Effects of biliary drainage in obstructive jaundice on microcirculation,phagocytic activity,and ultrastructure of the liver in rats

Background/Purpose: Biliary drainage before surgery for obstructive jaundice has been thought to be indispensable, because these patients tend to develop various complications after the surgery. We developed jaundiced rat models, and studied the effects of biliary drainage on the hepatic blood flow rate, portal pressure, and phagocytic activity. Methods: We generated rats with obstructive jaundice by surgical ligation followed by cutting of the common bile duct; some jaundiced rats then underwent biliary drainage. Lipopolysaccharide (LPS) was intraperitoneally administered to some rats. Control rats underwent open abdominal surgery alone. Ultrastructural changes of the liver sinusoidal endothelial cells were examined by scanning electron microscopy. Results: The hepatic blood flow rate and phagocytic activity in the jaundiced rats and the LPS-treated jaundiced rats were lower than those in the control rats. Biliary drainage improved the hepatic blood flow rate in both the jaundiced rats and the LPS-treated jaundiced rats to the control levels. Scanning electron microscopic observation of the liver sinusoids showed that, in the jaundiced rats, the endothelial cells were hypertrophic and there was a reduced number of fenestrae. In jaundiced rats that underwent biliary drainage, the hypertrophy was reduced, and the number of fenestrae was increased in comparison with those in the jaundiced rats without the drainage. Conclusions: These findings indicate that biliary drainage was effective in jaundiced and LPS-treated jaundiced rats. Received: November 16, 2001 / Accepted: February 11, 2002     

Additional Revascularization Using Multiple Burr Holes for PCA Involvement in Moyamoya Disease

In specific cases of moyamoya disease (MMD), posterior cerebral artery (PCA) stenosis can develop after treatment of the anterior circulation and require additional revascularization. Here, we report two cases that underwent additional posterior indirect revascularization with multiple burr holes for PCA involvement after bilateral revascularization treatment of the anterior circulation. They presented with transient ischemic attack even after bilateral superficial temporal artery–middle cerebral artery bypass, and magnetic resonance angiography (MRA) showed that PCA stenosis had worsened. Indirect revascularization with multiple burr holes using Benz-marked skin incisions was performed. After surgery, the symptoms improved without perioperative complications, and cerebral angiography showed collateral circulation via the burr hole. Indirect revascularization for MMD is often combined with direct revascularization, and there are only a few reports on the use of multiple burr hole surgery alone. In addition, there are few reports of posterior circulation, despite the emphasis on the importance of PCA involvement in MMD. Indirect revascularization with multiple burr holes alone can be performed in multiple areas and applied to patients who cannot undergo direct revascularization using the occipital artery. The procedure is simple and less invasive than traditional direct revascularization procedures. Therefore, it can be effective, especially in pediatric cases of MMD with PCA involvement.     

Estimation of the contribution of assisted and non-assisted reproductive technology fertility treatments to multiple births during the past 30 years in Japan: 1979-2008

The effect of assisted reproductive technology (ART) and non-ART ovulation stimulation fertility treatment on the number and rate of multiple live births from 1979-2008 in Japan was estimated using two independent data sources, ART statistics and vital statistics. Japanese ART statistics presented by the Japan Society of Obstetrics and Gynecology between 1989 and 2008 were gathered and reanalyzed. The number and rates of ART between 1984 and 1988 were interpolated using an approximation formula, using the values from 1983, when the first ART baby was born in Japan, and the 1989-1992 values. The number of ART multiples between 1979-1982 was set as equal to zero. The minimum (or maximum) number of non-ART iatrogenic multiple births was estimated by subtracting the maximum (or minimum) ART multiples from the total iatrogenic multiples, which was estimated by vital statistics assuming that spontaneous multiple-birth rates according to maternal age class would be constant. There was an overall increase in the non-ART multiple births during the 30-year period, whereas ART multiples tended to increase from 1983 to 2005, and then rapidly decreased thereafter. The number or percentage of ART multiples was almost consistently lower than that of non-ART multiples. The percentage of non-ART multiples (33%) among the total multiples was estimated to be about three times more than the ART multiples (11-12%) in 2008. Given the medical and social impact of multiple births, it is imperative to construct a hospital-based monitoring system for fertility treatments, specially non-ART fertility treatments and multiple births.     

Distal gastrectomy for advanced gastric cancer with vascular anomaly after coronary bypass grafting using the right gastroepiploic artery

A 77-year-old woman with a history of coronary artery bypass grafting 5 years earlier presented with anemia and was diagnosed with advanced gastric cancer involving the pylorus. Preoperative angiography revealed that the right gastroepiploic artery (RGEA) graft was patent. Multidetector-row computed tomography showed the running pattern of the RGEA graft and also revealed a vascular anomaly belonging to type V of Adachi's classification. Adachi's type V is a rare vascular anomaly in which the common hepatic artery originates from the superior mesenteric artery. The patient was treated successfully with a distal gastrectomy and removal of the D2 lymph node with preservation of the RGEA graft. Because of the difficulty in confirming the running pattern of the artery during the surgery, it is important to define the arterial running pattern preoperatively by using multidetector-row computed tomography, including 3-dimensional angiographic imaging.     

Transport of D-[1-14C]-amino acids into Chinese hamster ovary (CHO-K1) cells: implications for use of labeled d-amino acids as molecular imaging agents

INTRODUCTION: The fact that d-amino acids have been found in various tissues and are involved in various functions is a clue to how to develop new imaging agents. We examined d-amino acid transport mechanisms in Chinese hamster ovary (CHO-K1) cells because CHO-K1 cells are widely used in biomedical studies and are thought to be useful for expression of genes involved in metabolism of D-amino acids. METHODS: Uptake experiments were performed. CHO-K1 cells cultured in 60-mm plastic culture dishes under ordinary culture conditions were incubated with 18.5 kBq of radiolabeled amino acid in 2 ml of phosphate-buffered-saline-based uptake solution at 37 degrees C. The following radiolabeled amino acid tracers were used: D-[1-(14)C]-alanine, L-[1-(14)C]-alanine, D-[1-(14)C]-serine, L-[1-(14)C]-serine, D-[1-(14)C]-methionine, L-[1-(14)C]-methionine, D-[1-(14)C]-phenylalanine, L-[1-(14)C]-phenylalanine, D-[1-(14)C]-leucine, L-[1-(14)C]-leucine, D-[1-(14)C]-valine, L-[1-(14)C]-valine, D-[1-(14)C]-tyrosine, L-[1-(14)C]-tyrosine, D-[1-(14)C]-glutamic acid, L-[1-(14)C]-glutamic acid, D-[1-(14)C]-lysine, L-[1-(14)C]-lysine, D-[1-(14)C]-arginine and L-[L-(14)C]-arginine. We tested the inhibitory effects of the following compounds (1.0 mM) on transport: 2-(methylamino)isobutyric acid (a specific inhibitor of system A, in Na(+)-containing uptake solution) and 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (a specific inhibitor of system L, in Na(+)-free uptake solution). RESULTS: D-[1-(14)C]-methionine, D-[1-(14)C]-phenylalanine and D-[1-(14)C]-tyrosine accumulated mainly via system L. D-[1-(14)C]-alanine and D-[1-(14)C]-serine accumulated primarily via system ASC. High uptake of D-[1-(14)C]-alanine, D-[1-(14)C]-methionine, D-[1-(14)C]-phenylalanine and D-[1-(14)C]-leucine was observed. The uptake of radiolabeled serine, valine, tyrosine, glutamic acid and arginine into CHO-K1 was highly stereoselective for l-isomers. CONCLUSIONS: We observed high uptake of D-[1-(14)C]-alanine via system ASC (most likely alanine-serine-cysteine-selective amino acid transporter-1) and high uptake of D-[1-(14)C]-methionine and D-[1-(14)C]-phenylalanine via system L (most likely L-type amino acid transporter-1).     

Tissue engineering of small intestinal tissue using collagen sponge scaffolds seeded with smooth muscle cells

In a previously reported attempt to regenerate small intestine with autologous tissues, collagen scaffolds were used without cell seeding or with autologous mesenchymal stem cell seeding. However the regenerated intestine lacked a smooth muscle layer. To accomplish regeneration of a smooth muscle layer, this present study used collagen scaffolds seeded with the smooth muscle cells (SMC) in a canine model. Autologous SMC were isolated from stomach wall and cultured. Two types of scaffolds were fabricated: in SMC (+), cultured SMCs were mixed with collagen solution and poured into a collagen sponge; and in SMC (-), SMCs were omitted. Both scaffolds were implanted into defects of isolated ileum as a patch graft. Animals were euthanized at 4, 8, and 12 weeks; for the last time point, the ileal loop had been reanastomosed at 8 weeks. At 12 weeks, the SMC (-) group showed a luminal surface covered by a regenerated epithelial cell layer with very short villi; however only a thin smooth muscle layer was observed, representing the muscularis mucosae. In the SMC (+) group, the luminal surface was covered completely by a relatively well-developed epithelial layer with numerous villi. Implanted SMCs were seen in the lamina propria and formed a smooth muscle layer. Thus, we concluded that collagen sponge scaffolds seeded with autologous SMCs have a potential for small intestine regeneration.     

Role of inducible costimulator in the development of lupus in MRL/lpr mice

Inducible costimulator (ICOS) is a costimulatory molecule expressed in activated T cells and plays an important role in T-cell-dependent immune responses. We investigated the role of ICOS in the development of autoimmune diseases in MRL/Mpj-lpr/lpr (MRL/lpr) mice. ICOS was expressed on CD4(+) T cells from adult MRL/lpr mice. ICOS-deficient MRL/lpr mice showed mild lymphoadenopathy and a decreased memory type CD4(+) T cells in the spleen. The anti-dsDNA antibody levels were decreased. CD4(+) T cells from ICOS-deficient MRL/lpr mice showed less of a bias to Th1 and an enhanced production of IL-4 in response to anti-CD3 antibody in comparison to those from wild-type MRL/lpr mice. Although ICOS-deficiency abrogated renal vasculitis completely, the severity of glomerulonephritis was not altered. ICOS is considered to play a role in CD4(+) T cell activation, autoantibody production, and renal vasculitis. However, it is not essentially required in the development of glomerulonephritis.     

High expression of Toll-like receptor 4 on CD14+ monocytes in acute infectious diseases

Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS) and other exogenous and endogenous molecules, and is thought to contribute to defense mechanisms against infections. Our objective was to elucidate the clinical significance of TLR4 in acute infectious diseases by analyzing its sequential expression on CD14+ monocytes. Peripheral blood samples were obtained from 36 patients with acute infectious diseases on admission and after treatment within certain intervals. The TLR4 expression on CD14+ monocytes was analyzed using flow cytometry and was presented as a mean fluorescence intensity (MFI). TLR4 expression during the acute phase of infection was highly enhanced compared to that of normal subjects (MFI: 22.1 vs 8.5). TLR4 expression was promptly reduced to normal levels in parallel with the disease improvement. In patients who died despite treatment, the enhancement of TLR4 expression during the acute phase was less prominent compared to those who survived (MFI: 14.6 vs 23.5) and its sequential change was also subtle. These results indicate that monocytes respond to acute infections by the induction of TLR4 expression and that a poor response may be associated with a poor prognosis.     

Acceleration of the onset of collagen‐induced arthritis by a deficiency of platelet endothelial cell adhesion molecule 1

Objective

Platelet endothelial cell adhesion molecule 1 (PECAM‐1; CD31) is a member of the immunoglobulin superfamily that is expressed in platelets, leukocytes, and endothelial cells. PECAM‐1 has been shown to play a role in transendothelial migration of leukocytes and contains immunoreceptor tyrosine‐based inhibitory motifs in its cytoplasmic tail and inhibits cellular responses. We examined the role of PECAM‐1 in the development of collagen‐induced arthritis (CIA).

Methods

CIA was induced in PECAM‐1–deficient DBA/1 mice. The incidence of arthritis and the arthritis index were examined. Anti–type II collagen (anti‐CII) antibody levels and interferon‐γ (IFNγ) production by lymph node cells and spleen cells were determined. Lymphocytes from arthritic PECAM‐1–deficient and wild‐type mice were labeled with dye, transferred to arthritic PECAM‐1^+/− mice, and cell migration to inflamed joints was examined.

Results

PECAM‐1–deficient mice showed accelerated onset of arthritis and increased severity only during the early phase. Anti‐CII antibody levels were also increased during the early phase. IFNγ production by lymph node cells and spleen cells from PECAM‐1–deficient mice in response to CII was higher than that in wild‐type mice. Lymphocytes from arthritic PECAM‐1–deficient mice showed accelerated migration to inflamed joints, but not lymph nodes or spleen. The development of anti‐CII antibody–induced arthritis was similar in PECAM‐1–deficient and wild‐type mice.

Conclusion

These results indicate that PECAM‐1 negatively regulates humoral and cell‐mediated immune responses and lymphocyte migration into joints and, consequently, the development of CIA. In addition, the role of PECAM‐1 in the transendothelial migration of leukocytes appears to be redundant in this model.