Differential effects of dibutyryl cyclic adenosine monophosphate and simple sugars on NK and LAK activities suggesting differences of their cytotoxic mechanism.

The increase of intracellular cyclic AMP levels suppresses the cytotoxic activities of lymphocytes and monosaccharides interfere with cell to cell and cell to cytokine interactions, and these effects on natural killer (NK)/antibody-dependent cell-mediated cytotoxicity (ADCC) and lymphokine activated killer (LAK) activities were examined. Dibutyryl cyclic AMP markedly suppressed NK, IL-2-augmented NK and ADCC activities in a dose-dependent manner but not previously induced LAK activity. Induction of LAK was inhibited. Dibutyryl cyclic GMP had no effect. Addition of mannose 6-phosphate and galactose 6-phosphate strongly inhibited NK and ADCC activities, but not LAK activity. These results suggest that the lytic mechanism for NK and ADCC activity is different from that of LAK activity.     

Presenilin-1 is expressed in neural progenitor cells in the hippocampus of adult mice.

The functions of the presenilin-1 (PS-1) protein remain largely unknown. In adult brain PS-1 is expressed principally in neurons. However during development PS-1 is expressed more widely including in embryonic neural progenitors. To determine if PS-1 is expressed in neural progenitors in adult hippocampus we used bromodeoxyuridine (BrdU) labeling combined with immunostaining for BrdU, PS-1 and markers of neuronal or glial differentiation. Most BrdU labeled cells also expressed PS-1 at a time when few BrdU labeled cells expressed the early neuronal markers beta-III tubulin or TOAD-64 and none expressed mature neuronal (NeuN or calbindin) or astrocytic (GFAP) markers. Cells expressing PS-1 and the neural progenitor marker nestin were also found. Thus PS-1 is expressed in neural progenitor cells in adult hippocampus implying its possible role in neurogenesis in adult brain.     

Localization of identified advanced glycation end-product structures, Nε=(carboxymethyl)lysine and pentosidine, in age-related inclusions in human brains

The recent identification of age-related accumulation of advanced glycation end-products (AGE) of the Maillard reaction In neurons and vessels of the human brain suggests the involvement of AGE in the aging process. A variety of inclusions such as lipofuscin granules, corpora amylacea, Hirano bodies, granulovacuolar degenerations and ubiquitin-positive granular structures are found in the aged human brain. These age-related Inclusions contain insoluble and non-degradable proteins. Advanced glycation end-product-modified proteins are also known to be insoluble and protease resistant. The similarlty between proteins in such inclusions and AGE-modified proteins suggests the presence of AGE in inclusions. To investigate this possiblllty, the presence of two known AGE structures, N- (carboxymethyl)lysine (CML) and pentosidine, was exarnined in age-related inclusions. immunohistochemical examination of the medial temporal area of brain tissues obtained at autopsy from seven nondemented elderly individuals demonstrated positive reactions in lipofuscin granules and corpora amylacea but not in other inclusions for anti-CML and anti-pentosldine antibodies. As CML and pentosidine are glycoxidation products among AGE, the results suggest that glycation andor Oxidation may be involved In the formation of lipofuscin granules and corpora amylacea.     

Localization and expression of the aquaporin-1 water channel in mesangial cells in the human glomerulus

The expression and localization of the aquaporin-1 (AQP1) water channel were examined in the glomeruli of the human kidney. A ribonuclease protection assay showed the expression of AQP1 mRNA in human glomeruli but not in rat glomeruli. Western blot analysis revealed 28 kDa and 35 kDa bands corresponding to unglycosylated and glycosylated AQP1 proteins in human glomeruli. Immunoreactive AQP1 was demonstrated almost exclusively in the mesangium in the human glomeruli by immunohistochemistry. The endothelium of glomerular capillaries was only partly immunostained while podocytes and Bowman's capsule epithelia were not immunolabeled. Immunoelectron microscopy localized the immunoreactive AQP1 on the plasma membrane of mesangial cells in human glomeruli. The immouno-gold labeling was dense on the projections of mesangial cells protruding to the glomerular capillary lumen or to endothelial cells, but was sparse on other parts of the mesangial cell surface. No immunoreactivity for AQP1 was demonstrated in rat glomeruli. This study showed the distinct localization of AQP1 in the mesangial cells of human glomeruli, suggesting its role in water movement through these cells.     

Thoracic intradural extramedullary lesions causing progressive myelopathy as an initial manifestation of granulomatosis with polyangiitis: a case report and review of literature

Context: To our knowledge, only a few reports regarding the spinal involvement of granulomatosis with polyangiitis (GPA)—also termed as Wegener's granulomatosis—have been published. However, all these cases reportedly exhibited epidural tumor-like lesions or dural thickening.

Findings: We report the case of a 57-year-old woman with progressive myelopathy caused by multiple spinal lesions with GPA, which appeared to be protruding inwards, within the dura mater, on magnetic resonance imaging (MRI); these lesions were difficult to distinguish from intradural tumors. Moreover, these lesions exhibited low intensity on both T1- and T2-weighted MRI, and showed prominent enhancement on gadolinium-contrast imaging. Resection biopsy was effective for both diagnosis and the recovery of the neurological deficit.

Conclusion: Based on these findings, we suggest that GPA lesions can exhibit variable patterns in the spine. Nevertheless, clinicians should consider the possibility of GPA in such cases, particularly when multiple, inwardly protruding tumor-like lesions are detected within the dura mater on MRI.     

The analysis of mitral annular disjunction detected by echocardiography and comparison with previously reported pathological data

Background

Mitral annular disjunction is a structural abnormality of the mitral annulus fibrosus and is pathologically defined by a separation between the atrial wall–mitral valve junction and the left ventricular attachment. Mitral annular disjunction can cause hypermobility of the mitral valve apparatus and is often associated with mitral valve prolapse (MVP). The aim of this study was to investigate the frequency and characteristics of mitral annular disjunction in the patients referred to an echocardiography laboratory and to compare these with previously reported pathological data.

Methods and results

We retrospectively studied 1439 patients (mean age 65 ± 17 years, 58% male) referred to our echocardiography laboratory from 6 January 2014 to 31 March 2014. The echocardiographic parameters were compared between the patients with and without mitral annular disjunction. There were 125 cases (8.7%) with mitral annular disjunction, of which 15 (12%) also had MVP. The number of MVP patients in the group with mitral annular disjunction was significantly larger than in the group without mitral annular disjunction (p < 0.0001). The grade of mitral regurgitation was not significantly different between the two groups.

Conclusions

Mitral annular disjunction was detected not only in patients with a myxomatous mitral valve but also in normal cases. The number of MVPs was significantly larger in patients with mitral annular disjunction than patients without mitral annular disjunction. Further investigation is needed to clarify the clinical significance of the mitral annular disjunction detected by routine echocardiography.

     

Neoadjuvant CapeOx therapy followed by sphincter-preserving surgery for lower rectal cancer

Purpose

This retrospective study investigates the safety of neoadjuvant chemotherapy with oxaliplatin capecitabine (CapeOx), followed by laparoscopic surgery, for lower rectal cancer, and its efficacy in preserving the sphincter.

Methods

Ten patients with diagnosed lower rectal cancer received three or four cycles of neoadjuvant CapeOx chemotherapy, prior to undergoing low anterior resection or intersphincteric resection, with total mesorectal excision. The primary outcomes were R0 resection and the rate of sphincter preservation.

Results

Nine patients completed CapeOx as scheduled and a partial response was achieved in four; thus, the overall response rate was 40% (n = 4/10). After surgical intervention, 80% of tumors displayed downstaging. Postoperative anastomosis leakage developed in one patient. The distance from the anal verge to the tumor increased by 60% (median 1.5 cm) after CapeOx treatment. The anal sphincter was preserved in all patients and all pathological distal and radial margins were negative (R0 resections). A pathological complete response was achieved in one patient.

Conclusions

Neoadjuvant CapeOx chemotherapy is a promising approach, because it extended the distance from the anus to the tumor. Subsequent laparoscopic intervention for advanced lower rectal cancer could allow for safe preservation of the sphincter.