Significance of Heterogeneous Nuclear Ribonucleoprotein B1 as a New Early Detection Marker for Oral Squamous Cell Carcinoma

The development of an early tumor detection marker for oral cancer is an obvious need due to the high recurrence rate and poor survival rate. Based on our previous report that overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) B1 protein was found in 100% of squamous cell carcinomas of human lung, we applied the same immunohistochemical method, using anti-hnRNP B1 antibody, to human oral squamous cell carcinoma (OSCC). Seven human tissue sections of OSCC showed strong staining with anti-hnRNP B1 antibody, and hnRNP B1 protein of 37 kDa was identified in protein fractions isolated from six of the cancerous tissue sections, while it was not found in adjacent noncancerous tissue. Moreover, three non-homogeneous (nodular) leukoplakia sections showed significant anti-hnRNP B1 staining. The results suggest that this antibody detects precancerous lesions as well as advanced lesions (stages I to IV) of OSCC. We also present positive results of cytodiagnosis for two smear specimens. All of the above results indicate that hnRNP B1 is a new and useful marker for early detection of OSCC.     

Cardiac sympathetic denervation correlates with clinical and pathologic stages of Parkinson's disease

Attention has been drawn to cardiac sympathetic denervation in Parkinson's disease (PD) based on clinical studies using [123I] metaiodobenzylguanidine scintigraphy; however, the histologic correlates and time course of cardiac sympathetic denervation are poorly understood. To address these issues, we used tyrosine hydroxylase (TH) immunohistochemistry to detect cardiac sympathetic nerve fibers in the epicardium of 4 normal controls, 11 cases with incidental Lewy bodies (iLBs), and 14 cases of PD. Cardiac sympathetic innervation was significantly less in PD than in normal controls and cases with iLBs (P < 0.05). There was also a decrease in TH‐immunoreactive fibers in iLB cases compared to normal controls (P < 0.01). TH‐immunoreactive fibers correlated with the PD stage (r = ?0.75, P < 0.001), as well as with Hoehn & Yahr clinical stage (r = ?0.61, P < 0.001), and disease duration (r = ?0.63, P < 0.001). Immunohistochemistry for α‐synuclein showed neurites in epicardium in PD and iLB cases, but not in normal controls. The density of α‐synuclein neurites correlated with Braak PD stage (r = 0.38, P < 0.05), Hoehn & Yahr clinical stage (r = 0.44, P < 0.05), and disease duration (r = 0.42, P < 0.05). This study demonstrates that cardiac sympathetic degeneration and α‐synuclein pathology is present in presymptomatic phase of PD, and that both increase with disease duration and severity. © 2008 Movement Disorder Society.     

Penetration of oral telithromycin into female genital tissues

To estimate the potential efficacy of telithromycin in the treatment of gynecological infections, a pharmacokinetic study was conducted in 13 Japanese subjects. Telithromycin was administered orally, at a dose of 600mg, to patients undergoing hysterectomy, 3.0 to 7.5h prior to the hysterectomy. At surgical operation, cubital venous blood, uterine arterial blood, vaginal cervix uteri (portio vaginalis), supravaginal uterine cervix, uterine endometrium, uterine myometrium, oviduct, and ovary specimens were collected separately. The blood and tissue concentrations of telithromycin were measured with a bioassay, using Micrococcus luteus ATCC 9361 as the test organism. The concentrations of telithromycin in these tissues and their proportions in relation to that in cubital venous blood (in parentheses) were as follows: cubital venous blood, 0.119 to 1.270mg/l; uterine arterial blood, 0.111 to 1.230mg/l; vaginal cervix uteri (portio vaginalis), 0.356 to 1.850mg/kg (1.324 to 5.640), supravaginal uterine cervix, 0.376 to 4.520mg/kg (1.108 to 16.807), uterine endometrium, 0.234 to 5.300mg/kg (0.975 to 12.185), uterine myometrium, 0.309 to 5.050mg/kg (1.288 to 19.832), oviduct, 0.375 to 5.550mg/kg (1.563 to 10.000); and ovary, 0.495 to 5.250mg/kg (1.835 to 6.851). From these results, it was concluded that the concentrations of telithromycin in female genital tissues are generally higher than those in blood. Taking the antimicrobial spectrum of telithromycin into consideration, it was suggested that telithromycin could potentially be a good candidate for the treatment of gynecological infections, including cases associated with sexually transmitted diseases.     

Hypochondriasis as an early manifestation of dementia with Lewy bodies: an autopsied case report

Discrepancies between clinical and pathological diagnoses of dementia with Lewy bodies (DLB) may occur because the full disease progression remains unclear, especially during the early stage. Herein, we report the case of a 78‐year‐old Japanese man with hypochondriasis who had autopsy‐confirmed limbic‐type DLB pathology. He exhibited no core clinical features of DLB. We attempted to identify the clinicopathological correlations in the early stages of DLB. At the age of 77, he became hypochondriacal and exhibited progressive cognitive decline after the death of his wife. He was concerned about his poor physical condition, but hospital examinations did not identify any overtly abnormal findings. At 78 years of age, he consulted a neurologist with complaints of facial numbness and irritability. Neurological examination revealed no overt abnormality, and he scored 21 points on the Mini‐Mental State Examination. Magnetic resonance imaging of the brain showed mild bilateral ventricular enlargement. The patient was clinically diagnosed as having possible Alzheimer's disease. Approximately 1 month after his consult, he died of acute pneumonia in a psychiatric hospital to which he had been admitted for severe aggressive behaviour. He exhibited no core clinical features pointing towards a clinical diagnosis of DLB. Neuropathological investigation revealed limbic‐type Lewy body disease with concurrent minimum Alzheimer‐type pathology, which corresponds to high‐likelihood DLB pathology based on the Third Consortium DLB pathological criteria. The patient had minimum nigral degeneration, which is consistent with the absence of parkinsonism. This autopsied case suggests that some DLB patients exhibit hypochondriasis in the early stage of the disease, even if they lack the core clinical features of DLB.     

‘Lung age’ predicts post‐operative complications and survival in lung cancer patients

Background and objective: The Japanese Respiratory Society recently proposed ‘lung age’ as an easily understood concept of respiratory function. In this study, we evaluated whether ‘lung age’ could be a useful predictor of post‐operative respiratory complications and survival patients with lung cancer treated surgically. Methods: The study recruited 308 patients who underwent surgery for primary non‐small‐cell lung cancer. All patients had preoperative pulmonary function testing. ‘Lung age’ was determined using the methods advocated by the Japanese Respiratory Society. Based on the difference between ‘real age’ (R) and ‘lung age’ (L), patients were classified into five groups: group A: R?L > 15 (n = 37), B: 5 < R?L ≤ 15 (n = 50), C: ?5 ≤ R?L ≤ 5 (n = 73), D: ?15 ≤ R?L < ?5 (n = 54), E: ?15 > R?L (n = 94). Clinicopathological factors, post‐operative respiratory complications and survival were compared between the groups. Results: Gender, smoking status and index, histology, operative approach and FEV₁ were significantly associated with the group classification. The incidence of complications was significantly higher in group E compared with other groups (P = 0.003). Multivariate analysis showed that the group classification by ‘lung age’ was an independent predictor of post‐operative respiratory complications (P = 0.02). Overall survival differed significantly between the groups (P = 0.03). Conclusions: ‘Lung age’ could be useful for the prediction of post‐operative respiratory complications and survival in patients with lung cancer treated surgically.     

Significance of Serum Vascular Endothelial Growth Factor Level in Patients with Idiopathic Pulmonary Fibrosis

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, which has been implicated in the pathogenesis of fibrotic lung diseases, including idiopathic pulmonary fibrosis (IPF). The aim of this study was to examine the clinical significance of the serum VEGF level for evaluating disease severity and progression. The levels of VEGF in serum were measured in 41 patients with IPF, 14 patients with lung cancer, and 43 healthy volunteers. We measured the serum levels of CRP, LDH, KL-6, SP-D, and the parameters obtained from arterial blood gas analysis and pulmonary function tests. High-resolution computed tomography (HRCT) was performed to determine the extent of the interstitial and the alveolar opacities. The ability of each biomarker to predict disease severity was estimated by measuring the area under the receiver operating characteristic curve (AUC). The VEGF levels of IPF patients with high alveolar–arterial difference of oxygen (AaDO₂) levels were significantly elevated than those with low AaDO₂ levels and those of healthy volunteers. When examined within the IPF group, a significant positive correlation was found between the VEGF levels and the HRCT interstitial score (p = 0.027) and the KL-6 levels (p = 0.037). Among several serum biomarkers, VEGF showed the largest AUC for predicting disease severity as defined by a high AaDO₂ value. There was an inverse correlation between the baseline VEGF level and the monthly change in percent predicted vital capacity. The serum VEGF level may reflect the severity of IPF and offer clinical benefits to predict the disease’s progression.