Basic studies on a labeled anti-mucin antibody detectable by infrared-fluorescence endoscopy

Background. We developed a fluorescent dye, indocyanine green (ICG)-sulfo-OSu, which was excited by infrared rays and conjugated to various antibodies. We attempted to clarify the staining patterns of anti-sulfomucin and anti-MUC1 antibodies in gastrointestinal cancer. We then evaluated the potential of the dye as a fluorescent label for antibodies specific to cancer, to be used as a diagnostic method for microcancer, with infrared fluorescence endoscopy. Methods. Paraffin sections of samples collected from 10 patients with esophageal cancer, 30 patients with gastric cancer, and 20 patients with colorectal cancer were immunohistologically stained using an anti-sulfomucin antibody and an anti-MUC1 antibody, and the staining patterns were examined. If a section had a high staining intensity, it was reacted with the ICG-suflo-OSu-labeled antibody and evaluated with infrared fluorescence imaging. Results. The staining patterns with the antibodies varied depending on the organs and the histological types and depth of the cancers, but the staining was generally good and the staining on the mucosal surface of cancer tissues was retained. Good images of cancer cells could be obtained by infrared fluorescence observation using the ICG-sulfo-OSu-labeled anti-MUC1 antibody. Conclusions. The anti-MUC1 antibody stained gastrointestinal cancer cells well, and nearly specific infrared fluorescence in cancer tissues was observed using the labeled anti-MUC1 antibody. The ICG-sulfo-OSu-labeled anti-MUC1 antibody has possible usefulness for the screening of cancer via infrared fluorescence endoscopy. Received: December 8, 2000 / Accepted: September 28, 2001     

Both a Calcium Antagonist and ACE Inhibitor Reverse Hypertrophy in Hypertension But a Calcium Antagonist also Depresses Contractility

The aim of this study was to compare the effects of a calcium antagonist, nicardipine SR, with an angiotensin-converting enzyme (ACE) inhibitor, alacepril, on the regression of left ventricular hypertrophy (LVH) and function. Twenty patients with LVH, aged 42–73 years, were treated with nicardipine SR or alacepril. Ten patients were treated with nicardipine SR (40–80 mg) for 21 months, and the other 10 patients were treated with alacepril (25–100 mg) for 18 months. All patients underwent echocardiography to assess left ventricular structure and function before and after the treatment. After nicardipine SR or alacepril treatment, blood pressure was decreased significantly from 176.0 ± 13.9/97.0 ± 5.3 mmHg to 140.0 ± 14.0/77.4 ± 7.2 mmHg and from 168.2 ± 22.3/99.0 ± 5.5 mmHg to 138.4 ± 12.5/85.2 ± 9.7 mmHg, respectively (both p < 0.01), whereas heart rate did not change (73.8 ± 14.6 beats/min vs. 69.9 ± 13.5 beats/min and 71.6 ± 9.7 vs. 65.8 ± 8.1 beats/min, respectively). The left ventricular mass index decreased significantly from 133.2 ± 11.7 g/m2 to 114.4 ± 15.7 g/m2 with nicardipine SR and from 137.1 ± 14.8 g/m2 to 99.3 ± 23.0 g/m2 with alacepril (both p < 0.01). The fractional shortening, peak shortening rate, and peak lengthening rate all improved significantly after each treatment. The end-systolic wall stress/left ventricular end-systolic volume index, as an index of left ventricular contractility, was decreased significantly after treatment with nicardipine SR but was not changed after treatment with alacepril. In conclusion, both nicardipine SR and alacepril similarly reduced LVH and improved left ventricular systolic and diastolic function. However, alacepril did not alter left ventricular contractility, whereas nicardi-pine SR decreased left ventricular contractility.     

Co-existence of Mycobacterium tuberculosis and Mycobacterium intracellulare in one sputum sample

An 81-year-old man was admitted to the hospital with a severe sore throat and a low grade fever. A chest radiograph showed bilateral diffuse reticulonodular shadows. By fluorescent stain for mycobacteria, his sputum smear showed acid-fast bacteria. The initial polymerase chain reaction (PCR) of his sputum revealed Mycobacterium intracellulare (M. intracellulare), but not Mycobacterium tuberculosis (M. tuberculosis). However, a repeat PCR was performed because M. tuberculosis could not be ruled out due to his clinical symptoms and chest imaging. The second PCR detected both M. intracellulare and M. tuberculosis. From the standpoint of infection control, this case illustrates the possibility that M. tuberculosis could be a threat if a second PCR is not done. While PCR is a useful exam for diagnosing M. tuberculosis, it can produce false negative results. Therefore, for diagnosing tuberculosis, particularly in a case such as the present case, a second PCR, which is not normally necessary, should be done.     

Liver‐infiltrating CD56 positive T lymphocytes in hepatitis C virus infection

Abstract: Aim: Hepatitis C virus (HCV) is a major cause of post‐transfusional and sporadic hepatitis, and leads to chronic liver disease. It has been suggested that virus‐specific cytotoxic T lymphocytes are responsible for liver injuries that occur in HCV‐infected patients. However, the detailed characteristics of these lymphocytes have not yet been defined. We have previously reported that CD56⁺ T lymphocytes, as intermediates between natural killer cell and T lymphocytes, predominantly infiltrated the liver and were increased in patients with chronic hepatitis related to HCV (CH‐C). Material and Methods: We obtained peripheral blood and liver tissues from 32 patients diagnosed as having CH‐C, and 10 other liver disease patients (5 chronic hepatitis related to HBV, 5 alcoholics), and analyzed peripheral blood and liver‐infiltrating lymphocytes using flow cytometric and immunohistochemical techniques. Results: The CD56⁺ T lymphocyte ratio in the liver of patients with a high histology activity index (HAI) score for chronic hepatitis was higher than that of patients with a low HAI score and patients with other liver diseases. In addition, T lymphocytes from patients with chronic hepatitis with a high HAI score carried mostly γδ‐TCR. There was a correlation between the ratio of CH‐C and serum alanine aminotransferase, category I (periportal inflammation and necrosis), and IV (fibrosis) of the HAI scoring system. The ratio was highest in zone 1 of the hepatic lobules. Conclusion: The correlation between CD56⁺ T lymphocyte ratios and hepatocellular damage was examined. These findings suggest strongly that liver‐infiltrating CD56⁺ T lymphocytes play an important pathologic role in hepatocellular injury in CH‐C.     

Effects of betazole hydrochloride and cyclic AMP on the pepsinogen secretion by rabbit gastric mucosa in organ culture

The effects of betazole hydrochloride, dibutyryl cyclic AMP (DB-cyclic AMP) and betazole hydrochloride plus aminophylline on pepsinogen secretion by rabbit gastric mucosa were studied in organ culture. Betazole hydrochloride alone did not stimulate pepsinogen secretion at the concentrations of 10(-8), 10(-6), 10(-5) and 10(-4) M. However, 10(-3) M DB-cyclic AMP produced a significant stimulation of pepsinogen secretion into the culture medium when compared with the control. In the presence of 3 x 10(-3) M aminophylline, betazole hydrochloride in the concentration of 10(-5) and 10(-4) M stimulated pepsinogen secretion into the culture medium, and the magnitude of this increase was 2.0- and 2.8-fold, respectively, compared with the control. Aminophylline alone could not change pepsinogen secretion into the culture medium. These results suggested that the pepsinogen secretion, stimulated by betazole hydrochloride, was mediated by cyclic AMP in the chief cells.     

Gamma-glutamyl transferase and metabolic risk factors for cardiovascular disease

OBJECTIVE: To elucidate the mechanism of the reported association between serum gamma-glutamyl transferase (GGT) activity and cardiovascular mortality. METHODS: Cross-sectional analysis of the relationship between serum GGT activity and the risk factors for cardiovascular disease was performed. PATIENTS AND MATERIALS: Middle-aged Japanese male personnel of the Self-Defense Forces who underwent retirement check-up. RESULTS: Serum GGT activity was associated with total cholesterol, triglyceride, fasting plasma glucose, total homocysteine and systolic blood pressure. The association remained in the analysis adjusted for possible confounders including cigarette smoking, ethanol consumption and body mass index. CONCLUSION: The observed association between serum GGT and cardiovascular risk factors may partly explain the reported relationship between serum GGT activity and cardiovascular disease. Serum GGT activity may be regarded as a marker of cardiovascular risk factors or oxidative stress rather than a mere indicator of excessive ethanol consumption or obesity.     

Appendiceal adenocarcinoma: Long-term outcomes after surgical therapy

PURPOSE Appendiceal adenocarcinomas are very rare. We analyzed contemporary outcomes associated with surgical therapies for these malignancies.METHODS Retrospective outcomes for patients treated at a tertiary academic medical center from 1981 through 2001 were analyzed.RESULTS A total of 36 patients (22 females (61 percent) mean age, 52 years) with appendiceal adenocarcinoma were treated. Eighty-eight percent of patients presented with symptoms of acute appendicitis. Eighteen (50 percent) patients underwent curative resection (7 primary right hemicolectomies, 10 appendectomies + subsequent right hemicolectomy, and 1 appendectomy alone). Mean length of follow-up was 55 months. Overall five-year survival rate was 46 percent. The five-year survival rate after curative resection was 61 percent and after palliative surgery was 32 percent (P < 0.05). Among patients who underwent curative resection, factors associated with improved five-year survival rates included histologic type (79 vs. 32 percent for colonic vs. mucinous types, respectively; P < 0.05), T stage (75 vs. 47 percent for T1 and 2 vs. T3 and 4, respectively; P < 0.05), and tumor grade (100 vs. 46 percent for well-differentiated tumors vs. moderately or poorly differentiated tumors, respectively; P < 0.05).CONCLUSIONS Patients undergoing surgery for appendiceal adenocarcinoma can be stratified according to prognostic variables. The role of adjuvant therapies for patients with poor prognostic factors needs to be evaluated in a multi-institutional setting.Presented at World Congress of Digestive Surgery, Hong Kong, China, December 9 to 11, 2002.     

Assessment of the Systolic Left Ventricular Myocardial Velocity Profile and Gradient Using Tissue Doppler Imaging in Patients with Hypertrophic Cardiomyopathy

To determine the systolic characteristics of the hypertrophied myocardium in patients with hypertrophic cardiomyopathy (HCM), we evaluated the left ventricular [left ventricle (LV)] myocardial velocity profile (MVP) and gradient obtained from tissue Doppler imaging (TDI). Transmural wall-motion velocities in the ventricular septum and LV posterior wall were recorded in 12 patients with asymmetric septal hypertrophy and 12 healthy volunteers, and their profiles and gradients were determined. The maximum systolic myocardial velocity gradient in the ventricular septum was significantly lower in the HCM group than in the control group (0.88 ± 0.35 versus 2.24 ± 0.41; P < 0.001), whereas the gradient in the LV posterior wall was only slightly lower in the HCM group than in the control group (2.69 ± 0.82 versus 3.45 ± 0.96). In the control group, the MVPs in the ventricular septum and LV posterior wall were closely linear, suggesting that the transmural velocity is uniform during systole. MVPs in the ventricular septum and LV posterior wall in the HCM group also were closely linear, whereas the distribution of velocities in the ventricular septum was fairly dispersed compared with the control group. The myocardial velocity gradient on the right ventricular side of the ventricular septum decreased or disappeared in the patients with HCM, suggesting a nonuniform distribution of velocities. In conclusion, the MVP and gradient obtained from TDI may represent new indices for evaluating regional LV contractile abnormality in patients with HCM.