Circulating oxidized low density lipoprotein levels. A biochemical risk marker for coronary heart disease.

Recent studies have established oxidative modification of low density lipoprotein (LDL) as an important atherogenic factor. We examined the clinical relevance of circulating oxidized LDL (OxLDL) levels in atherosclerotic disease by an enzyme immunoassay with use of specific antibodies against OxLDL (FOH1a/DLH3) and apolipoprotein B. Plasma OxLDL levels were significantly higher in patients with coronary heart disease (n=65) than in control subjects (n=181; 201. 3+/-11.2 versus 112.4+/-3.3 U/dL, respectively; P<0.01). OxLDL levels were not associated with age, sex, total cholesterol, or apolipoprotein B levels in normal control subjects. Our results suggest that circulating OxLDL may be a possible biochemical risk marker for coronary heart disease.

Immunohistochemical expression of glutathione transferase-pi in untreated primary non-small-cell lung cancer.

Patients with unresectable non-small-cell lung cancer (NSCLC) usually have undergone chemotherapy; however, such problems as resistance to chemotherapeutic agents occur during the treatments. Recent studies have indicated that glutathione S-transferase-pi (GST-pi) may play an important role in the resistance of cancer cells to alkylating agents, including cisplatin compounds. We examined a possible relationship between immunohistochemical expression of GST-pi and the response to cisplatin plus etoposide chemotherapy in patients with untreated and unresectable primary NSCLC. Of the 89 patients, 50 (56.2%) were GST-pi-positive and 39 (43.8%) were GST-pi-negative. For the patients with negative GST-pi expression, the response rate was 66.7% (26 of 39 patients). In the patients with positive GST-pi expression, the response rate was 26% (13 of 50 patients). This difference was statistically significant (P = .0019). The results suggest that GST-pi expression in NSCLC tissues is related to response to cisplatin plus etoposide chemotherapy and may be useful as a predictor of chemotherapy response.

Technetium tin colloid test detecting symptomless dysphagia and ACE inhibitor prevented occurrence of aspiration pneumonia.

Symptomless dysphagia and swallowing disorders play a very important role in the pathogenesis of aspiration pneumonia. A videofluoroscopic examination and a simple two-step swallowing provocation test (STS-SPT) could be useful for detection of swallowing disorders in elderly patients with stroke, however, there is no report on such a test for detection of symptomless dysphagia. We administered 1 ml Technetium Tin Colloid (99mTC) to the patient during sleep via a nasal catheter placed in the mouth. At 09:00 h the next day, symptomless dysphagia was checked for by imaging. Improvement of the symptomless dysphagia was observed, and thus we could prevent the occurrence of aspiration pneumonia. The 99mTC test was particularly useful in detecting symptomless dysphagia in elderly patients with stroke.

[Present and prospects of telepathology].

Nearly ten years have passed since telepathology was introduced and real-time pathology consultations were conducted. Long distance consultations in pathology, cytology, computed tomography and magnetic resonance imaging, which are referred to as telemedicine, clearly enhance the level of medical care in remote hospitals where no full-time specialists are employed. To transmit intraoperative frozen section images, we developed a unique hybrid system "Hi-SPEED". The imaging view through the CCD camera is controlled by a camera controller that provides NTSC composite video output for low resolution motion pictures and high resolution digital output for final interpretation on computer display. The results of intraoperative frozen section diagnosis between the Gihoku General Hospital 410 km from SRL showed a sensitivity of 97.6% for 82 cases of breast carcinoma and a false positive rate of 1.2%. This system can be used for second opinions as well as for consultations between cytologists and cytotechnologists.

Cytological diagnosis and telomerase activity of cells in effusions of body cavities.

Telomerase is a ribonucleoprotein that synthesizes telometric DNA on chromosome ends, and may be related to the aging and immortality of cells. Recently, a telometric repeat amplification protocol (TRAP) assay for telomerase activity, using the polymerase chain reaction, was developed. We examined the limitations of TRAP assay by applying it to a cultured colon cancer cell line (COLO320) and 58 human cytological materials from body cavity effusions, and obtained the following results; i) The limits of the TRAP assay were 20-50 cells for the COLO320 cell line; ii) One COLO320 cell per 100 normal blood white cells was detectable; iii) Seventeen of 58 samples were positive for telomerase activity in this study. The sensitivity was 69% (9/13) and the specificity was 87.5% (28/32) between cytological diagnosis and telomerase activity; iv) Among 29 malignant cases, 15 were positive for telomerase activity, while there were 11 cytologically positive cases. The positive cases detected by the combination of cytology and telomerase activity accounted for 21 of the total 29 cases (72.4%). These results suggest that the measurement of telomerase activity in body cavity effusions may be useful as an adjunctive tool for cytological and clinicopathological diagnosis and that this technique is potentially applicable to remnant cytological materials.

[Oxidized LDL in patients with coronary heart disease and normal subjects].

Basic research has provided strong evidence that oxidation of LDL plays an important role in the progression of atherosclerotic vascular disease. The levels of plasma oxidized two-density lipoprotein (ox-LDL) were measured by sandwich ELISA using the monoclonal antibody (DLH3) recognized oxidatively modified lipoproteins and the anti-human apolipoprotein B monoclonal antibody in healthy subjects and patients with coronary heart disease (CHD). Plasma ox-LDL could be detected in normal subjects and patients with CHD. No sex-related difference was observed in normal subjects. The levels of ox-LDL in the forties and fifties were higher than those in the thirties and twenties. The levels of plasma ox-LDL were significantly higher in patients with CHD than in controls. There was no difference between the levels of ox-LDL of patients with single vessel disease and those with multivessel disease. These results suggest that elevated levels of oxidized LDL may be a marker for CHD.

Application of telomerase activity for screening of primary lung cancer in broncho-alveolar lavage fluid.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends using an RNA component as a template. Extension of telomeric repeats by telomerase prevents telomere shortening with cell divisions and contributes to chromosomal stability, possibly leading to immortalization of the cells. In the present study, we used a telomerase assay to detect primary lung cancer in broncho-alveolar lavage fluid (BALF). A total of 58 BALF samples were examined by telometric repeat amplication protocol assay. Thirty-five (29 cancers, 2 salcoidoses, 2 pulmonary tuberculoses and 2 normal samples) of 58 (60.3%) cases were found to be positive for telomerase activity. The sensitivity of telomerase activity was 78.4%, compared with 64.7% of BALF cytology. Among 37 primary lung cancer patients diagnosed histopathologically, 24 had positive cytology and 29 had positive telomerase activity. The number increased to 32 patients when cytodiagnosis and telomerase activity were considered. Of patients in whom the presence of primary lung cancer was strongly suspected clinically, although there was no histopathological evidence, two were telomerase-positive, initially diagnosed as normal by cytological examination and histological examination but finally diagnosed as primary lung cancer (adenocarcinoma) in subsequent histological examination using operation specimens. These findings suggest that telomerase assay using BALF samples might be a useful screening method for primary lung cancer especially when combined with BALF cytology.

Bronchial asthma induced by rice.

A 43-year-old patient with rice-induced bronchial asthma was first admitted to our hospital for developing bronchial asthma induced by mite and house dust. At that time, there was no sign of allergic response to rice. Two years later, he was readmitted in an emergency state, with a severe attack of bronchial asthma. This time, however, the result of immunoglobulin E (IgE)-radioallergosorbent test (RAST) for rice was positive, with those to mite and house dust were unexpectedly negative. The causative factors and pathological mechanisms of various kinds of food allergies still remain unknown. The patient is now followed up in an ambulatory setting, and has been eating hypoallergenic rice with no bronchial asthma-induced attack. The present case, being an adult patient with severe grain-induced bronchial asthma previously allergic to mite and house dust, seems to be rather rare in the literature.

[A case of mucosa associated lymphoid tissue (MALT) lymphoma].

We examined a 63-year-old female, who was referred to our hospital for a thorough examination of abnormal findings on the X-ray which were first detected in May, 1992, and suggested a tumor. After hospital admission, a bracheobronchial lymph node biopsy was performed, and the results suggested a pseudo-lymphoma. However, because the possibility of a malignant tumor was not completely negated and the patient, as well as her family, hoped to receive surgical treatment, we performed the tumor resection. The tumor had a clear border. S6 was 3 x 3.5 x 4 cm, S8 was 2 x 2.5 x 3 cm, and evaluation according to the tumor node metastasis (TNM) classification was T1 N0 M0, i.e., Stage I. In addition to an ordinary histopathological examination, an immunohistochemical examination was conducted for CD19+, CD20+, CD22+, IgD-, CD5-, CD10-. Overall, the tumor was diagnosed as a MALT lymphoma. Investigated IgH, TCR beta, bcl-1 and bcl-2 genes did not show reconstitution. Because it is difficult to differentiate a malignant lymphoma, primarily developed in the lung, from a MALT lymphoma on a morphological examination of a tissue specimen, immunohistochemical and genetic examinations are helpful for making a diagnosis.

[Correlation between an enzyme (glutathione S-transferase-pi) and effects of chemotherapy (cisplatin + etoposide)].

OBJECTIVES: We studied the correlation between cisplatin and etoposide chemotherapy and GST-pi staining in patients with untreated primary non-small cell lung cancer. METHODS: Of patients diagnosed as having primary lung cancer, 27 patients (26 men, 1 woman; median age 74.9 years) with stage III b or over were studied. Histological types included squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. A course of treatment consisted of cisplatin 100 mg/m2/day x one day and etoposide 100 mg/m2/day x 3 days during 28 days. After 2 courses of treatment, the therapeutic effects were judged and examined in relation to immunostaining levels obtained with anti-GST-pi antibody. RESULTS: Of patients with PR (14), 11 showed GST-pi (-) staining. CONCLUSION: There is a correlation between GST-pi staining and the effects of cisplatin and etoposide chemotherapy.