Resistance of Fc receptor- deficient mice to fatal glomerulonephritis

Immune complex-mediated inflammation is a common mechanism of various autoimmune diseases. Glomerulonephritis (GN) is one of these diseases, and the main mechanism of the induction of GN has been unclear. We examined the contribution of Fc receptors in the induction of nephrotoxic GN by establishing and analyzing mice deficient in the Fc receptor gamma chain (FcRgamma). Whereas all wild-type mice died from severe glomerulonephritis with hypernitremia by administration of anti-glomerular basement membrane (GBM) antibodies, all FcRgamma-deficient mice survived. Histologically, wild-type mice showed glomerular hypercellularity and thrombotic changes, whereas the renal tissue in FcRgamma-deficient mice was almost intact. Deposition of anti-GBM antibody as well as complement components in the GBM were equally observed in both wild-type and knockout mice. These results demonstrate that the triggering of this type of glomerulonephritis is completely dependent on FcR+ cells.     

Histochemical study on rat tear film and ocular surface epithelial cells

Fibroblasts of healthy and granulation gingiva are phenotypically heterogeneous with regard to binding C1q collagen-like (cC1qR) or C1q globular-heads (gC1qR) regions, respectively. Here, isolated fibroblast subsets, expressing either the cC1qR or the gC1qR phenotype, were stimulated with C1q, and assessed for changes in cytosolic free calcium [Ca2+]i, accumulation of inositol trisphosphate (IP3), and redistribution of Ca2+-dependent protein kinases-C (cPKCs) from cytosol to membranes. Changes in [Ca2+]i were determined using Indo-1 fluorescence in combination with adhering cell analysis and sorting (ACAS) cytometry. Accumulation of IP3 was quantified using a competitive radioreceptor binding assay. Redistribution of cPKCs was evaluated by immunoblotting with antibodies to PKCalpha/betaI-betaII/gamma. Subsets manifested different fluctuations in [Ca2+]i levels 20 seconds after C1q-stimulation in the presence of millimolar concentrations of external calcium. Whereas cC1qR fibroblasts responded with a 38% over baseline [Ca2+]i increase which was sustained for 20 to 30 minutes, gC1qR fibroblasts responded with a higher (264% over baseline) and more rapid (2 to 3 minutes) transient. Likewise, subsets exhibited different kinetics of IP3 accumulation. Whereas cC1qR fibroblasts responded with an IP3 increase of 32 +/- 3 pmol/10(4) cells over baseline after 5 seconds stimulation, gC1qR fibroblasts responded after 15 to 20 seconds with a lower increase (13 +/- 0.8 IP3 pmol/10(4) cells over baseline). Subsets differed in cPKCs redistribution which peaked in gC1qR-membranes 30 seconds after stimulation and remained sustained between 10 and 30 minutes. No cPKC redistribution was detectable in stimulated cC1qR-cells. We conclude that fibroblasts are heterogeneous in phosphoinositide-Ca2+ signaling and cPKC redistribution to C1q, and suggest that these differences may affect activities of normal and granulation gingiva.     

A metalloprotease-disintegrin, MDC9/meltrin-gamma/ADAM9 and PKCdelta are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor

The ectodomains of many proteins located at the cell surface are shed upon cell stimulation. One such protein is the heparin-binding EGF-like growth factor (HB-EGF) that exists in a membrane-anchored form which is converted to a soluble form upon cell stimulation with TPA, an activator of protein kinase C (PKC). We show that PKCdelta binds in vivo and in vitro to the cytoplasmic domain of MDC9/meltrin-gamma/ADAM9, a member of the metalloprotease-disintegrin family. Furthermore, the presence of constitutively active PKCdelta or MDC9 results in the shedding of the ectodomain of proHB-EGF, whereas MDC9 mutants lacking the metalloprotease domain, as well as kinase-negative PKCdelta, suppress the TPA-induced shedding of the ectodomain. These results suggest that MDC9 and PKCdelta are involved in the stimulus-coupled shedding of the proHB-EGF ectodomain.     

Suppression of charge carrier collection in diode with retrograde well and epitaxial layers for soft-error immunity

One of the solutions to the reduction of soft errors is suppression of carrier collection generated by an energetic particle emitted from typical contaminants of packaging or wiring materials. Suppression of carrier collection by a retrograde well or an epitaxial layer has been investigated by nuclear microprobes to clarify the validity of various well structures against soft errors in dynamic random access memories (DRAMs). The carrier collection efficiency of a retrograde well, a retrograde well with a buried layer on a Si wafer, and on an epitaxial wafer has been investigated for DRAM application using the ion-beam-induced-current (IBIC) measurement. The collection of carriers induced by proton microprobe irradiation could be reduced by the retrograde well formed at different boron doses. n⁺p diodes with retrograde well structures were fabricated by B⁺ implantation at 0.4–1.3 μm and to doses of 3.5 × 10¹⁶–3.4 × 10¹⁷ ions/cm³. It should be noted that an increase in the B⁺ implantation dose effetively reduces carrier collection efficiency, though a buried layer implanted with a higher dose degrades the characteristics of devices by the increase in leakage current. The carrier collection efficiency of the n⁺p diode with the higher dose retrograde well can be reduced by more than half compared to the diode with a retrograde well in an epitaxial layer.     

Three approaches for laparoscopic unroofing of simple and complicated renal cysts

We report 2 cases of simple renal cysts which were marsupialized with 2 laparoscopic approaches involving either transperitoneal, with reflection of the colon medially or dissection through the mesocolon, and a case of a multilocular renal cyst which was treated by the retroperitoneal approach. Although laparoscopic unroofing of a renal cyst is a safe and effective alternative to open surgical techniques, the transperitoneal approach should only be used for simple renal cysts. The retroperitoneal approach for complicated renal cysts may be indicated if preoperative examinations exclude the possibility of malignancy.     

Usefulness and limitation of phylogenetic analysis for hepatitis C virus core region: application to isolates from Egyptian and Yemeni patients

We report here the nucleotide sequences of the core region of HCV isolates from Egyptian and Yemeni patients and the method for classifying these HCV isolates by phylogenetic analysis. Sequence comparison suggested that the genotypes of these isolates were the same. Preliminary phylogenetic analysis of the HCV core region indicated that the genotypes of both isolates were 1c. However, an additional phylogenetic tree of the HCV core region constructed using a greater number of HCV isolates than that used in the preliminary analysis and on the basis of alignment of nucleotide sequences in an appropriate length indicated that the genotypes of these isolates were 4 and not 1c. For a more detailed analysis, the nucleotide sequences of the HCV E1 region as well as the core region for the same Yemeni patient were determined. A phylogenetic tree of the E1 region confirmed that the genotype of the HCV isolate from the Yemeni patient was 4. These data indicate that even when classifying HCV isolates using phylogenetic analysis, the misclassification would occur if care is not taken regarding the number and sequence lengths of the isolates included in the analysis.     

A water-soluble antitumor glycoprotein from Chlorella vulgaris

The great majority of children referred to Pediatric Gastroenterologic Units for chronic constipation have a functional disorder and do not require investigative techniques, since functional constipation is easily recognized an anamnestic and clinical basis. Severe chronic constipation indicates a chronic condition believed to be of functional type but unresponsive to the traditional pharmacologic treatment. However, several clinical features might suggest an organic type of constipation during the initial diagnostic approach: growth failure, distension, episodes of diarrhea intermingled with constipation, subocclusive events, dilatation of areas of the gut (megaduodenum, megajejunum) at x-ray examination of the entire gastrointestinal tract. Hirschsprung's disease is the best known organic type of constipation; however, there are other neurogenic and myogenic abnormalities of the colonic (and/or ileal) tract that mimick Hirschsprung's disease and represent development abnormalities of the enteric nervous plexus. Other organic types of constipation are due to systemic diseases, endocrine and metabolic disorders, central nervous system disorders. Organic constipation usually requires extensive investigative approach, including pathologic examination of enteric nervous plexus on full thickness biopsies.     

Participation of apoptosis in renal amyloidosis

Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). Thirty HCC patients underwent transcatheter arterial injection of 4 mg SMANCS-lipiodol emulsion. Their responses were evaluated by computed tomography 1 month after treatment. Complete response (CR) was defined as disappearance or 100% necrosis of all tumors. Partial response (PR) was defined as > or = 50% reduction and/or > or = 50% necrosis. We regarded the lipiodol accumulation in tumors as being necrotic. CR and PR were observed in 8 patients (27%) and 4 patients (13%), respectively, and the overall response rate (CR + PR/all patients) was 40% (12/30). Of 12 patients whose serum alpha-fetoprotein levels had been more than 200 ng/ml before treatment, 5 patients (42%) showed more than 50% reduction in this level within 1 month after treatment. Toxicity was quite acceptable, although grade 4 toxicity (WHO) was observed as liver dysfunction in 1 patient. Transarterial chemotherapy with SMANCS, which is well tolerated, appears to have moderate antitumor effect in patients with HCC.     

Histomorphometric study of iliac bones in cervical myelopathy with ossification of the posterior longitudinal ligament

To investigate whether there was any abnormal systemic bone metabolism in patients with ossification of the posterior longitudinal ligament (OPLL), we measured various histomorphometric indices of the iliac trabecular bones in 19 patients with OPLL (14 men, 5 women). For each index, the Z-score for each patient was calculated, using the SD and mean value for non-OPLL control group (n = 159) who underwent orthopaedic surgeries and had no systemic disease, age-matched for each decade. A Z-score of 1.0 meant that the observed data deviated 1 SD from the normal average, and a distribution from -2 to +2 was considered normal. All the averaged Z-scores were within +/-1.0 and there were no significant differences between the OPLL and the control groups. There was also no difference in Z-score among three types of OPLL (segmental, continuous, and mixed). From these results, we concluded that there was no common abnormal bone metabolism affecting the bone histomorphometry of the iliac bone in OPLL patients. However, in two patients, the Z-score for bone volume (BV/TV) was more than 2.0, with increased osteoid volume (OV/TV) and increased trabecular thickness, suggesting that there was some abnormal bone metabolism in these two patients with OPLL.