Fluctuations in Tumor Blood Flow under Normotension and the Effect of Angiotensin II-induced Hypertension

To elucidate the significance of angiotensin II (AID-induced hypertension chemotherapy, changes of tissue blood flow both in normal subcutis and in tumors (AH109A, LY80) were measured with the hydrogen gas clearance method. A newly-developed anesthetic machine was used to keep the animals' condition constant. Tissue blood flow in normal subcutis and tumors always fluctuated with time under normotension. The nature and the rate of fluctuation in tumor Wood flow were almost identical in two different types of tumors. However, the fluctuation of blood flow in tumor and that in normal subcutis were almost always inversely related when blood flows in these different tissues were measured simultaneously, i.e., when tissue blood flow in normal subcutis decreased, tumor blood flow increased, and vice versa. The findings supported the idea that the connection mode between the tumor vascular bed and normal vascular bed is a parallel circuit. Vascular resistance in the normal vascular bed under All-induced hypertension seemed to be greater than that under normotension, because the All-increased tumor blood flow always exceeded the maximum tumor blood flow under normotension. Due to the fluctuations of tumor blood flow, no-flow or low-flow areas, resistant to delivery of anti-cancer drugs, moved sporadically within the tumor under the normotensive condition. However, good conditions for drug delivery to tumor tissue were induced by All-induced hypertension.     

Classification of human liver transplant recipients by their preoperative CD8+ T cell subpopulation and its relation to outcome.

The primed status of T cells is markedly different among liver transplant recipients, due to a lifetime of antigen exposure and reduced thymopoiesis by aging, and diseases. This study aims to characterize the preoperative immunological status of CD8+ T cell subpopulations and relate it to the outcome for liver transplant recipients. We classified 112 liver transplant recipients into 5 groups, based on hierarchical clustering of the CD8+CD45 isoform proportion of T cells. In Groups I and II (pediatric), the naive T cell proportion was more than 50%. In adult recipients, Group III was characterized by a naive T cell proportion of 50%, Group IV had the greatest effector/memory T cells (EM), and Group V had the greatest proportion of effector T cells. In Groups IV and V, the effector T cell proportion was considerably higher, and was accompanied by marked downregulation of the CD27+CD28+ subsets and upregulation of interferon gamma (IFN)-gamma, tumor necrosis factor-alpha, and perforin expression. Group V recipients tended to be complicated postoperatively, with a significantly reduced survival rate (1 yr, 66.8%) and markedly reduced Eastern Cooperative Oncology Group performance status.     

Small Cell Carcinoma of the Prostate: A Case Report

A case of small cell carcinoma of the prostate without a primary lesion in the lung was reported. The cancer was diagnosed after the patient complained of lumbago caused by bone metastasis. The tumor was 5.9 times 5.0 times 4.6cm. The patient was treated with 4 courses of chemotherapy using cisplatin and etoposide. The tumor diminished to 4.0 times 4.0 times 3.5 cm after completion of the 4 courses of treatment. Prostatic antigen levels were less than 1.0ng/mL during the therapy. Neuron-specific enolase levels were 35.9ng/mL at the beginning of therapy, and decreased to 7.4 ng/mL after completion of 4 courses of treatment. The patient died 3 months after the completion of treatment. This regimen had some value for inhibiting the growth of small cell carcinoma.     

Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells

It is widely known that IL-4 and IL-13 act on various kinds of cells, including B cells, resulting in enhancement of proliferation, class switching to IgE and expression of several surface proteins. These functions are important for the recognition of the various antigens in B cells and are known to be involved in the pathogenesis of allergic diseases. However, it has not been known whether IL-4/IL-13 is involved in the metabolism of various kinds of xenobiotics including 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), and it remains undetermined whether TCDD, an environmental pollutant, influences IgE production in B cells, exaggerating allergic reactions. We identified IL-4- or IL-13-inducible genes in a human Burkitt lymphoma cell line, DND-39, using microarray technology, in which the AHR gene was included. The AHR gene product, the aryl hydrocarbon receptor (AhR), was induced by IL-4 in both mouse and human B cells in a STAT6-dependent manner. IL-4 alone had the ability to translocate the induced AhR to the nuclei. TCDD, a ligand for AhR, rapidly degraded the induced AhR by the proteasomal pathway, although IL-4-activated AhR sustained its expression. AhR activated by IL-4 caused expression of a xenobiotic-metabolizing gene, CYP1A1, and TCDD synergistically acted on the induction of this gene by IL-4. However, the induction of AhR had no effect on IgE synthesis or CD23 expression. These results indicate that the metabolism of xenobiotics would be a novel biological function of IL-4 and IL-13 in B cells, whereas TCDD is not involved in IgE synthesis in B cells.     

Toxoplasma gondii infection inhibits the development of lupus-like syndrome in autoimmune (New Zealand Black x New Zealand White) F1 mice

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies and lupus nephritis. In the present study using New Zealand Black (NZB) x New Zealand White (NZW) F1 (NZBW F1) mice, we planned to investigate the effects of Toxoplasma gondii infection on the progress of lupus nephritis. Female NZBW F1 mice at the age of 2 months were perorally infected with T. gondii. The T. gondii infection reduced the number of mice developing proteinuria and immune complex deposits in their kidneys and prolonged their life span. A marked decrease in the levels of IgM and IgG anti-DNA antibodies, especially IgG2a and IgG3 subclasses, was observed in T. gondii-infected NZBW F1 mice at 9 months of age. The level of anti-HSP70 IgG autoantibody in the sera of NZBW F1 mice was significantly higher than that in control mice at 9 weeks after T. gondii infection. Moreover, NZBW F1 mice treated with anti-self heat shock protein 70 (HSP70) monoclonal antibody were substantially protected against the onset of glomerulonephritis. Further, down-regulation of intracellular expression of IFN-gamma and IL-10 was shown in spleen cells of T. gondii-infected NZBW F1 mice. This was consistent with the previous data indicating the involvement of Th1-type and Th2-type cytokines in the development of lupus-like nephritis. These results suggest that T. gondii infection is capable of preventing the development of autoimmune renal disorder in NZBW F1 mice.     

Influence of culture method on the proliferation and osteogenic differentiation of human adipo-stromal cells in nonwoven fabrics

The initial attachment, proliferation, and osteogenic differentiation of stromal cells from human fat tissue were investigated in three-dimensional nonwoven fabrics prepared from polyethylene terephthalate (PET) fiber with different diameters. The largest number of cells initially attached was observed in the nonwoven fabrics prepared from PET fiber with a diameter of 22.0 microm, irrespective of fabric porosity. The number of cells attached was larger and the cells were distributed more homogeneously in the fabrics by the agitated seeding method than by the static seeding method. The culture method depended on the time profile of cell proliferation. Cell proliferation improved in the following order: stirred (spinner flask) culture method > agitated culture method > static culture method. In addition, cells proliferated homogeneously in fabrics by the stirred culture method. When evaluated as a measurement of cell osteogenic differentiation, the activity of alkaline phosphatase (ALP) was not influenced by the diameter of fabrics. The static culture method tended to enable cells to enhance ALP activity, in contrast with the stirred and agitated culture methods. It is concluded that fabric fiber diameter and culture method greatly affected the proliferation and differentiation of cells in nonwoven fabrics.     

Experimental myasthenia in mice. The role of the thymus and lymphoid cells

A possible function of the thymus gland with regard to developing neuromuscular block after immunization with thymus extract is discussed.

Inbred female C57BL/6 mice were immunized with thymus extract from female C57BL/6 (syngeneic), male C57BL/6 mice, AKR mice (allogeneic) and guinea-pigs and calves (xenogeneic). Two weeks later, the waning phenomenon was observed from the electromyography (EMG) in xenogeneically, allogeneically and syngeneically immunized mice. The waning reverted to a normal pattern following an intraperitoneal injection of neostigmine methylsulphate. EMG tracings revealed a decrease in the incidence of the waning phenomenon in those mice which were immunized after adult thymectomy.

The passive transfer of the waning phenomenon to non-thymectomized recipients could be achieved by the intravenous administration of lymph node cells obtained from the mice that had developed a myasthenic neuromuscular block after immunization. This finding was also observed in the recipients when the donors of lymph node cells had not developed the block.

On the other hand, administration of sera from mice with the waning phenomenon after immunization resulted in a neuromuscular block in both normal and adult-thymectomized mice. However, sera obtained from mice without waning did not have this feature.

     

Morphometric analysis of the immunohistochemical expression of Clara cell 10-kDa protein and surfactant apoproteins A and B in the developing bronchi and bronchioles of human fetuses and neonates

 Morphometric analyses of the immunohistochemical expression of the Clara cell secretory 10-kDa protein (CC10) and surfactant apoproteins A and B (SP-A and -B) were carried out on the developing bronchi and bronchioles of human fetuses and neonates. We analysed the ratio of the number of CC10-positive cells per subepithelial length of the bronchial or bronchiolar basement membrane and found that both the bronchial and the bronchiolar population of CC10-positive cells was significantly higher than that of either SP-A or SP-B. In addition, CC10 was found to be distributed mainly in the bronchiole. CC10-positive cells began to be recognized in the late pseudoglandular phase (15 weeks of gestation) and thereafter gradually increased in the canalicular and terminal sac phases, which correspond to the active development period of the acini or peripheral airways. The earliest expression of SP-A was also noted at 15 weeks of gestation, but its positive epithelial cells were present mainly in the larger bronchi. Double immunohistochemical staining for CC10 and SP-A revealed that the CC10-positive cells lining both the bronchi and bronchioles were different from the SP-A-positive cells. This finding suggests that CC10-positive cells are functionally and developmentally heterogeneous in both fetal and neonatal lungs in humans Received: 22 May 1997 / Accepted: 21 July 1997