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.

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.

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.

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.

Falciparum malaria in an overseas traveler complicated by disseminated intravascular coagulation and pulmonary edema.

A 24-year-old woman was infected with falciparum malaria during travel to Kenya, complicated by intravascular coagulation and pulmonary edema. She was successfully treated with anti-malarial drugs including chloroquine, quinine sulfate and pyrimethamine, with a combined regimen of heparin, antithrombin III and nafamostat mesilate for disseminated intravascular coagulation, and with methylprednisolone pulse therapy for pulmonary edema. The present case emphasizes the importance of early diagnosis and appropriate treatment in terms of falciparum malaria. This case, in particular, is believed to be worth reporting as overseas travel is increasing and yet anti-malarial drugs are not readily available to most physicians in Japan.

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.

Raman study of the lenses of spontaneously-occurring and streptozotocin-induced diabetic rats.

The WBN/Kob rat is an animal model of spontaneously occurring diabetes only in males at the age of around one year. The diabetic cataract develops about a half year after the onset of diabetes. Using laser Raman spectroscopy we monitored WBN/Kob rat lenses which had chronic hyperglycemic stress and streptozotocin-induced diabetic rat lenses which showed relatively acute cataract formation. WBN/Kob rat lenses revealed a marked increase in the lens water content only in the cortical portion. On the other hand, streptozotocin-induced diabetic rat lenses showed a pronounced increase in the lens water content both in the cortical and the nuclear portion.

Alteration of lens disulfide bonds in newly developed hereditary cataract rat.

A newly developed hereditary cataract rat named Shumiya Cataract Rat (SCR) is introduced. The lens opacity manifests spontaneously in the nuclear and perinuclear portions of the lens in this model at 11 weeks of age. Raman optical dissection studies reveal that lens protein disulfide bonds are considerably decreased in the SCR opaque lens nucleus. This tendency is also detected in the precataractous stage. The simultaneous increase of lens protein sulfhydryl groups is observed in the affected lens nucleus. The glutathione disulfide (oxidized glutathione) level, on the contrary, is elevated in the SCR opaque lens, whereas the glutathione sulfhydryl (reduced glutathione) level is decreased. It is suggested that the impaired formation of protein disulfide bonds is related to lens opacification in a hereditary manner.

[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.

[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.

[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.