Evidence of macrophage foam cell formation by very low-density lipoprotein receptor: interferon-gamma inhibition of very low-density lipoprotein receptor expression and foam cell formation in macrophages.

BACKGROUND: Expression of the VLDL receptor, primarily in macrophages, has been confirmed in human and rabbit atherosclerotic lesions. The high binding affinity of the VLDL receptor for remnant particles implicates the VLDL receptor pathway in the foam cell formation mechanism in macrophages. This study investigates the effect of interferon (IFN)-gamma on VLDL receptor expression in phorbol-12-myristate-13-acetate (PMA)-treated THP-1, HL-60 macrophages, and human monocyte-derived macrophages. METHODS AND RESULTS: THP-1 cells were induced to differentiate into macrophages by PMA treatment. IFN-gamma was added to the medium, and expression of the VLDL receptor was determined. (125)I-beta-VLDL degradation study and oil red O staining were examined. In THP-1 macrophages, VLDL receptor protein expression decreased at 2 days after PMA treatment but increased at 3 days and increased up to 5 days. Scavenger receptor proteins, which were not originally present, appeared at 3 days after PMA treatment. IFN-gamma inhibited VLDL receptor expression in a dose-and time-dependent manner in macrophages. However, no inhibitory effect was observed in monocytes. Moreover, IFN-gamma receptor mRNA increased during differentiation to macrophages. (125)I-beta-VLDL degradation study and oil red O staining showed that IFN-gamma significantly inhibited foam cell formation after the uptake of beta-VLDL. LDL receptor-related protein (LRP) and LDL receptor mRNAs were not expressed in macrophages. In PMA-treated HL-60 macrophages and human monocyte-derived macrophages, IFN-gamma also inhibited VLDL receptor expression and foam cell formation by beta-VLDL. CONCLUSIONS: VLDL receptor expression is upregulated during monocyte-macrophage differentiation. IFN-gamma inhibits VLDL receptor expression and foam cell formation only in macrophages. Remnant particles induce macrophage foam cell formation through the VLDL receptor pathway.

Effects of brief glucocorticoid exposure on growth of vascular smooth muscle cells in culture.

While prolonged exposure of vascular smooth muscle cells (VSMC) to glucocorticoid has been shown to inhibit cell proliferation, the effect of a brief pulse exposure is not known. We studied the short-term effects of pulse exposure to dexamethasone (DEX) on DNA synthesis in cultured VSMC. VSMC were pulsed with DEx for varying time intervals and [3H]thymidine incorporation into cells after 24 h was measured. Exposure to DEX for 24 h decreased [3H]thymidine incorporation, while pulse treatments with DEX from 2 min to 6 h significantly increased [3H]thymidine incorporation. Maximal proliferative effect was observed with a 20-min exposure. The effect of a 20-min pulse was dose-dependent, with the half-maximal dose of DEX being approximately 10(-7) M. A selective glucocorticoid receptor antagonist, RU486, inhibited the proliferative effect of DEx. Concentrated conditioned medium from cells exposed to 10(-6) M DEX increased [3H]thymidine incorporation by other VSMC in a dose-dependent manner. These results suggest that short-term pulse DEX exposure is capable of producing one or more autocrine growth factors in VSMC via a glucocorticoid receptor action. This effect of glucocorticoid pulses may contribute to the pathogenesis of arteriosclerosis and hypertension.

Assessment of hand-arm vibration exposure among traffic police motorcyclists.

The aims of this study were (1) to evaluate subjective symptoms in the hand-arm system of all traffic police motorcyclists of a city located in the central part of Japan and (2) to assess their hand-arm vibration exposure associated with traffic police motorcycle riding. The study population consisted of 119 motorcycling traffic policemen and 49 male controls. By means of a questionnaire, information on the occupational history and the presence of subjective symptoms in the hand-arm system of all subjects was obtained. Vibration was measured on the handlebars of the representative motorcycles and on the hands of the riders. The 4- and 8-h energy-equivalent frequency-weighted acceleration as well as the lifetime vibration dose were calculated for all police motorcyclists. The prevalence of finger blanching in the traffic police motorcyclists was 4.2%, but none of the controls had this symptom. The rates of finger numbness (19.3%), finger stiffness (16.0%), shoulder pain (13.4%), and shoulder stiffness (45.4%) were significantly higher among police motorcyclists as compared with controls. The root-mean-square (rms) frequency-weighted acceleration on the handlebars of police motorcycles was in the range of 2.2-4.9 m/s2 rms. The computed 4- and 8-h energy-equivalent frequency-weighted acceleration values were 2.8-4.5 and 2.0-3.2 m/s2 rms, respectively. A pattern of increasing percentage prevalence with increasing cumulative vibration dose was noticed. The subjects with a lifetime vibration dose of more than 20.1 m2 h3 s-4 (in scale) showed significantly higher prevalence rates for symptoms in the fingers and shoulders as compared with the control group. As occupational vibration exposure of traffic police motorcyclists might be considered a risk factor for the development of symptoms in the hand-arm system of the riders, its evaluation and control is needed for prevention methodology evolution.

[Relationship between the experience of steroids side effects and noncompliance with oral steroids treatment in collagen disease patients].

PURPOSE: To analyze the relationship between the experience of side effect and the compliance with oral steroids drug treatment of the patients in Collagen Disease Clinic. METHODS: A questionnaire survey through interview was conducted on 165 outpatients with various collagen disease at Saga Medical School Hospital. RESULTS: 94 patients (57%) had a history of noncompliance to the steroids drug. 49 patients (52.1%) adventitiously had forgotten to take the steroids as ordered and 45 patients (47.9%) intentionally had regulated their steroids dose or had discontinued the steroids drug treatment. Over 80% of the patients had experienced side effects of the steroids. The patients who experienced one or more of the following side effects, osteoporosis, bone fractures, menstrual disorders, moon face, central obesity, alopecia, acnelike eruption, manic-depressive state, and insomnia, intentionally regulated, or discontinued the steroids therapy. In addition, the patients who were not made cognizance about side effects of the steroids by their physicians and nurse tended to noncompliance group. CONCLUSION: To increase the compliance rate with oral steroids drug treatment, we must make conscious efforts to inform the patients on the condition of their medical states, the efficacy of the prescribed drugs, and the side effects and risk concerning discontinuation of the steroids. It is Also necessary to establish "Drug information and counseling day" in outpatient Department.

No relationship of salivary flow rate or secretory immunoglobulin A to dental caries in children.

To investigate the relationship between dental caries and the salivary flow rate, secretory immunoglobulin A (sIgA) or other components in children, nonstimulated whole saliva was collected and teeth status was examined in 138 boys and 134 girls aged 11-12 years. The subjects were apparently healthy. The mean salivary flow rate was faster in boys than in girls (0.29 vs 0.18 ml/min, p < 0.001). In both sexes, secretion of salivary sIgA and three other components (total protein, calcium and amylase activity) was markedly dependent on salivary flow rates. These results suggest that basal components of resting saliva are secondarily secreted with the flow of saliva fluid. The mean erupted permanent teeth was 21.0 teeth (range: 10-28 teeth) in boys, and 23.0 teeth (13-28 teeth) in girls (sex-difference: p < 0.001). The means of DMFT, the DMFT ratio (% of DMFT to erupted permanent teeth) and DT+dt (sum of decayed permanent and milk teeth, an index for active caries) were 3.4 DMFT (range: 0-11 DMFT), 16.0% (0-40.0%) and 0.5 DT+dt (0-7 DT + dt) in boys, and 3.8 DMFT (0-12 DMFT), 16.2% (0-44.4%) and 0.8 DT+dt (0-5 DT+dt) in girls, respectively (sex-differences: p>0.05 in all). The salivary flow rate or the four salivary components (either concentration or secretion rate) used here had no relationship to the DMFT ratio or to DT+dt in either sex. Variation in the flow rate or in the basal components of resting saliva may not influence caries development in healthy children.

[Self-assessed quality of mastication in relation to remaining teeth and self-assessed health status in elderly persons].

To explore factors related to quality of mastication, information about teeth status and self-assessed health status were obtained by a self-administered questionnaire from participants in a dental screening program. Invitation letters for participation in the program were distributed by members of the neighborhood association to 1.275 residents of a town in Gifu prefecture aged 65 years or older. Participation rate in the dental screening program was 40.5%. A total of 513 participants (245 males and 268 females) completed the program and the questionnaire. The results were as follows. 1. Overall, 32% had 20 teeth or more and 88.4% had bridge(s) and/or denture(s). 2. The mean number of remaining teeth were 12.9 for males and 12.5 for females. There was no statistical difference in the number of remaining teeth between males and females. The mean numbers of remaining teeth among those aged 65-69 years was 15.7 and two thirds of them had lost the Lower First Molar. 3. Those who reported to be satisfied with their present mastication were 83.3% of men and 86.3% of women. The proportions were not influenced by age or sex. 4. Quality of mastication was related to self-reported "good physical condition' and "not easily tired'. 5. The proportion of those satisfied with their mastication was large in the groups with remaining teeth index 0-8 and > or = 17, and small in the group with remaining teeth index 9-16, showing a U-shaped curve for satisfaction rate against remaining teeth index. These results suggest a relationship of quality of mastication on health status. The importance of primary dental care for the elderly persons is underlined.

[Salivary calcium and total protein in relation to dental caries].

To evaluate the relationship between salivary components (calcium: Ca, total protein: T-Pro) and dental caries, we collected nonstimulated and expectorated saliva from 131 primary school children aged 11 years old. All salivary samples were taken in the morning (11:00-11:30 A.M.) on Feb. 17, 1994, while the subjects were at rest. The salivary Ca concentration (mg/dliter), total salivary protein concentration (mg/mliter) and salivary flow rate (mliter/min) were measured based on the salivary sample taken for each person for 30 minutes at most. For each subject the Ca secretion rate (micrograms/min), T-Pro secretion rate (micrograms/min) and Ca/T-Pro ratio were determined. The numbers of permanent teeth erupted, and decayed, missing and filled (DMF) teeth for each subject were obtained from dental records. For the entire group we observed that the numbers of DMF teeth were highly correlated with the numbers of permanent teeth erupted, hence for further analysis we restricted the subjects to 18 boys and 29 girls who were classified as dental age IIIC-IVA (according to Hellman's classification). Multiple linear regression analysis was employed using the number of DMF teeth as a dependent variable. When we included the variables for the Ca/T-Pro ratio, numbers of erupted permanent teeth, sex and salivary flow rate into the model as independent variables, there was a statistically significant association (P < 0.05) between the Ca/T-Pro ratio and the numbers of DMF teeth. However, in other models there was no significant association between the numbers of DMF teeth with Ca concentration, Ca flow rate, total protein concentration, or total protein flow rate.(ABSTRACT TRUNCATED AT 250 WORDS)