Neurological response to early removal of ovarian teratoma in anti-NMDAR encephalitis.

We report an 18-year-old woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, who developed psychiatric symptoms, progressive unresponsiveness, dyskinesias, hypoventilation, hypersalivation and seizures. Early removal of an ovarian teratoma followed by plasma exchange and corticosteroids resulted in a prompt neurological response and eventual full recovery. Serial analysis of antibodies to NR1/NR2B heteromers of the NMDAR showed an early decrease of serum titres, although the cerebrospinal fluid titres correlated better with clinical outcome. The patients' antibodies reacted with areas of the tumour that contained NMDAR-expressing tissue. Search for and removal of a teratoma should be promptly considered after the diagnosis of anti-NMDAR encephalitis.

Simultaneous colorectal and liver resections for synchronous colorectal metastases.

BACKGROUND: The surgical strategy for the treatment of colorectal cancer and synchronous hepatic metastases remains controversial. Many surgeons fear anastomotic leakage and intraperitoneal abscesses when performing a one-step procedure. They prefer a two-step procedure with a liver resection 2 to 3 months after resection of the colorectal primary lesion. SUBJECTS AND METHODS: We analysed medical records from April 1994 to April 2002 for a total of 42 patients with colorectal cancer and synchronous liver metastases who underwent simultaneous liver and colorectal resections with a primary anastomosis. Special attention was paid to data on surgical procedures, postoperative morbidity, and mortality. RESULTS: Forty-two patients, 24 men and 18 women, were studied. Median operating time was 6.50 hours (3.75-11.0 hours), and median blood loss was 1522 ml (range 288 to 5650 ml). Postoperative complications included pleural effusion in 4 patients, ileus in 3, anastomotic leakage in 2, intraperitoneal pelvic abscesses in 1, pneumonia in 1, bile leakage in 1, atelectasis in 1, and wound infection in 1. There was no perioperative mortality. CONCLUSION: Simultaneous colorectal resection with a primary anastomosis and hepatectomy for synchronous liver metastases is considered a safe procedure.

Cytokeratin polypeptide profile of Merkel cells in human fetal and adult skin: difference of expression of cytokeratins in epidermal and dermal Merkel cells.

The origin of Merkel cells is uncertain, although current evidence by immunohistochemical keratin marker studies favors an epidermal derivation. We studied the expression of keratin species in Merkel cells of human fetus and adult using 19 anti-keratin antibodies. Epidermal and dermal Merkel cells contained not only simple epithelium-type but also some stratified epithelium-type keratins. Interestingly, expression of some keratins was different between epidermal and dermal Merkel cells, for example, AN3 (50, 58 kD) and CKB1 (50 kD) recognized epidermal Merkel cells, but not dermal Merkel cells. These results suggest that surrounding keratinocytes influence the expression of cytokeratins in Merkel cells or that dermal Merkel cells undergo a modification from keratin-producing epidermal Merkel cells to a more neural cell type by the association with nerve endings in the upper dermis. On the other hand, certain cytokeratin polypeptides recognizable with Ks19.1 (40 kD), CK5 (45 kD), and CAM5.2 (52.5 kD) were expressed in both epidermal and dermal Merkel cells. The expression of simple epithelium-type keratins in Merkel cells remained even after the epidermal basal cells gradually lost their expression.

Novel combretastatin analogues effective against murine solid tumors: design and structure-activity relationships.

A series of combretastatin A-4 (CA-4) analogues were synthesized, and their cytotoxic effects against murine Colon 26 adenocarcinoma and inhibitory activity on tubulin polymerization were evaluated. Since CA-4 has limited aqueous solubility, the target compounds were designed to improve solubility by introduction of a nitrogen-containing group. Among the compounds synthesized, those with an amino moiety in place of the phenolic OH of CA-4 showed potent antitubulin activity and cytotoxicity against murine Colon 26 adenocarcinoma in vitro. Some of the compounds which were potent in vitro were evaluated in the murine tumor model Colon 26 in vivo. Among these, 13bHCl, 21aHCl, and 21bHCl showed significant antitumor activity in the animal model, while CA-4 was ineffective. 13bHCl and 21aHCl were further evaluated in two murine tumor models (Colon 38 and 3LL) and human xenografts HCT-15. These compounds showed potent antitumor activity comparable or superior to that of CDDP. The structure-activity relationships of this series of compounds are also discussed.

Biological significance of dermal Merkel cells in development of cutaneous nerves in human fetal skin.

We detected epidermal Merkel cells in 12-week fetuses with monoclonal antibodies (MAb) against simple epithelium keratin and epithelial membrane antigen. In 15-week fetuses these Merkel cells began to descend into the dermis and expressed nerve growth factor receptors (NGF-R). At approximately the same time, cutaneous nerves, as detected with an MAb against neurofilaments, extended from the subcutaneous trunk and branched to form the subepidermal nerve plexus. The expression of NGF-R on dermal Merkel cells preceded their connection with immunoreactive small nerves. Initially, most of these fine nerve endings were directed towards dermal Merkel cells. In 23-week fetuses the subepidermal nerve plexus was well developed and immunoreactive dermal Merkel cells began to disappear. At all stage of fetal development the epidermal Merkel cells did not strongly express NGF-R. We postulate that dermal Merkel cells play an inductive and a promotional role in development of the cutaneous nerve plexus in the upper dermis.

Different growth properties in response to epidermal growth factor and interleukin-6 of primary keratinocytes derived from normal and psoriatic lesional skin.

Epidermal growth factor (EGF) family members and its receptor (EGFR) are thought to have an important role in the proliferation of epidermal keratinocytes. In this report, we investigated the EGF/EGFR system in primary keratinocytes derived from normal and psoriatic lesional skin. EGF elicited the growth of both normal human keratinocytes (NHKs) and psoriatic lesional keratinocytes (PLKs). Interleukin-6 (IL-6) potentiated the EGF-dependent growth of NHKs, but has no observable effect on PLKs, while IL-6 itself showed no growth-stimulating activities in both cell types. Immunodetection and in situ hybridization analyses revealed that IL-6 induces EGFR expression in NHKs in a time- and dose-dependent manner. This EGFR expression decreased reversibly to an undetectable level when IL-6-treated NHKs were re-cultured in IL-6-free conditions. On the other hand, PLKs expressed high levels of EGFR even when unstimulated and the expression level was not affected by IL-6 stimulation. These results suggest that the EGF/EGFR system is involved in the growth of NHKs and PLKs and that IL-6 potentiates NHK growth partly through the induction of EGFR. The different EGFR regulatory system may contribute to the pathogenesis of psoriasis.

Secretory component (polymeric immunoglobulin receptor) expression on human keratinocytes by stimulation with interferon-gamma and differences in response.

Secretory IgA (sIgA) is a major protective factor in the mucosal immune system because of its great ability to form complexes with bacteria. Secretory component (SC) is an 80-kDa glycoprotein, a component of sIgA, which functions as a polymeric immunoglobulin receptor for IgA and aids the secretion of sIgA from the epithelial surface. We studied SC production by keratinocytes which were involved in the inflammatory process using interferon-gamma (IFN-gamma) as one of the major inflammatory promoters produced by helper T cells. Using two human squamous cell carcinoma cell lines (HSCs) and normal human keratinocytes (NHKs), results from flow cytometric analysis, enzyme-linked immunosorbent assay (ELISA), and Northern blotting revealed that HSCs produced SC when stimulated with IFN-gamma, although their responses differed; one line exhibited enhanced SC production whereas the production in the other line was suppressed. NHKs also exhibited SC expression on the cell surface by means of immunocytochemical analysis, flow cytometry and ELISA, however the responses were also different in each strain. Although the reason for the diversity of SC expression on keratinocytes is not clear, these differences may influence epidermal sIgA secretion level.

Molecular cloning and developmental expression patterns of the MyoD and MEF2 families of muscle transcription factors in the carp.

cDNA clones encoding the myogenic regulatory factors (MRFs) myogenin, MyoD and myf-5 were isolated by reverse-transcription polymerase chain reaction from larvae and embryos of the common carp (Cyprinus carpio L.). Myocyte-specific enhancer factor 2 (MEF2) cDNAs were identified from a cDNA library from adult carp. Northern blot analysis showed that MyoD, myf-5 and MEF2C transcripts were present in three-somite embryos, whereas myogenin and MEF2A transcripts were not detected until the 15-somite stage. Intense signals of myogenin and MyoD transcripts were observed even in 1-month-old juveniles. Levels of MyoD, myogenin and MEF2A transcripts declined between 1 and 7 months after hatching, and myf-5 gave only a weak signal in the oldest fish. In contrast, levels of MEF2C transcripts were considerably higher in 7-month-old juveniles than in 1-month-old larvae. mRNAs encoding carp myosin heavy chain and -actin were first detected at approximately the time of the first heartbeat, and levels were maximal in juveniles 1 month post-hatching. The relatively high levels of MRF mRNA in juvenile fish probably reflect the recruitment of new muscle fibres from the satellite cell population. It was concluded that the relative importance of the different members of the MyoD and MEF2 families of transcription factors for muscle differentiation changes during ontogeny in the carp.

Secretory component (polymeric immunoglobulin receptor) as an intrinsic inhibitor of biological functions of interferon gamma in keratinocytes.

Secretory component (SC) acts as a transmembrane polymeric immunoglobulin receptor of epithelial cells and is known to bind to polymeric IgA and to contribute to the secretion of secretory IgA (sIgA). We describe a new biological function for free SC (FSC) by which the expression of intercellular adhesion molecule-1 (ICAM-1) and HLA-DR induced by interferon gamma (IFN gamma) is inhibited in human keratinocytes. This activity coincided with suppression of adenosine cyclic 3,5-monophosphate (cyclic AMP) production in keratinocytes. Keratinocytes produced SC after stimulation with IFN gamma and this production was suppressed by the addition of H-7 or propranolol. The addition of propranolol resulted in prolongation of ICAM-1 expression on keratinocytes induced by IFN gamma. These results suggest that endogenously produced SC, as well as exogenously added FSC, acts as an inhibitor of IFN gamma. Therefore, our results suggest that SC plays an antiinflammatory role in the pathogenesis of inflammatory skin diseases via inhibition in keratinocytes of IFN gamma induced expression of ICAM-1 and HLA-DR.

Prostaglandin I1 analogues, SM-10902 and SM-10906, affect human keratinocytes and fibroblasts in vitro in a manner similar to PGE1: therapeutic potential for wound healing.

The newly synthesized prostaglandin (PG) I1 analogues, SM-10902 and SM-10906, were compared with PGE1 in terms of their biological effects on cultured normal human keratinocytes (NHKs) and human dermal fibroblasts (HDFs) in order to evaluate their therapeutic potential for cutaneous wound healing. The PGI1 analogues had a direct effect on cell proliferation of HDFs as did PGE1, but inhibited cell growth of NHKs in contrast to the stimulatory effect observed with PGE1. In contrast to NHKs stimulated with PGI1 analogues, which exhibited low levels of adenosine 3,5-cyclic monophosphate (cAMP). HDFs stimulated with these analogues responded in a dose-dependent manner with extremely high levels of cAMP. Conditioned media (CM) derived from media in which HDFs had been incubated with both the PGI1 analogues promoted NHK proliferation. HDF production of interleukin (IL)-6 increased in response to the PGI1 analogues. Since IL-6 was shown to promote cell growth of NHKs, enhancement of NHK proliferation by CM was thought to be due to IL-6 derived from HDFs stimulated with the PGI1 analogues.

Regulatory effects of 1alpha,25-dihydroxyvitamin D3 on inflammatory responses in psoriasis.

Topical application of 1alpha,25-dihydroxyvitamin D3 (VD3) is thought to be beneficial in psoriasis because of its action in regulating keratinocyte proliferation and inflammation mediated by various cytokines. We assessed the effect of VD3 on the production levels of interferon (IFN)-alpha, interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha in mitogen-stimulated peripheral blood mononuclear cells (PBMC) of psoriatic patients. The results demonstrated that VD3 significantly inhibited IFN- , IL-6, and IL-8 levels produced by concanavalin A (Con A)-stimulated PBMC of psoriatic patients in a dose-dependent manner, and reduced mRNA expression for IFN- and IL-8. These findings suggest that in addition to the direct anti-proliferation effect on keratinocytes, VD3 may down-regulate the inflammatory cytokine production by infiltrating cells in psoriatic lesions.

Lagunamycin, a novel 5-lipoxygenase inhibitor. I. Taxonomy, fermentation, physico-chemical properties and biological characteristics.

Lagunamycin, a novel 5-lipoxygenase inhibitor, was isolated from the culture broth of Streptomyces sp. AA0310. This compound showed potent rat 5-lipoxygenase inhibitory activity (IC50 6.08 microM) without lipid peroxidation.

Epocarbazolins A and B, novel 5-lipoxygenase inhibitors. Taxonomy, fermentation, isolation, structures and biological activities.

New 5-lipoxygenase inhibitors, designated epocarbazolins A and B, were isolated from the culture broth of Streptomyces anulatus T688-8. These compounds showed potent rat 5-lipoxygenase inhibitory activity with weak antibacterial activity. Structural studies revealed that epocarbazolins are new carbazole antibiotics having a novel substitution pattern and an epoxide in the side chain.

Reconstruction of defects involving the upper one-third of the auricle.

We describe here a reconstructive technique for the repair of defects involving the upper one-third of the auricle using a combination of several flaps. For a defect of the preauricular surface only, a chondrocutaneous flap from the concha and a postauricular subcutaneous pedicle flap were used. For a full-thickness defect, the reconstruction was made by using the chondrocutaneous flap, the postauricular subcutaneous pedicle flap, and a postauricular skin flap. The final skin defect was collected in the postauricular region and was directly sutured or covered by skin grafting. Seven patients were treated by this procedure. Although the tip of the postauricular skin flap fell into partial necrosis in one patient, all of the other flaps were well healed without vascular stasis. All of the reconstructed auricles had good three-dimensional forms with satisfactory color and texture to match. There was neither constriction of the ear nor deformation owing to scar contracture.

A simple technique for reconstruction of the umbilicus, using two twisted flaps.

A successful umbilical reconstruction is described, using two twisted flaps with one pedicle. This technique is easy and simultaneously revises the scar of the abdominal wall. With this procedure, the umbilicus has a natural appearance with sufficient depression and normal-appearing wrinkles.

Functional reconstruction using a depressor anguli oris musculocutaneous flap for large lower lip defects, especially for elderly patients.

Described here is a new technique to reconstruct large lower lip defects using one or two musculocutaneous island flaps, which includes an innervated depressor anguli oris muscle and has a facial artery in its pedicle. Vermilion is simultaneously reconstructed using a mucosal transposition flap. Three patients who had a total lower lip defect and five patients who had a defect larger than one-half of the lower lip were treated by our procedure. All the flaps survived completely without any signs of vascular stasis. In six patients, sphincter function and sensation appeared within 3 months after surgery. In one patient who needed a total lower lip reconstruction, the depressor anguli oris muscle was atrophic and the motor nerve could not be found. This patient could not regain motion. One other patient complained of a sialorrhea accompanied by sensory loss; however, his sensation improved within 6 months after surgery. All of the reconstructed lower lips were large enough to enable the patient to wear dentures and were of a cosmetically acceptable appearance 1 year after surgery.

Stahl's ear caused by an abnormal intrinsic auricular muscle.

Stahl's ear in a 12-year-old girl was treated surgically. During the operation, we discovered that the transverse muscle had an abnormal course, and we concluded that this muscle had caused the deformity. Treatment was accomplished by cartilage incision and transposition of the muscle to its normal position. After 3 years of follow-up, the reconstructed ear has maintained a good appearance. The etiology of Stahl's ear is unknown. Although various techniques have been reported for the reconstruction of Stahl's ear, the course of the intrinsic auricular muscles have not been confirmed by surgeons during the operation. We think that this case provides insight into the etiology of Stahl's ear and provides guidance for a new surgical treatment.

Management of the hairline using a local flap in total reconstruction for microtia.

In cases of microtia with a low hairline, the manner in which hair is removed from the reconstructed auricle must be taken into consideration. This is one of the most common but difficult problems with reconstruction for microtia. The authors describe a new technique that uses a simple regional flap to resolve this problem. The hair-bearing skin in the estimated auricular region and its covering are removed using a local flap from the hairless mastoid region. This is done in the first stage of auricular reconstruction, the costal cartilage grafting is done in the second stage, and elevation of the auricle is done in the last stage. In 38 auricles of 36 patients who were treated from 1993 to 1995, eight auricles of eight patients were treated with this technique. In all cases, the hairless flap healed well, without vascular stasis or skin necrosis. In addition, no complications from using this technique occurred in the later stages of auricular reconstruction. With this technique, the skin of the flap provides a good texture and color match to the auricle. In addition, the skin of the flap has good elasticity for the cutaneous pocket for cartilage grafting. The harvested area of the flap can be hidden behind the reconstructed auricle. The authors initially wondered whether the marginal scar of the transposed flap's position in the auricle would be conspicuous. However, all of the scar became inconspicuous because it was positioned in the scaphoid fossa.

Reconstruction of congenital stenosis of external auditory canal with a postauricular chondrocutaneous flap.

We describe here a new surgical technique for treatment of congenital stenosis of the external auditory canal using a postauricular chondrocutaneous flap. Our technique prevents recurring stenosis by cartilage support and provides a sufficient extension of the canal. The chondrocutaneous flap is safely elevated, easily reaches the canal, and has ample blood supply. It is beneficial for its self-cleaning function that the remnant canal, which contains cerumen glands, is used as part of the reconstructed canal. Six patients with congenital stenosis of the external auditory canal were treated by our procedure. In these patients, three patients were treated by a postauricular approach and the others were treated by an endaural approach. All patients had very satisfactory results.

Computer controlled ESCA for nondestructive surface characterization utilizing a TV-type position sensitive detector.

A position sensitive detector system composed of a channel plate, a vidicon TV camera, and a computer is utilized for multichannel detection of ESCA spectra. It is demonstrated that the system achieves a marked improvement of measurement speed, S/N ratio, and sensitivity. The system also realized an improvement of spatial resolution while retaining energy resolution.