Amyloid Signature Proteins in Feline Amyloidosis.

In human amyloidoses, amyloid signature proteins (ASPs), such as serum amyloid P component (SAP) and apolipoprotein E (ApoE), are deposited in tissues together with amyloid fibrils and are implicated in the pathogenesis of amyloidosis. Few reports describe ASPs in animals. In this study, we examined feline amyloidosis and performed immunohistochemical and proteomic analyses of SAP, ApoE, apolipoprotein A-I (ApoAI) and apolipoprotein A-IV (ApoAIV). Ten cases of systemic amyloidosis, three cases of amyloid-producing odontogenic tumour and three cases of islet amyloidosis were used for immunohistochemistry (IHC) and/or proteomic analyses. IHC showed that ApoE was present in amyloid deposits in all samples. ApoAI and ApoAIV differed in the degree of co-deposition with amyloid depending on the type of amyloid and the affected organ. SAP was negative in all amyloid deposits. Proteomic analysis showed that ApoE was present in all samples, but ApoAI and ApoAIV were detected only in some samples and SAP was not detected in any samples. The observation that ApoE was detected in all types of amyloid suggests the involvement of ApoE in the development of feline amyloidosis. ASPs in feline amyloidosis are significantly different from those in human amyloidosis, suggesting that the involvement of ASPs in the pathological condition differs between animal species.

A genome-wide association study of coping behaviors suggests FBXO45 is associated with emotional expression.

Individuals use coping behaviors to deal with unpleasant daily events. Such behaviors can moderate or mediate the pathway between psychosocial stress and health-related outcomes. However, few studies have examined the associations between coping behaviors and genetic variants. We conducted a genome-wide association study (GWAS) on coping behaviors in 14088 participants aged 35 to 69 years as part of the Japan Multi-Institutional Collaborative Cohort Study. Five coping behaviors (emotional expression, emotional support seeking, positive reappraisal, problem solving and disengagement) were measured and analyzed. A GWAS analysis was performed using a mixed linear model adjusted for study area, age and sex. Variants with suggestive significance in the discovery phase (N = 6403) were further examined in the replication phase (N = 7685). We then combined variant-level association evidence into gene-level evidence using a gene-based analysis. The results showed a significant genetic contribution to emotional expression and disengagement, with an estimation that the 19.5% and 6.6% variance in the liability-scale was explained by common variants. In the discovery phase, 12 variants met suggestive significance (P < 1 × 10-6 ) for association with the coping behaviors and perceived stress. However, none of these associations were confirmed in the replication stage. In gene-based analysis, FBXO45, a gene with regulatory roles in synapse maturation, was significantly associated with emotional expression after multiple corrections (P < 3.1 × 10-6 ). In conclusion, our results showed the existence of up to 20% genetic contribution to coping behaviors. Moreover, our gene-based analysis using GWAS data suggests that genetic variations in FBXO45 are associated with emotional expression.

Casual serum triglyceride as a predictor of premature type 2 diabetes mellitus: an 8-year cohort study of middle-aged Japanese workers.

BACKGROUND: The utility of casual serum triglyceride (TG) as a predictor of type 2 diabetes mellitus (DM) is unclear, especially during the most productive years. METHODS: Participants were 3271 workers (913 men and 2358 women, age 20-57) without DM at baseline. They underwent consecutive annual medical check-ups for 8 years. The association between newly diagnosed DM and casual serum TG level was determined by classifying the participants into 4 groups according to casual serum TG level at baseline: below 50 mg/dL (group A), 50-100 mg/dL (group B), 100-150 mg/dL (group C), and ≥150 mg/dL (group D). The effects of casual serum TG level in combination with sex, obesity, or serum glucose level on newly diagnosed DM were also evaluated. RESULTS: A total of 222 newly diagnosed type 2 DM cases with a mean age of 50 years old were observed during the follow-up period, i.e., 10/406 in group A, 66/1534 in group B, 58/712 in group C, and 88/619 in group D. Compared with group A, the odds ratio (ORs) for newly diagnosed DM (after adjusting for DM-associated factors) was found to increase with casual serum TG level: 1.38 (group B), 1.79 (group C), and 2.36 (group D). Moreover, the OR for newly diagnosed DM was higher in participants with high casual serum TG levels who were also male (OR 2.46), obese (OR 4.18), or had a high serum glucose level (OR 6.96) than in the reference group. CONCLUSIONS: Serum TG level ≥150 mg/dL when fasting or nonfasting is a significant predictor of type 2 diabetes in middle-aged Japanese workers.

Serum Polyunsaturated Fatty Acid Composition and Serum High-Sensitivity C-Reactive Protein Levels in Healthy Japanese Residents: The KOBE Study.

BACKGROUND/OBJECTIVES: Serum polyunsaturated fatty acid (PUFA) composition reflects dietary intake and is related to risks for cardiovascular diseases. We hypothesized that serum n-3 PUFA composition, especially including long-chain n-3 PUFA such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is associated with inflammatory status, which is related to increased risk for cardiovascular diseases. SUBJECTS/METHODS: We investigated the relationship between serum PUFA composition and high-sensitivity C-reactive protein (hs-CRP) levels in a cross-sectional study among 1,102 healthy men and women aged 40-74 years who reside in Kobe City. Multiple linear regression models that predict hs-CRP level were prepared to confirm the contribution of serum total n-3 PUFA, long-chain n-3 PUFA, EPA and DHA compositions after adjusting for other PUFAs and atherosclerotic risk factors. RESULTS: The serum n-3 PUFA, particularly long-chain n-3 PUFA, compositions were inversely associated with the hs-CRP levels. The standardized regression coefficient was -0.089 (p < 0.01) for total n-3 PUFA, -0.091 (p < 0.01) for long-chain n-3 PUFA, -0.071 (p = 0.03) for EPA, and -0.068 (p = 0.04) for DHA. The n-6 PUFA compositions were also inversely associated with the hs-CRP levels (-0.169 [p < 0.01] for total n-6 PUFA and -0.159 [p < 0.01] for linoleic acid). CONCLUSIONS: The serum n-3 PUFA compositions were inversely related with the hs-CRP levels, similar associations were also observed in n-6 PUFA compositions. Our results suggest that dietary PUFA intake was inversely associated with attenuated inflammation in healthy Japanese population.

The relationship of brachial-ankle pulse wave velocity to future cardiovascular disease events in the general Japanese population: the Takashima Study.

Brachial-ankle pulse wave velocity (baPWV) is a non-invasive measure of arterial stiffness obtained using an automated system. Although baPWVs have been widely used as a non-invasive marker for evaluation of arterial stiffness, evidence for the prognostic value of baPWV in the general population is scarce. In this study, we assessed the association between baPWV and future cardiovascular disease (CVD) incidence in a Japanese population. From 2002 to 2009, baPWV was measured in a total of 4164 men and women without a history of CVD, and they were followed up until the end of 2009 with a median follow-up period of 6.5 years. Hazard ratios (HRs) for CVD incidence according to baPWV levels were calculated using a Cox proportional hazards model adjusted for potential confounding factors, including seated or supine blood pressure (BP). During the follow-up period, we observed 40 incident cases of CVD. In multivariable-adjusted model, baPWV as a continuous variable was not significantly associated with future CVD risk after adjustment for supine BP. However, compared with lower baPWV category (<18 m s(-1)), higher baPWV (< or = 18.0 m s(-1)) was significantly associated with an increased CVD risk (HR: 2.70, 95% confidence interval: 1.18-6.19). Higher baPWV (< or = 18.0 m s(-1)) would be an independent predictor of future CVD event in the general Japanese population.

Significant inverse association of marine n-3 fatty acids with plasma fibrinogen levels in Japanese in Japan but not in whites or Japanese Americans.

BACKGROUND/OBJECTIVES: Numerous studies reported beneficial effects of marine n-3 fatty acids (n-3 FAs) on cardiovascular disease (CVD) and its risk factors. However, the association of marine n-3 FAs with plasma fibrinogen, a risk factor for CVD, remains uncertain. SUBJECTS/METHODS: In a population-based, cross-sectional study of 795 men aged 40-49 without CVD (262 whites in Allegheny County, Pennsylvania, USA, 302 Japanese in Kusatsu, Japan and 229 Japanese Americans in Honolulu, Hawaii, USA), we examined the association of marine n-3 FAs with plasma fibrinogen. Serum FAs were measured by capillary gas-liquid chromatography. Marine n-3 FAs were defined as the sum of docosahexaenoic, eicosapentaenoic and docosapentaenoic acids. Plasma fibrinogen was measured by an automated clot-rate assay. Multiple linear regression analyses were performed to assess the association. RESULTS: White, Japanese and Japanese-American men had mean marine n-3 FAs levels of 3.47%, 8.78% and 4.46%, respectively. Japanese men had a significant inverse association of marine n-3 FAs with fibrinogen (standardized regression coefficient of -0.11, P=0.049), after adjusting for age, body-mass index and current smoking. The significant inverse association remained after further adjusting for diabetes, C-reactive protein, triglycerides and other variables. White or Japanese-American men did not show a significant association. CONCLUSIONS: We observed the significant inverse association of marine n-3 FAs with fibrinogen in Japanese, but not in whites or Japanese Americans. The observation suggests that marine n-3 FAs at very high levels, as seen in the Japanese, may decrease plasma fibrinogen levels.

Relationship of elevated casual blood glucose level with coronary heart disease, cardiovascular disease and all-cause mortality in a representative sample of the Japanese population. NIPPON DATA80.

AIMS/HYPOTHESIS: High fasting blood glucose is one of the well-known risk factors for CHD. However, in certain settings, patients cannot always be expected to fast. For example, community screenings for cardiovascular disease (CVD) risk factors in Japan are performed under non-fasting conditions to achieve high participation rates. Thus, we examined a representative cohort of the Japanese population (n=9,444, follow-up period 17.3 years) to clarify whether high casual blood glucose (CBG) can predict CVD mortality. METHODS: We defined CBG groups as follows: high CBG >or= 11.1 mmol/l or participants with a history of diabetes mellitus; borderline high, 7.77 or= 7.77 mmol/l, regardless of time since last meal. Multivariate-adjusted HRs (95% CI) of CHD mortality in high and borderline high CBG groups were 2.62 (1.46-4.67) and 2.43 (1.29-4.58), respectively. Similar results were observed for both CVD and all-cause mortality. Even within the normal blood glucose range, each 1 mmol/l increase in CBG was associated with a statistically significant increase in the HR for CVD mortality (1.12, 95% CI 1.02-1.22). Population-attributable fractions of the combined groups of high and borderline high CBG for CHD, CVD and all-cause mortality were 12.0, 4.9 and 3.5%, respectively. CONCLUSIONS/INTERPRETATION: Increases in CBG, even within the normal range, predict CVD mortality.

The advantage of using carbon nanotubes compared with edge plane pyrolytic graphite as an electrode material for oxidase-based biosensors.

Carbon nanotubes (CNTs) are promising materials for use in amperometric biosensors. The defect sites at their ends, and on their sidewalls, are considered to be edge plane-like defects and show high electrocatalytic activity toward several biological molecules. However, electrocatalytic activity toward H(2)O(2) has not been compared among bamboo-structured CNTs (BCNTs), which have many defect sites; hollow-structured CNTs (HCNTs), which have few defect sites; edge plane pyrolytic graphite (EPG); and traditional glassy carbon (GC). The advantages of using CNTs in electrodes for biosensors are still equivocal. To confirm the utility of CNTs, we analyzed the electrochemical performance of these four carbon electrodes. The slope of the calibration curve for H(2)O(2) at potentials of both +0.6 V and -0.1 V obtained with a BCNT paste electrode (BCNTPE) was more than 10 times greater than the slopes obtained with an HCNT paste electrode and a GC electrode, reflecting the BCNT's larger number of defect sites. Although the slope with the EPG electrode (EPGE) was about 40 times greater than that with BCNTPE at +0.6 V, the slopes with these two carbon electrodes were nearly equivalent at -0.1 V. EPGE demonstrated excessive electrochemical activity, detecting currents on the basis of consumption of oxygen and oxidation of ascorbic acid, even at -0.1 V. In contrast, BCNTPE could dominantly detect a cathodic current for H(2)O(2) at -0.1 V, even when interfering molecules were added. BCNTPE possesses appropriate electrochemical activity and is an effective electrode materials for developing interference-free oxidase-based biosensors operated by the application of an appropriate potential.

External Ca(2+) is essential for chloroplast movement induced by mechanical stimulation but not by light stimulation.

In the fern Adiantum capillus-veneris, chloroplast movement is induced by mechanical stimulation as well as by light stimulation. Directional movement of both types depends on an actin-based motile system. To investigate the physiological relationship between mechanical and light signaling in the regulation of chloroplast movement, we examined the mechano-response of chloroplasts whose motility had been already restricted after photo-relocation. Chloroplast mechano-avoidance movement was induced under all of the photo-relocation conditions tested, indicating that mechano-specific signals generated by mechanical stimulation dominate over the light signals and reactivate the motility of chloroplasts. When the effects of external Ca(2+) on the induction of mechano- and light responses were examined, strikingly different requirements of external Ca(2+) were found for each. In medium without Ca(2+), the mechano-response was suppressed but no effects were observed on photo-response. Mechano-relocation movement of chloroplasts was inhibited by 100 microM lanthanum (La(3+)), a plasma membrane calcium channel blocker, and by 10 microM gadolinium (Gd(3+)), a stretch-activated channel blocker. However, the same concentrations of these drugs did not affect the photo-relocation movement at all. These results suggest that the influx of external Ca(2+) is crucial for the early signaling step of chloroplast mechano-relocation but not for that of photo-relocation. This is the first report showing the separation of signaling pathways in mechano- and photo-relocation of chloroplasts.

Choice of tracks, microtubules and/or actin filaments for chloroplast photo-movement is differentially controlled by phytochrome and a blue light receptor.

Light induced chloroplast movement has been studied as a model system for photoreception and actin microfilament (MF)-based intracellular motilities in plants. Chloroplast photo-accumulation and -avoidance movement is mediated by phytochrome as well as blue light (BL) receptor in the moss Physcomitrella patens. Here we report the discovery of an involvement of a microtubule (MT)-based system in addition to an MF-based system in photorelocation of chloroplasts in this moss. In the dark, MTs provided tracks for rapid movement of chloroplasts in a longitudinal direction and MFs contributed the tracks for slow movement in any direction. We found that phytochrome responses utilized only the MT-based system, while BL responses had an alternative way of moving, either along MTs or MFs. MT-based systems were mediated by both photoreceptors, but chloroplasts showed movements with different velocity and pattern between them. No apparent difference in the behavior of chloroplast movement between the accumulation and avoidance movement was detected in phytochrome responses or BL responses, except for the direction of the movement. The results presented here demonstrate that chloroplasts use both MTs and MFs for motility and that phytochrome and a BL receptor control directional photo-movement of chloroplasts through the differential regulation of these motile systems.

Intracellular chloroplast photorelocation in the moss Physcomitrella patens is mediated by phytochrome as well as by a blue-light receptor.

The light-induced intracellular relocation of chloroplasts was examined in red-light-grown protonemal cells of the moss Physcomitrella patens. When irradiated with polarized red or blue light, chloroplast distribution in the cell depended upon the direction of the electrical vector (E-vector) in both light qualities. When the E-vector was parallel to the cross-wall (i.e. perpendicular to the protonemal axis), chloroplasts accumulated along the cross-wall; however, no accumulation along the cross-wall was observed when the E-vector was perpendicular to it (i.e. parallel to the protonemal axis). When a part of the cell was irradiated with a microbeam of red or blue light, chloroplasts accumulated at or avoided the illumination point depending on the fluence rate used. Red light of 0.1-18 W m-2 and blue light of 0.01-85.5 W m-2 induced an accumulation response (low-fluence-rate response; LFR), while an avoidance response (high-fluence-rate response; HFR) was induced by red light of 60 W m-2 or higher and by blue light of 285 W m-2. The red-light-induced LFR and HFR were nullified by a simultaneous background irradiation of far-red light, whereas the blue-light-induced LFR and HFR were not affected at all by this treatment. These results show, for the first time, that dichroic phytochrome, as well as the dichroic blue-light receptor, is involved in the chloroplast relocation movement in these bryophyte cells. Further, the phytochrome-mediated responses but not the blue-light responses were revealed to be lost when red-light-grown cells were cultured under white light for 2 d.

Dose-intensive weekly alternating chemotherapy for patients with small cell lung cancer: randomized trial, can it improve survival of patients with good prognostic factors?

We conducted a randomized trial of dose-intensive weekly alternating chemotherapy (CAV/PE-W) and standard alternating chemotherapy (CAV/PE) in small cell lung cancer (SCLC) patients with good prognostic factors. A total of 76 patients with SCLC was randomized. The CAV/PE-W consisted of 4 alternating cycles of cyclophosphamide: 500 mg/m2, doxorubicin: 30 mg/m2, and vincristine: 1 mg/m2 (day 1) and cisplatin: 50 mg/m2 (day 8) and etoposide: 75 mg/m2 (days 8 and 9). The CAV/PE consisted of 2 alternating cycles of cyclophosphamide: 800 mg/m2, doxorubicin: 50 mg/m2, and vincristine: 1.4 mg/m2 (day 1), cisplatin: 100 mg/m2 (day 22) and etoposide: 100 mg/m2 (days 22, 23 and 24). Eligibility criteria were no prior therapy, no active concomitant malignancy, ECOG PS of 0 or 1, age < or =75, adequate hematologic functions and no brain metastasis. The complete response (CR) rate for CAV/PE-W (14/38, 36.8%) was significantly higher than that for CAV/PE (6/38, 15.8%, chi2; p=0. 032). However, the response rate in patients on CAV/PE-W (36/38, 94. 7%) was not significantly higher than the rate for CAV/PE (31/38, 81. 6%, chi2; p=0.076). Progression-free survival for patients on CAV/PE-W was significantly longer than that of patients on CAV/PE (41.4 weeks vs. 21.3 weeks, log-rank; p=0.0007, generalized Wilcoxon; p=0.0034) as was overall median survival (67.0 weeks vs. 51.2 weeks, log-rank; p=0.028). Actual dose-intensity of CAV/PE-W was 1.74 times that of CAV/PE. Hematological toxicities were equally frequent and G-CSF contributes to treatment efficacy by allowing administration of dose-intensive chemotherapy. The CAV/PE-W achieved a higher CR rate and longer survival, than the CAV/PE.

Evaluation of expression of CD15 and sCD15 in non-small cell lung cancer.

Changes in cell membrane carbohydrate antigens play an important role in metastatic potential associated with carcinogenesis and in prognostic factors. We investigated immunohistochemically the expression of CD15 and sialyl CD15 (sCD15) in lung cancer tissue by using Leu-M1 antibody and MXKM-93 antibody, respectively, and then assessed the relationship between their expression and the patient outcome. Lung cancer tissue expression of CD15 was significantly higher in adenocarcinoma (55.9%) and squamous cell carcinoma (44.7%) than in small cell carcinoma (10%) (p=0.01, p=0.006). Expression of sCD15 was significantly higher in adenocarcinoma (52.9%) than in squamous cell carcinoma (10.5%) or small cell carcinoma (10%) (p<0. 0001, p=0.016). No association was found between CD15 expression and clinical stage, but sCD15 expression increased with clinical stage (stage I+II vs. III+IV: 16.7% vs. 39.6%; p=0.049). Expression of CD15 (1.5%) was significantly lower than expression of sCD15 (12.3%) in normal surrounding tissue. Examination of associations with outcome in NSCLC revealed that expression of sCD15 in resected cases, and expression of CD15 in non-resected cases were significantly correlated with shortening of median survival time (p<0.05). When associations with prognostic factors were assessed by univariate analysis, expression of sCD15 was found to be correlated with distant metastasis, and expression of CD15 with decrease in performance status (PS). In the multivariate analysis by the Cox proportional hazard model, sCD15 and CD15 negativity contributed to longer survival time after PS and clinical stage. The results of a combination assay of CD15 and sCD15 showed that expression of both carbohydrate antigens significantly shortened survival time in both the resected and non-resected group (log-rank test, p<0.05). This combination assay also appeared to be extremely useful in predicting the outcome in all clinical stages of NSCLC.

Mechanically induced avoidance response of chloroplasts in fern protonemal cells.

Cell response to mechanical stimulation was investigated at a subcellular level in protonemal cells of the fern Adiantum capillus-veneris L. by pressing a small part of the cell with a microcapillary. In cells receiving local stimulation, the chloroplasts moved away from the site of stimulation, whereas the nuclei failed to show such avoidance movement. Mechanical stimulation for a period as short as 0.3 min was enough to induce the avoidance response to a maximal level. The avoidance movement of chloroplasts started within 30 min and the plateau level of avoidance was attained around 2 h after stimulation. By tracing the movement of chloroplasts during the response, it was shown that the mobility of chloroplasts near the stimulation site increased transiently within 1 h after the stimulation. After 2 to 3 h, it slowed down to the control level without stimulation. The avoidance response was inhibited by 0.1 mM cytochalasin B and 25 mM 2, 3-butanedione monoxime but not by 3.3 microM amiprophosmethyl or 5 mM colchicine. These findings indicate that the protonemal cells were very sensitive to mechanical stimulation and that chloroplasts moved away from the mechanically stimulated site through the actomyosin motile system.

[Swyer-James syndrome with bronchial asthma and recurrent spontaneous pneumothorax].

An 18-year-old woman was admitted to our hospital for treatment of the fifth episode of spontaneous pneumothorax. She had a history of repeated pneumonia in childhood and mycoplasma pneumonia at 12 years of age. A chest X-ray film revealed a left-sided pneumothorax, atelectasis of the left upper lobe, and hyperlucency of the left lung. A bronchogram showed poor filling of the peripheral bronchi by contrast medium and mild cylindrical bronchiectasis in the proximal bronchi. Pulmonary arteriography showed small left pulmonary arteries. From these findings, Swyer-James syndrome was diagnosed. This case was complicated by bronchial asthma, with eosinophilia, a high level of IgE, and airway hyperresponsiveness. Atelectasis, multiple bullae, and bronchial asthma had been caused by mycoplasma pneumonia in childhood. Recurrent pneumothorax had been caused by emphysematous changes in the bronchioli and by underdeveloped pulmonary arteries. Surgery to treat the recurrent spontaneous pneumothorax was considered, but was not done because of the risk of relapse and the ventilation-perfusion imbalance due to the Swyer-James syndrome.

A phase III randomized trial of cisplatin plus vindesine versus cisplatin plus vindesine plus mitomycin C versus cisplatin plus vindesine plus ifosfamide for advanced non-small-cell lung cancer.

A randomized trial of chemotherapy in 105 patients with advanced and metastatic non-small-cell lung cancer (NCSLC) was conducted in order to compare the effect of the additional drug mitomycin C (PVM) or ifosfamide (PVI), to the combination of cisplatin plus vindesine (PV). An objective response rate was observed in 42.8% of the patients treated with PVM, 42.4% with PVI and 28.6% with PV and these response rates were not statistically significant (P > 0.20). No patient achieved the complete response with either of the three regimens. Comparison of the median response durations among the three regimens showed an advantage of PVI over PVM (P < 0.02) and PV (P < 0.05). The median survival times (MST) were similar for all three regimens (PVM, 33.5; PVI, 40.0 and PV, 36.5 weeks); moreover, the difference in survival time between the three regimens of responders was not statistically significant. The univariate analysis showed that significant predictors of survival were performance status (PS) zero (P = 0.0002), limited disease (P = 0.004), no previous weight loss (P = 0.01) and normal serum albumin (P = 0.016), and in multivariate analysis by a stepwise Cox proportional hazard model, these were PS zero (a hazard ratio of 2.3, P = 0.0001) and limited disease (a hazard ratio of 1.9, P = 0.048). Toxicity did not differ among the three treatment regimens.

[Clinical evaluation of fiberoptic bronchoscopy for the diagnosis of solitary pulmonary nodules 2 cm or less in diameter of chest roentgenogram].

The value of fiberoptic bronchoscopy in the diagnosis of solitary pulmonary nodules was studied. The subjects were 59 patients with chest-roentgenographic evidence of a solitary pulmonary nodule 2 cm or less in diameter. Definitive diagnoses were made in 34 patients (57.6%). Primary lung care was diagnosed 21 of 32 patients (65.6%), pulmonary tuberculosis in 7 of 12 (58.3%), metastatic lung cancer in 3 of 5 (60%), old lesions in 3 of 5 (60%), and pulmonary filariasis in 0 of 1 (0%). The diagnostic sensitivity of transbronchial biopsy was superior to that of curettage, and combining the two techniques further improved the diagnostic yield. Bronchial lavage was not effective for diagnosis of lung cancer, but was effective for diagnosis of pulmonary tuberculosis. Diagnostic yield was less for nodules in upper lobes than for those in other lobes, and most malignant tumors that were not diagnosed from the results of fiberoptic bronchoscopy were in upper lobes. We conclude that combining various fiberoptic bronchoscopic procedures can improve the diagnostic yield in patients with small pulmonary nodules. CT-guided needle biopsy and video-assisted thoracoscopic biopsy are two such procedures. Early diagnosis of small pulmonary nodules requires a skilled bronchoscopist who can choose the most appropriate method for biopsy.

A novel human monoclonal antibody directed to a tumor-associated antigen.

Twelve human monoclonal antibodies (HuMAb) were established by the fusion of (mouse x human) heteromyeloma cells with B-lymphoblastoid cells derived from the regional lymph nodes of three patients with squamous cell carcinoma of the lung. They were tested for reactivity to two kinds of proteins (purified protein derivatives and bovine serum albumin) by ELISA, Sq-19 (squamous cell carcinoma) culture cells by indirect membrane immunofluorescence tests, and Sq-19 tumor xenograft by immunohistological study. Among them, one HuMAb 904F (IgM, lambda) was selected. In indirect membrane immunofluorescence tests, this 904F antibody reacted with various kinds of cell lines, e.g. lung cancer, esophageal cancer, endometrial cancer, and stomach cancer. It did not react with malignant hematopoietic and diploid fibroblast cell lines. Immunohistologically, it stained the tumor nests of squamous cell carcinoma, adenocarcinoma, and large cell carcinoma of the lung. It also stained those of esophagus and colon, but not those of small cell carcinoma of lung, or stomach. On frozen-section specimens of normal tissues from various organs, it showed only limited areas of positive staining. Limited positive findings were observed at a reticular zone of the adrenal gland, at the esophagus as weak staining, and at islets of the pancreas as very weak staining. Western blotting analysis demonstrated that it recognized a 54 kDa trypsin-sensitive molecule which is expressed on the surface of tumor cells. These results suggest the 904F monoclonal antibody detects a novel tumor-associated antigen which is recognized by the human immune system.