Predominant role of FcgammaRIII in the induction of accelerated nephrotoxic glomerulonephritis

BACKGROUND: Nephrotoxic glomerulonephritis is induced by the administration of antibody against the glomerular basement membrane (GBM). We demonstrated previously that Fc receptors for immunoglobulin G (IgG) (FcgammaR) play crucial roles in the induction of accelerated nephrotoxic glomerulonephritis by using FcRgamma-deficient (-/-) mice. Since FcRgamma-/- mice lack the cell surface expression of two activating FcgammaRs, FcgammaRI and FcgammaRIII. The present study aims to identify the FcgammaR responsible for the induction of nephrotoxic glomerulonephritis. METHODS: Accelerated anti-GBM glomerulonephritis was induced in FcgammaRI-/-, FcgammaRIII-/-, and FcRgamma-/- mice by preimmunization with rabbit IgG followed by inoculation of rabbit anti-GBM antibody. Histologic analysis and immunostaining of renal sections were performed. RESULTS: FcgammaRI-/- mice as well as wild-type mice showed severe glomerulonephritis with hypernitremia by the administration of anti-GBM antibody. In contrast, FcgammaRIII-/- mice showed much milder renal involvement, similar to FcRgamma-/- mice. Histologically, FcgammaRI-/- mice showed intracapillary proliferation, glomerular thrombosis, and crescent formation, whereas FcgammaRIII-/- mice showed only glomerular hypercellular changes. The depositions of anti-GBM antibodies, autologous antibodies and complement C3 along the GBM were equally observed among all three FcR-/- mouse types by immunostaining. CONCLUSIONS: Accelerated nephrotoxic glomerulonephritis is induced predominantly through FcgammaRIII but not FcgammaRI.     

Effect of radioisotope sentinel node mapping in patients with cT1 N0 M0 lung cancer

BACKGROUND: Application of the sentinel node concept to lung cancer is still controversial. Patients with peripheral small lung cancers would gain the most benefit from this concept, if it were valid. We sought to determine whether it is possible to choose between limited lymph node sampling and systematic lymphadenectomy from the distribution of sentinel lymph nodes in patients with node-negative disease on the basis of imaging. METHODS: Sixty-five consecutive patients with cT1 N0 M0 non-small cell lung cancer were enrolled. A radioisotope tracer (4 mCi of technetium-99m tin colloid, 2.0 mL) was injected in the vicinity of the tumor before surgical intervention with computed tomographic guidance. The radioactivity of each resected lymph node was measured separately with a hand-held gamma probe after complete tumor resection. Sentinel nodes were identified, and the accuracy of sentinel node mapping was examined. Whether the location of the sentinel node depended on the site of the primary tumor was also examined. RESULTS: Of the 65 patients, 3 were excluded because of the final pathologic results. Successful radionuclide migration occurred in 39 (62.9%) of the 62 patients. There was 1 (2.6%) false-negative result among 39 patients with a sentinel node, and therefore the sensitivity was 90%, and the specificity was 100%. The most common sentinel lymph nodes were at level 12 (46.7%), followed by level 11 (18.3%), the mediastinum (16.7%), and level 10 (11.7%). CONCLUSION: The sentinel node concept is valid in patients with cT1 N0 M0 lung cancer. The lobar lymph nodes were identified as sentinel nodes more frequently than other lymph nodes. We need to make further efforts to increase the sentinel node identification rate. However, we believe that if sentinel nodes are identified, sentinel node mapping can allow the accurate intraoperative diagnosis of pathologic N0 status in patients with cT1 N0 M0 lung cancer.     

Subjective criteria of chest CT findings for predicting pathological features and postoperative outcomes of small peripheral lung cancer (< or = 2 cm)

One hundred fifty five patients with completely resected peripheral non-small cell lung cancer, clinically diagnosed 2 cm or less in diameter, are retrospectively reviewed on their preoperative chest CT films, clinico-pathological features, and postoperative outcomes. Pathologic type was classified according to Noguchi's classification. 7% and 8% of all the patients had pathologic N 1 and N 2 diseases, respectively. 19% of all the patients undergone limited resection (segmentectomy or partial resection). Maximum area of the tumor/soft tissue density area of the tumor (M/S ratio) was manually measured by chest CT film. According to the logistic regression analysis, M/S ratio was the only predicting factor of regional lymph node metastasis among factors including pleural indentation, spiculation, and maximum area of the tumor. Univariate analysis showed that maximum area of the tumor, pleural indentation, and M/S ratio were the significant factor for postoperative disease free survival. According to multivariate analysis of postoperative disease free survival with adjustment for operative modality, the result was same as that of univariate analysis. In conclusion, our determined criteria of the chest CT accurately predicted pathological status and postoperative outcome of patients with small peripheral lung cancer. These factors would be useful for stratification factor of prospective clinical study.     

Experimental and Clinical Studies Investigating the Efficacy of Distal Anastomosis with Patch Plasty in Bypass Operations with Expanded Polytetrafluoroethylene Grafts

Purpose: We investigated the efficiency of distal anastomosis with patch plasty (DAPP), both experimentally and clinically. Methods: In our experimental study, dogs were divided into two groups: a control group in which anastomosis was performed without DAPP (n = 7), and a DAPP group in which DAPP was performed at the distal anastomosis (n = 7). In our clinical study, 169 femoropopliteal bypasses were divided into three groups and analyzed. In one group, the saphenous vein was used (SVG group, n = 65); in one group, an expanded polytetrafluoroethylene (ePTFE) graft was used without DAPP (ePTFE group, n = 64); and in one group, an ePTFE graft was used with DAPP (DAPP group, n = 40). Results: In the experimental study, the ratio between the area of thrombus adherence and the entire area of the intraluminal surface of the graft, defined as the thrombus covering ratio, was 48.9% in the control group and 30.2% in the DAPP group. The ratio in the DAPP group was significantly lower than that in the control group. In the clinical study, although there were no significant differences among the three groups in cumulative patency rates of the femoral above-knee popliteal arterial bypasses, the patency in the DAPP group was excellent. The cumulative patency rates of the femoral below-knee popliteal arterial bypasses in the ePTFE group were significantly lower than those in the other two groups. Conclusion: There results suggest that the addition of DAPP may achieve excellent graft patency. Received: February 14, 2002 /Accepted: November 19, 2002 Reprint requests to: K. Dairaku     

Autopsy case of multiple anomalies with hypoplastic cerebrum,eyes, and endocrine organs,mimicking Micro syndrome

We report an autopsy case of multiple anomalies with severe micrencephaly, bilateral microphthalmos, and hypoplastic endocrine organs. We examined expressions of calcium-binding proteins and hypothalamic and pituitary hormones. A female proband presented with microcephaly, microphthalmia, and psychomotor development delay. At the age of 23 years, she died of cardiorespiratory failure. The endocrine organs demonstrated severe underdevelopment, and the hypoplastic eyeballs had remnant lens, vitreous hemorrhage, and retinal detachment. The brain weighed 260 g; the cerebrum, cerebellum, and brain stem were extremely small; and the tertiary sulci were absent in the cerebral surface. The cross-sectional area of cerebral cortex was reduced to about one third of those in the control, although six-layered lamination, density of pyramidal neurons, and expressions of calcium-binding proteins were comparatively preserved in the cerebral cortex. The third ventricle was hypoplastic, and the bilateral thalami appeared to be fused and the hippocampus was unrolled, whereas the corpus callosum was preserved. In the hypothalamus, the paraventricular nucleus was only identified, and the adenohypophysial somatotrophs were reduced. This may be the first autopsy report of Micro syndrome, which is characterized by microcephaly, brain malformations, optic atrophy, and hypogenitalism, although the case lacked agenesis of the corpus callosum.     

Oral delivery of xeno-antigen combined with non-depleting anti-CD4 monoclonal antibody induces significantly prolonged survival of concordant skin xenograft

Abstract: Oral administration can induce unresponsiveness to protein antigens. Therefore, we examined whether oral administration of xeno-antigen could induce the prolonged survival of xenogeneic skin grafts. CBA mice were given 1 × 10⁷ SD rat splenocytes orally, 7 days before transplantation of a SD rat skin in the presence or absence of a non-depleting anti-CD4 monoclonal antibody (mAb) (YTS177, 200 µg/dose, −8 and −7 days relative to transplantation). All skin grafts survived with a median survival time (MST) of 62 days when xeno-antigens were administered orally in combination with anti-CD4 mAb. Mice treated with anti-CD4 mAb alone or oral administration of xeno-antigen alone induced modest prolonged survival of rat skin grafts (MST = 18 and 19 days, respectively) while naive mice rejected rat skin acutely (MST = 12 days). Oral administration alone or combined with anti-CD4 mAb reduced the level of xeno-antibody production compared with that in untreated mice after transplantation. Xenogeneic mixed leukocyte response was reduced when splenocytes from mice pre-treated with oral administration of xenogeneic cells were used as the responder compared with that in untreated mice. Oral delivery of xeno-antigen plus non-depleting anti-CD4 mAb can induce prolongation of concordant xenogeneic skin grafts.     

Serum immunosuppressive acidic protein as a potent prognostic factor for patients with metastatic renal cell carcinoma

BACKGROUND: Estimation of survival probability of individual patients with metastatic renal cell carcinoma was difficult owing to diverse prognostic factors. We analyzed serum immunosuppressive acidic protein (IAP) levels and the cutoff value, then tested its validity for assessing patients' prognoses. METHODS: Serum IAP was measured longitudinally in 84 patients with metastatic disease. Before therapy, cutoff levels of IAP were tested every 20 microg/ml between 600 and 1200 microg/ml. The prognostic importance of IAP and its cutoff level was estimated. RESULTS: The cutoff level of IAP was set at 800 microg/ml for 40 patients who had metastatic disease with the primary tumor in situ and for 44 patients with recurrent disease. IAP was found to be a significant prognostic factor for both patient groups. CONCLUSIONS: Serum IAP is an important prognostic factor for patients with metastatic renal cell carcinoma. Stratification of patients according to prognosis is feasible using the cutoff level.     

Penetrating keratoplasty and cataract surgery

Of 46 eyes undergoing simultaneous penetrating keratoplasty and cataract extraction, 25 grafts (54%) remained clear with an average follow-up of 37 months. This low success rate can be party explained by the fact that more than 50% of our patients had unfavourable ocular conditions preoperatively. In case of simultaneous procedures, methods of cataract extraction (ICCE or ECCE) did not have any significant affect on the rate of clear grafts. In eyes with favourable ocular conditions preoperatively, the rates of clear grafts were similar (approximately 75%) in cases of simultaneous operation (21 eyes) and separate operation (8 eyes).     

Development Of The Human Mesencephalic Trigeminal Nucleus: A Morphometric Study

Anatomical development of the human mesencephalic trigeminal nucleus was assessed quantitatively and qualitatively, using serial sections of brains, with the help of a computer-assisted image-analyser. Five fetuses at 16, 18, 21, 23 and 27 weeks of gestation; five neonates at 30, 32, 33, 35 and 40 weeks of gestation; a two-month-old infant and a 63-year-old adult were studied. Morphometric analyses of the mesencephalic trigeminal nucleus revealed that orocaudal columnar length and neuronal areas gradually increased with gestational age. Diversity of neuronal areas appeared after 32 weeks of gestation, but neuronal numbers and shapes showed little change throughout prenatal and postnatal life.