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Notizen: Summary In young spontaneously hypertensive rats (SHR), dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) activities were examined in the brainstem nuclei. Activation of noradrenergic neurons in the locus coeruleus, A2 and spinal intermediolateral cell areas, resulting in enhanced sympathetic nervous activity in the periphery, initiates hypertension. Adrenergic neurons, unchanged in these and A1 cell areas of young SHR, are not involved in the development of hypertension in SHR.

Notizen: In this study the photolightening behavior of blond hair was investigated. The results demonstrated that visible (VIS) and ultraviolet (UV) light lighten blond hair through different mechanisms. VIS light was found to contribute much more to the lightening of blond hair than UV light, and acted directly, while UV light only lightened blond hair that had been washed following irradiation. VIS and UV light both, however, lightened to a similar degree isolated melanin granules and decomposed melanin granules that were exposed on a cross section of blond hair. These results indicate that melanin granules are equally sensitive to both forms of light while blond hair is most sensitive to VIS light. The results also indicate that hair tissues, excluding melanin granules, are damaged by UV light but not by VIS light. Based on these facts, the hypothetical lightening mechanism of UV light is assumed to be that UV light preferentially attacks and damages hair tissues rather than melanin granules. This occurs only after the hair is washed, as the washing process removes the melanin granules that effuse from loose hair fibers. In contrast, VIS light preferentially attacks and decomposes the melanin granules rather than other tissues, and also results in the lightening of blond hair but without the need for subsequent washing. We also found that while VIS light destroys the structure of isolated melanin granules, UV light does not act in a similar manner. Consequently, it is proven that VIS and UV light attack different sites of the melanin granule, even though the lightening rates from both light sources are similar.

Notizen: Non-alcoholic steatohepatitis is a distinct entity, characterized by fatty change, lobular inflammation and fibrosis of the liver. Some cases of non-alcoholic steatohepatitis progress to cirrhosis, but it is not easy to distinguish this disease from non-alcoholic fatty liver by non-invasive examinations. No proven therapy for non-alcoholic steatohepatitis exists. Transforming growth factor-β1 is implicated in the development of liver fibrosis, and is inhibited by α-tocopherol (vitamin E) in the liver. Therefore, in this study, the significance of the measurement of the level of plasma transforming growth factor-β1 and the effect of α-tocopherol on the clinical course of non-alcoholic steatohepatitis were investigated.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Twelve patients with non-alcoholic steatohepatitis and 10 patients with non-alcoholic fatty liver, with a diagnosis confirmed by liver biopsy, were studied. None of the patients had a history of alcohol abuse, habitual medicine or malignant or inflammatory diseases. All patients were negative for hepatitis B, C and G virus. Patients were given dietary instruction for 6 months, and then α-tocopherol (300 mg/day) was given for 1 year. Blood chemistries, measurement of plasma transforming growth factor-β1 level and liver biopsies were undertaken before and after the 1-year α-tocopherol treatment.〈section xml:id="abs1-3"〉〈title type="main"〉Results:The serum alanine transaminase level decreased in non-alcoholic fatty liver patients, but not in non-alcoholic steatohepatitis patients, after 6 months of dietary therapy. Although the serum alanine transaminase level in non-alcoholic steatohepatitis patients was reduced during the 1-year α-tocopherol treatment, α-tocopherol had no effect on the serum alanine transaminase level in non-alcoholic fatty liver patients. The histological findings, such as steatosis, inflammation and fibrosis, of the non-alcoholic steatohepatitis patients were improved after α-tocopherol treatment. The plasma transforming growth factor-β1 level in non-alcoholic steatohepatitis patients was significantly elevated compared with that in non-alcoholic fatty liver patients and healthy controls, and decreased, accompanied by an improvement in serum alanine transaminase level, with α-tocopherol treatment.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:lOur data suggest that the measurement of the level of plasma transforming growth factor-β1 represents a possible method of distinguishing between non-alcoholic steatohepatitis and non-alcoholic fatty liver. Long-term α-tocopherol treatment may be safe and effective for non-alcoholic steatohepatitis. A randomized, controlled, double-blind trial is needed to confirm the full potential of α-tocopherol in the management of non-alcoholic steatohepatitis.

Notizen: Summary Background Mutations of the patched (Ptc) gene, a developmental regulator implicated in the signalling pathway via sonic hedgehog (Shh) and smoothened (Smo), play an essential pathogenic role in the development of basal cell carcinomas (BCCs). We previously reported the upregulation of Shh signal transducers, including Ptc, Smo and hedgehog-interacting protein, in BCCs. In vertebrates, specific downstream effectors in the Shh signalling pathway include three zinc-finger transcription factors, Gli1, Gli2 and Gli3. Gli1 possesses only an activation domain, while Gli2 and Gli3 contain both activation and repression domains. It remains unclear which of these transcription factors are responsible for the development of BCCs. Objectives To examine the expression pattern of Gli2 mRNA by human BCCs in comparison with those by normal human skin and various skin tumours. Methods We performed quantitative reverse transcriptase–polymerase chain reaction analyses with a series of samples from BCCs, other skin tumours and normal skin. Results We found that Gli2 mRNA expression was enhanced in the BCCs we examined, whereas there was no significant increase in other skin tumours or normal skin. Of four spliced Gli2 isoforms designated Gli2α, β, γ and δ, the expression of Gli2β mRNA was increased the most in BCCs. Conclusions As Gli2β is an isoform spliced at the first splicing site containing a repression domain and consists of an intact activation domain, its overexpression may lead to the upregulation of the Shh signalling pathway, thereby inducing BCCs.

Notizen: Summary Background Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by eosinophilia and high serum IgE levels. The accumulated evidence suggests that various cytokines are involved in the lesional skin of patients with BP. Recently, thymus and activation-regulated chemokine (TARC/CCL17), a CC chemokine, was identified as a selective chemoattractant for CC chemokine receptor 4 (CCR4)-expressing cells. Objective In this study, we examined the involvement of TARC in patients with BP. Methods We determined the fluid and serum TARC levels in patients with BP by enzyme-linked immunosorbent assay and compared the serum TARC levels with the eosinophil numbers in peripheral blood. We also compared the serum TARC levels in five patients with BP before and after they were treated. Moreover, we examined TARC, CCR4 and CXC chemokine receptor 3 (CXCR3) expression in the lesional skin of patients with BP by immunohistochemical procedures. Furthermore, we measured CCR4 positivity in CD4+ CD45RO+ cells of peripheral blood mononuclear cells (PBMCs) in patients with BP and healthy control subjects. Results The fluid TARC levels in patients with BP were significantly higher than those in blisters from burn patients or suction blisters of healthy control subjects. The serum TARC levels in patients with BP were also significantly higher than those in pemphigus vulgaris (PV) patients and healthy control subjects, and decreased after the treatment. The serum TARC levels in patients with BP significantly correlated with the eosinophil numbers in peripheral blood (r = 0·72, P 〈 0·002). Immunohistochemistry showed a strong reactivity of TARC in the epidermal keratinocytes (KCs) of BP. Moreover, both CCR4 and CXCR3 were expressed on the dermal infiltrating CD4+ T cells mainly beneath the bullae of patients with BP. Fluorescence-activated cell sorting analysis showed a higher percentage of CCR4 positivity in CD4+ CD45RO+ cells of PBMCs in patients with BP than that in healthy control subjects, while there was no significant difference of CXCR3 positivity in CD4+ CD45RO+ cells of PBMCs between patients with BP and healthy control subjects. Conclusions These findings strongly suggest that TARC may be one of the important chemokines that are involved in the pathogenesis of BP.

Notizen: Ghrelin, a novel growth hormone (GH)-releasing peptide, was recently isolated from the rat stomach as an endogenous ligand to growth hormone secretagogue receptor (GHS-R). Ghrelin specifically stimulates the release of GH from the rat anterior pituitary gland, but the regulational effect of ghrelin on GH secretion has not yet been clarified. We used a perifusion system to examine the single effect and combined effects of ghrelin with growth hormone-releasing hormone (GHRH) and somatostatin on GH secretion from rat anterior pituitary cells. The increase in GH concentration due to ghrelin stimulation showed a transitory peak that was almost the same as that previously reported for GHS, but apparently distinct from that of GHRH. Ghrelin (10−10 M to 10−8 M) stimulated GH secretion from the rat anterior pituitary cells in a dose-dependent manner. Serial ghrelin stimulation of the dispersed cells at 1-h intervals decreased the GH response, but the response recovered with stimulation at 3-h intervals, indicating that ghrelin strongly desensitized cells. Costimulation with ghrelin and GHRH elicited neither a synergistic nor an additive GH response from the rat pituitary cells. Furthermore, pretreatment to anterior pituitary cells with somatostatin strongly abolished ghrelin- and/or GHRH-stimulated GH secretion. In this study, we demonstrated that ghrelin caused weaker GH secretion than that caused by GHRH, and we also showed that costimulation with GHRH had no additive or synergistic effect on GH secretion, suggesting that ghrelin indirectly affects coordinated GH release from pituitary gland, as found in vivo.

Notizen: Locomotion behaviour of the abalone, Nordotis discus (Reeve), N. gigantea (Gmelin) and Sulculus aquatilis (Reeve), was observed for 5- to 10-day periods during the early summer and autumn from 1997 to 1999. Before sunset, the animals were individually put beneath each shelter situated on the flat concrete floor of indoor and outdoor tanks. For tracing of the locomotion path, a luminous rod was fixed on the animal's shell. Except for non-appearance, the locomotion behaviour showed leaving or homing; these ratios against each total observation according to each species were 70.0% and 16.7% in N. discus, 47.1 and 23.5% in N. gigantea and 57.6 and 24.2% in S. aquatilis respectively. Irrespective of species, recurrences to the home were frequently recognized during the locomotion. For the homing behaviour, its critical distance was approximately 1 m from the home. Moonlight did not completely restrain the abalone appearance from the home, though the appearance frequency during the period around the full moon was lowered and in some cases the time of initial appearance was retarded.

Notizen: Some metabolic end-products in tissues and physiological parameters of haemolymph of the Japanese clam Ruditapes philippinarum (Adams & Reeve) were investigated under aerial exposure at 15 °C with low relative humidity (RH) (22%) or high RH (91%). Acclimated clams in water at 15 °C were used as a control and to supply the low or high RH experiment. The low RH experiment was conducted at air exposure for 50 h (LH50), and the high RH experiment for 50 h (HH50) and 100 h (HH100). Accumulation of succinate and alanine in the tissues proved that the clam shifted its metabolism to anaerobiosis. Lactate accumulation did not occur. Glucose concentrations in tissues increased slightly during exposure except for HH50. The total free amino acid contents (363–410 μmol g−1) were higher than those of glucose (530–804 μmol 100 g−1), suggesting that the free amino acids might play a more dominant role in the metabolism. Increase in the haemolymph pco2 did not influence the acid–base balance in the haemolymph during exposure at both humidity conditions. Increase in the haemolymph ammonia from 48.2 to 57.1 μmol 100 g−1 and to 131.0 μmol 100 g−1 at LH50 and HH100, respectively, suggested that ammonia might function as an important buffering factor during aerial exposure. Retention values of the haemolymph po2 even at the longest exposure time (16.30 mmHg at LH50 and 14.69 mmHg at HH100) indicated that the clams depend partially on some aerobic manner.