Prognostic Factors for Short-term Survival in Patients with Stage IV Non-small Cell Lung Cancer

Prognostic factors which can forecast short-term survival in patients with stage IV non-small cell lung cancer have not been well evaluated. Characteristics of such factors may be different from those for overall survival, and would be an important eligibility criterion for clinical trials of chemotherapy. We retrospectively analyzed the data of 158 patients with stage IV non-small cell lung cancer whose performance status was 0, 1 or 2. Univariate and multivariate logistic regression models revealed demographic variables which significantly correlated with the survival at 8 or 12 weeks. The univariate model showed the following significant variables: T factor, N factor, number of organs with metastases, grade of performance status, weight loss within 6 months, evidence of metastasis either at bone or lymph node, and lactate dehydrogenase level. The subsequent multivariate model demonstrated that both grade of performance status under 2 and number of metastasized organs less than 3 are important factors for 8- or 12-week survival. The survival rate in patients meeting the two criteria (grade of performance status under 2 and number of metastasized organs less than 3) and in those meeting only one of them was 93% versus 80% at 8 weeks (P=0.030) and 88% versus 62% at 12 weeks (P<0.001), respectively. Grade of performance status and number of organs with metastases appear to be important prognostic factors for short-term survival in patients with stage IV non-small cell lung cancer.     

Anaphylactoid purpura and the complement system: particularly in terms of C3a and IgA (author's transl)]

We measured the immunoglobulin, beta1 C globulin, beta1E globulin, C3a, and CH50 in 20 patients with anaphylactoid purpura (Sch?nlein-Henoch purpura). IgA values proved to be elevated in 5 out of 11 cases. beta1 C globulin values were lower in 2 out of 8 cases and fell within the range of normalcy in the remaining 6 cases. beta1 E globulin values were normal in all cases measured (5 patients). A 130% increase in C3a was found in 7 out of 9 cases; patients with higher C3a values suffered from lasting petechial hemorrhages. It can, therefore, be concluded that the activation of the "alternative pathway" induced by IgA led to the release of C3a.     

Mucocutaneous lymph node syndrome. A cross-sectional echocardiographic diagnosis of coronary aneurysms

The cross-sectional echocardiographic technique for detecting coronary artery aneurysms of mucocutaneous lymph node syndrome (MLNS) was examined. When cutting the aortic root in round slices by the echocardiographic scanner, each of the right and left coronary arteries was imaged as a linear echo-free structure arising from the aortic root. Of 22 normal subjects, the left main coronary artery was imaged in all, the anterior descending branch in 18, the circumflex branch in six, and the right coronary artery in 18. Of 41 patients with MLNS, coronary artery aneurysms were detected as large echo-free spaces in four patients who were proved later to have these lesions by coronary angiography or autopsy. In addition, in four patients, whose echocardiograms demonstrated the coronary arteries to be normal, the angiographic studies showed that the coronary arteries were intact. These results suggest that the cross-sectional echocardiographic technique is a useful noninvasive diagnostic method for imaging the coronary arteries and the aneurysms in MLNS.     

Congenital lactic acidosis due to pyruvate carboxylase deficiency: Absence of an inhibitor of TPP-ATP phosphoryl transferase

Two children are described who suffered from episodes of metabolic acidosis and progressive mental and motor deterioration. The patients showed periodic elevation of blood lactate, pyruvate and alanine, which was accompanied by vomiting, hypotonia or convulsions. The concentrations of lactate and pyruvate in cerebrospinal fluid were found to be increased. Liver biopsies revealed a decrease in pyruvate carboxylase activity and normal pyruvate decarboxylase activity. No inhibitor of TPP-ATP phosphoryl transferase was detected in urine from the patients.These findings suggest that congenital lactic acidosis due to pyruvate carboxylase deficiency is probably a different disease entity from Leigh's encephalomyelopathy. A possible mechanism of brain damage caused by a defect in pyruvate carboxylase is postulated.Supported by Grant from the Ministry of Education and the Ministry of Public Welfare, Japan     

A case of aortitis syndrome and IgA nephropathy: possible role of human leukocyte antigens in both diseases

A 51-year-old woman, who had both aortitis syndrome (Takayasu arteritis) and IgA nephropathy, presented with hypertension, fever, a high erythrocyte sedimentation rate, high C-reactive protein and serum IgG levels, proteinuria, and renal dysfunction. Renal arteriography showed stenosis and poststenotic dilatation at the origin of the right renal artery, as well as tortuosity of the left renal artery branches and marked atrophy of the left kidney. Renal biopsy showed IgA nephropathy with deposits of IgA, C3, and fibrinogen in the glomeruli and arteriolosclerosis. The present patient had human leukocyte antigen (HLA)-B 52, which is reported to be related to the aortitis syndrome, as well as HLA-DR 4, which is possibly related to IgA nephropathy, suggesting that HLA status may be involved in the pathogenesis of both diseases.     

Possible Neuroprotective Effects of l-Carnitine on White-Matter Microstructural Damage and Cognitive Decline in Hemodialysis Patients

Although l-carnitine alleviated white-matter lesions in an experimental study, the treatment effects of l-carnitine on white-matter microstructural damage and cognitive decline in hemodialysis patients are unknown. Using novel diffusion magnetic resonance imaging (dMRI) techniques, white-matter microstructural changes together with cognitive decline in hemodialysis patients and the effects of l-carnitine on such disorders were investigated. Fourteen hemodialysis patients underwent dMRI and laboratory and neuropsychological tests, which were compared across seven patients each in two groups according to duration of l-carnitine treatment: (1) no or short-term l-carnitine treatment (NSTLC), and (2) long-term l-carnitine treatment (LTLC). Ten age- and sex-matched controls were enrolled. Compared to controls, microstructural disorders of white matter were widely detected on dMRI of patients. An autopsy study of one patient in the NSTLC group showed rarefaction of myelinated fibers in white matter. With LTLC, microstructural damage on dMRI was alleviated along with lower levels of high-sensitivity C-reactive protein and substantial increases in carnitine levels. The LTLC group showed better achievement on trail making test A, which was correlated with amelioration of disorders in some white-matter tracts. Novel dMRI tractography detected abnormalities of white-matter tracts after hemodialysis. Long-term treatment with l-carnitine might alleviate white-matter microstructural damage and cognitive impairment in hemodialysis patients.     

ABC transporter AtABCG25 is involved in abscisic acid transport and responses

Abscisic acid (ABA) is one of the most important phytohormones involved in abiotic stress responses, seed maturation, germination, and senescence. ABA is predominantly produced in vascular tissues and exerts hormonal responses in various cells, including guard cells. Although ABA responses require extrusion of ABA from ABA-producing cells in an intercellular ABA signaling pathway, the transport mechanisms of ABA through the plasma membrane remain unknown. Here we isolated an ATP-binding cassette (ABC) transporter gene, AtABCG25, from Arabidopsis by genetically screening for ABA sensitivity. AtABCG25 was expressed mainly in vascular tissues. The fluorescent protein-fused AtABCG25 was localized at the plasma membrane in plant cells. In membrane vesicles derived from AtABCG25-expressing insect cells, AtABCG25 exhibited ATP-dependent ABA transport. The AtABCG25-overexpressing plants showed higher leaf temperatures, implying an influence on stomatal regulation. These results strongly suggest that AtABCG25 is an exporter of ABA and is involved in the intercellular ABA signaling pathway. The presence of the ABA transport mechanism sheds light on the active control of multicellular ABA responses to environmental stresses among plant cells.     

Prognostic significance of programmed cell death‐1‐positive cells in follicular lymphoma patients may alter in the rituximab era

Programmed cell death‐1 (PD‐1) is involved in one of the inhibitory pathways of the B7‐cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T‐cell responses and promotion of T‐cell tolerance. PD‐1 is known to negatively regulate T‐cell receptor‐mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Although several studies have shown that high levels of PD‐1‐positive cells in follicular lymphoma (FL) patients influence their prognosis, those studies included patients treated without rituximab, and the prognostic impact of PD‐1 positivity in the rituximab era (R‐era) has not yet been elucidated. We retrospectively studied 82 patients with FL uniformly treated with standard R‐CHOP therapy at six institutions between 2001 and 2009 (median follow‐up for survivors: 55 months). We also collected and examined biopsy specimens for diagnosis with respect to PD‐1 positivity. The PD‐1 positivity was significantly higher in male patients and patients with high beta‐2 microglobulin (B2M ≥ 3.0) (P = 0.03 and 0.003, respectively). Three‐year progression free survival (PFS) and overall survival (OS) were 60% and 86%, respectively. By univariate analysis, elevated LDH (P = 0.07) worsened PFS. Male gender (P = 0.03), high FLIPI score (P = 0.05), and high B2M levels (P = 0.08) worsened OS. Multivariate analysis detected no significant prognostic factors, including PD‐1 positivity. However, in male subgroup, high levels of PD‐1‐positive cells were found to be a prognostic factor for PFS. Addition of rituximab might have altered the prognostic impact of PD‐1‐positive cells.