Neutralization of blood group A-antigen by a novel anti-A antibody: overcoming ABO-incompatible solid-organ transplantation

BACKGROUND: The major barrier to ABO-incompatible solid-organ transplantation is acute humoral rejection. It is known to be triggered by antidonor blood group A/B antibodies, which might bind to A/B-antigen on the endothelium of the graft. Various strategies to reduce antiblood group antibody by overcoming ABO-incompatible transplantation have been tried. However, antigen-suppressing procedures have not been performed. METHODS: We produced a novel anti-A antibody (K7508) by immunizing mice with salivary mucin of a blood group A individual, thereby clarifying that blood group A-antigen is expressed in endothelial cells of the liver. We investigated whether K7508 can mask A-antigen on the cells in vitro. Next, we immunized mice with A-antigen-expressing cells coated with K7508 or its Fab fragment, and measured anti-A antibody production in the mice. RESULTS: Blood group A-antigen-expressing cells, such as blood group A-red blood cells (A-RBCs) and A431 cells, coated with K7508 were not recognized by another anti-A antibody in flow cytometry, indicating that A-antigen was masked by K7508 in vitro. The A-antigen on the paraffin-embedded liver tissue was also masked by K7508. Furthermore, the production of anti-A antibody in mice immunized with A-antigen-expressing cells coated with K7508 or its Fab fragment was significantly suppressed compared to that in mice immunized with non-coated cells alone, indicating that A-antigen was neutralized by K7508 in vivo. CONCLUSIONS: The neutralization of blood group antigen by antiblood group antibody and especially its Fab fragment might represent one strategy to overcome ABO-incompatible organ transplantation.     

Use of a gum elastic bougie for tracheal intubation with Pentax-AWS airway scope

Pentax-AWS laryngoscope (Pentax, Tokyo, Japan) consists of a disposable anatomically shaped blade, a 12-cm cable with a charge-coupled device (CCD) camera and a 2.4-inch liquid crystal device (LCD) color monitor display. A tracheal tube can be attached to the right side of the blade. The device may be useful in patients with difficult airways. One limitation of the device is that intubation may be difficult if it is difficult to position the glottis to the target symbol on the monitor display. We experienced such a difficulty in four patients, and the use of a gum elastic bougie enabled intubation. In a 57-year-old woman with a difficult airway, tracheal intubation using either a Macintosh laryngoscope or a fiberscope had failed. By inserting the AWS laryngoscope, the glottis was easily seen on the monitor display. Nevertheless, it was difficult to position the glottis to the target symbol, and advancing a tracheal tube collided with the tissue around the glottis. A bougie was passed through the tracheal tube, and it became possible to insert the bougie into the trachea by adjusting the angle of its tip. The tracheal tube was then easily passed over the bougie into the trachea. We successfully used the same technique in other three patients. We believe that the gum elastic bougie can be useful for tracheal intubation using the Pentax-AWS laryngoscope.     

Renal cell carcinoma with unusual metastasis to the gallbladder

Gallbladder involvement in patients with renal cell carcinoma (RCC) is extremely rare. We present a report of a 61-year-old man with a synchronous RCC metastasis to the gallbladder presenting as an intraluminal polypoid mass simulating primary gallbladder carcinoma. Enhanced abdominal computed tomography demonstrated a well-enhanced polypoid lesion in the gallbladder. Intraoperative rapid pathological examination of the gallbladder tumor showed clear cell-type cancerous cells. Microscopically, tumor cells of both the resected kidney and gallbladder had round uniform nuclei, clear cytoplasm, and well-defined cytoplasmic borders, forming alveolar patterns. Immunohistochemically, the tumor cells were negative for cytokeratin 7 (CK7) and carcinoembryonic antigen (CEA), which is usually positive in primary clear cell carcinoma of the gallbladder. Therefore, the final diagnosis was RCC with a synchronous gallbladder metastasis.     

Changes of D-dimer after total hip arthroplasty in patients with and without intraoperative heparin

Introduction Marked activation of thrombosis is common in patients undergoing total hip arthroplasty, especially during reaming of the femur and after insertion of the femoral prosthesis. This suggests that management designed to minimize deep vein thrombosis and fatal pulmonary embolism after total hip arthroplasty should be focused on the period during insertion of the femoral component. In some previous studies, a low dose of heparin administered intraoperatively was shown to suppress the formation of fibrin. Objective The present study was performed to evaluate the influence of intraoperative heparin administration on the D-dimer level and on the prevention of pulmonary embolism after total hip arthroplasty. Material/methods A total of 22 and 26 consecutive patients respectively underwent total hip arthroplasty with and without intraoperative administration of unfractionated heparin. Postoperatively, all patients wore knee-high elastic stockings and were fitted with calf-to-thigh intermittent pneumatic compression devices. Active ankle flexion and extension exercises were commenced as soon as motor function recovered. None of the 48 patients received prophylactic anticoagulants postoperatively. Results There was a significant difference of the mean D-dimer level on the 1st day between the patients with and without intraoperative administration of heparin (8.9 ± 6.6 vs. 15.7 ± 12.7, P < 0.05). Although there were no patients with symptomatic deep venous thrombosis and pulmonary embolism, asymptomatic pulmonary embolism was detected by pulmonary perfusion scintigraphy in three patients who did not receive intraoperative heparin. The operative blood loss and postoperative drainage were similar in both groups and no bleeding complications were observed. In conclusion, we recommend a safe and inexpensive regimen comprising 1,000 U of intravenous unfractionated heparin intraoperatively, postoperative pneumatic compression, and early active mobilization for prevention of thoromboembolic complications after total hip arthroplasty.     

Differences in cell kinetic changes among renal cancer cell lines treated with interferon-α

BACKGROUND: Interferon (IFN)-alpha shows certain clinical effects on the treatment of renal cell carcinoma. The purpose of the present study was to investigate its direct effects and to compare the responses among different human renal cancer cell lines. METHODS: Three cell lines, ACHN, RCC10RGB and OS-RC-2, were incubated with IFN-alpha and evaluated using MTT assay for cell proliferation and two-color flow cytometry for cell-cycle-specific cyclin expressions coupled with DNA ploidy analysis. RESULTS: Interferon-alpha inhibited cell proliferation and caused cell accumulation at S and G2/M phases. However, IFN-alpha induced no significant change in cyclins D1, E, A or B1 expression. Interestingly, cell kinetic changes caused by IFN-alpha were different among cell lines. Cell proliferation was suppressed most in ACHN, then RCC10RGB and least in OS-RC-2. Comparing DNA histograms, ACHN showed distinct increase of G2/M cells associated with elevation of late S cells. RCC10RGB showed a predominant increase of whole S cells accompanied with a slight increase of G2/M. OS-RC-2 showed a modest increase of S cells with a little change of G2/M cells. Chronological observation revealed that S-phase increase and proliferative inhibition appeared on day 1 and day 3, respectively, in ACHN and RCC10RGB, and on day 5 in OS-RC-2. CONCLUSIONS: Interferon-alpha induced substantial cell kinetic interference directly in the tested human renal carcinoma cell lines. The degree of change was different according to the nature of the cell line. It may partly indicate the variety of the efficacy of IFN-alpha treatment against renal cancers.     

Parathyroid hormone increases the expression level of matrix metalloproteinase-13 in vivo

Parathyroid hormone (PTH) increases serum calcium (Ca) by enhancing bone resorption and renal Ca reabsorption. However, detailed mechanisms of enhanced bone resorption by PTH remain to be elucidated. Although PTH has been shown to increase the expression level of osteoblastic matrix metalloproteinase (MMP)-13 in vitro, only limited results are available regarding the in vivo regulation of MMP expression. In the present study, we have examined expression levels of MMPs in PTH-infused rats. Infusion of 1.5 or 2.0 nmol/kg/day rat PTH(1–34) for 3 days resulted in a dose-dependent increase in serum Ca. PTH infusion also decreased serum phosphate levels and increased urinary excretion of Ca and phosphate. Infusion of PTH for 7 days resulted in less severe hypercalcemia and hypophosphatemia. Urinary Ca and phosphate excretion in rats infused for 7 days was less than that in rats infused for 3 days. Northern blot analysis showed that PTH infusion increased the expression level of MMP-13 in calvaria, although it did not affect MMP-2 expression. Furthermore, the time-course and severity of hypercalcemia and hypercalciuria correlated with the expression level of MMP-13. In situ hybridization also showed that PTH infusion increased the expression level of MMP-13 in femora. These results indicate that PTH enhances MMP-13 expression in vivo and suggest that PTH stimulates bone resorption at least partly by enhancing MMP-13 expression. Received: June 5, 2000 / Accepted: January 12, 2001     

A novel approach to restore atrial function after the maze procedure in patients with an enlarged left atrium.

OBJECTIVE: Left atrial (LA) volume reduction surgery concomitant with the maze procedure has been reported to facilitate sinus rhythm recovery even in patients with refractory atrial fibrillation (AF) with an enlarged LA. However, it is unknown whether the procedures can also restore effective atrial function of the enlarged LA with over-stretched myocardium. METHODS: The maze procedures in association with mitral valve surgery were performed to 57 AF patients with an enlarged LA (LA diameter >or=60mm). Among them, 32 patients had concomitant LA volume reduction surgery (VR group). Another 25 patients did not have the volume reduction (control group). RESULTS: Three months postoperatively LA end-diastolic volume (LAEDV, ml) assessed by magnetic resonance (MR) imaging was larger in the VR group than that in the control group (291+/-117 vs 223+/-81 ml, p<0.05). Postoperatively, sinus rhythm recovery rate was better (84 vs 68%, p<0.05) and LAEDV was drastically smaller (118+/-48 vs 203+/-76 ml, p<0.001) in the VR group than those in the control group. Among the patients with sinus rhythm recovery in both groups, LA contraction ejection fraction (%) improved in the VR group but not in the control group (22.3+/-7.8 vs 10.3+/-4.7%, p<0.001). CONCLUSIONS: The LA volume reduction surgery concomitant with the maze procedure restored contraction of the enlarged LA; however, the maze procedure alone did not restore LA contraction in spite of successful sinus rhythm recovery. LA volume reduction surgery may be desirable to the patients with refractory AF with over-stretched LA.     

The prevalence of intrinsic subtypes and prognosis in breast cancer patients of different races

A recent report indicated that a high prevalence of basal-like breast tumors (estrogen receptor [ER]-negative, progesterone receptor [PR]-negative, human epidermal growth factor receptor [HER] 2-negative, and cytokeratin 5/6-positive and/or HER1-positive) could contribute to a poor prognosis in African American women with breast cancer. It has been reported that Japanese women with breast cancer have a significantly better survival rate than other races in the USA. These findings suggest that breast cancers in Japanese women have favorable biological characteristics. To clarify this hypothesis, we conducted a cohort study to investigate the prevalence of intrinsic subtypes and prognosis for each subtype in 793 Japanese patients. This study revealed a very low prevalence (only 8%) of basal-like breast tumors with aggressive biological characteristics in Japanese patients. Survival analysis showed a significantly poorer prognosis in patients with basal-like tumors than in those with luminal A tumors (ER- and/or PR-positive, and HER2-negative) with favorable biological characteristics. These findings support the hypothesis that breast cancers in Japanese women have more favorable biological characteristics and a better prognosis than those in other races. In conclusion, the prevalence of basal-like breast tumors could influence the prognosis of breast cancer patients of different races. The prevalence of intrinsic subtypes should be taken into account when analyzing survival data in a multi-racial/international clinical study.     

Mismatch recovery of regional cerebral blood flow and brain temperature during reperfusion after prolonged brain ischemia in gerbils

BACKGROUND: Recovery of cerebral reperfusion after stroke or cardiac arrest can take a long time. We aimed to identify differences in the postischemic recovery of physiologic parameters between short and prolonged brain ischemia. METHODS: Eighteen Mongolian gerbils were assigned to one of three groups: 5-minute (G5), 15-minute (G15), or 30-minute (G30) ischemia. With the use of our original microspectroscopy system, global ischemic reperfusion was performed. We measured changes in regional cerebral blood flow (r-CBF), microvessel diameter, and brain temperature (BrT) simultaneously. We also monitored somatosensory evoked potentials (SEPs) to evaluate electrophysiologic response. RESULTS: Both G5 and G15 showed concurrent recovery of r-CBF and BrT with hyperemia and hyperthermia, respectively, 10 to 15 minutes after reperfusion. The increase in BrT was <1 degree C and recovered to baseline within 60 minutes after reperfusion. In G30, recovery of r-CBF was significantly delayed relative to that of BrT. The increase in BrT was >2 degrees C, peaking approximately 15 minutes after reperfusion, and then maintained increases of >1 degree C for 120 minutes. SEPs in G5 and G15 showed concomitant recovery with that of r-CBF, whereas SEP recovery in G30 was delayed relative to that of r-CBF, eventually disappearing. All except one of the G30 gerbils died within 24 hours, but all in G5 and G15 survived. CONCLUSIONS: These results suggest that mismatch recovery of r-CBF and BrT after prolonged ischemia initiates metabolic derangement in brain tissue, leading to the electrochemical dysfunction and mortality.