Association between low MCV in early pregnancy and perinatal mental health in the Japan Environment and Children's Study and the possible effect of iron deficiency.

BACKGROUND: Postpartum anemia and iron deficiency are associated with postpartum depression. This study investigated the association between a low mean corpuscular volume (MCV) without anemia (which implies early-stage iron deficiency) in early pregnancy and perinatal mental health outcomes. METHODS: The fixed data from the Japan Environment and Children's Study (JECS), a Japanese nationwide birth cohort, were used. Perinatal mental health was assessed using the Kessler 6-item psychological distress scale (K6) in mid-pregnancy and the Edinburgh Postnatal Depression Scale (EPDS) at 1- and 6-months postpartum. RESULTS: Among the 3635 women with MCVs <85 fL in early pregnancy, the proportions of women with K6 scores ≥13 in mid-pregnancy and EPDS scores ≥9 at 1- and 6-months postpartum were 2.7 %, 12.8 %, and 9.9 %, respectively, compared with the 33,242 women with MCVs ≥85 fL at 1.9 %, 11.9 %, and 9.0 %, respectively. Multivariate logistic regression models showed that an MCV <85 in early pregnancy was associated with a K6 score ≥ 13 in mid-pregnancy and an EPDS score ≥ 9 at 1- and 6-months postpartum (adjusted odds ratio (95 % confidence interval): 1.48 (1.16-1.87), 1.14 (1.01-1.28), and 1.09 (0.95-1.24), respectively). LIMITATIONS: Low MCV values do not necessarily represent iron deficiency. Ferritin, currently the best indicator of iron deficiency, was not measured in the JECS. CONCLUSIONS: This study results suggest that a low MCV without anemia in early pregnancy is associated with a slightly increased risk of perinatal mental health deterioration.

Analysis of absorption and spreading of moisturizer on the microscopic region of the skin surface with near-infrared imaging.

BACKGROUND/PURPOSE: Near-infrared (NIR) light with high water absorption enables us to visualize the water content distribution appeared in the superficial skin layer. The light penetration depth with the wavelength of 1920 nm is almost 100 µm from the skin surface. Thus, the water distribution in the stratum corneum can be effectively imaged by detecting the wavelength band around 1920 nm. The aim of this article was to measure the time-lapse behavior of the tiny droplet of the moisturizer spreading on the skin surface by imaging in 1920 nm wavelength band for investigating the correlation with the traditional index of the skin condition such as the water content and transepidermal water loss (TEWL). METHODS: Experiment is performed with three moisturizer products and seven volunteer subjects. The NIR image is acquired by an originally designed imaging scope equipped with the white light of the strong brightness [super continuum (SC) light], the bandpass filter with the center wavelength of 1920 nm, and the NIR image sensor. A tiny droplet of the moisturizer is put on the surface of the skin and the time-lapse images are saved. Each acquired image is analyzed from a view point of the droplet area and elapsed time for absorption into the skin. The water content and TEWL of all subjects are measured by the conventional electrical method for investigating the relationship with the measured droplet dynamics parameters. RESULTS: Elapsed time for moisturizer droplet to be absorbed into the skin, the droplet area just before absorption for three moisturizer products, skin water contents, and TEWL for seven subjects were measured and correlation coefficients for each parameters were calculated. It was found that the skin with higher water contents or lower TEWL absorbed the moisturizer faster and spreads moisturizer wider. Also absorption and spreading speed depend on moisturizer property (moisturizing or fresh) which is originated from the moisturizer constituents. CONCLUSION: The correlation values between the moisturizer dynamics on the skin surface and the traditional index of the skin property were clarified. It was found that the skin with the high water content or low TEWL absorbs the moisturizer droplet fast. The spreading area depends not only on the skin property but on the constituents of the moisturizers.

Imaging wavelength and light penetration depth for water content distribution measurement of skin.

BACKGROUND/PURPOSE: We investigate the measurement sensitivity for the water content distribution in Near-infrared (NIR) imaging ranging up to 2 µm. METHODS: To evaluate the sensitivity, our attention is focused to the light penetration depth in the skin tissue because the thickness of a layer where the water content can be varied is very thin and deep light penetration decreases the signal variation. The light penetration depths in the wavelengths of 1300, 1450, and 1920 nm are calculated theoretically based on the Monte Carlo light transport simulation. RESULTS: It is clarified that the wavelength of 1920 nm gives the smallest penetration depth. A NIR imaging experiment is demonstrated to verify the difference of imaging sensitivity. The experiment result shows that the NIR image taken at 1920 nm gives the most sensitive measurement of the water content distribution in skin.

In vivo evaluation of two forms of urea in the skin by Raman spectroscopy after application of urea-containing cream.

BACKGROUND/PURPOSE: As urea is one of the natural moisturizing factor (NMF) components in the stratum corneum, it has been used in topical products to improve skin conditions. However, the penetration behavior of urea in the skin after application of urea-containing cream has not been determined as there has been no technique with which to measure the urea content in the skin in vivo non-invasively. We therefore applied Raman spectroscopy to evaluate the depth profile of urea content in the skin. We investigated changes in depth profiles of two forms of urea to evaluate the penetration behavior of urea after application of urea-containing cream. METHODS: Commercially available moisturizing creams F and R in quantities of 2.2-mg/cm(2) and containing 20% (w/w) urea were applied to volar forearm skin of six Japanese subjects. Raman spectra of the skin were measured at 2-µm intervals from the skin surface toward the interior using a confocal Raman spectrometer (model 3510 SCA) before and 15, 60, and 120 min after the application of the creams. The amounts of the two forms of urea, urea in water solution and urea in a solid state, were calculated by adding the spectra of solid urea and the cream base to a previously reported algorithm including the spectrum of urea in water solution. RESULTS: The characteristic band of urea in water solution was observed at approximately 1004/cm and that of the solid state at approximately 1010/cm in the Raman spectra of the skin after application of either cream. There was more urea in water solution form in the area where cream F was applied than in the area where cream R was applied. There was more urea in a solid state in the area where cream R was applied than in the area where cream F was applied at all depths and measurement times. In particular, there was significantly more urea in a solid state below a depth of 2 µm in the area where cream R was applied than in the area where cream F was applied 15 min after application. CONCLUSION: The present study demonstrated that we can measure both urea forms in the skin after the application of urea-containing creams. The proposed technique would be useful in the evaluation of characteristics of the penetration behavior of urea in the skin after the application of various urea-containing moisturizers.

Long-term forskolin stimulation induces AMPK activation and thereby enhances tight junction formation in human placental trophoblast BeWo cells.

BeWo cells, derived from human choriocarcinoma, have been known to respond to forskolin or cAMP analogues by differentiating into multinucleated cells- like syncytiotrophoblasts on the surfaces of chorionic villi of the human placenta. In this study, we demonstrated that long-term treatment with forskolin enhances the tight junction (TJ) formation in human placental BeWo cells. Interestingly, AMPK activation and phosphorylation of acetyl-CoA carboxylase (ACC), a molecule downstream from AMPK, were induced by long-term incubation (>12h) with forskolin, despite not being induced by acute stimulation with forskolin. In addition, co-incubation with an AMPK inhibitor, compound C, as well as overexpression of an AMPK dominant negative mutant inhibited forskolin-induced TJ formation. Thus, although the molecular mechanism underlying AMPK activation via the forskolin stimulation is unclear, the TJ formation induced by forskolin is likely to be mediated by the AMPK pathway. Taking into consideration that TJs are present in the normal human placenta, this mechanism may be important for forming the placental barrier system between the fetal and maternal circulations.

The sentinel node concept in prostate cancer: Present reality and future prospects.

A sentinel node (SN) is defined as the first site where cancer cells are carried by lymph flow from a tumor. If this definition (SN concept) correctly reflects the clinical reality, intraoperative SN biopsy would facilitate precise nodal staging. In malignant melanoma, a prolonged survival has been evidenced by a large-scale randomized controlled study. On the contrary, research on SN concept in deeply located cancers including prostate cancer, is still investigative, and no concrete data from clinical trials are yet available. Since 1993, several investigators have demonstrated that the SN concept could be applied in prostate cancer patients as well with high accuracy. Although promising and technically feasible in pre-clinical settings, many hurdles remain to be cleared before clinical application can be recommended. This review addresses the current status and related issues of the SN concept in prostate cancer, and discusses the future directions.

Comparison of the depth profiles of water and water-binding substances in the stratum corneum determined in vivo by Raman spectroscopy between the cheek and volar forearm skin: effects of age, seasonal changes and artificial forced hydration.

BACKGROUND: Dermatologists and cosmetic scientists are becoming increasingly interested in stratum corneum (SC) hydration because the SC plays an important role in keeping the skin surface soft and smooth. However, conventional in vivo noninvasive methods do not provide direct information about the depth profiles of water content or SC components that hold water. OBJECTIVES: To study the depth profiles of water and SC components in vivo by Raman spectroscopy, and to analyse the changes due to age, anatomical location, season and water application. METHODS: In vivo Raman spectra of the skin of the cheek and the volar forearm were obtained from 50 healthy Japanese volunteers of different ages (age range 22-76 years) with a confocal Raman spectrometer. The depth-dependent profiles of water and of SC water-binding components were calculated from the respective Raman spectra. RESULTS: The depth profile of the SC water content was observed in a pattern ranging from around 30% (water/wet tissue) at the outermost layer of the SC to about 70% at the deeper living layer. Although the water content at a depth of 10-30 microm in the forearm skin tended to be lower in older subjects than in younger subjects, no such difference was found in the much thinner SC of the cheek. Moreover, there was no seasonal difference in depth profile of water content from the mid part of the SC to an 80-microm depth from the skin surface both in the cheek and in the forearm. The water content of all the evaluated SC components showed a gradual decrease from the surface to deeper portions. The mean amounts of lactate in the forearm skin and cholesterol in the cheek skin were significantly higher in younger subjects than in older subjects. In contrast, the levels of free amino acids and trans-urocanic acid were higher in the forearm skin of older subjects than in younger subjects. The relative amounts of urea and lactate were the highest in summer, when that of trans-urocanic acid was the lowest. Prolonged water application on the forearm skin even for 90 min resulted in a remarkable increase in water content throughout the SC, even reaching the granular layer, which was only gradually released from the upper part of the SC after discontinuation of the hydration procedure. CONCLUSIONS: Our present findings suggest that changes in the concentration depth profiles of water, free amino acids and lipids in the skin depend on age, anatomical site and season. These findings indicate the important roles played by various water-holding substances in the SC in the regulation of SC water content.

A new method for detecting the abomasal position and characteristics of movement at the onset of the left displacement of the abomasum in cows.

A new method has been developed by us to observe the movements of the abomasum by using a magnet and digital magnetometer. Four cows with left displacement of the abomasum underwent conventional correction by rolling without tacking. A doughnut-type magnet was sutured to the pyloric region in a routine operation. The same was done in three control cows. The position of the pyloric region was observed with a digital magnetometer from outside the cow's body. The magnets in the pyloric region of the control cows were located at the right side of the abdominal cavity at 10-30 cm anterior to the udder base, and moved slightly in various directions within the span of a day. On the other hand, the magnets in the pyloric region of cows with abomasal displacement moved widely in the abdominal cavity from the normal right side to the abnormal left front side. A large movement of the magnet from the normal right side to the abnormal left side of the abdominal cavity was observed within 12 h of the onset of abomasal displacement.

The effect of acupuncture on the coronary arteries as evaluated by coronary angiography: a preliminary report.

The Neiguan acupuncture point (EH-6) of the heart meridian is often used for circulatory disorders. To clarify this effect, we measured coronary diameters in patients with angina pectoris following acupuncture stimulation using cardioangiography. Two kinds of acupuncture stimulation, the leaving needle (LN) and the sparrow pecking method (SPM), were employed for this study. No significant differences were found between LN and SPM. Concerning the pattern of coronary reaction, coronary constriction following acupuncture showed a relationship to patients with vasospastic angina. Coronary dilation following acupuncture showed a relationship to patients with Syndrome X. The mean dilatation with acupuncture was 68.8% of that caused by isosorbide dinitrate. These findings may help to clarify the mechanism of acupuncture treatment.

Antitumor effect of reduction of 150-kDa oxygen-regulated protein expression in human prostate cancer cells.

Heat shock proteins (HSPs)/stress proteins are molecular chaperones that are induced by various environmental and physiological stimuli. Evidence of the relations between the expression of HSPs and the regulation of cell growth or transformation has accumulated. The 150-kDa oxygen-regulated protein (ORP150), a new member of HSP family, functions as a molecular chaperone in the endoplasmic reticulum. We have examined whether transduced antisense ORP150 cDNA reduces tumorigenicity and angiogenicity. Relations between these stress proteins and cancer and possibilities for anticancer gene therapy are described.

A conditional replication-competent adenoviral vector, Ad-OC-E1a, to cotarget prostate cancer and bone stroma in an experimental model of androgen-independent prostate cancer bone metastasis.

Prostate cancer has a high propensity to metastasize to bone, which often resists hormone, radiation, and chemotherapies. Because of the reciprocal nature of the prostate cancer and bone stroma interaction, we designed a cotargeting strategy using a conditional replication-competent adenovirus to target the growth of tumor cells and their associated osteoblasts. The recombinant Ad-OC-E1a was constructed using a noncollagenous bone matrix protein osteocalcin (OC) promoter to drive the viral early E1a gene with restricted replication in cells that express OC transcriptional activity. Unlike Ad-PSE-E1a, Ad-OC-E1a was highly efficient in inhibiting the growth of PSA-producing (LNCaP, C4-2, and ARCaP) and nonproducing (PC-3 and DU145) human prostate cancer cell lines. This virus was also found to effectively inhibit the growth of human osteoblasts and human prostate stromal cells in vitro. Athymic mice bearing s.c. androgen receptor-negative and PSA-negative PC-3 xenografts responded to a single intratumoral administration of 2 x 10(9) plaque-forming unit(s) of Ad-OC-E1a. In SCID/bg mice, intraosseous growth of androgen receptor-positive and PSA-producing C4-2 xenografts responded markedly to i.v. administrations of a single dose of Ad-OC-E1a. One hundred percent of the treated mice responded to this systemic Ad-OC-E1a therapy with a decline of serum PSA to an undetectable level, and 80% of the mice with PSA rebound responded to the second dose of systemic Ad-OC-E1a. Forty percent of the mice were found to be cured by systemic Ad-OC-E1a without subsequent PSA rebound or tumor cells found in the skeleton. This cotargeting strategy shows a broader spectrum and appears to be more effective than systemic Ad-PSE-E1a in preclinical models of human prostate cancer skeletal metastasis.

Intermetatarsophalangeal bursitis induced by a plantar epidermal cyst.

A 44-year-old woman was admitted to the authors' institution for evaluation of two masses in the right forefoot. Standard radiographs showed foci of calcification within the mass. Magnetic resonance imaging and macroscopic findings during surgery revealed the lesion was composed mainly of two different portions: dorsal cystic masses and a solid mass in the plantar side of the fifth metatarsal head. Histologic and immunohistochemical examinations showed that the former was an intermetatarsophalangeal bursitis induced by keratinous material, whereas the latter was a ruptured epidermal cyst. To the best of the authors' knowledge, the current case is the first report of intermetatarsophalangeal bursitis caused by an untreated epidermal cyst.

Expression and adhesive ability of gicerin, a cell adhesion molecule, in the pock lesions of chorioallantoic membranes infected with an avian poxvirus.

The expression and adhesive activities of gicerin, a cell adhesion protein, in the pock lesions on chicken chorioallantoic membranes (CAM) infected with an avian poxvirus were studied. In normal CAMs, gicerin was found on the flattened epithelial cells, and neurite outgrowth factor (NOF) was in the basement membrane. However, in the pock lesions on infected CAMs, gicerin was overexpressed on the cell membranes of hyperplastic epithelial cells forming thick epithelial layers. Neurite outgrowth factor was also found mainly in the basement membrane, but occasionally showed aberrant expression among hyperplastic cells. In vitro analyses, using the dissociated cells from pock lesions, demonstrated that an anti-gicerin polyclonal antibody inhibit cell aggregation activity and cell adhesion to NOF. These results suggest that gicerin might promote the cell-cell and cell-extracellular matrix protein bindings of the hyperplastic epithelial cells by its homophilic and heterophilic adhesive activities, and contribute to pock formation on the infected CAMs.

[Prospects for molecular research in urological oncology: bladder cancer].

This report consists of a description of our research findings relating to the mechanism of cancer metastasis and target molecules for early diagnosis or cancer therapy. First, we investigated the significance of metastasis-related genes expressed to various extents in three human bladder cancer cell lines using two in vivo models. The relationship between the gene expression pattern and the behavior of cancer cells implicated a loss of E-cadherin expression as a critical factor in facilitating the progression of bladder cancer. Second, we examined the expression of human telomerase reverse transcriptase (hTERT) mRNA in voided urine samples in patients with bladder cancer. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed a higher positive rate as compared with cytological examination, suggesting that the expression of hTERT in urine samples may be a useful diagnostic marker for bladder cancer. Finally, we searched for a molecule to which antisense can be applied as a treatment modality. The 150 kDa oxygen regulated protein (ORP 150), a kind of heat shock proteins, functions as a molecular chaperone in the endoplasmic reticulum. We demonstrated that the adenoviral-mediated antisense ORP150 cDNA transfer resulted in the suppression of vascular endothelial growth factor (VEGF) expression and tumor growth in vivo. In addition, the significant correlation between ORP150 and matrix metalloproteinase 2 (MMP-2) expression was observed in bladder cancer, suggesting that ORP150 functions as a molecular chaperon to MMP-2 secretion for tumor invasion. Anti-sense ORP150 may therefore have a potentially stronger antitumor effect because of its multitargeting capability as a molecular chaperone.

Intrarenal varix mimicking a cystic renal tumor.

BACKGROUND: A case of intrarenal varix in a 60-year-old woman is reported. METHODS/RESULTS: The preoperative diagnosis was cystic tumor in the central part of the left kidney. Retrospectively, gadolinium-enhanced magnetic resonance (MR) imaging demonstrated a layered gadolinium sign, indicating the vascular nature of the mass. CONCLUSIONS: Our experience shows that urologists should be aware of the possible presence of a renal cystic mass of vascular origin and of the usefulness of gadolinium-enhanced MR examination for making an identification.

Uptake of BrdU in olfactory and respiratory epithelium of rabbits with experimental sinusitis.

Sinusitis was induced in six rabbits in order to evaluate its influence on the proliferation of cells in the olfactory epithelium compared with the respiratory epithelium during conservative antibiotic therapy. Then 1% ofloxacin was injected into the paranasal sinuses. Three normal rabbits were not administered any treatment and served as controls. The rabbits were sacrificed under intravenous anesthesia and the olfactory and respiratory mucosa was excised 24 hours after intravenous administration with the labeling reagent 5-bromo-2'-deoxyuridine (BrdU). The extent of cell proliferation in these tissues was estimated by immunohistochemical staining with BrdU-specific antibody. The uptake of BrdU was significantly increased (p = 0.0099) in the respiratory mucosa, but not in the olfactory mucosa. Furthermore, in olfactory epithelium, 79.2% and 16.7% of all BrdU-positive cells were olfactory and basal, respectively. Thus, turnover of epithelial cells due to sinusitis was not as accelerated in the olfactory mucosa as in the respiratory mucosa during antibiotic treatment.

Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame Herba, on rats fed a high-fat diet.

OBJECTIVE: To investigate the inhibitory effects of CT-II, extract of Nomame Herba, on lipase activity in vitro and on obesity in rats fed a high-fat diet in vivo. DESIGN: The assay for the inhibitory effect of CT-II on lipase activity was performed by measuring released free fatty acids after the incubation of the medium with CT-II, porcine pancreatic lipase and triolein (experiment 1). In vivo experiments, lean rats or obese rats (570-718 g) were fed a high-fat diet containing 60% fat with or without CT-II for 8 weeks (experiment 2), for 14 days (experiment 3) or for 12 weeks (experiment 4), respectively. MEASUREMENT: The time course of body weight, food intake, organ weight (parametrial fat, liver, heart and kidney) and plasma parameters (triglyceride, total cholesterol, glucose, AST, ALT and insulin), fecal output of total fat and total cholesterol were measured. Hepatic histological examinations were also performed. RESULTS: CT-II inhibited the porcine lipase activity dose-dependently in vitro (experiment 1). Body and liver weight were reduced and hepatic histological examination showed an amelioration of fatty liver in CT II treated animals (experiment 2). CT-II significantly inhibited body weight gain and plasma triglyceride elevation in a dose-dependent manner, without affecting food intake in lean rats fed the high-fat diet. Elevated plasma AST and ALT were also decreased (experiment 3). When obese rats fed the high-fat diet were treated with CT-II for up to 6 months, body weight was initially reduced and thereafter weight gain was significantly suppressed. Total body fat was also significantly reduced and significant reduction of plasma AST and ALT was observed (experiment 4). CONCLUSIONS: These results demonstrated that the lipase inhibitor CT-II is effective in preventing and ameliorating obesity, fatty liver and hypertriglyceridemia in rats fed a high-fat diet.

Liposarcoma associated with multiple intramuscular lipomas. A case report.

A 71-year-old slender, previously healthy man was admitted to the authors' institution because of a huge painless mass in his left scapular area. Physical examination revealed a second soft tissue mass in his right scapular region and a third soft tissue mass in the anterior side of his right shoulder. Surgical treatment including marginal resection of the second and third small masses followed by wide local resection of the huge tumor was performed. Histologic examination showed that the first mass was a well differentiated lipomalike liposarcoma, whereas the second and third lesions were identified as intramuscular lipomas. A review of the literature showed two cases of retroperitoneal liposarcoma associated with multiple subcutaneous lipomas and two cases of liposarcoma involving an extremity associated with multiple subcutaneous lipomas. There is no previous report in which intramuscular liposarcoma was associated with multiple intramuscular lipomas.

[Correlation between expression of metastasis-related genes and lymph node metastasis in testicular cancer].

To investigate the factors related to lymph node metastasis of testicular germ cell tumors, we first established a seminoma orthotopic model with lymph node metastasis in SCID mice by inoculating small fragments from subcutaneous xenografts. Second, we compared the expression patterns of metastasis-related genes of the seminoma xenografts and of the TCam-2 cells which were established as a seminoma cell line from a primary testicular seminoma. Third, we immunohistochemically analyzed human germ cell tumors (25 seminomas, 17 nonseminomas) using monoclonal antibodies to CD34, VEGF, VEGF-C, Flt-4, MMP-2 and E-cadherin. Testicular seminoma xenografts grew in 32/32 (100%) of the inoculated mice, of which 15 (47%) developed macroscopic metastasis to the renal hilar lymph node. Circulating tumor cells were detectable by using a PCR assay for the human beta-globin gene in 25/32 (78%) mice, although metastatic foci were not histologically evident in the visceral organs, including lungs, liver, kidneys and spleen. This may reflect the lymphophilic characteristics of the seminoma cells used. Regarding mRNA expression of metastasis-related genes, an increased expression of MMP-2 and VEGF compared with that in the s.c. xenografts was demonstrated by RT-PCR assay in the testicular seminoma xenografts. In addition, uPAR, MMP-1, MMP-2, MT1-MMP and MT3-MMP showed a a stronger expression and PAI-2 a weaker expression in the seminoma xenografts than did TCam-2 cells. These results suggest a higher metastatic potential of the seminoma xenografts, especially testicular xenografts, as compared with TCam-2 cells. In the immunohistochemical study, a significant correlation was found between MMP-2 expression and lymph node metastasis, which is compatible with the results for the metastasis-related gene expression from the seminoma xenografts.