Efficacy and safety of plasma exchange in interstitial lung diseases with anti-melanoma differentiation-associated 5 gene antibody positive clinically amyopathic dermatomyositis.

OBJECTIVE: Clinically amyopathic dermatomyositis (CADM) patients frequently develop refractory interstitial lung disease (ILD), with a poor prognosis. We aimed to verify the efficacy and safety of plasma exchange (PE) treatment for ILD in CADM. METHOD: A retrospective case-control study was conducted to compare clinical outcomes with and without PE treatment in CADM-ILD patients refractory to combination therapy of high-dose glucocorticoids, calcineurin inhibitors, and cyclophosphamide. Among 19 enrolled patients, 11 were further treated with PE. We compared survival rates and other clinical characteristics. PE consisted of either fresh-frozen plasma or albumin as a replacement solution. RESULTS: Basal clinical characteristics at diagnosis, including age, gender, serum ferritin, Krebs von den Lungen-6 (KL-6), C-reactive protein, and respiratory function tests, did not differ between the two groups. The survival rate for treatment with PE was higher than for treatment without PE (91% and 50%, respectively, p < 0.05). Among PE-treated patients, anti-melanoma differentiation-associated gene-5 (anti-MDA-5) antibody titre, ferritin, and KL-6 as serological activity markers were sustainably reduced only after initiating PE. Therapeutic intervention with PE reduced the frequency of exacerbation of ILD requiring methylprednisolone pulse therapy. The occurrence of bacterial, fungal, and cytomegalovirus infection did not differ between the groups with and without PE, and adverse events associated with PE resolved with appropriate intervention. CONCLUSION: Combination therapy with PE was associated with an improved survival rate, and may be effective for the management of refractory ILD in CADM patients. A personalized therapeutic strategy including PE could be introduced for fatal rapidly progressive ILD.

Angiotensin receptor blocker vs ACE inhibitor effects on HDL functionality in patients on maintenance hemodialysis.

BACKGROUND AND AIMS: Angiotensin receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACEI) reduce cardiovascular events in the general population. Maintenance hemodialysis (MHD) patients are at high cardiovascular risk but few studies have directly addressed the comparative efficacy of these drugs. MHD disrupts the normally atheroprotective actions of high density lipoprotein (HDL), therefore, we compared ACEI or ARB treatment on HDL functions in MHD. METHODS AND RESULTS: HDL was isolated at the starting point (pre) and 3-6 months later (post) in 30 MHD randomly assigned to placebo, ramipril or valsartan. Outcomes included cholesterol efflux, inflammatory cytokine response, effects on Toll-like receptors (TLR), superoxide production, methylarginine and serum amyloid A (SAA) levels. HDL from ARB- or ACEI-treated subjects was more effective in maintaining efflux than HDL of placebo. HDL from ARB- or ACEI-treated subjects but not placebo lessened cellular superoxide production. In contrast, neither ARB nor ACEI improved HDL anti-inflammatory effect. Indeed, HDL of ACEI-treated subjects potentiated the cytokine responses in association with activation of TLR but did not alter the HDL content of methylarginines or SAA. CONCLUSION: Both ACEI and ARB stabilized HDL cholesterol acceptor function and sustained cellular anti-oxidative effects but not anti-inflammatory effects, and ACEI-treatment instead amplified the HDL inflammatory response. The findings reveal possible utility of antagonizing angiotensin actions in MDH and suggest a possible mechanism for superiority of ARB vs ACEI in the setting of advanced kidney disease.

First demonstration of MC-EDFA-repeatered SDM transmission of 40 x 128-Gbit/s PDM-QPSK signals per core over 6,160-km 7-core MCF.

We demonstrate the first 7-core multicore erbium-doped fiber amplified (MC-EDFA) transmission of 40 x 128-Gbit/s PDM-QPSK signals over 6,160-km 7-core multicore fiber (MCF). The crosstalk (XT) from all of the other 6 cores of a MC-EDFA and a 55-km length MCF are about -46.5 dB and -45.6 dB at center core, respectively. The core-to-core rotation approach at every amplified span is used to average the XT of all cores. The averaged optical signal-to-noise ratio (OSNR) after 6,160-km transmission is 15.6 dB with 0.1 nm resolution bandwidth. The Q-factor of all 40 channels surpasses the threshold of the forward-error-correction of 6.4 dB with 1 dB margin after 6,160 km. The total net capacity is 28.8 Tbit/s per fiber and achieved capacity-distance product is 177 Pbit/s.km per fiber. We confirmed the feasibility of MC-EDFA repeatered systems for trans-oceanic transmission.

Efficacy of a "provisional incision" for longitudinal flap division after free-flap surgery.

Fix and flap surgery for severe open limb fractures is already a standard treatment. In cases where the fracture is complicated or accompanied by bone defects, secondary surgery is required for fracture sites covered with a myocutaneous flap after the soft tissue condition has stabilized. We applied the delayed procedure concept used for distant flaps and attempted to prevent postoperative myocutaneous flap necrosis by performing a provisional incision prior to the longitudinal incision of the flap. We report the course of five cases of the longitudinal division of the myocutaneous flap using "provisional incision" after free-flap surgery for severe open fracture and verify its usefulness. In this case series, five patients with severe open limb fractures treated from 2020 to 2021 who underwent longitudinal incision of the myocutaneous flap using provisional incision after free-flap surgery were included. The types of flaps used for soft tissue reconstruction in the acute phase, the reasons for the need for secondary surgery, the period from soft tissue reconstruction to additional surgery, and the healing status of soft tissue after secondary surgery were all investigated retrospectively. The types of flaps used for soft tissue reconstruction were latissimus dorsi myocutaneous flap in four cases and anterolateral thigh flap in one case. The breakdown of secondary surgery was osteosynthesis in one case, plate removal in one case, and bone cement removal and autologous bone grafting in three cases. The period from soft tissue reconstruction to secondary surgery ranged from 6 weeks to 4 months. In all cases, the wound healed without necrosis of the myocutaneous flap. For the treatment of severe open limb fractures, longitudinal division of the myocutaneous flap using "provisional incision" is a safer approach to the necessary secondary surgery and reduces the possibility of necrosis of the flap.

Bend-insensitive lasing characteristics of single-mode, large-mode-area ytterbium-doped photonic crystal fiber.

The bend-insensitive lasing characteristics of a newly designed ytterbium-doped photonic crystal fiber (YPCF) are evaluated numerically. The designed YPCF remains single-mode and possesses large-mode-area of 1400 microm(2) at 1064 nm wavelength with the beam quality factor (M(2)) of 1.15, suggesting a diffraction-limited and continuous-wave lasing operation. The doped-region size is optimized for maximum conversion efficiency and it is found through numerical simulations that the doped radius should be more than 21 microm. The "mode expansion", which is the self-expansion of the fundamental mode within the doped region with wavelength increments on bending the fiber, is the basic physical mechanism to give the bend-insensitive lasing performances of YPCF. It leads to an unusual variation of overlap factor when the wavelength is increased. A 41 cm long piece of YPCF demonstrates more than 83% of slope efficiency with 75% of conversion efficiency when pumped with a 975 nm laser source delivering an input power of 1 W.

Strategies for realizing photonic crystal fiber bandpass filters.

Numerical design strategies are presented to achieve efficient broad or narrow band-pass filters based on index-guiding, solid-core, and single-mode photonic crystal fibers (PCFs). The filtering characteristics have been verified through BPM solver. By scaling the pitch constant, the bandpass window can be shifted accordingly. The fiber design constitutes a fluorine-doped central core, enlarged air-holes surrounding the down-doped core, and small air-holes in the cladding. The proposed bandpass filter is based on controlling the leakage losses, so one can tune filter characteristics simply by changing its length. From numerical simulations we show that for large values of air-hole diameter in the first ring, the bandpass window is narrow, while for low doping concentration and small sized air-holes in the first ring, bandpass window is very broad. We also simulate how the hole-size and number of rings in the PCF cladding affects the device characteristics. We find that a 5-cm long PCF with down-doped core and eleven rings of air-holes can result in approximately 440 nm 3-dB bandwidth with more than 90% of transmission. The longer device has reduced transmission and smaller 3-dB bandwidth. Tolerance analysis has also been performed to check the impact of fiber tolerances on the performance of the PCF bandpass filter. It has been observed that the decrement in cladding hole-diameter by 1% reduces the transmission to 21% from its peak value of 93%, however +/-1% tolerance in the inner hole-diameter degrades the transmission to 75% from its peak.

Measurement of chromatic dispersion and Raman gain efficiency of a hole-assisted fiber: Influence of bend.

We have experimentally measured the Raman gain efficiency (RGE) and chromatic dispersion (CD) of a hole-assisted fiber (HAF). The RGE of a HAF was characterized using standard pump on/off technique while the CD of the fiber was measured using optical network analyzer. Theoretical simulations of the modal characteristics and the RGE of HAF were carried out using an accurate full-vectorial finite element method. Further, the bending effects on the CD and the RGE of a HAF with a smallest feasible bending radius are demonstrated. It was found that the CD increases while the RGE is decreased by bending HAF in a smallest bending radius of 5 mm. Numerical predictions from the theory are shown to be in good agreement with the experimental results.

Sugar chain of alpha-fetoprotein produced in human yolk sac tumor.

The carbohydrate moiety of alpha-fetoprotein purified from human yolk sac tumors grown in nude mice was quantitatively released from the polypeptide chain as oligosaccharides by hydrazinolysis. The oligosaccharides were separated into a neutral and two acidic oligosaccharides by paper electrophoresis. By sequential exoglycosidase digestion in combination with per-O-methylation study and periodate oxidation, their structures were determined to be: Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(GlcNAc beta 1 leads to 4) (Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAcOT, Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(GlcNAc beta 1 leads to 4) (Sia alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAcOT; and Sia alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(GlcNAc beta 1 leads to 4) (Sia alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4 GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAcOT, in which Gal is galactose, GlcNac is N-acetylglucosamine, Man is mannose, Fuc is fucose, Sia is sialic acid, and Subscript OT is the NaB3H4-reduced oligosaccharide.

Different karyotypic patterns in early and advanced stage neuroblastomas.

Of 23 untreated and 7 treated (relapsed) neuroblastomas, 14 (11 untreated, 3 treated) had modal chromosome numbers in the diploid (45 to 51), 9 (8 untreated, 1 treated) in the triploid (60 to 77), and 6 (3 untreated, 3 treated) in the hypotetraploid (81 to 88) range, and one (untreated) had hypertetraploidy (100). The near-or-pseudodiploid and hypotetraploid tumors were characterized by numerous structural abnormalities, most frequently of 1p, and frequent presence of double minutes or homogeneously staining regions. The near-triploid tumors were characterized by three almost complete haploid sets of chromosomes, and few structural abnormalities. N-myc amplification was found in five of the near-or-pseudodiploid or hypotetraploid tumors but in none of the near-triploid tumors. Most near-triploid tumors were found in infants at stage I or II, and the near-or-pseudodiploid or hypotetraploid tumors in children at stage II or IV mostly 1 year old or older. Among the untreated patients, all 8 with a near-triploid tumor were alive with no evidence of the disease, and the 11 with a near-or-pseudodiploid tumor had a median survival of only 376 days (P less than 0.05), 7 of the 11 being dead. Thus, the near-triploid patients had well recognized favorable prognostic factors and an excellent prognosis, and the near-or-pseudodiploid patients had unfavorable prognostic factors and a dismal prognosis. The hypotetraploid tumors seemed to have karyotypic and clinical features in common with the near-or-pseudodiploid tumors. We presume that the near-triploid tumors and the near-or-pseudodiploid or hypotepraploid tumors may constitute distinctly different subcategories within neuroblastomas.

Amplification of IMR-32 clones 8, G21, and N-myc in human neuroblastoma xenografts.

Amplification of clones 8, G21, and N-myc, which were derived from human neuroblastoma cell lines IMR-32 and NB-19, were studied in nine neuroblastoma xenografts. N-myc was amplified from 50- to 120-fold in eight of nine xenografts, clone 8 was amplified in five of the xenografts, and clone G21 was amplified in four of these five. Each of these clones was localized by in situ hybridization to homogeneously staining regions in metaphase spreads of xenograft chromosomes. In one xenograft a DNA rearrangement of clone 8 was observed, and only two of the sequences detected by G21 were amplified. Restriction enzyme mapping indicated that the rearrangement within clone 8 occurred at a position close to the rearrangement previously noted in neuroblastoma cell line NB-9.

Long-term survivors of advanced neuroblastoma with MYCN amplification: A report of 19 patients surviving disease-free for more than 66 months.

PURPOSE: According to initial reports, stage 4 neuroblastoma patients with amplification of the MYCN proto-oncogene developed progressive disease within 8 months. The prognosis for such patients, however, should now be reevaluated in light of recent results achieved with up-to-date combination chemotherapy. PATIENTS AND METHODS: Patients with stage 3, 4, and 4S neuroblastoma and more than 10 copies of MYCN received induction chemotherapy, which from January 1985 to February 1991 consisted of regimen A(1 )(cyclophosphamide 1,200 mg/m(2) on day 1, vincristine 1.5 mg/m(2) on day 1, pirarubicin 40 mg/m(2) on day 3, and cisplatin 90 mg/m(2) on day 5) and from March 1991 to September 1993 consisted of regimen A(3 )(cyclophosphamide 1,200 mg/m(2) on days 1 and 2, pirarubicin 40 mg/m(2) on day 3, etoposide 100 mg/m(2) on days 1 through 5, and continuous infusion cisplatin 25 mg/m(2) on days 1 through 5). Most of these patients underwent radical surgery to remove the original tumor and local metastases, irradiation, and supralethal preconditioning regimens, followed by blood stem-cell transplantation (SCT). Data on the patients were collected in December 1998, and the factors contributing to disease-free survival were analyzed. RESULTS: During the study period, 66 patients with more than 10 copies of MYCN were treated. Five of nine patients with stage 3 disease, 13 of 55 with stage 4, and one of two with stage 4S survived for at least 66 months. It is interesting that all but one patient who survived for more than 66 months underwent SCT, in contrast with only five of 45 patients who died. CONCLUSION: Not all patients with advanced neuroblastoma who have more than 10 copies of MYCN will die. The requisites for survival in such patients seem to be intensive induction chemotherapy, effective surgery, irradiation, and the use of SCT.

Phosphoenolpyruvate carboxylase kinase involved in C(4) photosynthesis in Flaveria trinervia: cDNA cloning and characterization.

In C(4) plants, phosphoenolpyruvate carboxylase (PEPC; EC 4.1.1.31), a key enzyme in C(4) photosynthesis, is controlled by reversible phosphorylation of a conserved Ser residue near the N-terminus. We now report the first cloning of a cDNA from a C(4) plant, Flaveria trinervia, which encodes the specific protein kinase (FtPEPC-PK) involved in the phosphorylation of C(4)-form PEPC. Several lines of supportive evidence are: strict substrate specificity of the recombinant enzyme, prominent light/dark response of the transcript level and abundant expression in leaves of C(4) plant (F. trinervia) but very low expression in a C(3) plant of the same genus (Flaveria pringlei). We also discuss the possibility that the FtPEPC-PK gene has co-evolved with the PEPC gene to participate in C(4) photosynthesis.

Evaluation of leukocyte dynamics in choroidal circulation with indocyanine green-stained leukocytes.

PURPOSE: To develop a new method with which to visualize leukocytes moving through the choroidal vessels of pigmented animals and enable the evaluation of leukocyte dynamics in the choroidal microcirculation. METHODS: Pigmented rabbits and monkeys were used in this study. Leukocytes, collected by centrifugal separation of autologous blood, were stained with indocyanine green (ICG) dye. The ICG-stained leukocyte fluid was injected into the vein, and the fundus image was obtained with a scanning laser ophthalmoscope. The image was recorded on videotapes and analyzed with a personal computer-based image analysis system. RESULTS: In pigmented rabbits, fluorescent leukocytes moving in the choroidal circulation were clearly visible for more than 1 hour. In monkeys, distinct fluorescent dots were seen moving approximately 50 to 200 microm in the foveal avascular zone for more than 30 minutes after the injection of the ICG-stained leukocyte fluid. Dim fluorescent dots were seen moving in the fundus. Although the movement of these dim dots was difficult to trace, they seemed to be moving in the choroidal vessels. In the rabbits, the mean flow velocity of leukocytes moving without plugging was 0.48 +/- 0.14 mm/sec in the peripheral choriocapillaris. In the monkeys, the mean flow velocity of distinct fluorescent leukocytes without plugging was 2.45 +/- 0. 48 mm/sec in the posterior choroid. CONCLUSIONS: In pigmented rabbits and monkeys, this method allows visualization of leukocytes passing through the choroidal vessels and provides a new way to investigate, noninvasively and in vivo, leukocyte dynamics in the choroidal microcirculation.

Oral versus intraperitoneal administration of irinotecan in the treatment of human neuroblastoma in nude mice.

The present study evaluated the plasma pharmacokinetics of irinotecan (CPT-11) and its effects against a human neuroblastoma in xenograft, given by different administration routes. One-third of the LD50 was administered either intraperitoneally (59 mg/kg mouse weight (MW)) or orally (404 mg/kg MW) to nude mice. The plasma levels of CPT-11 and its active metabolite SN-38 decreased rapidly when CPT-11 was administered intraperitoneally, but remained relatively high for 4-8 h after oral administration. Then, a human neuroblastoma xenograft was inoculated in another set of 21 nude mice. When the estimated tumor weight reached 150-200 mg, CPT-11 was administered in the total LD50 either intraperitoneally or orally in three doses at 4-day intervals (q4d x3) to the mice in each experimental group. Oral administration was found to be superior to intraperitoneal injection in terms of tumor inhibition and to be an effective route for CPT-11 administration in the treatment of human neuroblastoma in nude mice.

Effects of granisetron in children undergoing high-dose chemotherapy: a multi-institutional, cross-over study.

The efficacy of granisetron hydrochloride 20 microg/kg and 40 microg/kg were compared using a cross-over method to determine the optimal dose in children with solid tumors receiving high-dose chemotherapy. Granisetron controlled the onset of vomiting in 17 of 23 patients (73.9%) who were given 40 microg/kg of granisetron, while 8 of 21 patients (38.1%) were free of vomiting in the 20 microg/kg group. The average frequency of vomiting was 7.22 times in the 20 microg/kg dose versus 4.44 times in the 40 microg/kg dose. No safety problems were associated with either dose. The 40 microg/kg dose of granisetron appears to be more optimal.

The effect of aging and arteriosclerosis on human skin blood flow.

Skin blood flow in the deltoid region of 65 men was measured by the xenon 133 clearance method and in studying the correlation of age, total cholesterol and systolic blood pressure to skin blood flow, the following results were obtained. (1) Skin blood flow significantly decreased with increase in age. In calculating skin blood flow at 20 and 70 years of age from the regression line between skin blood flow and age, it was estimated that skin blood flow at 70 years of age decreased to 40% of that at 20 years of age. (2) Skin blood flow significantly decreased with increase in total cholesterol and systolic blood pressure. (3) Skin blood flow showed the closest correlation with age, followed by total cholesterol and systolic blood pressure which showed a weak correlation. It is estimated from the foregoing results that as skin blood flow in patients with arteriosclerosis decreases more in elderly individuals than in young persons, their wound healing is delayed.