Serum ferritin level is a prognostic marker in patients with peripheral T-cell lymphoma.

INTRODUCTION: The prognostic value of serum ferritin level in patients with peripheral T-cell lymphoma (PTCL) remains unknown. METHODS: We retrospectively analyzed clinical data from 78 consecutive patients with newly diagnosed PTCL that were treated with anthracycline-containing regimens between 1998 and 2011. RESULTS: The patients consisted of 50 males and 28 females with a median age of 64 years (range, 16-83 years). The subtypes of PTCL were 39 PTCL, not otherwise specified and 39 angioimmunoblastic T-cell lymphoma (AITL). The median observation period for the surviving patients was 50 months. The overall survival (OS) was poorer in patients with serum ferritin level above the upper normal limit (n = 28), compared with patients with serum ferritin level within normal range (n = 50; 4-year OS: 23% vs. 72%; P < 0.001). In the multivariate analysis, poor performance status (P = 0.006) and elevated serum ferritin level (P = 0.018) were independent risk factors for poor OS. CONCLUSION: Serum ferritin level is a useful prognostic marker for PTCL.

Dietary habits, ethanol and tobacco consumption as predictive factors in the development of esophageal carcinoma in patients with head and neck neoplasms.

Patients with primary head and neck cancers have a higher risk of developing esophageal cancer. The aim of this study was to investigate esophageal cancer prevalence, its risk factors (ethanol and tobacco consumption) and dietary habits in patients with head and neck cancer. Three hundred and twenty-six adults with primary head and neck cancer were followed by a retrospective observational study in a general university hospital in Sao Paulo, Brazil. Flexible videoendoscopy with lugol chromoscopy was the method used to investigate esophageal cancer prevalence. All subjects were interviewed face-to-face, revealing detailed information about their tobacco and alcohol use, as well as their dietary habits. Thirty-six patients with esophageal cancer were diagnosed and the overall prevalence rate was 11.04%. Patients who developed second esophageal tumors had the following characteristics: earlier age of initial ethanol consumption (P < 0.05), longer duration period of ethanol consumption (P < 0.05) and higher weekly consumption rate (P < 0.05). There was an increased risk of esophageal carcinoma in those patients who both smoked and drank (P < 0.05). There was no association between carcinoma of the esophagus and dietary habits in patients who developed esophageal neoplasms, compared with those who did not. Prevalence rate of esophageal neoplasms was 11.04% in patients with head and neck carcinoma, whose ethanol consumption was associated with esophageal cancer. There was an increased risk between ethanol and tobacco consumption and esophageal carcinoma development. On the other hand, there was no association regarding dietary habits between patients who developed esophageal cancer and those who did not.

Adjuvant radiotherapy to an initial bulky mass in diffuse large B-cell lymphoma: lack of survival benefit.

The role of adjuvant radiotherapy to the site of the initial bulky mass in lymphoma remains to be determined. We retrospectively analyzed clinical data for 35 consecutive patients with diffuse large B-cell lymphoma who had an initial bulky mass were treated successfully by chemotherapy reaching complete remission or complete remission unconfirmed according to International Workshop Criteria. Median age was 57 years. Median follow-up period for surviving patients after completion of chemotherapy was 45 months. Twenty patients (group A) received adjuvant radiotherapy to the bulky mass, while 15 (group B) did not. Median dose of radiation in group A was 40 Gy (range, 30-60 Gy). In group A, four relapses occurred, all from other sites; group B included three relapses from bulky and one from other sites. Overall survival (P = 0.15) and recurrence-free survival (P = 0.48) did not differ significantly between groups. Although adjuvant radiotherapy to the initial bulky site is useful for controlling local disease, no survival benefit was seen.

Two alloalleles of Xenopus laevis hairy2 gene--evolution of duplicated gene function from a developmental perspective.

Gene duplication is a fundamental source of a new gene in the process of evolution. A duplicated gene is able to accept many kinds of mutations that could lead to loss of function or novel phenotypic diversity. Alternatively, the duplicated genes complementarily lose part of their functions to play original roles as a set of genes, a process called subfunctionalization. Pseudotetraploid frog Xenopus laevis has four sets of genes, and it is generally thought that the alloalleles in X. laevis have mutually indistinguishable functions. In this paper, we report differences and similarities between Xhairy2a and Xhairy2b in the neural crest, floor plate, and prechordal plate. Knockdown studies showed that Xhairy2a seems not to function in the neural crest, although both of them are required in the floor plate and the prechordal plate. Temporal expression pattern analysis revealed that Xhairy2a is a maternal factor having lower zygotic expression than Xhairy2b, while Xhairy2b is not loaded in the egg but has high zygotic expression. Spatial expression pattern analysis demonstrated that future floor plate expression is shared by both alloalleles, but Xhairy2b expression in the neural crest is much higher than Xhairy2a expression, consistent with the results of individual knockdown experiments. Therefore, our data suggest that subfunctionalization occurs in Xhairy2.

Human herpesvirus-6 encephalitis after unrelated cord blood transplantation.

Here we describe 2 patients with acute leukemia in whom human herpesvirus-6 (HHV-6) encephalitis developed after cord blood transplantation. In patients 1 and 2, generalized seizure and coma developed on day 62 and day 15, respectively, after cord blood transplantation, which failed to engraft in patient 1. Magnetic resonance imaging (MRI) of patient 1's brain showed low-intensity signals at the gyri of the bilateral lateral lobes on T1-weighted images and high-intensity signals on T2-weighted images. MRI of patient 2's brain showed high-intensity signals in bilateral white matter on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. Cerebrospinal fluid examination revealed an increased protein level with pleocytosis in patient 1 and a normal protein level without pleocytosis in patient 2. Polymerase chain reaction analysis detected HHV-6 DNA in the cerebrospinal fluid of both patients. Patient 1 recovered after administration of gancyclovir for 3 weeks. However, she again suffered from encephalitis after discontinuation of gancyclovir, and died of sepsis. Patient 2 died from an anoxic brain caused by generalized seizure. When neurological symptoms and signs appear in hematopoietic stem cell transplantation recipients, we should consider HHV-6 encephalitis and promptly and empirically treat them with gancyclovir or foscarnet.

Acrogeria (Gottron type): a vascular disorder?

We report a 27-year-old Japanese man with the peculiar clinical features of acrogeria. He had had perniosis since early childhood. Prominent atrophic skin changes over the hands, hallux valgus, shortened distal phalanges and atrophic scars on his auricles were noted. X-ray of the hands revealed acro-osteolytic changes of the distal phalanges, and arteriography demonstrated multiple occluded branches of the digital arteries. There were no histological changes of systemic sclerosis in his forearm skin, nor antinuclear antibodies or coagulation disorders. Western immunoblotting demonstrated decreased production of type III collagen by dermal fibroblasts both from an affected finger and from the unaffected upper arm. Although the pathogenesis of acrogeria is unknown, the present case suggests that peripheral circulatory disturbance, as well as a congenital abnormality in type III collagen synthesis, may partly account for the pathogenesis of Gottron-type acrogeria.

Transport of solar wind into Earth's magnetosphere through rolled-up Kelvin-Helmholtz vortices.

Establishing the mechanisms by which the solar wind enters Earth's magnetosphere is one of the biggest goals of magnetospheric physics, as it forms the basis of space weather phenomena such as magnetic storms and aurorae. It is generally believed that magnetic reconnection is the dominant process, especially during southward solar-wind magnetic field conditions when the solar-wind and geomagnetic fields are antiparallel at the low-latitude magnetopause. But the plasma content in the outer magnetosphere increases during northward solar-wind magnetic field conditions, contrary to expectation if reconnection is dominant. Here we show that during northward solar-wind magnetic field conditions-in the absence of active reconnection at low latitudes-there is a solar-wind transport mechanism associated with the nonlinear phase of the Kelvin-Helmholtz instability. This can supply plasma sources for various space weather phenomena.

Reduction of abdominal pressure in patients with ascites reduces gastroesophageal reflux.

The effect of the reduction of intra-abdominal pressure on the lower esophageal sphincter pressure (LESP) and the 24-hour pH monitoring were studied in 16 patients with ascites before and after paracentesis. LESP did not change (P > 0.05) with the reduction of intra-abdominal pressure (before paracentesis: 17.48 mmHg and postparacentesis: 18.67 mmHg). The results were divided into two groups according to the achieved reduction in intra-abdominal pressure group A were those in who the reduction was greater than 70% and B consisted of those a reduction of less than 70%. LESP did not change even when results for each group were considered separately (P > 0.05): group A (before: 15.60 mmHg; after: 18.09 mmHg); group B (before: 23.09 mmHg; after: 20.40 mmHg). However the 24-h pH monitoring showed pathological reflux in patients with ascites that was reduced with the paracentesis (P < 0.05; total number of reflux episodes before paracentesis was 520.26, and after, 136.26). All pH-monitoring parameters were statistically different (P < 0.05) before and after the reduction of intra-abdominal pressure for group A but not for group B. LESP does not change significantly (P > 0.05) when the intra-abdominal pressure is significantly reduced (P < 0.05). Patients with ascites showed gastroesophageal reflux. Intra-abdominal pressure reduction greater than 70% lead to a significant reduction in gastroesophageal reflux.

Yersinia pseudotuberculosis infection in breeding monkeys: detection and analysis of strain diversity by PCR.

In the last three decades, several monkeys reared in outdoor/indoor-outdoor breeding colonies and cages of the Primate Research Institute, Kyoto University, died of yersiniosis caused by Yersinia pseudotuberculosis, necessitating introduction of a method to detect the bacteria rapidly and thus allow preventive measures to be undertaken. A rapid nested polymerase chain reaction (PCR) method for identification of Y. pseudotuberculosis in fecal samples and a random amplified polymorphic DNA (RAPD)-PCR approach for distinguishing between bacterial strains were therefore developed. Yersinia pseudotuberculosis isolates from monkey specimens were found to be classifiable into several types. To determine the source of infection, hundreds of fecal samples of wild rats, pigeons, and sparrows were collected from around the breeding colonies and cages, and subjected to PCR analyses. Yersinia pseudotuberculosis was detected in 1.7% of the fecal samples of wild rats. The DNA fingerprints of the bacteria revealed by RAPD-PCR were the same as that of one strain isolated from macaques, suggesting the wild rat to be a possible source of infection.

Teaching continuous curvilinear capsulorhexis using a postmortem pig eye with simulated cataract(2)(2).

We modified an inexpensive, easily prepared model using a postmortem pig eye for training ophthalmology residents to perform continuous curvilinear capsulorhexis. To reduce the tension and elasticity of the porcine anterior lens capsule, 0.05 mL of formalin mixed with hydroxyethylcellulose or a viscoelastic material is injected into the anterior chamber via the corneal limbus to fix the surface of the central anterior lens capsule of the pig eye in situ. One or 2 minutes after the injection, only the anterior lens capsule is fixed and corneal transparency is maintained. The reduction in tension and elasticity of the anterior lens capsule caused by its fixation increases the resemblance of the simulated cataract to the human cataract.

Activation of a protease cascade involved in patterning the Drosophila embryo.

Dorsoventral patterning of the Drosophila embryo is initiated by a ventralizing signal. Production of this signal requires the serine proteases Gastrulation Defective (GD), Snake, and Easter, which genetic studies suggest act sequentially in a cascade that is activated locally in response to a ventral cue provided by the pipe gene. Here, we demonstrate biochemically that GD activates Snake, which in turn activates Easter. We also provide evidence that GD zymogen cleavage is important for triggering this cascade but is not spatially localized by pipe. Our results suggest that a broadly, rather than locally, activated protease cascade produces the ventralizing signal, so a distinct downstream step in this cascade must be spatially regulated to restrict signaling to the ventral side of the embryo.

Gastrulation defective is a serine protease involved in activating the receptor toll to polarize the Drosophila embryo.

The dorsoventral axis of the Drosophila embryo is induced by a ventrally restricted ligand for the receptor Toll. The Toll ligand is generated by a proteolytic processing reaction, which occurs at the end of a proteolytic cascade and requires the gastrulation defective (gd), nudel, pipe, and windbeutel genes. Here we demonstrate that the GD protein is a serine protease and that the three other genes act to restrict GD activity to the ventral side of the embryo. Our data support a model in which the GD protease catalyzes the ventral activation of the proteolytic cascade that produces the Toll ligand.

A novel Drosophila serpin that inhibits serine proteases.

Serpins define a large protein family in which most members function as serine protease inhibitors. Here we report the results of a search for serpins in Drosophila melanogaster that are potentially required for oogenesis or embryogenesis. We cloned and sequenced ovarian cDNAs that encode six distinct proteins having extensive sequence similarity to mammalian serpins, including residues important in the serpin inhibition mechanism. One of these new serpins in recombinant form inactivates, and complexes with, trypsin-like proteases in vitro. To our knowledge, these results represent the first evidence for a serpin in Drosophila that functions as a serine protease inhibitor.

The nudel protease of Drosophila is required for eggshell biogenesis in addition to embryonic patterning.

The dorsoventral axis of the Drosophila embryo is defined by a ventral signal that arises within the perivitelline space, an extracellular compartment between the embryo plasma membrane and the vitelline membrane layer of the eggshell. Production of the ventral signal requires four members of the serine protease family, including a large modular protein with a protease domain encoded by the nudel gene. Here we provide evidence that the Nudel protease has an integral role in eggshell biogenesis. Mutations in nudel that disrupt Nudel protease function produce eggs having vitelline membranes that are abnormally permeable to the dye neutral red. Permeability varies among mutant nudel alleles but correlates with levels of Nudel protease catalytic activity and function in embryonic dorsoventral patterning. These mutations also block cross-linking of vitelline membrane proteins that normally occurs upon egg activation, just prior to fertilization. In addition, Nudel protease autoactivation temporally coincides with vitelline membrane cross-linking and can be triggered in mature eggs in vitro by conditions that lead to egg activation. We discuss how the Nudel protease might be involved in both eggshell biogenesis and embryonic patterning.

Biochemical defects of mutant nudel alleles causing early developmental arrest or dorsalization of the Drosophila embryo.

The nudel gene of Drosophila is maternally required both for structural integrity of the egg and for dorsoventral patterning of the embryo. It encodes a structurally modular protein that is secreted by ovarian follicle cells. Genetic and molecular studies have suggested that the Nudel protein is also functionally modular, with a serine protease domain that is specifically required for ventral development. Here we describe biochemical and immunolocalization studies that provide insight into the molecular basis for the distinct phenotypes produced by nudel mutations and for the interactions between these alleles. Mutations causing loss of embryonic dorsoventral polarity result in a failure to activate the protease domain of Nudel. Our analyses support previous findings that catalytic activity of the protease domain is required for dorsoventral patterning and that the Nudel protease is auto-activated and reveal an important role for a region adjacent to the protease domain in Nudel protease function. Mutations causing egg fragility and early embryonic arrest result in a significant decrease in extracellular Nudel protein, due to defects in post-translational processing, stability, or secretion. On the basis of these and other studies of serine proteases, we suggest potential mechanisms for the complementary and antagonistic interactions between the nudel alleles.

[Idiopathic mediastinal and subcutaneous emphysema in a patient with acute lymphocytic leukemia after allogeneic bone marrow transplantation].

A 45-year-old man was diagnosed as having Ph1+ acute lymphocytic leukemia (ALL) in February 1997. Complete remission was achieved by chemotherapy. Allogeneic BMT from his HLA-identical sister was performed on June 11, 1997. Engraftment was relatively quick, but acute GVHD (grade I) developed. The patient was discharged on day 113. Seven months after BMT, in January 1998, exertional dyspnea developed gradually. Chest X-ray examination showed diffuse interstitial pneumonia, for which corticosteroid was started immediately. The symptoms and signs gradually improved. However, on the 20th hospital day (February 23), bilateral subcutaneous emphysema developed in the neck and supraclavicular region. Chest X-ray and CT examinations showed pneumomediastinum without pneumothorax. The pneumomediastinum and subcutaneous emphysema gradually subsided after 3 weeks of bed rest. Subcutaneous emphysema and pneumomediastinum are relatively rare complications of allogeneic BMT.