Water wells as possible indicators of tectonic strain.

Coseismic water level changes associated with the Izu-Hanto-oki earthquake of 9 May 1974 were recorded in 59 among 95 observation wells located in the districts of Tokai and Kanto, Japan. The spatial distribution of wells in which the groundwater level rose or fell is rather systematic. The areas in which these wells are located closely coincide with the areas of contraction and dilatation expected by the faulting. This strongly suggests a possible correlation between the observed changes in groundwater level and the tectonic strain. The results may indicate that the water level of wells is able to monitor at least acute coseismic strain changes.

Lunar anorthosites: rare-Earth and other elemental abundances.

Elemental abundances of major (Ti, Al, Fe, and Ca), minor (Na, Mn, and Cr), and trace elements [14 rare-earth elements (REE), Y, In, Cd, Rb, Cs, Ba, Co, and Sc] in lunar anorthosites separated from Apollo 11 sample 10085 coarse fines have been determined by means of instrumental and radiochemical neutron activation analysis. The REE distribution pattern of lunar anorthosites, relative to ordinary chondrites, has a positive Eu anomaly. On the assumption that (i) the lunar composition is similar to that of ordinary chondritic meteorites low in total Fe ( approximately 13 percent); (ii) lunar anorthosites are derived from highland cratering events and are representative of the highlands; and (iii) the moon differentiated into olivine, hypersthene, and basaltic and anorthositic phases, and plagioclase crysstallization began after approximately 93 percent solidification, then mass balance calculations yield approximately 30-kilometer and approximately 10-kilometer thicknesses for the lunar highlands for the melting and chemical differentiation of the entire moon and of the upper 200 kilometers, respectively. Corresponding thicknesses of the basaltic basement rocks were approximately 5 kilometers and approximately 2 kilometers, respectively. Alternatively, if the anorthosites of this study are representative of the highlands and the onset of plagioclase crystallization occurred after approximately 50 percent solidification of the initially melted moon, calculations with REE and Ba partition coefficients suggest that the REE and Ba abundances in the primeval moon were similar to those observed in basaltic achondrites.

Precursory chemical changes in ground water: kobe earthquake, Japan.

Chloride (Cl(-)) and sulfate (SO(4)(2-)) ion concentrations of ground water issuing from two wells located near the epicenter of the Kobe earthquake in Japan fluctuated before the disastrous magnitude 7.2 event on 17 January 1995. The samples measured were pumped ground water packed in bottles and distributed in the domestic market as drinking water from 1993 to April 1995. Analytical results demonstrate that Cl(-)and SO(4)(2-) concentrations increased steadily from August 1994 to just before the earthquake. Water sampled after the earthquake showed much higher Cl(-) and SO(4)(2-) concentrations. The precursory changes in chemical composition may reflect the preparation stage of a large earthquake.

Abundances of 30 elements in lunar rocks, soil, and core samples.

Abundances of 30 elements in seven lunar rocks and soil were determined by instrumental and radiochemical activation analysis. Seven major and minor elements in chips from 27 rocks were determined by instrumental activation analysis. Abundances of ten bulk elements overlap for the breccia rocks and soil samples. All lunar rare earth elements distribution patterns resemble those found in terrestrial abyssal subalkaline basalt, but with Eu depleted by about 60 percent in all lunar samples compared to the adjacent rare earth elements. Precipitation of plagioclase and hypersthene achondritic-like minerals from a melt could account for Eu depletion and the observed distribution of rare earth elements. Abundances of Ti, Al, Ca, Na, and Mn determined by instrumental activation analysis in five core-tube soil samples indicate uniformity for Al and Mn and apparent differences (10 to 20 percent) for Ti, Ca, and Na at 7.8 and 10.5 centimeters as compared to 0to5.2 centimeter depths.

Radon Anomaly: A Possible Precursor of the 1978 Izu-Oshima-kinkai Earthquake.

Precursory changes in the radon concentration of groundwater were observed prior to the Izu-Oshima-kinkai earthquake (magnitude 7.0) 14 January 1978. The distance from the epicenter to a continuous radon-monitoring station at Nakaizu was about 25 kilometers. A sudden drop and a subsequent increase in the radon concentration recorded on 9 January 1978 were significant. The size of the spike-like change was about 15 percent. After the earthquake, a remarkable increase in the radon concentration occurred.

Hydrogen release: new indicator of fault activity.

The hydrogen concentration in soil gas has been measured in the area around the Yamasaki Fault, one of the active faults in southwestern Japan. Degassing of a significant amount of hydrogen (up to more than 3 percent by volume) has been observed for sites along the fault zone. The hydrogen concentration in soil gas at sites away from the fault zone was about 0.5 part per million, almost the same as that found in the atmosphere. The spatial distribution of sites with high hydrogen concentrations is quite systematic. A hypothesis on the production of hydrogen by fault movements is postulated.

"Helium spots": caused by a diapiric magma from the upper mantle.

"Helium spots," where a significant amount of helium is present in the soil [up to 350 parts per million with a high (3)He to (4)He ratio of (8.90 +/- 0.31) x 10(-6)], have been found along the fault zone formed by the 1966 Matsushiro swarm earthquakes. The formation of the "helium spots" and the occurrence of the earthquakes are interpreted as the results of a diapiric uprise of a magma approximately 1 kilometer in diameter.

Venting of carbon dioxide-rich fluid and hydrate formation in mid-okinawa trough backarc basin.

Carbon dioxide-rich fluid bubbles, containing approximately 86 percent CO(2), 3 percent H(2)S, and 11 percent residual gas (CH(4) + H(2)), were observed to emerge from the sea floor at 1335- to 1550-m depth in the JADE hydrothermal field, mid-Okinawa Trough. Upon contact with seawater at 3.8 degrees C, gas hydrate immediately formed on the surface of the bubbles and these hydrates coalesced to form pipes standing on the sediments. Chemical composition and carbon, sulfur, and helium isotopic ratios indicate that the CO(2)-rich fluid was derived from the same magmatic source as dissolved gases in 320 degrees C hydrothermal solution emitted from a nearby black smoker chimney. The CO(2)-rich fluid phase may be separated by subsurface boiling of hydrothermal solutions or by leaching of CO(2)-rich fluid inclusion during posteruption interaction between pore water and volcanogenic sediments.

Chemical composition of sawdust from lunar rock 12013 and comparison of a java tektite with the rock.

Abundances of 11 major and minor elements and 11 trace elements have been determined by instrumental neutron activation analysis of two Apollo 12013 rock fragments, a sample of rock 12013,17 sawdust, and a Java tektite (J2). Although the abundances of major elements in tektite J2 are similar to those of rock 12013, comparison of the minor and trace elements shows that no fragment or sawdust of rock 12013 that has been analyzed to date is chemically similar to tektite glass. Rock sawdust is representative of "whole rock" composition only if the amount of contamination from the sawing process is known. After appropriate correction for saw wire contamination, analyses of sawdust yield fairly accurate averaged elemental compositions of complex clastic lunar and other rocks.

Study of dose escalation and sequence switching of administration of the combination of docetaxel and doxorubicin in advanced breast cancer.

The objectives of the present study were to evaluate whether a schedule-dependent pharmacokinetic and/or pharmacodynamic interaction exists between two sequences of docetaxel and doxorubicin administration and to determine the maximal tolerated dose (MTD) of this combination. Patients with chemotherapy-naïve metastatic or recurrent advanced breast cancer were enrolled. In the crossover design, tandem dose escalation of docetaxel and doxorubicin was performed. Docetaxel, in doses ranging from 50-70 mg/m2, was administered for 1 h by drip infusion either just before or after a 5-min bolus i.v. injection of doxorubicin at dosages from 40-50 mg/ m2. The sequence of drug administration was switched after the first course in each patient, and the sequence of drug administration thereafter depended on the patient's choice. Twenty-five patients were initially assessable for toxicity. The MTD in the sequence of doxorubicin after docetaxel was 40 and 50 mg/m2, respectively, with the dose-limiting toxicity of neutropenia. On the other hand, the MTD of the sequence of docetaxel after doxorubicin was 70 and 50 mg/m2, respectively. The dose-limiting toxicities in this sequence were neutropenia and diarrhea. Duration of grade 4 neutropenia in the sequence of docetaxel followed by doxorubicin was significantly longer than that in the alternate sequence (P = 0.0062). However, there was no difference in pharmacokinetic parameters of docetaxel, doxorubicin, and doxorubicinol between the two sequences. The sequence of 50 mg/m2 doxorubicin followed by 60 mg/m2 docetaxel is recommended for subsequent clinical trials for practical reasons.

Composition of free long-chain (sphingoid) bases in stratum corneum of normal and pathologic human skin conditions.

The composition of molecular species of free long-chain bases (FLCB) isolated from stratum corneum of various human skin conditions was analyzed by the high-performance liquid chromatographic and fast atom bombardment mass spectrometric methods. FLCB with carbon length ranging from 16 to 20 comprised about 0.3% of total lipids in stratum corneum of normal and pathologic skin conditions. Major FLCB included sphinganines and sphingenines with 18 to 20 carbons and some phytosphingosines such as t17:1, t18:1, t18:0, t20:1, and t20:0. Compared with stratum corneum of normal lower legs, molar percentages of FLCB having 18 carbons and those with 20 carbons were slightly higher and lower, respectively, in normal plantar epidermis, showing site-related differences in normal skin. Psoriatic scales and hyperkeratotic stratum corneum from clavus and plantar keratoderma contained increased levels of FLCB with 18 carbons and decreased levels of FLCB with 20 carbons. These findings may reflect abnormal keratinization in hyperkeratotic skin conditions.

Staphylococcal enterotoxin B upregulates expression of ICAM-1 molecules on IFN-gamma-treated keratinocytes and keratinocyte cell lines.

The effects of staphylococcal enterotoxin B (SEB), a Staphylococcus aureus-derived bacterial superantigen, on expression of intercellular adhesion molecule-1 (ICAM-1) were examined in cultured normal and transformed (DJM-1 cells) human keratinocytes by flow cytometry, confocal microscopy, digital image processing, and reverse transcriptase-polymerase chain reaction. SEB significantly upregulated ICAM-1 expression in the interferon-gamma (IFN-gamma)-pretreated, HLA-DR-positive normal keratinocytes and DJM-1 cells in a dose-dependent manner, but not in the untreated, HLA-DR-negative cells. Other toxins such as diphtheria and pertussis toxins did not have the effect. The distribution of SEB and HLA-DR molecules was identical on the IFN-gamma-treated, HLA-DR-positive DJM-1 cells by confocal microscopy. Digital image processing analysis demonstrated that SEB induced a transient increase of intracellular calcium concentration only in the IFN-gamma-treated DJM-1 cells. Pretreatment of the IFN-gamma-treated DJM-1 cells with anti-major histocompatibility complex class II monoclonal antibody completely blocked the effect of SEB. Furthermore, ICAM-1 mRNA was detected in the IFN-gamma-pretreated, SEB-exposed normal keratinocytes by reverse transcriptase-polymerase chain reaction. Our results demonstrate that SEB binds to keratinocytes, presumably via major histocompatibility complex class II molecules such as HLA-DR, triggers calcium mobilization, and induces the synthesis of ICAM-1 molecules. We speculate that, in various cutaneous disorders, SEB penetrates the epidermis and interacts with HLA-DR-positive keratinocytes to upregulate ICAM-1 expression, thus modulating the course of the inflammatory process.

Immunohistochemical distribution of adult T-cell leukemia-derived factor/thioredoxin in epithelial components of normal and pathologic human skin conditions.

Tissues from normal human skin and various skin diseases were studied with the immunoperoxidase technique using an antibody to adult T-cell leukemia-derived factor (ADF), a homologue of human thioredoxin. Normal human skin showed positive immunostaining for ADF/thioredoxin in the outer root sheath of hair follicle, sebaceous glands, and secreting components of apocrine and eccrine sweat units, but not in the unexposed interfollicular epidermis and other parts of both hair follicles and the sweat units. Immunoreactivity of benign skin tumors gave similar distribution to their normal counterparts; trichilemmal cyst, nevus sebaceus, senile sebaceous hyperplasia, and mixed cell tumor were positive for immunostaining, whereas epidermal cyst and pilomatricoma were not. No immunoreactivity was detected in malignant skin tumors such as basal cell carcinoma and poorly differentiated squamous cell carcinoma. Solar keratosis, well-differentiated squamous cell carcinoma, some of metastatic lesions of squamous cell carcinoma, and extramammary Paget's disease reacted with the antibody. These immunoreactivities reflected numerous functions of thioredoxin in higher organisms. Our findings suggest that the expression of ADF/thioredoxin in both normal and abnormal human skin is related to epithelial cell differentiation.

Inhibitors of sphingolipid synthesis modulate interferon (IFN)-gamma-induced intercellular adhesion molecule (ICAM)-1 and human leukocyte antigen (HLA)-DR expression on cultured normal human keratinocytes: possible involvement of ceramide in biologic action of IFN-gamma.

To elucidate the participation of sphingosine and ceramide in the biologic action of cytokines on epidermal keratinocytes, we studied whether inhibitors of sphingolipid synthesis modulate interferon (IFN)-gamma-induced intercellular adhesion molecule (ICAM)-1 and human leukocyte antigen (HLA)-DR expression on cultured normal human keratinocytes. Pretreatment of keratinocytes with L-cycloserine or fumonisin B1, but not 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), significantly suppressed both ICAM-1 and HLA-DR expression induced by IFN-gamma. Because the synthesis of all kinds of sphingolipids is blocked by L-cycloserine and all except that of sphinganine by fumonisin B1, whereas PDMP inhibits the synthesis of glucosylceramide and glycosphingolipids, the result suggests the participation of ceramide and/or sphingosine in IFN-gamma-induced ICAM-1 and HLA-DR expression. Exogenous C2-ceramide reversed the effects of L-cycloserine and fumonisin B1. On the other hand, sphingosine reversed the effect of L-cycloserine, but not of fumonisin B1. These results indicate that ceramide participates in this pathway, as fumonisin B1, but not L-cycloserine, inhibits the synthesis of ceramide from sphingosine. In addition, reverse transcriptase polymerase chain reaction showed that L-cycloserine reduced the mRNA for ICAM-1, HLA-DR alpha, and HLA-DR beta induced by IFN-gamma, and C2-ceramide and sphingosine antagonized the effect of L-cycloserine. Furthermore, the degradation rate of fluorescent sphingomyelin into ceramide in keratinocytes was increased by IFN-gamma, suggesting that IFN-gamma activates sphingomyelin hydrolysis in keratinocytes. These observations suggest the possible role of ceramide in IFN-gamma-induced ICAM-1 and HLA-DR expression on keratinocytes. Ceramide may function as an endogenous modulator mediating the cytokine signals in keratinocytes.

T-cell proliferation to superantigen-releasing Staphylococcus aureus by MHC class II-bearing keratinocytes under protection from bacterial cytolysin.

Skin colonization with Staphylococcus aureus may exacerbate skin disorders by activation of lesional T cells with release of superantigens. Although T cells are effectively stimulated by staphylococcal superantigens in the presence of epidermal accessory cells, it remains to be elucidated whether in vivo cutaneous colonization with S. aureus can activate T cells. We examined how T cells are stimulated in the presence of keratinocytes by mitomycin C (MMC)-treated S. aureus that are unable to propagate but retain their ability to produce superantigens. Peripheral blood mononuclear cells (PBMCs) proliferated well in response to MMC-treated superantigen-producing S. aureus and bacterial supernatants. When purified T cells were cultured with MMC-treated S. aureus or supernatant in the presence of interferon-gamma-pre-treated keratinocytes, the supernatant, but not MMC-treated S. aureus, stimulated T cells. MMC-treated S. aureus had a cytotoxic effect on keratinocytes. Furthermore, keratinocytes were highly susceptible to alpha-toxin compared with monocytes and B cells functioning as accessory cells in PBMCs. This suggests that a lack of response of T cells to S. aureus plus keratinocytes is due to damage of superantigen-presenting function of keratinocytes by cytolysin. The activity of alpha-toxin was much less stable than that of superantigen during incubation. Given that S. aureus-colonized skin provides circumstances in which viable keratinocytes are exposed to superantigens but not to active cytolysin(s), skin-infiltrating T cells may be effectively stimulated by S. aureus.

Th2 suppressor cells are more susceptible to sphingosine than Th1 cells in murine contact photosensitivity.

Murine contact photosensitivity (CPS) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) is a cutaneous delayed-type hypersensitivity reaction in which both positive and negative regulatory pathways exist. The latter pathway is mediated by antigen-specific, CD4+ suppressor T cells (CPS-Ts) that are Th2 cells. We examined the effects of sphingosine and synthetic cell-permeable analogs of ceramide on the cellular kinetics of CPS-Ts and immune lymph node cells from TCSA-photosensitized mice (CPS-LNC), along with other murine T-cell populations. The addition of sphingosine at 10 or 3 microM to in vitro cultures suppressed DNA synthesis of CPS-Ts and Th2 clones, including D10 cells and 24-2 cells, but not that of CPS-LNC or Thl clones, including 23-1-8 and 28-4 cells. This suggested that sphingosine exerts its inhibitory effects preferentially on the proliferation of Th2 cells. Although suppressing DNA synthesis, sphingosine augmented the production and mRNA expression of interleukin-4 (IL-4) and enhanced the expression of the IL-4 receptor in CPS-Ts. In addition, the ability of sphingosine to induce signal transduction of CPS-Ts was confirmed by elevation of the intracellular free Ca++ concentration. Because CPS-Ts exposed to sphingosine exhibited a lower G2M/G1 ratio than control, these seemingly ambivalent phenomena may be caused by retardation of the G1 to S phase progression, a cell-cycle dysregulation known to augment cytokine production. In contrast to sphingosine, cell-permeable ceramide did not affect the proliferation of these cells when stimulated with mitogen/antigen and did not augment IL-4 production by CPS-Ts. Our study suggests that sphingosine modifies the Th1/Th2 balance by preferentially affecting the cellular kinetics of Th2.

Treatment of T lymphocytes with 8-methoxypsoralen plus ultraviolet A induces transient but biologically active Th1-skewing cytokine production.

8-Methoxypsoralen plus ultraviolet A light is suggested to shift T lymphocytes from Th2 to Th1 cells. To clarify this issue, we examined the effects of 8-methoxypsoralen/ultraviolet A on the expression/production of cytokines in peripheral blood mononuclear cells from normal subjects and a Sézary syndrome patient. 8-Methoxypsoralen/ultraviolet A augmented the expression of mRNAs for interferon-gamma and interleukin-2 and reduced those for interleukin-4 and interleukin-10. It seems that this enhancement of Th1 cytokines is caused by increment of cytokine production by Th1 cells but not by conversion of Th2 cells to produce Th1 cytokines. The number of interferon-gamma-secreting lymphocytes was markedly increased in 8-methoxypsoralen/ultraviolet A-treated peripheral blood mononuclear cells 20 h after treatment, whereas that of Th2 cytokine-producing cells was decreased. Accordingly, the amount of interferon-gamma was elevated in culture supernatants from 8-methoxypsoralen-phototreated peripheral blood mononuclear cells, whereas interleukin-4 was significantly reduced. This enhanced production of interferon-gamma, however, was found only until 3 d after 8-methoxypsoralen phototreatment and was declined by 5 d after treatment. Finally, 8-methoxypsoralen/ultraviolet A treatment of T cells regulated their ability to induce keratinocyte CD54 expression. Our results show that 8-methoxypsoralen/ultraviolet A has a transient but biologically active Th1-skewing action in human T cells, suggesting that 8-methoxypsoralen/ultraviolet A exerts a beneficial therapeutic effect on Th2-mediated or Th2-malignant diseases.

Sphingosylphosphorylcholine stimulates proliferation and upregulates cell surface-associated plasminogen activator activity in cultured human keratinocytes.

Of the various sphingolipid metabolites, including sphingosine, sphingosylphosphorylcholine (SPC), dimethylsphingosine, sphingosine-1-phosphate, N-acetylsphingosine, and skin-specific ceramides, only SPC accelerated cutaneous wound healing in full-thickness excision wounds in genetically healing-impaired diabetic (db/db) mice. A histologic examination revealed that SPC promoted not only granulation tissue formation, but also the re-epithelization of epidermal keratinocytes. As the direct effects of SPC on keratinocytes are completely unknown, we investigated the effects of SPC on normal cultured human keratinocytes. SPC concentration-dependently enhanced DNA synthesis in keratinocytes, with an increase in intracellular calcium concentrations due to the release of calcium ions from intracellular stores. SPC upregulated cell surface plasminogen activity, and at the same time increased the cell surface expression of urokinase-type plasminogen activator (uPA) and urokinase-type plasminogen activator-receptor (uPA-R) in keratinocytes. Furthermore, SPC promoted the in vitro wound repair of cultured keratinocytes, which was partially blocked by an anti-uPA monoclonal antibody. Our results suggest that one of the mechanisms responsible for the SPC-mediated promotion of cutaneous wound healing seems to be an enhancement of re-epithelization caused by the direct stimulation of the proliferation of keratinocytes, and an activation of the uPA/uPA-R system, which enhances the migration of keratinocytes.

Spontaneous autoimmune skin lesions of MRL/n mice: autoimmune disease-prone genetic background in relation to Fas-defect MRL/1pr mice.

The autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mouse is characterized by the lpr mutation, which is a defect in the Fas antigen. Since Fas mediates apoptosis, this defect results in CD4-CD8- double negative T-cell proliferation, lupus nephritis, and macroscopic lupus erythematosus-like skin lesions. The control counterpart of MRL/lpr mouse is the MRL/Mp-+/+ (MRL/n) mouse, which lacks the lpr mutation and is almost normal during the first 6 mo of life. The lpr mutation, however, accelerates autoimmune phenomena in MRL/lpr mice. Thus, it is important to investigate autoimmune diseases like systemic lupus erythematosis in relation to the autoimmune disease-prone genetic background of MRL/n mice. We found that skin lesions in aged MRL/n mice had unique characteristics. The first characteristic is spontaneous occurrence, and the second is epidermal cell nuclear immunostaining with IgGs by direct immunofluorescence. The skin lesions in aged MRL/n mice showed milder inflammation than in MRL/lpr mice. A homogeneous pattern of epidermal cell nuclear staining was always associated with nuclear staining in kidney cells and also correlated with the in vitro binding of sera to keratinocytes cultured from newborn MRL/n mice. These results suggest that the skin lesions of aged MRL/n mice are a good model for certain types of cutaneous lupus erythematosus and also can provide new insights into the long-standing controversy whether epidermal cell nuclear staining occurs in vivo.

Caudoputamen is damaged by hypocapnia during mechanical ventilation in a rat model of chronic cerebral hypoperfusion.

BACKGROUND AND PURPOSE: Postoperative brain dysfunction, such as delirium, is a common complication of anesthesia and is sometimes prolonged, especially in patients with cerebrovascular disease. In the present study we investigated the effect of hypocapnia during anesthesia on neuronal damage using a rat model of chronic cerebral hypoperfusion. METHODS: Chronic cerebral hypoperfusion was induced by clipping the bilateral common carotid arteries in male Wistar rats. Fourteen days after the operation, these animals were mechanically ventilated for 2 hours and then kept in suitable conditions for an additional 14 days. Twenty-four rats were assigned to 4 groups: those with chronic cerebral hypoperfusion with either hypocapnia or normocapnia during anesthesia, and those given sham operation with either hypocapnia or normocapnia. White matter lesions in the brain sections were evaluated with Klüver-Barrera staining. Proliferation of glial cells was estimated with the use of immunohistochemistry of glial fibrillary acidic protein, a marker for astroglia, and CD11b, a marker for microglia. Computer-assisted morphometry was applied to the immunohistochemical results of microtubule-associated protein 2 to evaluate the loss of neurons. RESULTS: The histological damage was localized almost exclusively in the white matter in the rats subjected to chronic cerebral hypoperfusion but without hypocapnia. Neuronal damage and astroglial proliferation occurred with aggravated white matter lesions in the caudoputamen in the rats with chronic cerebral hypoperfusion and hypocapnia. No lesions were observed in sham-operated rats with either hypocapnia or normocapnia. CONCLUSIONS: These results indicate that hypocapnia during anesthesia causes tissue damage in the caudoputamen, which may be responsible for long-lasting postoperative delirium in patients with stroke and/or dementia.