Extrarenal expression of α-klotho, the kidney related longevity gene, in Heterocephalus glaber, the long living Naked Mole Rat.

The Naked Mole Rat (NMR), Heterocephalus glaber, provides an interesting model for studying biomarkers of longevity due to its long lifespan of more than 30 years, almost ten times longer than that of mice and rats. α-Klotho (klotho) is an aging-suppressor gene, and overexpression of klotho is associated with extended lifespan in mice. Klotho is predominantly expressed in the kidney. The expression profile of klotho in the NMR has not previously been reported. The present investigation studied the expression of klotho in the kidney of NMR with that of Rattus Norvegicus (RN) and demonstrated that klotho was expressed in the kidney of NMR at the same level as found in RN. Besides, a significant expression of Kl mRNA was found in the liver of NMR, in contrast to RN, where no hepatic expression was detected. The Klotho expression was further confirmed at the protein level. Thus, the results of the present comparative study indicate a differential tissue expression of klotho between different species. Besides its important function in the kidney, Klotho might also be of significance in the liver of NMR. It is suggested that the hepatic extrarenal expression of klotho may function as a further longevity-related factor in supplement to the Klotho in the kidney.

Correlates of high-density lipoprotein cholesterol in black and white women.

The relationships of high-density lipoprotein (HDL) cholesterol with body composition, leisure-time physical activity, cigarette smoking, and education were examined in a community-based sample of 480 Black and 1337 White women. Univariate and multivariate analyses indicated inverse associations of HDL with body mass index and waist-to-hip ratio in both groups, and with cigarette smoking and low educational attainment among White women only. Since correlates of HDL cholesterol differ for Black and White women, further investigation of the differences in these correlates is warranted.

Evaluating South Carolina's community cardiovascular disease prevention project.

A community cardiovascular disease prevention program was undertaken as a cooperative effort of the South Carolina Department of Health and Environmental Control and the Centers for Disease Control of the Public Health Service. As part of the evaluation of the project, a large scale community health survey was conducted by the State and Federal agencies. The successful design and implementation of the survey, which included telephone and in-home interviews as well as clinical assessments of participants, is described. Interview response rates were adequate, although physical assessments were completed on only 61 percent of those interviewed. Households without telephones were difficult and costly to identify, and young adults were difficult to locate for survey participation. The survey produced baseline data for program planning and for measuring the success of ongoing intervention efforts. Survey data also have been used to estimate the prevalence of selected cardiovascular disease risk factors.

In vitro cytotoxicity of chrysotile asbestos to human pulmonary alveolar macrophages is decreased by organosilane coating and surfactant.

Human pulmonary alveolar macrophages were used to quantitate the cytotoxic effect of surface-altered chrysotile asbestos. Little difference was observed in mortality between chrysotile asbestos that was surface-treated to a 42% extent by a hydrophobic organosilane or untreated chrysotile. Little or no effect on mortality was observed when human pulmonary alveolar macrophages were cultured with untreated chrysotile or acid-leached asbestos in the presence of 10 mM dipalmitoyl lecithin. However, when human pulmonary alveolar macrophages were cultured with a hydrophobically-treated (to a 42% or 95% extent) chrysotile asbestos in the presence of 10 mM dipalmitoyl lecithin, a statistically significant decrease in mortality was observed compared to untreated chrysotile. No mutagenic activity was observed when V79 cells were cultured with acid-leached, or 42% hydrophobically-treated chrysotile asbestos, even when human pulmonary alveolar macrophages were included as an activation source. The 95% hydrophobically-treated and acid-leached chrysotile also exhibited decreased binding of benzo[a]pyrene compared to untreated chrysotile asbestos.

Ultrastructural diagnosis of epithelial malignant mesothelioma.

Examination of microvilli (MV) by electron microscopy (EM) may help distinguish epithelial malignant mesotheliomas (EMM) from metastatic adenocarcinomas (AC). The goal of this study was to assess the diagnostic utility of microvillous length to width (l/w) measurements of EMM and AC, and to determine if ultrathin sections can be used to accurately assess lengths of villi not completely contained within a single section. Therefore, in addition to the usual ultrathin (600-800 A) sections used for standard transmission EM, thicker (up to 1 mu) sections were also prepared for study by scanning transmission EM. Seven cases of EMM and 3 of AC were analyzed. In each case, length and width were measured for all MV with identifiable bases (18-60 MV/case), using an electronic planimeter, and the mean l/w ratio calculated. The dimensionless l/w ratio is independent of magnification and does not require calibration, facilitating intercase comparison. In the 3 AC, the mean l/w was 5.39, versus 11.44 in the 7 EMM cases. Four EMM were analyzed using both standard ultrathin and thicker sections, disclosing a thin section l/w of 13.34 and a thick section of 12.26, supporting the confidence of measurements made from standard ultrathin sections. Examination of data also showed that equally good separation of EMM from AC could be obtained using the mean ratio of only the 10 longest MV (16.11 versus 8.93). By these techniques, EMM often may be distinguishable from AC, with a l/w ratio twice as large in EMM and a mean l/w greater than 11 supportive of a diagnosis of EMM.

Ultrastructure of acute ammonia toxicity in the human lung.

A tanker truck carrying anhydrous ammonia (NH3) fell off a freeway, releasing a dense cloud of NH3 gas, killing several people. The driver was dead upon impact. To our knowledge, pulmonary NH3 toxicity in humans has not been studied previously by electron microscopy (EM). Therefore, in two cases, the paraffin-embedded tissue blocks of lung were deparaffinized and reembedded in plastic for 1-mu sections and EM examination. The lung tissue of a third case, the truck driver, was similarly processed as a control. Light-microscopic pulmonary findings in the acute NH3 deaths included denudation of the tracheobronchial epithelium, edema of the lamina propria, and marked alveolar edema, congestion, and hemorrhage. In contrast, in the truck driver's lungs, the bronchial epithelium was intact, and there was no gross odor of NH3. Massive pulmonary hemorrhages in his lungs were attributed to trauma rather than NH3 inhalation. EM examination of the lungs of the truck driver showed no discernible toxic alterations in either the capillary endothelial cells or the Type I or II alveolar epithelial cells, and alveolar and capillary basement membranes were intact. In contrast, EM study of the lungs from two individuals dying acutely of NH3 inhalation showed marked swelling and imbitional edema of Type I alveolar epithelial cells; however, alveolar basement membranes and capillary endothelial cells appeared as usual. These electron-microscopic findings demonstrate the Type I epithelial cell to be the target cell of acute alveolar wall injury in NH3 inhalation.

Influence of alpha-adrenergic blockade on platelet-mediated thrombosis in stenosed canine coronary arteries.

The functional significance of platelet alpha-adrenergic receptors in vivo is uncertain. The aim of this study was to elucidate their role in experimental coronary thrombosis. In 46 open-chest dogs with a critical coronary stenosis produced by plicating the coronary artery wall with a suture, blood flow showed cyclical reductions followed by an abrupt return to control levels. The flow reduction were previously shown to be caused by platelet aggregation. In the present study they were unaffected by heparin (1,000 U . kg-1 . h-1) at the start of the experiment but consistently abolished by aspirin (30 mg . kg-1) at the end of the protocol, further supporting platelet aggregation as the primary mechanism. After 1 h of observation, dogs were assigned to one of the following groups: control (no intervention, n = 9), phentolamine (a nonselective alpha-blocker) "low dose" (0.07 mg . kg-1 bolus followed by 0.1 mg . kg-1 . min-1, n = 4), phentolamine "high-dose" (3 mg . kg-1 bolus followed by 0.07 mg . kg-1 . min-1, n = 6), prazosin (an alpha 1-blocker, 2 mg . kg-1, n = 8), yohimbine (an alpha 2-blocker, 3 mg . kg-1, n = 11) or prazosin + yohimbine (same doses, n = 8). In controls, cyclical reductions in flow continued unchanged for another hour. Phentolamine effected a partial dose-related inhibition of flow reductions; however, prazosin and yohimbine, given separately or in combination, failed to produce any significant effect despite an alpha-blocking action equivalent to or greater than that of phentolamine (alpha-agonist dose-response studies).(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet-mediated thrombosis in stenosed canine coronary arteries: inhibition by nicergoline, a platelet-active alpha-adrenergic antagonist.

The effects of nicergoline, a new agent that blocks alpha-adrenergic receptors and inhibits platelet phospholipase, were evaluated in a canine model of platelet-mediated coronary thrombosis. In 48 open chest dogs, the circumflex coronary artery was stenosed by plicating the artery wall with a suture. Thirty-four of the 48 dogs exhibited cyclic reductions in flow in the stenotic vessel, followed by a sudden return to control levels. The reductions in flow were unabated in all but two dogs after heparin administration (1,000 U/kg per h), unaffected by large doses of nitroglycerin and nifedipine and associated with platelet aggregates in the stenotic segment (demonstrated by histologic and electron microscopic examination). These observations support the conclusion that the flow reductions were caused by platelet aggregation rather than by fibrin deposition or vasospasm. Twenty dogs were monitored for 1 hour after heparin administration and then assigned to a control (n = 7) or nicergoline-treated (n = 13; 1 mg/kg intravenously) group. In control dogs, cyclic reductions in flow continued unchanged for another hour, whereas in the treated group they were markedly decreased in 1 dog and completely abolished in the other 12 dogs. Aspirin (30 mg/kg intravenously) suppressed flow reductions in all control dogs, confirming the primary role of platelet aggregation in the phenomenon. This study provides a modified model of platelet-mediated thrombosis in stenosed coronary arteries. Furthermore, the results indicate that nicergoline can effectively interfere with platelet function in vivo. The potent antithrombotic activity exhibited by nicergoline might enhance the therapeutic usefulness of this vasodilator.

Pulmonary melanoma. Primary vs metastatic.

We report one of the few cases of apparently primary pulmonary melanomas documented by both clinical and autopsy examination. The possibility of spontaneous regression of a melanoma primary in another site after metastasis has occurred may explain some of these cases.

Hurthle cell tumors of the thyroid gland.

Hurthle cell lesions of the thyroid gland, which are derived from follicular cells, occur in a variety of thyroid diseases. Hurthle cell neoplasms are generally easy to differentiate from non-neoplastic lesions, but the separation of benign from malignant Hurthle cell tumors is difficult on a purely histologic basis unless capsular or vascular invasion or metastases are present. Since this distinction is so difficult to make, the authors recommend treating all Hurthle cell neoplasms as potentially malignant. Treatment includes total thyroidectomy, peritracheal node dissection and if palpable jugular nodes are present, a regional node dissection. A series of 11 patients with this disease and the literature are reviewed to document these recommendations.

Impaired polymorphonuclear leukocyte motility in malnourished infants: relationship to functional abnormalities of cell adherence.

The humoral and cellular contributions to PMN motility in vitro were studied in 37 malnourished (PCM) pediatric patients. Early-phase directed migration to BCF and to ZANS was diminished significantly (p less than 0.001) in severe PCM patients as compared to healthy adult or age-matched controls or respective nutritionally restored patients. Abnormalities were reversible after nutritional restoration and unrelated to occurrence of clinical infection. To determine the pathogenic mechanism of impaired PMN mobility in PCM, studies of cell morphology and adhesive function were performed. Abnormalities observed in severe PCM suspensions included significantly (p less than 0.001) increased baseline (unstimulated) adherence values and impaired CF modulation of adhesive function. Diminished enhancement of PMN adherence or decreased (relative to baseline) adherence values were observed in response to BCF (mean % delta = +5) or f-Met-Leu-Phe (mean % delta = -6) as compared to adult PMN values of +28% delta and +31% delta, respectively. That these abnormalities may result from in vivo CF prestimulation was suggested by findings of "activated" PMN morphology in suspensions prior to in vitro stimulation, and abnormalities of the distribution of PMN surface adhesion sites under conditions of chemotactic stimulation. Further investigations will be required to determine the underlying pathogenic mechanism(s) accounting for our observations.

Isolation of an actin polymerization stimulator from bovine thyroid plasma membranes.

An actin polymerization stimulator was purified from bovine thyroid plasma membranes by DNase I affinity column chromatography. Although the molecular weight of the protein was about 42,000 (42K) by sodium dodecyl sulfate polyacrylamide gel electrophoresis, it did not comigrate with actin. In the presence of 30 mM KC1, the 42K protein facilitated formation of actin filaments when analyzed by a centrifugation method, accelerated the initial phase of actin polymerization as measured in an Ostwald viscometer and increased the length of filaments as shown by electron microscopy. The 42K protein also accelerated the initial phase of actin polymerization in the presence of 100 mM KC1 and 2 mM MgCl2 but did not affect the final viscosity. The effect of the 42K protein was diminished by 5 uM cytochalasin B or 1 uM cytochalasin D. This 42K protein may anchor actin filaments onto the thyroid plasma membrane.

Viscoelastic measurement of clot formation: a new test of platelet function.

Assessment of platelet function presents a challenge to the investigators in the clinical field. An instrument, Sonoclot, is described which measures changes in the viscoelastic properties (clot impedance on a vibrating probe) of plasma as it is recalcified. Platelet poor plasma (PPP) and platelet rich plasma (PRP) show distinct and characteristic Sonoclot tracings. Tracings of PPP show a lag period and a primary wave. These parameters correspond to recalcification time and fibrin polymerization. Tracings of PRP show, in addition, a secondary wave and a downward wave. These parameters correspond to the incorporation of platelets in the clot and retraction of the clot. The PRP parameters are influenced by the number and quality of the platelets. This instrument was utilized to assess the platelet function in patients after coronary artery bypass surgery (CAB). In 69 patients studied, 20 patients did not have excessive bleeding. The clot impedance tracings in this group were normal. Twenty-four patients had excessive bleeding, normal clot impedance, and coagulation tests indicating the possibility of surgical bleeding. This was confirmed in 22 (92 percent) patients upon exploration to control bleeding. Twenty-five patients had excessive bleeding, normal coagulation tests and abnormal clot impedance suggesting platelet dysfunction. In twenty-one (84 percent) of the patients, transfusion of platelet concentrate controlled the bleeding with corresponding correction of clot impedance. Sonoclot studies are quick and easy to perform, and appear to be a valuable and reliable adjunct in the diagnosis of hemostatic problems after CAB surgery.

Pulmonary sclerosing hemangioma: sometimes a form of pulmonary hamartoma.

Previous light and electron microscopic examinations of sclerosing hemangiomas of the lung have raised questions regarding their varying microscopic patterns and cells of origin. We describe two additional cases: one studied by light microscopy revealed the classic pattern of a sclerosing hemangioma of endothelial origin, and a second, studied by combined light and electron microscopy, had incomplete small peripheral airways and occasional alveolar-like spaces derived from epithelial and mesothelial cells. It is concluded that sclerosing hemangiomas of the lung may sometimes consist of admixtures of tissues of epithelial, mesothelial, and endothelial cell origins and thus represent a form of pulmonary hamartoma.