folliculo-stellate cell (FS cell) was implanted into nude mice together with cells from a rat pituitary somatotrophic tumor cell line (MtT/S) to determine whether the former enhances pituitary tumor growth. For as long as 2-3 mo after implantation, MtT/S cells implanted either alone or together with fibroblasts formed either no tumors or only very small tumors in the nude mice. In contrast all of the nude mice that had received MtT/S cells implanted together with TtT/GF cells developed large tumors. Furthermore, the mice bearing the MtT/S and TtT/GF implants showed a significantly higher body weight and serum growth hormone level than those bearing only MtT/S cells or a combination of MtT/S cells and fibroblasts. The TtT/GF cell line itself had no tumorigenicity during the experimental period. Therefore, the TtT/GF cell line as a model of FS cells enhanced pituitary endocrine cell tumor formation. Additionally, immunocytochemistry showed that TtT/GF cells positive for glial fibrillary acidic protein (GFAP) or S-100 protein were present in the parenchymatous tissue elements or connective tissue surrounding the tumor nests. In the parenchymatous tissue, the TtT/GF cells exhibited a stellate appearance and surrounded neighboring tumor cells with their long cell processes. These results suggest that TtT/GF cells can serve as a model for pituitary FS cells, and are capable of stimulating pituitary tumor growth either by modifying the microenvironment or producing growth factors.     

Regulatory volume decrease in northern fur seal (<Emphasis Type="Italic">Callorhinus ursinus</Emphasis>) red blood cells

The cation transport and regulatory volume decrease (RVD) were investigated in the red blood cells (RBCs) of northern fur seals (Callorhinus ursinus). Extracellular Ca-dependent Na efflux was increased to threefold by hypotonicity. K–Cl cotransport activity was not detected by hypotonic medium, but measured only by nitrite or N-ethylmaleimide stimulation. RBCs were restored to their original volume after being swollen in hypoosmotic medium with Ca, though this recovery was inhibited by the addition of quinidine. Based on these results, Na/Ca exchange transporter played the major role in the regulatory volume decrease in the RBCs of northern fur seals. H. Fujise has passed away.