Long-term efficacy of tacrolimus ointment for recalcitrant facial erythema resistant to topical corticosteroids in adult patients with atopic dermatitis.
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Administration, Topical↗
Biomedical subjects
M Uehara
Publications and source records attributed to M Uehara.
Developmental study of the shortened spinal cord in the adult tiger puffer fish, Takifugu rubripes (Teleostei).
ABSTRACT The spinal cords of vertebrates are generally divided into the cord proper and the minute filum terminale. While the spinal cord extends the entire length of the vertebral canal in the adult tiger puffer, Takifugu rubripes, the cord proper is greatly reduced in length and almost all of the canal is occupied by the filum terminale, which is tape-like rather than thread-like. The dorsal and ventral roots of the spinal nerves extend, respectively, above and below the filum terminale; as a whole, these form a massive cauda equina. Supramedullary cells are found in the rostral half of the medulla oblongata caudal to the cerebellum. In 4-mm long tiger puffers, the spinal cord is cylindrical and supramedullary cells are found in the rostral half of the cord. In 7-mm puffers, the longitudinally arranged ventral roots appear ventrally in the middle portion of the spinal cord. In 15-mm puffers, the dorsal and ventral roots run longitudinally along the spinal cord and have noticeably increased in number. Supramedullary cells are located in the rostral 15% of the cord. In 21-mm puffers, the spinal cord in large part becomes dorsoventrally flattened. In 30-mm puffers, the spinal cord becomes much flatter, and supramedullary cells now are located mainly in the medulla oblongata. These observations indicate that formation of the shortened spinal cord proper is due to at least two developmental processes. First, the elongation of the spinal cord proper is remarkably less than that of the vertebral canal. Second, the bulk of the spinal cord proper is translocated to the cranial cavity, where it is transformed into part of the medulla oblongata.
Animals↗
Induction and inhibition of testicular germ cell apoptosis by fluoroacetate in rats.
Fluoroacetate (FA), an inhibitor of aconitase, is known to lower the intracellular level of adenosine triphosphate (ATP), which recently has been suggested to be a possible determinant of the form of cell death, apoptosis or necrosis. To investigate which form of germ cell death occurs in FA-induced testicular toxicity, adult Sprague Dawley rats were given a single oral dose of FA (0.5 or 1.0 mg/kg) and euthanized at 3, 6, 12, 24, 48, and 72 h thereafter. Germ cell degeneration was histologically first found in early round spermatids at stage I and in spermatogonia at stages II-IV of seminiferous tubules 6 and 12 h, respectively, after dosing. Degenerating spermatogonia exhibited characteristic features of apoptosis as demonstrated by both electron microscopy and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), whereas spermatids did not. At the 24 and 48 h time points, degenerating spermatids were continually present and subsequently formed multinucleated giant cells, while the number of degenerating spermatogonia and TUNEL-labeled spermatogonia was drastically and/or significantly decreased compared to those from the control group, indicating that spontaneous male germ cell apoptosis is inhibited. Coincident with these morphological changes, DNA laddering on gel electrophoresis was apparent only 12 h after dosing. The results demonstrate that FA induces either apoptosis or necrosis of male germ cells in the early stage after dosing and subsequently inhibits spontaneous apoptosis.
Aconitate Hydratase↗
Enhancement of the photodynamic antitumor effect by streptococcal preparation OK-432 in the mouse carcinoma.
Biological response modifier antitumor effects are enhanced by the activation of the host defense mechanisms. We have investigated the antitumor effect of photodynamic therapy (PDT) and/or local administration of a biological response modifier, the streptococcal preparation OK-432, on transplanted NR-S1 mouse squamous cell carcinoma. Hematoporphyrin oligomers (20 mg/kg body weight) were used to photosensitize PDT. A pulsed Nd:YAG dye laser, tuned at 630 nm, was used as the light source. The laser power was 15 mJ cm(-2) pulse(-1), and the irradiation time was 40 min. The photosensitizer was injected intraperitoneally 48 h before laser irradiation. Where used, OK-432 was injected into the tumor either 3 h prior to PDT or immediately afterwards. The antitumor effects were evaluated 48 h after each protocol by (a) estimating the area of tumor necrosis (%) in hematoxylin/eosin-stained specimens, and (b) bromodeoxyuridine immunohistochemistry. Furthermore, the tumor sizes were evaluated 3, 7 and 10 days after each protocol, and the survival time after each protocol was evaluated as well. The antitumor effect of PDT was enhanced by administration of OK-432 3 h before PDT, whereas the administration of OK-432 immediately after PDT did not potentiate a PDT antitumor effect. Treatment with OK-432 alone had little effect on tumors. Photodynamic therapy in combination with local administration of OK-432 3 h before PDT is considered to be a useful treatment modality.
Animals↗
Time-resolved fluoroimmunoassay of plasma daidzein and genistein.
We present a method for the determination of the phytoestrogens daidzein and genistein in plasma (serum). These weakly estrogenic isoflavones occur in soybeans and in smaller amounts in some other beans and plants. It has been suggested that they may afford protection against prostate and breast cancer. The method is based on time-resolved fluoroimmunoassay (TR-FIA) using a europium chelate as a label. After synthesis of 4'-O-carboxymethyl-daidzein and 4'-O-carboxymethyl-genistein the compounds are coupled to bovine serum albumin (BSA), then used as antigens to immunize rabbits. The tracers with the europium chelate are synthesized using the same 4'-O-derivative of the isoflavones. After enzymatic hydrolysis and ether extraction the immunoassay is carried out using the VICTOR 1420 multilabel counter (Wallac Oy, Turku, Finland). The antisera cross-reacted to some extent with some isoflavonoids but not with flavonoids. The cross-reactivity seems not to influence the results, which were highly specific for both compounds. The correlation coefficients between the TR-FIA methods and the reference method based on isotope dilution gas chromatography-mass spectrometry were high; r-values were about 0.95-0.99 depending on concentration. The intra-assay coefficients of variation (CV%) for daidzein and genistein at three different concentrations vary 3.2-4.5 and 3.2-4.1, respectively. The inter-assay CVs vary 5.0-6.3 and 4.5-5.3, respectively. The working ranges of the daidzein and genistein assays are 1.0-216 and 1.7-370 nmol/l, respectively. The plasma values (n = 80) of daidzein and genistein are very low in Finnish subjects (mean for daidzein, 3.8+/-6.8 and for genistein, 3.2+/-7.6 nmol/l; median value for daidzein 1.5 and for genistein 1.4 nmol/l).
Animals↗
The organization of the spinocerebellar tract neurons in the chicken.
The organization of spinocerebellar tract (SCT) neurons in the chicken was studied quantitatively using retrograde wheat germ agglutinin-horseradish peroxidase labelling. The chicken spinal cord was divided into five regions based on the distribution of SCT neurons: the cervical region (the spinal segments [SS], 1-12, which contained 32% of the total number of SCT neurons), the cervical enlargement (SS13-15, 13.4%), the thoracic region (SS16-20, 13%), the thoraco-lumbosacral region (SS21-26, 34.6%), and the posterior lumbosacral region (SS27-30, 7%). Clarke's column was found in two regions, a cervical one (SS12-16) and a lumbar one (SS21-28). The spinal border cells were less numerous and also present in two parts, a cervical one (SS10-15) and a caudal one (SS20-24). SCT neurons of the ventral part of the ventral horn were found in the cervical enlargement and SS16 (lamina VIII), and in the thoraco- and posterior lumbosacral regions (laminae VIII and IX). The ventral marginal nucleus consisted exclusively of SCT neurons but the major and minor marginal nuclei did not contain SCT neurons. In the cervical region most of SCT neurons were observed in the ventral horn, while the central cervical nucleus, which consists of SCT neurons in mammals, was not identified in the chicken.
Animals↗
Skin barrier function in patients with completely healed atopic dermatitis.
Although it has been well established that the dry skin often seen in patients with atopic dermatitis shows a deranged barrier function, there is no unanimity of opinion as to whether the barrier in normal-appearing skin of patients with the disease is deranged or not. Hence, it remains unclear whether individuals with atopic dermatitis constitution have an intrinsic derangement of skin barrier function or not. To settle this problem, in the present study we examined transepidermal water loss and stratum corneum water content in normal appearing skin of the upper back of 16 patients with completely healed atopic dermatitis who had been free from skin symptoms for 5 years or more, 30 patients with active atopic dermatitis, and 39 healthy subjects. The transepidermal water loss values and the stratum corneum water content values in normal-appearing skin of the completely healed patients were not different from the values in normal controls. These findings indicate that skin barrier function is not disturbed in patients with completely healed atopic dermatitis.
Adult↗
Rapid analysis of phytoestrogens in human urine by time-resolved fluoroimmunoassay.
A time-resolved fluoroimmunoassay (TR-FIA), with europium labeled phytoestrogens as tracers, was developed for the quantitative determination of enterolactone, genistein and daidzein in human urine. The aim was to create a method for the screening of large populations in order to assess the possible correlations between the urinary levels and the risk of Western diseases. After the synthesis of the 5'-carboxymethoxy derivative of enterolactone and 4'-O-carboxymethyl derivatives of daidzein and genistein, the respective compound was coupled to bovine serum albumin and then used as an antigen in the immunization of rabbits. The same derivatives of the phytoestrogen were used in preparing the europium tracers. After the enzymatic hydrolysis, the TR-FIA was carried out using the Victor 1420 multilabel counter. The method has sufficient sensitivity to measure the phytoestrogens at concentrations even below 5 nmol/l. The intra- and inter-assay coefficients of variation, at three different concentrations, varied from 1.9 to 5.3 and from 2.4 to 9.7, respectively. We measured urinary enterolactone, genistein and daidzein in 215 samples from Finnish healthy women and found that more than 50% of the values ranged between 1 and 7, <0.1 and 0.6 and below 0.6 micromol/24 h, respectively. The TR-FIA method including only a hydrolysis step gave higher values than those measured by gas chromatography-mass spectrometry (GC-MS). However, the assay results by the present method showed strong correlation with those obtained by GC-MS. It is concluded that the TR-FIA is suitable for population screening of urinary phytoestrogens.
4-Butyrolactone↗
Ultrastructural characteristics and lectin-binding properties of M cells in the follicle-associated epithelium of chicken caecal tonsils.
To clarify the nature of M cells, the detailed ultrastructural characteristics and lectin-binding properties of M cells were investigated in follicle-associated epithelium (FAE) of chicken caecal tonsils. M cells presented various outlines from columnar to dome shaped. Their polymorphism was dependent on the number of harboured intraepithelial migrating cells. The lighter and larger nuclei of M cells were situated at more apical levels in the epithelial lining compared with those of neighbouring microvillous epithelial cells. The microvilli, which were significantly shorter and thicker than those of adjacent microvillous epithelial cells, were sparsely distributed or completely absent on the apical surfaces of M cells. In general, the apical cytoplasm of M cells without microvilli protruded slightly into the intestinal lumen. Numerous small vesicles were often contained in the apical cytoplasm. The numerous small invaginations of the apical and lateral cell surfaces suggested active transportation of luminal substances. No canaliculi existed in the apical cytoplasm of M cells whereas they were often detected in the neighbouring microvillous epithelial cells. A noteworthy finding was the frequent detection of multivesicular bodies in the apical cytoplasm of M cells. These multivesicular bodies suggest some degradation of ingested luminal substances during transcytoplasmic transportation. WGA and 4 other lectins strongly reacted with all epithelial cells except for M cells, this negativity suggesting a means of detecting M cells in chicken caecal tonsils. Three lectins, DSL, ConA and Jacalin, reacted weakly with the glycocalyx on M cells. The positive reactivity might allow chicken M cells to be utilised for specific antigen delivery into the mucosal immune system in some parenteral vaccinations.
Animals↗
Comparative study of the lamina cribrosa and the pial septa in the vertebrate optic nerve and their relationship to the myelinated axons.
The optic nerve contains the connective tissues, i.e. the lamina cribrosa and pial septa. This report presents a histological comparison of the lamina cribrosa and pial septa in the five classes (mammals, birds, reptiles, amphibians and teleosts) of vertebrates. Furthermore, the distribution of myelinated fibers was observed from the optic nerve through the retina in the same animals. The lamina cribrosa is found in mammals except for mice, and in birds. Structural complexity of the lamina was different in animals but generally dependent of the optic nerve thickness. The pial septa were present in the optic nerve proper of the mammals except for the mice, in birds and in a part of teleosts. Fasciculation of the optic nerve by the pial septa tended to be more prominent as the optic nerve become thicker. The optic nerve consisted of largely myelinated fibers in vertebrates. The retina contained some myelinated fibers in submammals but was thoroughly devoid of myelinated fibers in mammals. The borderline between myelinated and unmyelinated portions in the optic nerve of different species did not related to the lamina cribrosa. Amphibians had exceptionally only a few myelinated fibers in the optic nerve and no myelinated fibers in the retina.
Amphibians↗
Increased extra domain-A containing fibronectin and hepatic dysfunction during septic response: an in vivo and in vitro study.
A massive inflammatory reaction resulting from systemic cytokine release is the common pathway underlying sepsis or multiple organ dysfunction. The role of extra domain sequence A-containing fibronectin (EDA+FN) formation during the septic response is not known. The present study investigates the role of EDA+FN during the septic response under in vitro and in vivo conditions. The direct effects of interleukin-1, interleukin-6, and tumor necrosis factor-alpha on EDA+FN production were evaluated in primary cultured human hepatocytes and fibroblasts. Serial plasma EDA+FN levels were measured using an enzyme-linked immunosorbent assay in 24 patients who developed postoperative sepsis following general abdominal surgery of which there were 17 survivors and 7 non-survivors. EDA+FN secretion was significantly increased in cultured hepatocytes but not fibroblasts at 24 and 48 h following exposure to IL-1 compared to controls. In the clinical setting plasma EDA+FN levels in non-survivors were significantly higher than in survivors. Moreover, the EDA+FN levels were correlated closely with liver function tests. EDA+FN levels may represent a specific marker of vascular injury or systemic inflammatory response syndrome that is associated with an adverse clinical outcome.
APACHE↗
High P diet induces acute secretion of parathyroidhormone without alteration of serum calcium levels in rats.
To find whether a high phosphorus (P) diet stimulate the secretion of PTH, a high-P diet was fed to rats and an increase in serum P levels has occurred. All rats were fed a control diet (0.5% calcium (Ca), 0.5% P) for 7 days, while they were being adapted, for 1 hour at 8:00 AM and again at 8:00 PM. Four groups were switched to the high-P diet (0.5% Ca, 1.5% P) at the time of their morning meal for 1 hour. The other 4 groups continued to receive the control diet. Blood samples were collected from the rats in the remaining group, which served as a pre-feeding control. Every 30 minutes after the start of feeding (30, 60, 90, 120 min), blood samples were collected from the rats in the groups fed the control and high-P diets. Serum P concentrations increased upon intake of the high P diet, within 30 minutes after the start of feeding. Serum PTH levels also increased upon intake of the high P diet, within 30 minutes after the start of feeding, and the levels were significantly higher in the high-P group than in the control group. However, no significant difference was observed in serum Ca levels between the two groups. From these results, our findings suggest that an increase in serum P concentration might be a trigger of PTH secretion without any changes of serum calcium levels.
Acute-Phase Reaction↗
Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake.
Biological effects of dietary isoflavones, such as daidzein and genistein are of interest in preventive medicine. We estimated the dietary intake of isoflavones from dietary records and compared the values with the plasma concentrations and urinary excretions in Japanese middle-aged women. The dietary intake of daidzein and genistein was 64.6 and 111.6 mumol /day/capita (16.4 and 30.1 mg/day/capita), respectively. The isoflavones intake was mostly attributable to tofu, natto and miso. The median of plasma daidzein and genistein concentration was 72.46 and 206.09 nmol/L, respectively. The median of urinary excretion was 20.54 mumol /day for daidzein, 10.79 for genistein, 15.74 for equol and 1.64 for O-desmethylangolensin (O-DMA). Equol and O-DMA were excreted by 50% and 84% of all participants, respectively. Equol metabolizers were significantly lower the plasma and urinary daidzein and urinary O-DMA. The dietary intake of daidzein and genistein after the adjustment for total energy intake was significantly correlated with the urinary excretion (r = 0.365 for daidzein and r = 0.346 for genistein) and plasma concentration (r = 0.335 for daidzein and r = 0.429 for genistein). The plasma concentration of isoflavones was also significantly correlated with the urinary excretion. We conclude that in epidemiological studies measurements of plasma concentration or urinary excretion of these isoflavones are useful biomarkers of dietary intake and important for studies on their relation to human health.
Adult↗
Phyto-oestrogen content of berries, and plasma concentrations and urinary excretion of enterolactone after a single strawberry-meal in human subjects.
Quantitative data on phyto-oestrogen, particularly lignan, content in edible plants are insufficient. We, therefore, measured isoflavonoids and lignans in nine edible berries using an isotope dilution gas chromatography-mass spectrometry method for foods and found substantial concentrations of the lignan secoisolariciresinol (1.39-37.18 mg/kg DM), low amounts of matairesinol (0-0.78 mg/kg DM) and no isoflavones. To determine pharmacokinetics and urinary excretion pattern of the mammalian lignan enterolactone derived from plant lignans, a study with human subjects was conducted. Five healthy women and two men consumed, after a 72 h period of a phyto-oestrogen-free regimen, a single strawberry-meal containing known amounts of plant lignans. Basal and post-meal blood and urine samples were collected at short intervals. The samples were analysed using time-resolved fluoroimmunoassay of enterolactone. The meal increased plasma concentration of enterolactone after 8-24 h and in urine in the 13-24 h and 25-36 h urine collections. High individual variability of the metabolic response was observed. Enterolactone excreted in the urine collected throughout the 48 h post-meal yielded on average 114% of the plant lignans consumed. It is concluded that berries containing relatively high concentrations of plant lignans contribute to plasma and urinary levels of mammalian enterolactone in human subjects.
Adult↗
Consumption of wholemeal rye bread increases serum concentrations and urinary excretion of enterolactone compared with consumption of white wheat bread in healthy Finnish men and women.
Rye is an important source of plant lignans in Finland. In the present crossover trial we wanted to study the effect of rye bread as part of the usual diet on serum and urine enterolactone (ENL) concentrations in healthy volunteers. Eighteen men aged 43 (sem 2.0) years and twenty-one women aged 43 (sem 1.6) years consumed wholemeal rye bread and white wheat bread in random order for 4 weeks. The bread periods were separated by a 4 week wash-out period. The breads provided at least 20% of the daily energy intake. The mean intakes of rye bread were 219 (sem 14.6) and 162 (sem 5.3) g/d and those of wheat bread were 200 (sem 9.6) and 153 (sem 5.8) g/d for men and women respectively. Blood samples were collected from all subjects and three 24 h urine samples were collected from ten men and twelve women at the end of both bread periods for the determination of serum concentration and urinary excretion of ENL. The mean serum ENL concentrations in both men and women at the beginning of baseline period and at the end of the rye-bread period remained constant and were significantly higher than those at the end of the wheat-bread period. Correspondingly, daily urinary ENL excretion increased significantly during the rye-bread period compared with the wheat-bread period and was 5- and 10-fold higher in men and women respectively in comparison with the amount of plant lignan precursors measured in the rye bread. These data indicate the presence of other precursors for ENL in rye which are not detected by the current method of measuring plant lignans in food. The possible role of fibre in enhancement of the formation of mammalian lignans from their plant precursors in the gut also remains to be determined.
4-Butyrolactone↗
Cell kinetics of mouse tumour subjected to photodynamic therapy--evaluation by proliferating cell nuclear antigen immunohistochemistry.
Tumour reaction and tumour cell kinetics in mouse NR-S1 carcinoma subjected to photodynamic therapy (PDT) were evaluated by percentage of necrotic area as well as by proliferating cell nuclear antigen (PCNA) immunohistochemistry, and an effective PDT fractionation interval was proposed. PDT was carried out in mouse NR-S1 carcinomas using a photosensitizer (haematoporphyrin oligomers: 20 mg kg body weight) and pulsed Nd:YAG dye laser. The percentages of tumour necrotic area and PCNA labelling indices (LIs) in the tumours were assessed at intervals of 0, 0.5, 5, 2.5, 6, 24, 48, and 72 h after PDT. It was demonstrated that maximum damage and repopulation of the tumour cells emerge at 24 and 48 h, respectively, following PDT, suggesting that subsequent light treatment should be performed within 24 h to enhance the therapeutic effect of PDT.
Animals↗
Dietary heme iron does not prevent postgastrectomy anemia but fructooligosaccharides improve bioavailability of heme iron in rats.
Gastrectomized rats exhibit iron deficiency anemia. We observed the effects of dietary heme-iron and short chain frucooligosaccharides (Sc-FOS) in relation to prevention of postgastrectomy anemia in rats. Twelve laparotomized (sham-operated) rats were fed iron-citrate (control) as iron source diet without or with Sc-FOS (75 g/kg of diet) and twenty four totally gastrectomized (Bilroth II) rats, were fed a iron-citrate (control) or heme-iron (heme) as iron source diet without or with Sc-FOS (75 g/kg of diet) for 4 weeks. All rats received an intramuscular injection of vitamin B-12 every two weeks. Tail blood was collected every other week for determination of hematocrit and hemoglobin concentration. At the end of the experiment, the rats were killed and whole blood was collected. The total gastrectomy induced the postgastrectomy anemia. Dietary Sc-FOS increase iron absorption and thereby prevented completely this anemia in gastrectomized rats fed the control diet but this effect of Sc-FOS in rats fed heme diet was not complete. Dietary heme iron could not prevent postgastrectomy anemia itself, but fructooligosaccharides improve bioavailability of not only non-heme iron such as iron-citrate, but also heme-iron in rats.
Anemia↗
Association between mast cell chymase genotype and atopic eczema: comparison between patients with atopic eczema alone and those with atopic eczema and atopic respiratory disease.
BACKGROUND: It has remained unclear whether genetic background of patients with atopic eczema (AE) alone is identical to that of patients with both AE and atopic respiratory disease. OBJECTIVE: We aimed to assess whether there is a genetic difference between these two groups of AE patients. METHOD: We determined the genotype with regard to an allelic polymorphism in the gene for mast cell chymase (MCC; a serine protease secreted from mast cells) in 169 AE patients. RESULTS: MCC genotype was significantly associated with pure AE patients who did not have a predisposition to atopic respiratory disease and whose serum IgE concentration was < 500 IU/mL. The distribution of MCC genotypes also differed significantly between the latter patients and those AE patients with bronchial asthma and a serum IgE concentration of > 2000 IU/mL. CONCLUSION: These results suggest that pure AE is associated with genetic variants of MCC, and that the genetic basis of pure AE differs from that of AE associated with atopic asthma.
Adolescent↗