Association of low back pain and sleep quality with presenteeism.

BACKGROUND: Low back pain (LBP) and poor subjective sleep quality (SSQ) are major risk factors for presenteeism. However, no studies have investigated whether combined LBP and poor SSQ are associated with presenteeism. AIMS: We aimed to examine whether a combination of LBP and poor SSQ is associated with presenteeism. METHODS: This cross-sectional study included 936 workers (median age, 38 years; men, 89%), with evaluated presenteeism using the work limitations questionnaire. We divided them into 'no presenteeism' and 'presenteeism' categories. The presence of LBP was defined as a numerical rating scale (NRS) score of ≥1 in current pain intensity. SSQ was assessed using a single question regarding whether the participants typically got enough sleep. We categorized the participants into four groups: (i) LBP + poor SSQ, (ii) non-LBP + poor SSQ, (iii) LBP + good SSQ and (iv) non-LBP + good SSQ. Logistic regression analysis was used to investigate the association between presenteeism and the presence of LBP and poor SSQ, adjusting for age, sex, work type, education, marital status, smoking status, body mass index and weekly working hours. RESULTS: The data from 533 participants were used for analysis (median age, 38 years; men, 90%, response rate, 66%). Combined LBP and poor SSQ were significantly associated with presenteeism (non-LBP + poor SSQ: adjusted odds ratio = 0.56, 95% CI 0.32-0.96; LBP + good SSQ: 0.33, 0.20-0.56; non-LBP + good SSQ: 0.29, 0.18-0.48). CONCLUSIONS: Evaluating both LBP and SSQ may be beneficial in considering presenteeism.

Effects of pre-surgical nasoalveolar moulding on maxillary arch and nasal form in unilateral cleft lip and palate before lip surgery.

OBJECTIVES: To investigate the effects of pre-surgical nasoalveolar moulding (PNAM) on the maxillary arch and nasal form in patients with unilateral cleft lip and palate (UCLP). SETTING AND SAMPLE POPULATION: This is a retrospective case series study. The subjects were infants with complete UCLP who were treated with PNAM (n = 18) at Kagoshima University Medical and Dental Hospital (Japan) between 2006 and 2013. MATERIAL AND METHODS: Maxillary dental casts and facial photographs were taken at the time of the first visit and immediately prior to lip surgery to evaluate the maxillary arch and nasal form changes. The dental casts were scanned with a laser scanner, and changes in the 3-Dimensional coordinates of anatomical landmarks and alveolar cleft width were analysed. Moreover, we investigated the correlation between the changes in the maxillary alveolar arch and nasal form. RESULTS: Regarding the maxillary alveolar arch form, the anterior points of the major segment had moved significantly to the cleft side just prior to the time of lip repair, and the alveolar cleft width was significantly decreased. For nasal form, the inclination and displacement of the columella were significantly improved. The improvement of columella inclination was moderately correlated with the posterior movement of the anterior points of the major segment. CONCLUSIONS: These findings indicate that PNAM for infants with UCLP enhanced symmetry in the maxillary alveolar arch and nasolabial form. In addition, the posterior movement of the anterior points of the maxillary alveolar arch was correlated with the improvement of columella deformation.

Toxicity of 50-nm polystyrene particles co-administered to mice with acetaminophen, 5-aminosalicylic acid or tetracycline.

We investigated whether nano-sized polystyrene particles affect drug-induced toxicity. The particles, which are widely used industrially, had diameters of 50 (NPP50), 200 (NPP200) or 1000 (NPP1000) nm. The toxic chemicals tested were acetaminophen (APAP), 5-aminosalicylic acid (5-ASA), tetracycline (TC), and sodium valproate (VPA). All treatments in the absence of the nanoparticles were non-lethal and did not result in severe toxicity. However, when mice were injected with APAP, 5-ASA or TC together with polystyrene particles, synergistic, enhanced toxicity was observed in mice injected with NPP50. These synergic effects were not observed in mice co-injected with NPP200 or NPP1000. On the other hand, co-administration of VPA and NPP50, NPP200 or NPP1000 did not elevate toxicity. The results show that NPP50 differs in hepatotoxicity depending on the drug co-administered. These findings suggest that further evaluation of the interactions between polystyrene nanoparticles and drugs is a critical prerequisite to the pharmaceutical application of nanotechnology.

Influence of 50-nm polystyrene particles in inducing cytotoxicity in mice co-injected with carbon tetrachloride, cisplatin, or paraquat.

The toxicity of nanomaterials has yet to be fully investigated. In particular, the interactions between nanomaterials and therapeutic drugs require further study. We investigated whether nano-sized polystyrene particles affect drug-induced toxicity. The particles, which are widely used industrially, had diameters of 50 (NPP50), 200 (NPP200) or 1000 (NPP1000) nm. The toxic chemicals tested were carbon tetrachloride, cisplatin (a popular anti-tumor agent), and a widely used herbicide, paraquat. Mice were treated intraperitoneally with either carbon tetrachloride (0.01 ml/kg), cisplatin (100 micromol/kg) or paraquat (50 mg/kg), with or without intravenous administration of polystyrene particles. All treatments in the absence of the nanoparticles were non-lethal and did not result in severe toxicity. However, when mice were injected with paraquat or cisplatin together with polystyrene particles, synergistic, enhanced toxicity was observed in mice injected with NPP50. These synergic effects were not observed in mice co-injected with NPP200 or NPP1000. These findings suggest that further evaluation of the interactions between polystyrene nano-particles and drugs is a critical prerequisite to the pharmaceutical application of nanotechnology.

Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK mitogen-activated protein kinase.

Gab1 has structural similarities with Drosophila DOS (daughter of sevenless), which is a substrate of the protein tyrosine phosphatase Corkscrew. Both Gab1 and DOS have a pleckstrin homology domain and tyrosine residues, potential binding sites for various SH2 domain-containing adapter molecules when they are phosphorylated. We found that Gab1 was tyrosine phosphorylated in response to various cytokines, such as interleukin-6 (IL-6), IL-3, alpha interferon (IFN-alpha), and IFN-gamma. Upon the stimulation of IL-6 or IL-3, Gab1 was found to form a complex with phosphatidylinositol (PI)-3 kinase and SHP-2, a homolog of Corkscrew. Mutational analysis of gp130, the common subunit of IL-6 family cytokine receptors, revealed that neither tyrosine residues of gp130 nor its carboxy terminus was required for tyrosine phosphorylation of Gab1. Expression of Gab1 enhanced gp130-dependent mitogen-activated protein (MAP) kinase ERK2 activation. A mutation of tyrosine 759, the SHP-2 binding site of gp130, abrogated the interactions of Gab1 with SHP-2 and PI-3 kinase as well as ERK2 activation. Furthermore, ERK2 activation was inhibited by a dominant negative p85 PI-3 kinase, wortmannin, or a dominant negative Ras. These observations suggest that Gab1 acts as an adapter molecule in transmitting signals to ERK MAP kinase for the cytokine receptor gp130 and that SHP-2, PI-3 kinase, and Ras are involved in Gab1-mediated ERK activation.

Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK.

Tec/Btk tyrosine kinases are members of a subgroup of Src tyrosine kinase family. They are reported to be activated in response to cytokines, such as IL-3 and IL-6. Janus kinases (JAKs) are known to associate with certain cytokine receptors, e.g. gp130, the signal transducing subunit of IL-6 receptor, and the common beta chain of IL-3 receptor, which can be activated upon receptor dimerization in response to cytokines. Here we show the association between Jak1/Jak2 and Tec or Jak1 and Btk. Furthermore, Jak1 but not Jak2 induces tyrosine phosphorylation of Btk, but not Tec. These observations suggest that upon cytokine stimulation JAKs activate Tec/Btk or induce their dimerization resulting in endogenous tyrosine phosphorylation. Furthermore using a yeast two-hybrid system we have identified the target molecules for Tec, the p85 and p55PIK subunits of PI-3 kinase, and Vav. Tec associated with Vav through its SH2 domain independently of its kinase activity. In contrast the p85 and p55PIK subunits of PI-3 kinase associated with the SH2-kinase domain of Tec, dependent on Tec kinase activity. Consistent with these, IL-6 or IL-3 induced the association between Tec and the p85 subunit of PI-3 kinase in mammalian cells. These findings suggest that Tec tyrosine kinase links cytokine receptors to PI-3 kinase probably through JAKs.

An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT.

JAK is believed to be an essential tyrosine kinase that mediates signals from the cytokine receptor to its downstream events. JAK associates with the cytoplasmic domain of the type I cytokine receptor superfamily and upon the ligand stimulation it can be activated, resulting in the receptor phosphorylation. In signaling from gp130, a common signal transducer for the IL-6 family cytokines, STAT3, a transcription factor that contains an SH2 domain, is recruited by phosphotyrosines on gp130 and is subsequently phosphorylated by gp130-associated JAKs. In this study, we attempted to find a new target for JAK that is directly activated by JAK, independent of gp130 tyrosine phosphorylation, by using a yeast two-hybrid system. In the process we found that the JH2 domain of JAK1, JAK2 or JAK3 could specifically associate with the carboxy-terminal portion of STAT5, but not with STAT3 or STAT1. The interaction was confirmed using both a transient expression system in a cell line and a GST-fusion protein binding assay. Furthermore, we showed that the activation of STAT5 via gp130 did not need any phosphotyrosines on gp130 while that of STAT3 strictly depended on phosphotyrosines on gp130. Mutations of STAT5 that eliminated the interaction with JAK1 reduced the activation of STAT5 upon the gp130 stimulation, although such mutants could be still activated through erythropoietin receptor. These results indicate that STATs are activated through cytokine receptors by two distinct mechanisms, one dependent on receptor tyrosine phosphorylation and the other mediated by the JAK-STAT direct interaction.

The elongation factor Tu.GTPase reaction: effect of 2'(3')-O-aminoacyl oligoribonucleotides.

The activity of synthetic (2'(3')-O-aminoacyl trinucleotides, C-C-A-Phe, C-C-U-Phe, C-U-A-Phe, U-C-A-Phe and C-A-A-Phe, in promoting the EF-Tu.70 S ribosome-catalyzed GTP hydrolysis was investigated. It was found that the activity decreases in the order C-C-A-Phe greater than C-U-A-Phe greater than U-C-A-Phe greater than C-A-A-Phe much greater than C-C-U-Phe. Thus, the substitution in 'natural' C-C-A sequence with other nucleobases weakens binding of 2'(3')-O-aminoacyl trinucleotides to EF-Tu, with the substitution at the 3'-position having the most profound effect. Since the 2'(3')-O-aminoacyl oligonucleotides mimic the effect of the aa-tRNA 3'-terminus on EF-Tu.GTPase, it follows that EF-Tu probably directly recognizes structure of nucleobases in the aa-tRNA 3'-terminus, with the 3'-terminal adenine playing the most important role.

Antiapoptotic activity is dispensable for insulin-like growth factor I receptor-mediated clonogenic radioresistance after gamma-irradiation.

PURPOSE: The purpose of this study was to evaluate the relationship between apoptotic activity and clonogenic radiosensitivity in vitro using an insulin-like growth factor I receptor (IGF-IR) signaling model, which is known to exert tumorigenic and antiapoptotic effects. EXPERIMENTAL DESIGN: We used mouse embryo fibroblast cell lines expressing either human IGF-IR [R+(Wt) and R+] or the marker gene alone [R-(puro)]; these cell lines were derived from R- cells, which are deficient in IGF-IR. After gamma-irradiation, apoptotic activity was determined by the presence of DNA fragmentation and caspase-3-, -8-, and -9-like activities. Clonogenic radiosensitivity was determined by a colony-forming assay. RESULTS: R+(Wt) and R+ cells expressed similar levels of IGF-IR, transducing phosphorylation signals to major downstream substrates on insulin-like growth factor I stimulation. R+ cells were resistant to the induction of apoptosis after gamma-irradiation; however, both R+(Wt) and R-(puro) cells demonstrated significant DNA fragmentation and increase in caspase-3-, -8-, and -9-like activities. Both R+(Wt) and R+ cells were radioresistant (to a similar extent) compared with R-(puro) cells as measured by a colony-forming assay. Clonogenic radioresistance was not influenced by the inhibition of Akt/protein kinase B through treatment with wortmannin at low concentrations specifically inhibiting phosphatidylinositol 3'-kinase. CONCLUSIONS: Our findings indicate that apoptotic activity does not necessarily predict clonogenic survival after exposure to ionizing radiation. This study provides clinical implications in the evaluation of apoptotic activities observed during the course of radiotherapy to predict accurate tumor response or local control.

Cultured retinal pericytes stimulate in vitro angiogenesis of endothelial cells through secretion of a fibroblast growth factor-like molecule.

Interaction between cultured endothelial cells (EC) and pericytes (PC) was studied in vitro to clarify the mechanism of diabetic proliferative retinopathy. Conditioned medium (CM) from retinal PC strongly increased the proliferation and moderately stimulated migration of retinal EC. Moreover, CM from PC caused stimulation of angiogenesis of retinal EC and umbilical cord vein EC in vitro at the same extent as basic fibroblast growth factor (bFGF). PC also stimulated angiogenesis by EC in mixed cultures. The angiogenic, proliferative and migration activities in CM from PC were inhibited by an antibody to bFGF. These data suggest that PC play an important role in angiogenesis through secretion of an FGF-like molecule.

Mechanism of angiogenic effects of saponin from ginseng Radix rubra in human umbilical vein endothelial cells.

1. The effects of saponin from Ginseng Radix rubra on angiogenesis (tube formation) and its key steps (protease secretion, proliferation and migration) in human umbilical vein endothelial cells (HUVEC) were examined to elucidate the mechanism of the tissue repairing effects of Ginseng Radix rubra. The effect on a wound healing model was also studied. 2. Tube formation was measured by an in vitro system. The activity and immunoreactivity of tissue-type plasminogen activator (tPA) as a protease for angiogenesis and the immunoreactivity of its inhibitor, plasminogen activator inhibitor-1 (PAI-1), were measured in conditioned medium of HUVEC stimulated for 24 h with saponin. Cell proliferation was measured by counting the cell numbers at 2-7 days after seeding. Migration was measured by Boyden's chamber method. The effect on wound healing was studied in the skin of diabetic rats. 3. Saponin at 10-100 micrograms ml-1 significantly stimulated tube formation by HUVEC in a dose-dependent manner. Saponin in a similar concentration-range increased the secretion of tPA from HUVEC as estimated by immunoreactivity and enzyme activity. On the other hand, PAI-1 immunoreactivity was slightly increased at 10 micrograms ml-1 of saponin, but then was significantly decreased at 50 and 100 micrograms ml-1. Cell proliferation was only slightly enhanced by 1-100 micrograms ml-1 of saponin, but migration was significantly enhanced by 10-100 micrograms ml-1 in a dose-dependent manner. Moreover, saponin stimulated wound healing with enhanced angiogenesis in vivo. 4. These results indicate that saponin stimulates tube formation mainly by modifying the balance of protease/protease inhibitor secretion from HUVEC and enhancing the migration of HUVEC, and that it is effective in vivo.

Effects of leptin on secretion of LH and FSH from primary cultured female rat pituitary cells.

BACKGROUND: Leptin, which is the product of the obese gene, is believed to play important roles in pubertal development and reproductive function in females. In a study using adult male rats, it was found that leptin stimulated secretion of gonadotropin from the pituitary in a dose-related manner. However, there has been no such study in female rats. OBJECTIVE: To investigate the effects of leptin on the production of LH and FSH from the pituitary in female rats, using primary cultured pituitary cells. METHODS: In this study, we determined body weight, serum leptin concentration and serum estradiol (E(2)) concentration in female Wistar rats at 3, 5, 6, 7, 9 and 11 weeks of age, and cultured pituitary cells from 6-week-old female Wistar rats with leptin (0--10(-7) mol/l) and GnRH (0 or 10(-8) mol/l). Then basal and GnRH-stimulated extra- and intracellular LH and FSH were assayed by RIA. RESULTS: Serum leptin concentration increased with increases in body weight and E(2) concentration. The pubertal serum leptin concentration was about 10(-10) mol/l. At a lower or moderate concentration, leptin produced dose-related increases in both basal and GnRH-stimulated extra- and intracellular LH and FSH in pituitary cells. At a concentration of 10 mol/l, leptin significantly (P<0.05) stimulated both basal and GnRH-stimulated extra- and intracellular LH and FSH. However, at greater concentrations, these effects diminished. CONCLUSIONS: These results indicated that leptin induced pituitary cells to produce and secrete both LH and FSH, with or without GnRH. The concentration of leptin that induced the greatest production of gonadotropins by pituitary cells was 10(-10) mol/l, which was the same as the physiological pubertal concentration. Leptin may be involved in the onset of puberty. It is also conceivable that leptin may be a cause of ovulatory failure, not only in weight loss but also in weight gain.

Cell kinetic study of human and mouse hair tissues using anti-bromodeoxyuridine monoclonal antibody.

To determine sites of cell proliferation in hair tissues, in vitro and in vivo labeling with bromodeoxyuridine (BrdU) and immunohistochemical demonstration of BrdU incorporation sites by anti-BrdU monoclonal antibody were performed on human and mouse hairs and hair follicles. The germinative area of the hair bulb of human anagen hair was divided into three portions: (A) the upper and inner portion, (B) the middle portion and (C) the lowest outer portion. A-cells intermingled with melanocytes, were regarded as germinative cells of the hair cortex. B-cells appeared to develop into Huxley's layer, cuticle of inner root sheath (IRS), and hair cuticle. C-cells seemed to develop into bulbar outer root sheath (ORS), the innermost cell (IMC) layer of the ORS and Henle's layer. The suprabulbar portion, where the ORS abruptly increased in thickness, was found to be the fourth main germinative portion (D). The ORS cells, except for the IMCs, seemed to originate mostly from the D-cells. In the late anagen phase, first, C-cells became BrdU negative, then, A- and B-cells gradually turned negative, and finally, D-cells lost their germinative activity. In catagen and telogen hair tissues, BrdU-positive cells were found in the two outer cell layers in the ORS. The structure of anagen hair tissues seems to be maintained by the coordinated mitotic activities of characteristically distributed germinative cells of various hair cell layers. The sequential cessation of mitotic activity of these cells is associated with the morphological changes from anagen through catagen to telogen. These findings were common to both human and mouse hair tissues.

Investigation of germinative cells in generating and renewed anagen hair apparatus in mice using anti-bromodeoxyuridine monoclonal antibody.

To elucidate the cell kinetics in generating and renewed anagen hair apparatus in mice, S-phase cells in dorsal skin of new-born and 14 to 25-day-old mice were labeled with bromodeoxyuridine (BrdU) and stained immunohistochemically using anti-BrdU monoclonal antibody. In primary hair germ, lower and outer cells were positively stained. In hair peg, the positive cells were divided into upper and lower portions. In bulbous hair peg, the lower positive cells gathered at the suprapapillary area, whereas the upper positive cells were located in the outer part of the hair apparatus. The latter positive cells were further divided in the middle and upper parts of the epithelial cord. The upper cells were going to form a sebaceous gland. From the suprapapillary group of germinative cells, hair cortex through the innermost cell layer of the outer root sheath were considered to be produced. The positive cells of the outer middle group may be important for elongation of hair apparatus and produce outer root sheath cells. At the end of anagen phase, first the suprapapillary cells became negative and then the outer root sheath cells became negative. BrdU-positive cells reappeared at the bottom of telogen hair apparatus and formed a secondary hair germ. Then, a similar cell kinetics was repeated in the renewed anagen hair apparatus. The germinative cells were separated into a few groups during the generation and cyclic changes of hair apparatus. Each cell group formed the individual part of the hair apparatus in a coordinate fashion, resulting in dynamic changes of the hair apparatus.

Diabetic control and progression of retinopathy in elderly patients: five-year follow-up study.

OBJECTIVE: To assess whether control of diabetes mellitus is as important in the elderly as in young and middle-aged diabetic patients in terms of progression of retinopathy. DESIGN: A 5-year longitudinal cohort study. SETTING: Outpatient diabetic clinic. PATIENTS: One hundred fourteen non-insulin-dependent diabetic patients (30 males, 84 females) > or = 60 years of age. MEASUREMENTS: Retinopathy was checked at the beginning and end of the follow-up period. During the 5-year follow-up period, demographic variables, body mass index, HbA1c, blood pressure, and plasma lipids were monitored. Retinopathy was classified as follows: grade 0, no lesion; grade 1, non-proliferative retinopathy; grade 2, pre-proliferative retinopathy; grade 3, proliferative retinopathy. Progression of retinopathy during the 5-year follow-up was defined as an increase in its grade. RESULTS: At the start of the study, 13% of the patients already had retinopathy, all of grade 1. The 5-year follow-up study showed that progression of retinopathy was 23.6% in all cases, 22.2% in those with grade 0 initially, and 33.3% in those with grade 1 initially. The progression rates of retinopathy as a function of the mean HbA1c during the follow-up were as follows: lower than 7%, 2%; 7-8%, 20%; 8-9%, 40%; more than 9%, 61%. Multiple logistic regression analysis showed that, of the parameters examined, only HbA1c was a significant risk factor for progression of retinopathy. CONCLUSIONS: Control of diabetes mellitus is the most important factor associated with prevention of progression of retinopathy in elderly patients.

Chromium (III) decreases carbon tetrachloride-originated trichloromethyl radical in mice.

Effects of the administration of trivalent chromium (Cr(III)) to mice and the activation of carbon tetrachloride (CCl4) to form trichloromethyl radicals (.CCl3) in the liver were studied. The lipid peroxidation in liver microsomes induced in vitro by CCl4 in the presence of NADPH was decreased by the preadministration of Cr(III) to mice. The activity of NADPH-cytochrome C reductase, which presumably catalyzes the formation of .CCl3 from CCl4 in liver microsomes, was depressed by Cr(III) administration and kept at a level lower than that of the control group for at least 2 hr after CCl4 dosing. Furthermore, the frequency of appearances of ESR signals of .CCl3 in the liver homogenate of mice 1 min after CCl4 administration was markedly decreased by Cr(III) preadministration, similarly to DL-alpha-tocopherol. These results suggest that Cr(III) preadministered to mice decreases the formation of .CCl3 from CCl4, an activating process of CCl4, in the liver, presumably by scavenging the radical.

Protective effect of chromium(III) on acute lethal toxicity of carbon tetrachloride in rats and mice.

Trivalent chromium (Cr(III)) preadministered intraperitoneally (5 mg Cr/kg body weight) to rats and mice protected these animals from acute lethal toxicity of carbon tetrachloride (CCl4). Some other metals, Cr(VI), Cu(II), and Zn(II), had no effect on CCl4 lethal toxicity. DL-alpha-tocopherol, one of the antioxidative agents, showed similar protective effects to Cr(III). Activities of serum GOT and GPT in mice were increased sharply by the administration of CCl4, but these elevations were depressed by Cr(III) preadministration. Serum glucose levels of mice increased transiently after CCl4 administration and then in the control group fell to hypoglycemic levels after 6 hr, whereas the Cr(III)-pretreated group kept to homeostatic levels. Lipid peroxidation of microsomes in mice 24 hr after Cr(III) administration was lower than that of the control. These results suggest that Cr(III) preadministered to mice might act as a radical scavenger to CCl4 to form trichloromethyl radicals which are a major initial product of CCl4 in liver cells.

Differential analysis of the human anagen hair apparatus using lectin binding histochemistry.

Cell differentiation in the human anagen hair apparatus was examined by lectin-binding histochemistry using seven different lectins: Con A, WGA, RCA-I, PNA, SBA, DBA and UEA-I. Con A and WGA positively stained almost all the cells in the hair apparatus. RCA-I and PNA positively stained the outer cells of the outer root sheath (ORS), but they did not stain the innermost cells (IMCs) of the ORS in the suprabulbar region. However, in the isthmus region, the IMCs showed positive staining with RCA-I, and more intense staining with PNA than that of the outer ORS cells. The ORS cells, including the IMCs, were negative with SBA and DBA below the suprabulbar region, whereas the IMCs became more strongly positive with these two lectins than the other ORS cells in the isthmus region. UEA-I strongly stained the IMCs, but not the outer ORS cells in the hair bulb. The latter cells became positive for UEA-I above the suprabulbar region. These findings indicate that the surface glycoconjugate distribution of the IMCs differs from that of the outer ORS cells. It is concluded that the IMCs of the ORS may undergo an independent cell differentiation process.

Histopathogenesis of inflammatory linear verrucose epidermal naevus: histochemistry, immunohistochemistry and ultrastructure.

Skin lesions of three patients with inflammatory linear verrucose epidermal naevus (ILVEN) were examined. Histologically, orthokeratosis and parakeratosis were alternately seen in the acanthotic epidermis. By N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide staining, the horny cells in the parakeratotic epidermis showed a cytoplasmic SH pattern and a weak membranous SS pattern. The orthokeratotic epidermis revealed an increased involucrin expression, whereas the parakeratotic epidermis showed almost no involucrin expression. Ultrastructurally, in the parakeratotic epidermis, the living keratinocytes had prominent Golgi apparatuses and vesicles in the cytoplasm. In the intercellular spaces in the upper spinous layer through to the lower horny layer, an electron dense, homogeneous substance was deposited. The cytoplasm of the horny cells was filled with keratin filaments and contained remnants of nucleus and cytoplasmic membrane structures, and some lipid droplets. The marginal band formation was incomplete. Most of these ultrastructural abnormalities were not found in the orthokeratotic epidermis. There are both similarities and differences in histopathogenesis of the parakeratotic epidermis between ILVEN and psoriasis. A unique finding was the lack of involucrin expression in the ILVEN parakeratotic epidermis.

B cell subsets in postmenopausal women and the effect of hormone replacement therapy.

OBJECTIVES: In elderly subjects the capacity for antibody production is depressed. This immunosenescence state of humoral immunity is associated with the occurrence of autoimmune disorders involving CD5+ B (B-1) cells. Since estrogen is capable of stimulating the production of autoantibodies, this sex steroid hormone may be a contributing cause of the higher incidence of autoimmune diseases in women. In the present study, B cell subsets in women during the postmenopausal period was determined. The effect of hormone replacement therapy (HRT) on B cell subsets was examined to establish whether the administration of gonadal hormones influence humoral immunity in postmenopausal women. METHODS: Forty six untreated pre- and postmenopausal women and 39 women on HRT were studied. The proportion of B-1 (CD5+) and conventional CD5- B (B-2) lymphocytes was determined by two-color flow cytometry. Serum autoantibodies to a nuclear antigen and to interleukin (IL)-1alpha were measured by immunofluorescence and by radioimmunoassay, respectively. Thirteen women were examined prospectively before and during HRT. RESULTS: In late postmenopausal women (> or = 30 years postmenopausal period), the proportion of B-2 cells was significantly reduced (p<0.01) compared to those of premenopausal and perimenopausal women. HRT induced a significant (p<0.01) increase in the percentage of B-2 cells, while that of B-1 cells remained unchanged. HRT did not affect autoantibody production. CONCLUSION: HRT may retard the progress of immunosenescence by increasing the production of B-2 cells. Moreover, HRT appears not to increase the risk of autoimmune diseases developing in postmenopausal women.