Depressed natural killer cell activity due to decreased natural killer cell population in a vitamin E-deficient patient with Shwachman syndrome: reversible natural killer cell abnormality by α-tocopherol supplementation

Natural Killer (NK) cell activity was examined in a 16-month-old Japanese boy with Shwachman syndrome associated with severe vitamin E deficiency. As evaluated by ⁵¹Cr-release assay from K562 cells, NK cell activity was constantly decreased. After 8 weeks of oral α-tocopherol (α-Toc) supplementation (100 mg/day), NK cell activity had normalised. When α-Toc supplementation was interrupted for 16 weeks, NK cell activity again decreased. Flow cytometry of peripheral lymphocytes revealed a lowered number of CD16⁺ CD 56⁻ fraction, which has the most potent NK cell activity. Single cell-in-agarose assay, to investigate the binding and cytolytic activity of NK cell at the single cell level, revealed that the number of NK cells which bind to K562 cell was decreased, but that the cytolytic activity of the individual binding cell was relatively unaffected. A second supplementation of α-Toc for 8 weeks successfully restored NK cell activity, the number of cells expressing NK cell markers and the number of K562-binding cells as compared to the age-matched normal range. Conclusion These results indicate that severe vitamin E deficiency caused impaired NK cell activity due to a decrease in the number of CD16⁺ CD56⁻ NK cells and that this abnormality is reversible with α-Toc supple‐mentation. Received: 30 January 1996 and in revised form: 19 November 1996 / Accepted: 22 November 1996     

Primary Mitral Valve Sarcoma in Infancy

Primary cardiac sarcoma is a rare tumor, found especially in children, particularly in the left side of the heart. This report describes a rare case of primary mitral valve sarcoma in a 7-month-old male infant with hemiparesis and heart murmur who underwent mitral valve replacement because of excessive invasion of the mitral valve by the tumor. The patient remains well, free of recurrence and cerebral metastasis, and without adjuvant therapy 18 months after the operation.     

Multivariate analysis of long-term results after an axillobifemoral and aortobifemoral bypass in patients with aortoiliac occlusive disease

BACKGROUND: Controversy still remains regarding the long-term results and indications for axillofemoral bypass (AxFB). A comparison of axillobifemoral bypass (AxBFB) and aortobifemoral bypass (ABFB) was thus conducted to determine whether AxFB is an acceptable alternative vascular procedure to anatomic bypass for high-risk patients. METHODS: Sixty-three patients who underwent a total of 25 AxBFBs and 38 ABFBs for aortoiliac occlusive disease were reviewed retrospectively, and both univariate and multivarate analyses were perfomed. RESULTS: The overall survival was 82.8% at five years. A univariate analysis revealed significantly lower survival rates for patients with limb-threatening ischemia, coronary disease, and cerebrovascular disease. A multivariate analysis disclosed no significant factors influencing survival rates. The overall primary patency was 79.8% at five years. The primary patency rates for AxBFB (67.7% at five years) were significantly lower than for ABFB (88.5% at five years) based on a univariate analysis (p=0.0045). In addition, the secondary patency rates for AxBFB (80.3% at five years) were significantly lower than for ABFB (96.5% at five years, p=0.0025). A multivariate analysis disclosed significantly lower primary patency rates for grafts with a higher angiographic outflow score and simultaneous infrainguinal reconstructive procedures, but the differences between AxBFB and ABFB were not significant. CONCLUSIONS: The survival and primary patency for the AxBFB group were both inferior to the ABFB group, however a multivarate analysis disclosed no significant differences between the two groups. Poor femoral run-off and the presence of synchronous infrainguinal reconstructive procedures significantly affected graft patency, and these factors modulated the patency of AxBFB. AxFB for aortoiliac occlusive disease is therefore considered to be an acceptable procedure in appropriately selected patients.     

Potential role of vacuolar H-adenosine triphosphatase in neointimal formation in cultured human saphenous vein

OBJECTIVE: Vacuolar H(+)-adenosine triphosphatase plays a pivotal role in pH regulation and molecular transport across the vacuolar membranes and is involved in cell proliferation and transformation. In the present study, possible involvement of vacuolar H(+)-adenosine triphosphatase in neointimal formation was investigated in an organ culture model of human saphenous vein. Methods and results: Cultured saphenous vein segments developed neointimal formation and marked thickening of the media within 14 days. Neointimal formation and medial thickening were completely inhibited by 10 nmol/L bafilomycin A(1), a selective inhibitor of vacuolar H(+)-adenosine triphosphatase, although structurally related macrolide antibiotics FK-506 and erythromycin were without an effect. The neointimal cells were positive for alpha-smooth muscle actin and vimentin but negative for desmin, indicative of myofibroblasts. The emergence of myofibroblasts was inhibited, and endothelial cells were preserved in the saphenous vein segments treated with bafilomycin A(1). Uptake of bromodeoxyuridine, a proliferation marker, by myofibroblasts was abrogated in the saphenous vein segments treated with 10 nmol/L bafilomycin A(1). Detection of apoptotic cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling concomitant with identification of desmin-expressing smooth muscle cells demonstrated that neointimal myofibroblasts, but not medial smooth muscle cells, that expressed desmin underwent apoptosis by treatment with bafilomycin A(1). CONCLUSIONS: These results suggest that vacuolar H(+)-adenosine triphosphatase may be involved in myofibroblast growth that contributes to neointimal formation and medial thickening in cultured human saphenous vein. Increased sensitivity of myofibroblasts, but not endothelial cells, and differentiated smooth muscle cells to bafilomycin A(1) may have potential therapeutic implications in the treatment for vein graft disease.     

Presenilin-1 in late-onset depressive disorder

Late-onset depressive disorder (LOD) is thought to be associated with dementia. Allele 1 in the presenilin-1 (PS-1) gene is a risk factor for Alzheimer's disease. An association study on this polymorphism was performed in depressive patients and control subjects. The patients were subdivided into those with early onset and late onset, using 50 years as the cut-off age. There was no statistically significant difference in the age of onset of depressive disorders according to the PS-1 genotype. There was also no association between early/late-onset depressive disorders and the PS-1 genotype. Our results suggest there is no association between the PS-1 allele and LOD.     

Somatic mutations of epidermal growth factor receptor in colorectal carcinoma.

PURPOSE: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non-small cell lung carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA. EXPERIMENTAL DESIGN: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction and PCR, we examined EGFR mutations by sequencing genomic DNA. RESULTS: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma. CONCLUSIONS: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these tumors may be susceptible to gefitinib treatment.