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The dynamics of hobo elements of Drosophila melanogaster in Japan is studied with the goal of better understanding the invasion and evolution of transposons in natural populations. The findings suggest that the hobo element invaded Japanese populations in the mid-1950s, at about the same time as the P element invasion in Japan.

Human RSa cells are highly sensitive to apoptotic-like cell death by ultraviolet irradiation (UV) while UV[sup r]-1 cells are their variant with an increased resistance to UV. Three days after UV at 10 J/m², the viability of RSa cells was approximately 17% while that of UVr[sup r]-1 cells was 65%. This different survival might reflect apoptotic cell death since apoptosis-specific DNA ladder was more clearly observed in RSa cells than in UV[sup r]-1 cells after UV. Addition of ALLN/calpain inhibitor I to the culture medium after UV resulted in similar survival (14-18%) between RSa and UV[sup r]-1 cells. Immunoblot analysis showed down-regulation of protein kinase Cθ, Src, Bax and µ-calpain after UV was more prominent in UV[sup r]-1 than in RSa cells. Activated µ-calpain appeared within 1 h post-UV only in UV[sup r]-1 cells. The expression of calpastatin, a specific endogenous inhibitor of calpain, was higher in RSa than in UV[sup r]-1 cells. To further examine the role of calpain in UV-induced cell death, cDNA of human calpastatin was transfected into UV[sup r]-1 cells. The results showed that overexpression of calpastatin suppressed down-regulation of Src, µ-calpain and Bax. Concomitantly, colony survival after UV was reduced in calpastatin-transfected cells as compared to vector control cells. Our results suggest that activation of calpain might account for, at least in part, the lower susceptibility to UVinduced cell death in UV[sup r]-1 cells. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of MRI findings for differentiating between ovarian metastasis from stomach cancer (OMSC) and colorectal cancer (OMCC)., Methods: Twenty-six patients with histopathologically proven ovarian metastasis (n = 8 with 12 OMSCs and n = 18 with 25 OMCCs) were enrolled in the study. All patients had undergone pelvic MRI before surgery. We retrospectively reviewed MRI findings and compared them between the two pathologies. The black scrunchie sign was defined as a thick (> 5 mm) and lobulated hypointense rim (> 180°) with central hyperintense areas on T2-weighted images., Results: Predominantly solid lesions (100% vs. 20%, p < 0.01), black scrunchie sign (33% vs. 0%, p < 0.01), and flow void (67% vs. 20%, p < 0.01) were frequently observed in OMSCs than in OMCCs. The signal intensity ratio of solid components on T2-weighted images (3.30 ± 0.70 vs. 2.52 ± 0.77, p < 0.01) and gadolinium-enhanced T1-weighted images (2.21 ± 0.57 vs. 1.43 ± 0.32, p < 0.01) were significantly higher in OMSCs than in OMCCs. Furthermore, hyperintense areas within cystic components on T1-weighted images (71% vs. 18%, p < 0.01) and stained-glass appearance (44% vs. 0%, p < 0.01) were frequently observed in OMCCs than in OMSCs., Conclusion: The black scrunchie sign was only observed in OMSCs. OMSCs always exhibited predominantly solid lesions and had higher signal intensity of solid components on T2- and gadolinium-enhanced T1-weighted images. OMCCs usually presented as cystic lesions, usually accompanied by hyperintense areas within the cystic components on T1-weighted images., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest. Ethical approval The authors declare that they preserve ethical standards., (© 2024. The Author(s).)

Background: Fosravuconazole L-lysine ethanolate (F-RVCZ) is a prodrug of ravuconazole and a triazole antifungal drug used for the treatment of onychomycosis. It has been reported in previous studies that the kidney injury caused by F-RVCZ is 1% or less., Methods: Serum creatinine levels were compared, and glomerular filtration rate and urine protein were estimated before and after starting the administration of F-RVCZ, as well as after the end of the administration period. The cause of kidney injury was investigated using renal pathology, and risk factors were also investigated., Results: F-RVCZ was administered to 46 patients. Ten of these patients were excluded because three were maintenance dialysis patients and seven were not measured for serum creatinine. Remaining 36 patients were included in the analyses. Kidney injury occurred in 27.8% of patients treated with F-RVCZ; this condition persisted in 10% of patients after the end of the administration period. No changes were observed in the urinalysis after the administration of F-RVCZ. A kidney biopsy was performed in one patient, but no lesions were found that could be the cause of kidney injury. Patients who developed kidney injury were significantly more likely to be receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (odds ratio 18.9, 95% confidential interval: 1.69-210, p = 0.0169)., Conclusion: Kidney injury is caused by F-RVCZ more frequently than previously reported, but the mechanism remains unclear., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

A coronavirus disease 2019 (COVID-19) outbreak in a psychiatry hospital revealed specific challenges in its response such as difficulty in isolation, transfer, and identification of close contacts, suboptimal infection control practices, and shortage of personal protective equipment, which were overcome by support from the public health center and a neighboring university hospital., (© The Author(s) 2022.)

Steroid inhalation is the standard bronchial asthma therapy and it includes powdered metered doses, dry powder, and nebulizer suspension. However, particle sizes vary widely. The research goal was to demonstrate that different budesonide administration forms and devices have various deposition rates in the airway obstruction region. Here, we compared relative inhalation therapy efficacies and identified therapies that delivered the highest drug doses to the airway obstruction region. Weibel's anatomy data were used to identify the airway obstruction region in asthma. Based on European Standardization Committee data, we investigated the diameters of the drug particles being deposited there and evaluated the average particle size and distribution of the budesonide dosage forms and application devices. Drug dose depositions were measured by HPLC at each stage of a Cascade Impactor. Weibel's anatomy data indicated that the 1 st -4 th bronchial generations comprised the airway obstruction region and corresponded to the tracheobronchial area. According to the European Standardization, particles 2-6  µ m in diameter were readily deposited there. The proportions of particles in this size range were 33.0%, 32.0%, 59.0%, and 78.0% for Turbuhaler, Symbicort, mesh-type NE-U22 suspension, and jet-type NE-C28 suspension, respectively. We localized the airway obstruction regions of bronchial asthma and identified the optimal inhalation therapy particle size. An electric nebulizer was more efficacious for budesonide administration than dry powder delivery. The NE-C28 treatment deposited 2.36x more budesonide in the airway obstruction region than dry powder delivery systems., Competing Interests: The authors declare that they have no conflicts of interest and received no funding for this project. The cost of Cascade Impactor experimentation was covered by Omuron Health Care Corporation, Kyoto, Japan., (Copyright © 2019 Norihide Murayama et al.)

Objective: Eosinophilic inflammation is thought to play a role in childhood asthma. Thus, examination of nasal eosinophils, instead of sputum, may be useful for the diagnosis of not only eosinophil-positive rhinitis but also persistent asthma. Nasal eosinophil examination is a routine for the diagnosis of nasal eosinophil-positive rhinitis in patients with rhinorrhea symptoms. This retrospective study investigated whether testing for nasal discharge eosinophils is useful for diagnosing childhood allergic asthma and whether nasal discharge eosinophils are predictive of persistent asthma., Methods: Infants and young children ( n = 180) with at least 3 recurrent episodes of respiratory symptoms and bronchodilator inhalation improvements at intervals of ≥1 week were divided into the asthma group and the nonasthma group, and the presence or absence of nasal discharge eosinophils was examined by age. Correlations between nasal discharge eosinophils and other predictive factors for persistent asthma were also examined., Results: The evaluation of nasal discharge eosinophils in the asthma group showed a significantly higher positive rate in older age groups than in the 0-1-year-old age group ( p < 0.05-0.001). However, none of the asthma patient groups had any significant changes between the 0-1-year-old and older groups. This pattern was similar for other risk factors, showing correlations between nasal discharge eosinophils and other predictive factors., Conclusions: Testing for nasal discharge eosinophils with asthma symptoms increases with age. Nasal discharge eosinophils with asthma symptoms may be a predictive factor for persistent asthma. This trial is registered with UMIN Clinical Trials (registration number UMIN000030776).

Nasal eosinophil examination is routine for the diagnosis of nasal eosinophil-positive rhinitis in patients with rhinorrhea symptoms. This retrospective data investigated whether testing for nasal discharge eosinophils is useful for diagnosing childhood allergic asthma, and changes of positive rates by each age. Infants and young children ( n = 180) with at least 3 recurrent episodes at intervals of ≥ 1 week of respiratory symptoms and bronchodilator inhalation improvements, were divided into an asthma group and a non-asthma group, and the presence or absence of nasal discharge eosinophils was examined by age. Correlations between nasal discharge eosinophils and other predictive factors for persistent asthma were also examined. The evaluation of nasal discharge eosinophils in the asthma group showed a significantly high positive rate in older age groups than in the 0-1-year-old age group ( p < 0.05-0.001). However, none of the asthma patient groups had any significant changes between the 0-1-year-old group and older groups. This pattern was similar for other risk factors, showing correlations between nasal discharge eosinophils and other predictive factors.

People all over the world should work in each individual against global warming due to greenhouse gas that is made up of a majority of carbon dioxide. On the other hand chloro-fluoro-carbon (CFC) was used with pressured metered-dose inhaler steroid therapy, but CFC became banning the use because of ozone depleting substance. Hydrofluorocarbon (HFA134a, tetra-fluoro-methane) is used as alternative CFC until now. Less-famously hydro-fluoro-carbon (HFA134a) have 1300-fold (mole ratio) energy of heat-trapping relative to carbon dioxide. On an extremely localized story, we derived substantial gravity of carbon dioxide from sales total of pressured metered-dose inhaler (pMDI) steroid drugs for the year in Japan. The amount of total sales of inhaled corticosteroid drugs on annual 2006 year was 320 hundred-millions yen. 88 hundred-millions yen (27.4% for total ICS sales) was accounted for pressured metered-dose inhaler steroid. Now in Japan there are three kinds of pressured metered-dose inhaler steroid drugs which all use tetra-fluoro-methane (HFA134a). In fact total gravity of tetra-fluoro-methane (HFA134a) from pressured metered-dose inhaler steroid for annual 2006 year was 19.7 t and substantial gravity of carbon dioxide was 10.8 thousand ton. As total gravity of carbon dioxide production throughout the year in Japan was 13 hundred-million ton. Therefore substantial gravity of carbon dioxide by steroids pressured metered-dose inhaler was very small (0.001%) compared to total carbon dioxide production in Japan. Until today carbon-dioxide reducing make very slow progress, for that reason medical service worker unexceptionally should exert an effort for carbon-dioxide reduction if only slightly through the daily clinical examination.

Food-dependent exercise-induced anaphylaxis (FDEIAn) is an anaphylactic reaction induced by physical exercise after ingestion of certain meals. FDEIAn is not very frequent, but recent case reports associated with various meals indicate an upward trend. Here, we report the data of various food specific IgEs and the clinical course of an experience with a patient who exhibited a unique FDEIAn reaction. Various food specific IgEs including staple food were positive with high levels. We could not find out the cause food of FDEIAn. Therefore we started preventive drug treatment. Specifically, only the skin symptoms (urticaria) were prevented by administering anti-histamine (hydroxyzine) daily, and respiratory symptoms (wheezing and distress) were prevented by daily administration of a leukotriene receptor antagonist (montelukast).

Background: Ultrasonic, jet, and mesh nebulizers have all been used in the treatment for asthma. Mesh nebulizers reportedly offer the best inhalation efficiency., Methods: This study aimed to clarify the utility of the mesh nebulizer, compared to jet nebulizers, in the treatment of pediatric asthma patients. Participants included 88 children <6 years old who were receiving treatment for asthma at Murayama Pediatric Clinic. Heart rate, peripheral oxygen saturation in arterial blood, and Mitsui symptom scores were compared before and after treatment with a mesh nebulizer ( n = 43) or jet nebulizer ( n = 45) using a salbutamol inhalation solution (0.2 ml for children ≧ 2 years old, n = 51; 0.1 ml for children < 2 years old, n = 37)., Results: Other than required inhalation time, clinical findings did not differ between mesh and jet groups. In both groups, heart rate increased significantly in patients treated with 0.2 ml (1000 microg) of salbutamol., Conclusions and Clinical Relevance: The required inhalation time of the mesh nebulizer was superior to the jet nebulizer. Children ≧ 2 years with mild asthma attacks experienced a significantly increased heart rate in both groups. The dose of salbutamol (0.2 ml for ≧2 years) used for asthma attacks should be reconsidered in mild asthma.

Among inhaled asthma therapies, the present study aimed to identify factors for selecting the type of inhalation therapy for asthma. Three methods are used to deliver inhaled cromoglycate, and the airway deposition rate was evaluated using a cascade impactor with 3 dosage forms: dry powder (DP), pressurized metered dose inhaler (pMDI), and solution (jet- and mesh-types). The percentage of particles with diameters of 2-6  μ m was 17.0% for the capsule, 51.8% for pMDI, 49.0% for jet-type NE-C28, and 40.4% for mesh-type NE-U22. The amounts of drug deposited in the bronchi were based on the particle distribution of the various dosage forms: 3.4 mg for the capsule, 1.0 mg for pMDI, 9.8 mg for one solution (jet-type NE-C28), and 8.1 mg for the other solution (mesh-type NE-U22). Jet-type or mesh-type electric nebulizers delivered 2-3 times more of the drug than capsules, and, compared with pMDI, 8-9 times more of the drug was deposited in the bronchi/bronchioles. Electric nebulizers are considered the best method. This study suggests that the size of particles deposited at sites of obstruction is larger than previously reported, and no obstruction of small airways occurs (<2 mm).

Backgrounds: Podocytes are highly differentiated epithelial cells involved in glomerular filtration. This study determines the clinical and histological significance of podocyte detachment and excretion in urine in patients with chronic kidney diseases., Methods: Renal biopsy was performed in 59 patients (30 males, 29 females; mean age 48 ± 2 years), including 24 patients with immunoglobulin (Ig)A nephropathy, six each with focal segmental glomerulosclerosis, membranous nephropathy, and minimal change nephrotic syndrome, and 17 with other renal disorders. The number of glomerular podocytes and severity of morphological damage were evaluated in renal biopsy samples. Urinary podocytes were detected by anti-human podocalyxin antibody. The urinary IgG/albumin ratio and urinary peroxide products were assessed by gel electrophoresis and the 2',7'-dichlorodihydrofluorescein-diacetate method, respectively., Results: A decrease in glomerular podocytes was associated with age (r = -0.33; P < 0.05), glomerulosclerosis (r = -0.43; P < 0.01), tubulointerstitial lesions (r = -0.46; P < 0.01), and low estimated glomerular filtration rates (r = 0.32; P < 0.05). Increased urinary podocyte excretion correlated with proteinuria (r = 0.36; P < 0.01), and was observed more frequently in patients with active histological lesions. Podocyte loss correlated with lower selectivity of proteinuria in patients with minimal change nephrotic syndrome and focal segmental glomerulosclerosis (r = -0.90; P < 0.001). Moreover, urinary peroxide products increased in association with glomerulosclerosis (r = 0.39; P < 0.05)., Conclusions: Urinary podocyte excretion reflects ongoing glomerular injury in various kidney diseases, and podocyte loss correlated with glomerulosclerosis and impaired selectivity of proteinuria.

Crustacean cardioactive peptide (CCAP)-expressing neurons undergo programmed cell death (PCD) within 24 hours after adult eclosion. A subset of the doomed CCAP neurons in the ventral nerve cord also expressed the neuropeptide bursicon and thus are referred to as bursCCAP neurons. In this study, we undertook comprehensive genetic and transgenic analyses to dissect the PCD mechanisms of bursCCAP neurons. Expression of a versatile caspase inhibitor, p35, blocked PCD of bursCCAP neurons, suggesting caspase-dependent apoptosis. Further genetic analyses showed that Dronc/Dark and Drice are key caspases, but they are not sufficient to carry out the PCD fully. We did not find a role for other known caspases, Strica, Dredd, Damm, or Decay. Of interest, Dcp-1 is required not for the death of bursCCAP neurons per se but for the removal of neural projections. DIAP1 is an important survival factor that inhibits premature death of bursCCAP neurons. We found that grim functions as a principal death inducer, whereas other death genes, hid, reaper, and sickle, show no endogenous function. Taken together with other studies, our work supports the role of grim as a major death inducer particularly for the removal of obsolete larval neurons during CNS metamorphosis. Results from the ectopic expression of the mutant grim lacking either N-terminal IBM or internal GH3 domain indicated that both domains are necessary to induce CCAP cell death., (Copyright © 2013 Wiley Periodicals, Inc.)

Dysfunctional regulation of brain dopamine (DA) functions has been found in patients with drug addiction and various neurological disorders that frequently accompany disturbance in sleep behavior. In this study, the roles of the dopaminergic nervous system on the regulation of daily locomotor activity rhythm were investigated in Drosophila melanogaster. Reduced synaptic DA release by expressing tetanus toxin gradually attenuated peak activity levels by altering activity patterns, particularly under constant darkness. Besides, flies with a mutant dopamine transporter fumin (fmn), in which the synaptic DA levels were elevated, displayed increased activities in both daytime and nighttime, but did more so at nighttime, suggesting that DA function is involved in regulation of fruit fly's nocturnal locomotor activities. Furthermore, flies treated with bromocriptine, an agonist of Drosophila dopamine D2 receptor (dD2R), exhibited nocturnal locomotor hyperactivity in a dose-dependent manner and this effect was inhibited in dD2R knockdown flies. When mutant flies null for period (per), timeless (tim), dClock (dClk), or cycle (cyc) were treated with bromocriptine, only cycle-null flies (cyc(01)) did not show induced nocturnal hyperactivities, suggesting that cyc might play a role in bromocriptine-induced nocturnal hyperactivities. Elevation of experimental temperature also increased nocturnal activities at the expense of daytime activities. The heat-induced increase in nocturnal activities gradually returned to basal levels at continuously elevated temperature. Inhibition of DA synthesis did not suppress heat-induced early development of nocturnal hyperactivity but prevented gradual decrement of initially elevated nocturnal activities, suggesting that DA impinges on certain adaptive roles in response to changes in environmental temperature. These results overall suggest that controlling dopaminergic transmission is important for daily locomotor behavior and bromocriptine-induced nocturnal hyperactivity which is mediated through dD2R receptor and CYC functions. In parallel to these results, excessive activation of dopaminergic neurotransmission, the primary cause of schizophrenia, is associated with abnormally elevated nocturnal locomotor activities through D2-type receptor in Drosophila. The results suggest that fruit flies are an excellent model system to provide some answers to previously unexplainable observations regarding the compromised dopaminergic nervous system and the related therapeutic agents.

In Drosophila melanogaster, combinatorial activities of four death genes, head involution defective (hid), reaper (rpr), grim, and sickle (skl), have been known to play crucial roles in the developmentally regulated programmed cell death (PCD) of various tissues. However, different expression patterns of the death genes also suggest distinct functions played by each. During early metamorphosis, a great number of larval neurons unfit for adult life style are removed by PCD. Among them are eight pairs of corazonin-expressing larval peptidergic neurons in the ventral nerve cord (vCrz). To reveal death genes responsible for the PCD of vCrz neurons, we examined extant and recently available mutations as well as RNA interference that disrupt functions of single or multiple death genes. We found grim as a chief proapoptotic gene and skl and rpr as minor ones. The function of grim is also required for PCD of the mitotic sibling cells of the vCrz neuronal precursors (EW3-sib) during embryonic neurogenesis. An intergenic region between grim and rpr, which, it has been suggested, may enhance expression of three death genes in embryonic neuroblasts, appears to play a role for the vCrz PCD, but not for the EW3-sib cell death. The death of vCrz neurons and EW3-sib is triggered by ecdysone and the Notch signaling pathway, respectively, suggesting distinct regulatory mechanisms of grim expression in a cell- and developmental stage-specific manner.

To evaluate the significance of the renal resistive index (RI) as a noninvasive marker of renal histological damage and a prognostic indicator, we examined RI by Doppler ultrasonography in 202 chronic kidney disease (CKD) patients who underwent renal biopsy. RI increased as the CKD stage progressed and correlated with age, systolic blood pressure, estimated glomerular filtration rate (eGFR), and renal histological changes, including glomerulosclerosis, arteriolosclerosis, and tubulointerstitial damage. Prognostic evaluation with a median follow-up period of 38.5 months revealed that patients with RI ≥ 0.7 (high RI group, n = 39) had significantly poorer renal survival than those with RI < 0.65 (normal RI group, n = 120) and 0.65 ≤ RI < 0.7 (high-normal RI group, n = 43). The patients in the high-normal RI group showed good response to steroids. However, in the high RI group, steroid therapy did not significantly improve renal survival. Of the clinical indices studied, RI ≥ 0.7, hypertension, proteinuria, and low eGFR at diagnosis were independent risk factors for worsening renal dysfunction. In conclusion, RI in CKD patients was considered as a marker of renal function, histological damage, and renal prognosis, and a possible determinant of indication for steroids.

Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis is usually classified as a pauci-immune type. However, it sometimes shows immune complex deposition of unknown origin. We examined the glomerular localization of myeloperoxidase by double immunofluorescence and immunoelectron microscopy in cases of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis with membranous nephropathy-like immunoglobulin G deposition to investigate the immune complex antigens in these cases. Six (35%) of the biopsy samples from 17 cases with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis showed granular deposition of immunoglobulin G along the glomerular capillary walls. Light microscopy revealed necrotizing crescentic glomerulonephritis with segmental thickening of the glomerular basement membrane. Electron microscopy showed electron-dense deposits in intramembranous and mesangial areas. However, the size and distribution of the deposits were irregular and segmental in the examined cases, unlike typical global and subepithelial lesions of membranous nephropathy. Double immunofluorescence using Alexa Fluor 594-labeled anti-myeloperoxidase antibody and fluorescein isothiocyanate-labeled anti-immunoglobulin G antibody, as well as immunoelectron microscopy using anti-myeloperoxidase antibody labeled with 25-nm gold particles revealed partial colocalization of myeloperoxidase and immunoglobulin G within the glomerular basement membrane and mesangium. In some cases of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, myeloperoxidase may form immune complexes and develop membranous nephropathy-like lesions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A great number of obsolete larval neurons in the Drosophila central nervous system are eliminated by developmentally programmed cell death (PCD) during early metamorphosis. To elucidate the mechanisms of neuronal PCD occurring during this period, we undertook genetic dissection of seven currently known Drosophila caspases in the PCD of a group of interneurons (vCrz) that produce corazonin (Crz) neuropeptide in the ventral nerve cord. The molecular death program in the vCrz neurons initiates within 1 hour after pupariation, as demonstrated by the cytological signs of cell death and caspase activation. PCD was significantly suppressed in dronc-null mutants, but not in null mutants of either dredd or strica. A double mutation lacking both dronc and strica impaired PCD phenotype more severely than did a dronc mutation alone, but comparably to a triple dredd/strica/dronc mutation, indicating that dronc is a main initiator caspase, while strica plays a minor role that overlaps with dronc's. As for effector caspases, vCrz PCD requires both ice and dcp-1 functions, as they work cooperatively for a timely removal of the vCrz neurons. Interestingly, the activation of the Ice and Dcp-1 is not solely dependent on Dronc and Strica, implying an alternative pathway to activate the effectors. Two remaining effector caspase genes, decay and damm, found no apparent functions in the neuronal PCD, at least during early metamorphosis. Overall, our work revealed that vCrz PCD utilizes dronc, strica, dcp-1, and ice wherein the activation of Ice and Dcp-1 requires a novel pathway in addition to the initiator caspases.

Although the corazonin gene (Crz) has been molecularly characterized, little is known concerning the function of this neuropeptide in Drosophila melanogaster. To gain insight into Crz function in Drosophila, we have investigated the developmental regulation of Crz expression and the morphology of corazonergic neurons. From late embryo to larva, Crz expression is consistently detected in three neuronal groups: dorso-lateral Crz neurons (DL), dorso-medial Crz neurons (DM), and Crz neurons in the ventral nerve cord (vCrz). Both the vCrz and DM groups die via programmed cell death during metamorphosis, whereas the DL neurons persist to adulthood. In adults, Crz is expressed in a cluster of six to eight neurons per lobe in the pars lateralis (DLP), in numerous neuronal cells in the optic lobes, and in a novel group of four abdominal ganglionic neurons present only in males (ms-aCrz). The DLP group consists of two subsets of cells having different developmental origins: embryo and pupa. In the optic lobes, we have detected both Crz transcripts and Crz promoter activity, but no Crz-immunoreactive products, suggesting a post-transcriptional regulation of Crz mRNA. Projections of the ms-aCrz neurons terminate within the ventral nerve cord, implying a role as interneurons. Terminals of the DLP neurons are found in the retrocerebral complex that produces juvenile hormone and adipokinetic hormone. Significant reduction of trehalose levels in adults lacking DLP neurons suggests that DLP neurons are involved in the regulation of trehalose metabolism. Thus, the tissue-, stage-, and sex-specific expression of Crz and the association of Crz with the function of the retrocerebral complex suggest diverse roles for this neuropeptide in Drosophila.

The Fc receptor for IgA and IgM (Fcalpha/muR) is of particular interest because it can bind antibodies of both IgM and IgA isotypes and thus may play a pivotal role in systemic and mucosal immunity. Using IgM and IgA ligands and newly generated Fcalpha/muR specific monoclonal antibodies we have defined biochemical features and cellular distribution of the human Fcalpha/muR. Both recombinant and native forms of human Fcalpha/muR are expressed on the cell surface as remarkably stable homodimeric transmembrane glycoproteins that can bind specifically polymeric IgM or IgA. The only human B cells to express Fcalpha/muR, albeit at very low levels, are found in the pre-germinal center subpopulation defined by the IgD+/CD38+ phenotype. Hence the expression pattern differs from that of the mouse wherein Fcalpha/muR is expressed by both circulating and resident B cell populations. Significantly, the predominant cell type expressing the Fcalpha/muR in humans is the follicular dendritic cell of germinal centers. The Fcalpha/muR may thus function in antigen presentation and B cell selection in the germinal center response.

It is important to clarify the molecular mechanisms of physiological responses of the human body to changes in gravity. Previous reports demonstrated that gravity-changing stress increases the human urinary concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG). However, it has yet to be clarified whether repetitive parabolic flight modulates the urinary concentration of 8-OHdG after exposure to gravity-changing stress. In the present study, the effects of the number of previous experiences with parabolic flight on urinary excretion of 8-OHdG and concentration of serum ACTH were examined in 12 healthy volunteers.

Dipeptidyl carboxypeptidase (DCP) from the polychaete Neanthes virens, resembling mammalian angiotensin I converting enzyme (ACE), was studied to discover some of its molecular and inhibitory properties, as the first evidence of these in a marine invertebrate. Amino acid and carbohydrate contents were analyzed. The N-terminal amino acid sequence of N. virens DCP was (NH2)D-E-E-A-G-R-Q-W-L-A-E-Y-D-L-R-N-Q-T-V-L-. Peptide maps of N. virens DCP from lysyl endopeptidase digestion were different from rabbit p-ACE. The far-ultraviolet circular dichroic spectra of N. virens DCP indicated that the secondary structure of this enzyme seemed to be an alpha-helical structure and was similar to that of rabbit p-ACE, but the near-ultraviolet circular dichroic spectra of N. virens DCP indicated that the aromatic amino acid residue circumambience of this enzyme was different from rabbit p-ACE. The effects of several reagents for chemical modification of amino acids on the activity of N. virens DCP were tested. Arg, Tyr, Glu, and/or Asp, His, Trp, and Met caused loss of the activity. In addition, the IC50 and Ki values for a well-known ACE inhibitor, Val-Tyr, which was a competitive inhibitor of N. virens DCP, were 263 and 20 microM, respectively. These results suggested that N. virens DCP is different from mammalian ACE in the molecular and inhibitory properties, although the same substrate specificity was demonstrated in a previous paper.

UVr-1 UV-resistant cells were established from UV-sensitive human RSa cells. We looked for genes expressed differentially between UVr-1 and RSa cells using PCR-based mRNA differential display to elucidate the molecular mechanisms underlying UV resistance. The transcription levels of syndecan-1 mRNA were increased in UVr-1 cells compared with those of RSa cells. Syndecan-1 is a transmembrane heparan sulfate proteoglycan and associates with cell adhesion and the cytoskeleton. Flow cytometric analysis using anti-syndecan-1 monoclonal antibody revealed that syndecan-1 was more abundant in UVr-1 cells than in RSa cells. The MTT method revealed that UVr-1 cells treated with the antibody showed higher sensitivity to UV cell killing than mock-treated cells. Studies using antisense oligonucleotides for syndecan-1 showed that antisense-treated UVr-1 cells became sensitive to UV cell killing. Thus, syndecan-1 might be involved in UV resistance in UVr-1 cells., (Copyright 1998 Academic Press.)

Patient 1 was a 36-year-old male and diagnosed as APL in April 1989, and treated with BHAC-DMP and BHAC-AMP. In January 1990, a diagnosis of exudative otitis media was made, but intractable. In June, left facial paralysis appeared and cytodiagnosis of the discharge from the middle ear confirmed leukemic cells. Otitis media and facial paralysis improved after high dose Ara-C, but developed again 5 months later. The condition improved after high dose Ara-C and irradiation of the temporal bones. In September 1992, he died of recurrence but no aggravation in facial paralysis or otitis media. Patient 2 was a 24-year-old female and diagnosed as APL in July 1989, and treated with BHAC-DMP. In May 1990, exudative otitis media was appeared. In July, recurrence was observed but improved by high dose Ara-C. In October, otitis media was aggravated again, and cytodiagnosis confirmed leukemic cell infiltration. She was treated with high dose Ara-C and irradiation of the temporal bones, then achieved complete remission. Maintenance therapy was continued until August 1992, she has been alive. When exudative otitis media developed during the course of leukemia, cytodiagnosis of the discharge from the middle ear should be performed. High dose Ara-C and irradiation of the temporal bone were effective.

A 49-year old man was admitted in November 1989, because of anemia, abnormal shadowing on chest X ray and hyperproteinemia. Biclonal gammopathy (IgG kappa + IgA kappa) was shown in serum, and Bence Jones protein in urine. The bone marrow examination showed an increased number of abnormal plasma cells (15.7%) and no evidence of lymphoma, A diagnosis of multiple myeloma (MM) was made. In April 1990, while the patient was treated with the modified M2 regiman, swelling of the right cervical lymph node was observed. Lymph node biopsy revealed that he had non-Hodgkin's Lymphoma (:NHL, diffuse, mixed, B cell type). He was retreated with the CHOP regimen for both disease, but died of respiratory failure in October. 1991. To establish the clonal origin of this case of concominant MM and B-cell NHL, the immunoglobulin gene rearrangements in his lymph node and bone marrow were analyzed. Southern blot analysis with the JH probe and Ck probe showed one common band and one different band in the two samples. Our data suggest that two B-cell malignancies may have arisen from a single B-cell progenitor.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) stimulates the growth of myeloid leukemic cells and increases their susceptibility to cell-cycle specific agents. We treated a patient with acute myelogenous leukemia (AML) in a state of second resistant relapse, with high-dose chemoradiotherapy combined with rhGM-CSF (total body irradiation: TBI 3Gy x 4, on days -8 & -7; cytosine arabinoside: Ara-C 3g/m2, iv, q12h, on days -5-2; rhGM-CSF 250 micrograms/m2/day, cont.iv, on days -5-2) followed by autologous peripheral blood stem cell transplantation (PBSCT). In this case, rhGM-CSF enhanced the proliferation of leukemic cells in vitro. The test dose of rhGM-CSF (84 micrograms/m2 over 8 hours) also promoted leukemic cell proliferation in vivo, resulting in an increase in the percentage of leukemic cells in the peripheral blood and reappearance of chromosomal aberrations in the bone marrow. The toxicity of rhGM-CSF-combined conditioning regimen included fever and mild liver damage. The patient achieved a complete remission lasting for 2 months, then relapsed. The rhGM-CSF-combined conditioning regimen was tolerated by this patient, but further studies will be required to confirm not only its safety but also its effectiveness in the treatment of refractory AML.