Adherence ability and serum resistance of different hospital clusters of Acinetobacter baumannii.

The role of mechanical ventilation and catheters in favouring Acinetobacter baumannii infections needs to be better understood. This study evaluated the adherence of 19 isolates of different hospital clusters of A. baumannii to abiotic surfaces and epithelial cells (HEp-2). Of the hydrophobic isolates, 80% adhered to polystyrene, indicating a close relationship between hydrophobicity and adherence. All isolates adhered to epithelial cells to different degrees, and 73·7% showed an aggregated pattern. Analysis of the serum resistance of catheter-tip isolates showed that all were resistant. These worrisome results showed that the high capacity of A. baumannii to adhere to surfaces and survive in human serum could hinder treatment and control of this pathogen.

Search for a Variation of the Fine Structure Constant around the Supermassive Black Hole in Our Galactic Center.

Searching for space-time variations of the constants of Nature is a promising way to search for new physics beyond general relativity and the standard model motivated by unification theories and models of dark matter and dark energy. We propose a new way to search for a variation of the fine-structure constant using measurements of late-type evolved giant stars from the S star cluster orbiting the supermassive black hole in our Galactic Center. A measurement of the difference between distinct absorption lines (with different sensitivity to the fine structure constant) from a star leads to a direct estimate of a variation of the fine structure constant between the star's location and Earth. Using spectroscopic measurements of five stars, we obtain a constraint on the relative variation of the fine structure constant below 10^{-5}. This is the first time a varying constant of nature is searched for around a black hole and in a high gravitational potential. This analysis shows new ways the monitoring of stars in the Galactic Center can be used to probe fundamental physics.

A rare synaptonemal complex protein 3 gene variant in unexplained female infertility.

Synaptonemal complex protein 3 (SYCP3) plays a critical role in homologous chromosome pairing and recombination in meiosis, and mice deficient in this gene show infertility in males and subfertility in females. The aim of our current study was to determine whether genetic alterations in the SYCP3 gene are associated with female infertility in humans. We examined sequence variations of the SYCP3 gene in genomic DNA from 88 Japanese women with unexplained infertility and 165 samples obtained from a fertile control group. Case-control study using seven tagging single nucleotide polymorphisms revealed no significant association between common SYCP3 variants and unexplained infertility. However, only infertile women were homozygous for the minor allele of a novel rare variant in the coding region, c.666A>G (222Q>Q). The minor allele frequency was significantly higher in the infertile cohort (P< 0.05). This variant is predicted to create a cryptic splice site, although the expression of a mini-gene harboring the variant in HeLa cells or mouse testis did not demonstrate any effects on gene splicing. Our current findings therefore suggest that the c.666A>G variant in the SYCP3 gene might possibly contribute to female infertility in humans, although larger studies are needed to assess the possible effects of SYCP3 gene variation on human female infertility.

Superconductivity in 5d transition metal Laves phase SrIr2.

We report here the superconducting properties of a Laves phase superconductor SrIr2, which has a cubic MgCu2 structure. SrIr2 is a type-II superconductor, with a T c of 5.9 K. The estimated superconducting parameters of lower critical field µ 0 H c1 and upper critical field µ 0 H c2, coherence length ξ(0), penetration depth λ(0) and Ginzburg-Landau (GL) parameter κ(0) are approximately µ 0 H c1 = 101 Oe, µ 0 H c2(0) = 5.9 T, ξ(0) = 7.47 nm, λ(0) = 237 nm, and κ(0) = 31.7, respectively. The specific-heat data indicate that SrIr2 is a strong-coupling superconductor because the value of ΔC/γT c is approximately 1.71, which is larger than the value of 1.43 that is expected from the BCS theory. The physical properties obtained in this study are explained well by theoretical calculations including spin-orbit coupling (SOC). This result indicates that the physical properties of SrIr2 are strongly affected by the presence of SOC.

Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders.

BACKGROUND: Mikulicz's disease (MD) has been considered as one manifestation of Sjögren's syndrome (SS). Recently, it has also been considered as an IgG(4)-related disorder. OBJECTIVE: To determine the differences between IgG(4)-related disorders including MD and SS. METHODS: A study was undertaken to investigate patients with MD and IgG(4)-related disorders registered in Japan and to set up provisional criteria for the new clinical entity IgG(4)-positive multiorgan lymphoproliferative syndrome (IgG(4)+MOLPS). The preliminary diagnostic criteria include raised serum levels of IgG(4) (>135 mg/dl) and infiltration of IgG(4)(+) plasma cells in the tissue (IgG(4)+/IgG+ plasma cells >50%) with fibrosis or sclerosis. The clinical features, laboratory data and pathologies of 64 patients with IgG(4)+MOLPS and 31 patients with typical SS were compared. RESULTS: The incidence of xerostomia, xerophthalmia and arthralgia, rheumatoid factor and antinuclear, antiSS-A/Ro and antiSS-B/La antibodies was significantly lower in patients with IgG(4)+MOLPS than in those with typical SS. Allergic rhinitis and autoimmune pancreatitis were significantly more frequent and total IgG, IgG(2), IgG(4) and IgE levels were significantly increased in IgG(4)+MOLPS. Histological specimens from patients with IgG(4)+MOLPS revealed marked IgG(4)+ plasma cell infiltration. Many patients with IgG(4)+MOLPS had lymphocytic follicle formation, but lymphoepithelial lesions were rare. Few IgG(4)+ cells were seen in the tissue of patients with typical SS. Thirty-eight patients with IgG(4)+MOLPS treated with glucocorticoids showed marked clinical improvement. CONCLUSION: Despite similarities in the involved organs, there are considerable clinical and pathological differences between IgG(4)+MOLPS and SS. Based on the clinical features and good response to glucocorticoids, we propose a new clinical entity: IgG(4)+MOLPS.

Effect of common driving sources to the feedback analysis of heart rate variability.

OBJECTIVES: This paper examines the operational characteristics of the multivariate autoregressive analysis applied to the simultaneous recordings of the instantaneous heart rate (IHR) and the change in systolic blood pressure (SBP). METHODS: The multivariate autoregressive model has been utilized to reveal the feedback characteristics between IHR and SBP. The model assumes the presence of independent set of driving forces to activate the system. However, it is likely that the driving forces may have correlation due to the presence of a common fluctuation source. This paper examines the effect of the presence of correlated components in the driving forces to the estimation accuracy of impulse responses characterizing the feedback properties. The two-dimensional autoregressive model driven by two correlated 1/f noises was chosen for the analysis of operational characteristics. The driving force was generated by a moving average system which simulates non-integer order integration. RESULTS: Computer simulation revealed that the mean square estimation errors of impulse responses sharply increase as relative power of common driving force exceeds 50%. However, the estimation accuracy and bias are found to be in permissible range in practice. CONCLUSIONS: These findings ensure the practical validity of utilizing multivariate autoregressive models for the feedback analysis between IHR and SBP where both signals have the common driving force.

Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG.

This study investigates the relation between the serological status of NMO (neuromyelitis optica)-IgG and the clinical and MRI features in Japanese patients with multiple sclerosis. Serum NMO-IgG was tested in 35 Japanese patients diagnosed with multiple sclerosis, including 19 with the optic-spinal form of multiple sclerosis (OSMS), three with the spinal form of multiple sclerosis (SMS), and 13 with the conventional form of multiple sclerosis (CMS), which affects the brain. NMO-IgG was detected in 14 patients, 12 with OSMS and 2 with CMS. In these patients, longitudinally extensive (> 3 vertebral segments) spinal cord lesions (93% v 57%) and permanent, complete blindness (no perception of light) in at least one eye (50% v 0%) were the noticeable features as compared with NMO-IgG-negative OSMS. The two patients having CMS with NMO-IgG had unusual brain lesions, but in other respects had features suggesting OSMS. NMO-IgG was detected in more than half the number of patients with OSMS and in some patients with CMS. This newly discovered serum autoantibody was markedly associated with longitudinally extensive spinal cord lesions and with complete blindness, suggesting severe optic-spinal disease.

Prediction of flood abnormalities for improved public safety using a modified adaptive neuro-fuzzy inference system.

It is widely accepted that an efficient flood alarm system may significantly improve public safety and mitigate economical damages caused by inundations. In this paper, a modified adaptive neuro-fuzzy system is proposed to modify the traditional neuro-fuzzy model. This new method employs a rule-correction based algorithm to replace the error back propagation algorithm that is employed by the traditional neuro-fuzzy method in backward pass calculation. The final value obtained during the backward pass calculation using the rule-correction algorithm is then considered as a mapping function of the learning mechanism of the modified neuro-fuzzy system. Effectiveness of the proposed identification technique is demonstrated through a simulation study on the flood series of the Citarum River in Indonesia. The first four-year data (1987 to 1990) was used for model training/calibration, while the other remaining data (1991 to 2002) was used for testing the model. The number of antecedent flows that should be included in the input variables was determined by two statistical methods, i.e. autocorrelation and partial autocorrelation between the variables. Performance accuracy of the model was evaluated in terms of two statistical indices, i.e. mean average percentage error and root mean square error. The algorithm was developed in a decision support system environment in order to enable users to process the data. The decision support system is found to be useful due to its interactive nature, flexibility in approach, and evolving graphical features, and can be adopted for any similar situation to predict the streamflow. The main data processing includes gauging station selection, input generation, lead-time selection/generation, and length of prediction. This program enables users to process the flood data, to train/test the model using various input options, and to visualize results. The program code consists of a set of files, which can be modified as well to match other purposes. This program may also serve as a tool for real-time flood monitoring and process control. The results indicate that the modified neuro-fuzzy model applied to the flood prediction seems to have reached encouraging results for the river basin under examination. The comparison of the modified neuro-fuzzy predictions with the observed data was satisfactory, where the error resulted from the testing period was varied between 2.632% and 5.560%. Thus, this program may also serve as a tool for real-time flood monitoring and process control.

Complement-dependent and -independent aquaporin 4-antibody-mediated cytotoxicity in human astrocytes: Pathogenetic implications in neuromyelitis optica.

BACKGROUND: Neuromyelitis optica (NMO) is an inflammatory disease caused by the aquaporin (AQP)-4-antibody. Pathological studies on NMO have revealed extensive astrocytic damage, as evidenced by the loss of AQP4 and glial fibrillary acidic protein (GFAP), specifically in perivascular regions with immunoglobulin and complement depositions, although other pathological patterns, such as a loss of AQP4 without astrocyte destruction and clasmatodendrosis, have also been observed. Previous studies have shown that complement-dependent antibody-mediated astrocyte lysis is likely a major pathomechanism in NMO. However, there are also data to suggest antibody-mediated astrocyte dysfunction in the absence of complement. Thus, the importance of complement inhibitory proteins in complement-dependent AQP4-antibody-mediated astrocyte lysis in NMO is unclear. In most of the previous studies, the complement and target cells (astrocytes or AQP4-transfected cells) were derived from different species; however, the complement inhibitory proteins that are expressed on the cell surface cannot protect themselves against complement-dependent cytolysis unless the complements and complement inhibitory proteins are from the same species. To resolve these issues, we studied human astrocytes in primary culture treated with AQP4-antibody in the presence or absence of human complement and examined the effect of complement inhibitory proteins using small interfering RNA (siRNA). METHODS: Purified IgG (10 mg/mL) was obtained from 5 patients with AQP4-antibody-positive NMO, 3 patients with multiple sclerosis (MS), and 3 healthy controls. Confluent human astrocytes transfected with Venus-M1-AQP4-cDNA were incubated with IgG (5% volume). After washing, we cultured the cells with human complements with or without heat inactivation. We observed time-lapse morphological and immunohistochemical changes using a fluorescence microscope. We also evaluated cytotoxicity using a propidium iodide (PI) kit and the lactate dehydrogenase (LDH) assay. RESULT: AQP4-antibody alone caused clustering and degradation followed by endocytosis of membraneous AQP4, thereby resulting in decreased cellular adherence and the shrinkage of astrocytic processes. However, these changes were partially reversed by the removal of IgG in culture. In contrast, following the application of AQP4-antibody and non-heated human complements, the cell bodies and nuclei started to swell. At 3 h, most of the astrocytes had lost mobility and adherence and were eventually destroyed or had swollen and were then destroyed. In addition, the remaining adherent cells were mostly PI-positive, indicating necrosis. Astrocyte lysis caused by rabbit complement occurred much faster than did cell lysis with human complement. However, the cell lysis was significantly enhanced by the transfection of astrocytes with siRNA against human CD55 and CD59, which are major complement inhibitory proteins on the astrocyte membrane. AQP4-antibody-negative IgG in MS or control did not induce such changes. CONCLUSION: Taken together, these findings suggest that both complement-dependent and complement-independent AQP4-antibody-mediated astrocytopathies may operate in NMO, potentially contributing to diverse pathological patterns. Our results also suggest that the effect of complement inhibitory proteins should be considered when evaluating AQP4-antibody-mediated cytotoxicity in AQP4-expressing cells.

Negative ion production and beam extraction processes in a large ion source (invited).

Recent research results on negative-ion-rich plasmas in a large negative ion source have been reviewed. Spatial density and flow distributions of negative hydrogen ions (H(-)) and positive hydrogen ions together with those of electrons are investigated with a 4-pin probe and a photodetachment (PD) signal of a Langmuir probe. The PD signal is converted to local H(-) density from signal calibration to a scanning cavity ring down PD measurement. Introduction of Cs changes the slope of plasma potential local distribution depending upon the plasma grid bias. A higher electron density H2 plasma locally shields the bias potential and behaves like a metallic free electron gas. On the other hand, the bias and extraction electric fields penetrate in a Cs-seeded electronegative plasma even when the electron density is similar. Electrons are transported by the penetrated electric fields from the driver region along and across the filter and electron deflection magnetic fields. Plasma ions exhibited a completely different response against the penetration of electric fields.

Effectiveness of an antioxidant in preventing restenosis after percutaneous transluminal coronary angioplasty: the Probucol Angioplasty Restenosis Trial.

OBJECTIVES: The Probucol Angioplasty Restenosis Trial was a prospective, randomized, controlled study that investigated the effectiveness of probucol therapy in reducing the rate of restenosis after percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Antioxidants have an inhibitory effect on smooth muscle cell growth in experiments in vitro and in vivo, which suggests a possible pharmacologic effect on restenosis after PTCA. METHODS: One hundred one patients were randomly assigned to receive 1,000 mg/day of probucol or control (no lipid-lowering) therapy 4 weeks before PTCA. After 4 weeks of premedication, both groups underwent PTCA. Probucol was continued until follow-up angiography 24 weeks after PTCA. Angiographic results were analyzed at a core laboratory by quantitative coronary angiography. RESULTS: Dilation was successful in 46 of 50 patients in the probucol group and 45 of 51 in the control group. At follow-up angiography 24 weeks after angioplasty, angiographic restenosis occurred in 9 (23%) of 40 patients in the probucol group and 22 (58%) of 38 in the control group (p = 0.001). Minimal lumen diameter was 1.49 +/- 0.75 mm (mean +/- SD) in the probucol group and 1.13 +/- 0.65 mm in the control group (p = 0.02). Percent diameter stenosis at follow-up angiography in the probucol group was significantly lower than that in the control group (43.9% vs. 56.4%, p = 0.009). The late loss was 0.37 +/- 0.69 mm in the probucol group and 0.60 +/- 0.62 mm in the control group (p = 0.13). The loss/gain ratio was 0.32 +/- 0.74 in the probucol group and 0.56 +/- 0.81 in the control group (p = 0.059). Net gain was greater in the probucol group than in the control group (0.77 +/- 0.70 vs. 0.48 +/- 0.59 mm, p = 0.053). CONCLUSIONS: Probucol administered beginning 4 weeks before PTCA appears to reduce restenosis rates.

Inversion of thermosensing property of the bacterial receptor Tar by mutations in the second transmembrane region.

The aspartate chemoreceptor Tar of Escherichia coli serves as a warm sensor that produces attractant and repellent signals upon increases and decreases in temperature, respectively. However, increased levels of methylation of the cytoplasmic domain of Tar resulting from aspartate binding convert Tar to a cold sensor with the opposite signaling behavior. Detailed analyses of the methylation sites, which are located in two separate alpha-helices (MH1 and MH2), have suggested that intra- and/or intersubunit interactions of MH1 and MH2 play a critical role in thermosensing. These interactions may be influenced by binding of aspartate, which could trigger some displacement of MH1 through the second transmembrane region (TM2). As an initial step toward understanding the role of TM2 in thermosensing, we have examined the thermosensing properties of 43 mutant Tar receptors with randomized TM2 sequences (residues 190-210). Among them, we identified one mutant receptor (Tar-I2) that functioned as a cold sensor in the absence of aspartate. This is the first example of attractant-independent inversion of thermosensing in Tar. Further analyses identified the minimal essential divergence from the wild-type Tar sequence (Q191V-W192R-Q193C) required for the inverted response. Thus, displacements of TM2 seem to influence the thermosensing function of Tar.

Kinetics of zinc status in children with IDDM.

OBJECTIVE: To ascertain zinc deficiency in patients with insulin-dependent diabetes mellitus (IDDM) and evaluate the relationship between zinc clearance and body height velocity. RESEARCH DESIGN AND METHODS: Six boys and 11 girls with IDDM and zincuria and glycosuria were studied. Study quality and specific descriptive information concerning relationship and outcome measurement were assessed. RESULTS: The values of total-body zinc clearance in IDDM patients were higher than in the control subjects (24.6 +/- 1.8 vs. 15.1 +/- 0.6 ml.kg-1.h-1, P less than 0.01). There was a negative correlation between body zinc clearance values and height velocity in IDDM patients. CONCLUSIONS: Patients with IDDM have a secondary zinc deficiency, and normal growth may be stunted.

Differential impacts of duration of untreated psychosis (DUP) on cognitive function in first-episode schizophrenia according to mode of onset.

BACKGROUND: The mode of onset and the course of schizophrenia illness exhibit substantial individual variations. Previous studies have pointed out that the mode of onset affects the duration of untreated psychosis (DUP) and clinical outcomes, such as cognitive and social functioning. This study attempted to clarify the association between the DUP and clinical features, taking the different modes of onset into consideration, in a prospective longitudinal study examining patients with first-episode schizophrenia. METHODS: This study was conducted in six areas of Japan. Patients with first-episode schizophrenia were followed for over 18 months. Cognitive function, psychopathology, and social functioning were assessed at baseline and at 6, 12, and 18-month follow-up points. RESULTS: We identified 168 patients and sufficient information was available to determine the DUP and the mode of onset for 156 patients (92.9%): 79 had an acute onset, and 77 had an insidious onset. The DUP was significantly associated with quality of life (QOL), social functioning, and cognitive function at most of the follow-up points in the insidious-onset group. The DUP and negative symptoms at baseline were significant predictors of cognitive function at the 18-month follow-up in the insidious-onset group. CONCLUSIONS: The present results further support the hypothesis that the DUP affects QOL, social functioning, and cognitive function over the course of illness, especially in patients with an insidious onset. Effective strategies for detecting and caring for individuals with insidious onset early during the course of schizophrenia will be essential for achieving a full patient recovery.

Sulfhydryl and disulfide stainings in amyloids of skin-limited and systemic amyloidoses.

Disulfide (S-S) bonds and sulfhydryl (-SH) groups in skin-limited and systemic amyloidoses in frozen and paraffin-embedded sections were examined with a thiol reagent, N-(7-dimethylamino-4-methyl-3-coumarinyl)-maleimide (DACM). In frozen sections, dermal amyloids of skin-limited amyloidoses contained a large number of S-S bonds but no -SH groups [macular amyloidosis (9 cases), lichen amyloidosis (4), and skin tumor-associated (seborrheic keratosis) amyloidosis (1)]. In contrast, amyloids of systemic amyloidoses contained no S-S bonds or -SH groups [primary and myeloma-associated amyloidoses (1 each)]. The identical results were obtained from paraffin-embedded sections in skin-limited amyloidoses [macular (31), biphasic (4), lichenoid (9) and skin tumor-associated Bowen's disease (3), seborrheic keratosis (2), solar keratosis (2), porokeratosis Mibelli (1), and basal cell epithelioma (1) amyloidoses], systemic amyloidoses [primary (3), myeloma-associated (2), and secondary (2) amyloidoses] and tumefactive amyloidoses of the tongue (2). Furthermore, amyloid-like deposits confirmed by various histochemical stainings were found in the epidermis in 27/67 cases of skin-limited amyloidoses in both frozen and paraffin sections. These intraepidermal amyloid-like deposits contained S-S bonds in all cases (27/27) and -SH groups in 10 of 27 cases. In contrast, an intraepidermal amyloid-like deposit was not observed in any systemic amyloidoses (0/9) or tumefactive amyloidoses of the tongue (2). These results showed that skin-limited amyloidoses could be differentiated from systemic amyloidoses by DACM methods (this appears to depend upon the differences of amino acid composition between skin-limited and systemic amyloidoses) and that paraffin-embedded sections were usable for DACM methods. Present study further suggests that amyloids ion skin-limited amyloidoses are, at least in part, derived from epidermal keratinocytes.

Differential staining of skin-limited amyloid and colloid bodies with immunofluorescence after pretreatments.

We examined whether immunoglobulin (Ig) and complement (C) components of amyloid and colloid bodies were inherent parts of these substances or were present due to nonspecific absorption only. In direct immunofluorescence (IF) studies without pretreatment, skin-limited and systemic amyloid and colloid bodies in all cases showed positive staining for Ig or C. When these sections were pretreated with 0.1 M glycine buffer (pH 7.2) or 0.05% Tween-20 solution, Ig and C in skin-limited amyloid deposits were negative or weakly positive. In contrast, positive fluorescence of colloid bodies and systemic amyloid masses was not influenced by pretreatment. Existence of amyloid masses before and after pretreatment were confirmed by Thioflavin-T and Dylon stains. In addition, pretreatment did not alter disulfide bonds by DACM staining or the reactivities of amyloid with monoclonal antikeratin antibody EKH4. These results suggest that skin-limited amyloid can be differentiated from systemic amyloid or colloid bodies by these methods. We can infer from the present studies that most of the Ig and C in skin-limited amyloid masses are a result of nonspecific absorption due to penetration of serum, which is different from Ig in systemic amyloid and colloid bodies in as much as in these conditions immunobinding is specific.

HLA-DR and melanoma-associated antigen (p97) expression during the cell cycle in human melanoma cell lines, and the effects of recombinant gamma-interferon: two-color flow cytometric analysis.

Using monoclonal antibodies, recombinant human gamma-interferon, and fluorescence-activated cell sorter, 2 human melanoma cell lines (KHm-1/4 and A101D) were examined quantitatively for HLA-DR and 97-kD melanoma-associated antigen (p97) expression throughout the cell cycle. Two-color flow cytometric analysis showed that the mean cell volume increased (KHm-1/4, 2.6 times; A101D, 3.6 times) during the progression of the cell cycle, and that fluorescence intensity of HLA-DR and p97 correlated well with cell volume, i.e., both antigens were maximally detected during the G2-M phase. The density of HLA-DR and p97 on the cell surface remained relatively constant throughout the cell cycle with the exception that cells in S phase showed a slightly lower density compared with those in G0/G1 and G2-M phases. gamma-Interferon treatment (500 IU/ml, 72 h) increased HLA-DR+ cells (KHm-1/4, 65% to 89%; A101D, 34% to 84%) and p97+ cells (KHm-1/4, 8% to 12%; A101D, 19% to 35%). Increased antigen densities were also relatively constant throughout the cell cycle as in nontreated cells. Cells treated with gamma-interferon tended to accumulate at G0/G1 phase (KHm-1/4, 21% to 37%; A101D, 17% to 53%), and had a reduced cell volume (0.82-0.95 times) throughout cell cycle. This study revealed that both melanoma cell lines showed heterogeneity in the expression of HLA-DR and p97, and that this heterogeneity was influenced, at least in part, by cell cycle and immunologic events such as gamma-interferon treatment.

Deposition of the membrane attack complex of complement in pemphigus vulgaris and pemphigus foliaceus skin.

The present study was performed to determine whether complement activation in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) results in the assembly of the terminal complement sequence or membrane attack complex (MAC) in skin lesions. Biopsy specimens of skin lesions from five patients with PV and three patients with PF contained C5, C7, C9, and the MAC related neoantigen (C5b-9 neoantigen) in intercellular substance areas (ICS), as well as IgG and the early complement components Clq, C4, and C3. The presence of these late complement components and the C5b-9 neoantigens in ICS sites of the skin lesions is indicative of complement activation by the pemphigus antibody, with subsequent assembly of the MAC. The binding of IgG and early complement components to ICS was observed in both non-lesional (normal appearing) skin and in skin lesions. However, no MAC could be detected in the normal appearing skin of our pemphigus patients. It was also noted that the MAC could be generated in vitro on cryostat sectioned normal human skin by pemphigus antibody in the presence of complement. Results of these studies suggest that complement activation may be related to membrane damage of epidermal cells in both PV and PF.

Pigment production in murine melanoma cells is regulated by tyrosinase, tyrosinase-related protein 1 (TRP1), DOPAchrome tautomerase (TRP2), and a melanogenic inhibitor.

Using antibodies that recognize either tyrosinase, tyrosinase-related protein-1 (TRP1), or tyrosinase-related protein-2 (TRP2, DOPAchrome tautomerase), the quantities of those melanogenic enzymes were analyzed in five melanoma cell lines that possess various degrees of melanin production. All cells except JB/MS-W increased melanin production four to 30 times after 4 d of melanocyte-stimulating hormone (MSH) treatment. Melanin production by JB/MS-W cells was always under background, with or without MSH treatment. There was a positive correlation between quantities and synthetic rates of those melanogenic enzymes and their melanin formation or DOPAchrome tautomerase activities. The activity of a heat-resistant melanogenic inhibitory factor was also analyzed. The results showed, surprisingly, that pigmented cells showed higher levels of melanogenic inhibitors activity. Tyrosinase activity was increased dramatically whereas the level of melanogenic inhibitor was remarkably decreased following MSH treatment. Interestingly, melanogenic inhibitor derived from JB/MS-W cells suppressed not only tyrosinase but also DOPAchrome tautomerase, another enzyme functional in melanin production. These results clearly suggest that melanin production is regulated by a subtle balance between the activities of these enzymes and other factors such as the melanogenic inhibitor.

Renal handling of phosphate can predict height velocity during growth hormone therapy for short children.

Renal tubular reabsorption of phosphate in response to GH administration was studied in 28 short Japanese children, aged 5-11 yr (height SD score, less than -2.0 SD). Three groups included a classical GH deficiency (group 1; n = 12), a partial GH deficiency (group 2; n = 7), and children with non-GH deficiency (group 3; n = 9), depending on the peak response of serum GH in four provocative tests. Serum phosphorus, alkaline phosphatase, insulin-like growth factor-I (IGF-I), osteocalcin, and ratio of the maximum tubular reabsorption rate for phosphorus to the glomerular filtration rate (Tmp/GFR) were all significantly lower in group 1 compared with findings in groups 2 and 3 (P less than 0.05, P less than 0.01, and P less than 0.001). After the administration of GH (0.1 U/kg.day) for 4 consecutive days, increments in serum phosphorus and Tmp/GFR were significantly higher in group 1 than in group 2 (P less than 0.01 and P less than 0.01) or group 3 (P less than 0.01 and P less than 0.01), whereas the increment in IGF-I was similar in all 3 groups, and the levels of serum alkaline phosphatase and osteocalcin remained unchanged in all 3 groups. The calculated ratio of the increment in Tmp/GFR to the increment in IGF-I (delta Tmp/GFR/delta IGF-I) was highest in group 1, intermediate in group 2, and lowest in group 3 (P less than 0.001). One year after the GH treatment (0.5 U/kg.week), height velocity was 7.9 +/- 2.2 cm/yr in group 1 and 5.9 +/- 1.2 cm/yr in group 2; no child in group 3 was treated. When the above calculated parameters, delta Tmp/GFR/delta IGF-I and increment in height velocity (difference between pre- and posttherapy values), were taken into account, there was a significant positive correlation (n = 19; r = 0.78; P less than 0.001). This parameter can be used for purposes of predicting the outcome after 1 yr of GH therapy.