bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential roles of NaV1.2 and NaV1.6 in neocortical pyramidal cell excitability
Authors: Garcia Joshua D , Wang Chenyu , Banks Emmie , Fenton Timothy , DeKeyser Jean-Marc , Abramova Tatiana V , George Alfred L , Ben-Shalom Roy , Hackos David H , Bender Kevin J
Published: February 2025

Mature neocortical pyramidal cells functionally express two sodium channel (Na
V
) isoforms: Na
V
1.2 and Na
V
1.6. These isoforms are differentially localized to pyramidal cell compartments, and as such are thought to contribute to different aspects of neuronal excitability. But determining their precise roles in pyramidal cell excitability has been hampered by a lack of tools that allow for selective, acute block of each isoform individually. Here, we leveraged aryl sulfonamide-based molecule (ASC) inhibitors of Na
V
channels that exhibit state-dependent block of both Na
V
1.2 and Na
V
1.6, along with knock-in mice with changes in Na
V
1.2 or Na
V
1.6 structure that prevents ASC binding. This allowed for acute, potent, and reversible block of individual isoforms that permitted dissection of the unique contributions of Na
V
1.2 and Na
V
1.6 in pyramidal cell excitability. Remarkably, block of each isoform had contrasting—and in some situations, opposing—effects on neuronal action potential output, with Na
V
1.6 block decreasing and Na
V
1.2 block increasing output. Thus, Na
V
isoforms have unique roles in regulating different aspects of pyramidal cell excitability, and our work may help guide development of therapeutics designed to temper hyperexcitability through selective Na
V
isoform blockade.
Development and assessment of a sustainable PhD internship program supporting diverse biomedical career outcomes
Authors: Brandt Patrick , Whittington Dawayne , Wood Kimberley D , Holmquist Christopher , Nogueira Ana T , Gaines Christiann H , Brennwald Patrick , Layton Rebekah L
Published: February 2025

A doctoral-level internship program was developed at the University of North Carolina at Chapel Hill with the intent to create customizable experiential learning opportunities for biomedical trainees to support career exploration, preparation, and transition into their postgraduate professional roles. We report the outcomes of this program over a 5-year period. During that 5-year period, 123 internships took place at over 70 partner sites, representing at least 20 academic, for-profit, and non-profit career paths in the life sciences. A major goal of the program was to enhance trainees’ skill development and expertise in careers of interest. The benefits of the internship program for interns, host/employer, and supervisor/principal investigator were assessed using a mixed-methods approach, including surveys with closed- and open-ended responses as well as focus group interviews. Balancing stakeholder interests is key to creating a sustainable program with widespread support; hence, the level of support from internship hosts and faculty members were the key metrics analyzed throughout. We hypothesized that once a successful internship program was implemented, faculty culture might shift to be more accepting of internships; indeed, the data quantifying faculty attitudes support this. Furthermore, host motivation and performance expectations of interns were compared with results achieved, and this data revealed both expected and surprising benefits to hosts. Data suggests a myriad of benefits for each stakeholder group, and themes are cataloged and discussed. Program outcomes, evaluation data, policies, resources, and best practices developed through the implementation of this program are shared to provide resources that facilitate the creation of similar internship programs at other institutions. Program development was initially spurred by National Institutes of Health pilot funding, thereafter, successfully transitioning from a grant-supported model, to an institutionally supported funding model to achieve long-term programmatic sustainability.
Potential transoceanic dispersal of Geodia cf. papyracea and six new tetractinellid sponge species descriptions within the Hawaiian reef cryptofauna
Authors: Nunley Rachel M. , Rutkowski Emily C. , Toonen Robert J. , Vicente Jan
Published: February 2025

Kāne‘ohe Bay has historically been known for the introduction of alien species from the Caribbean and the Western Indo-Pacific. Recent efforts that explore the reef cryptofauna have shown that in addition to the diversity of non-indigenous species, patch reef environments are rich with undescribed species. Here we integrate molecular phylogeny and systematics to distinguish introduced species from those that are potentially native or endemic. We focus on the order Tetractinellida and document the potential transoceanic dispersal of Geodia papyracea from the Caribbean to Hawai‘i. Our integrative approach allowed us to describe new species of Stelletta (Stelletta kela sp. nov., Stelletta hokunalohia sp. nov., Stelletta kuhapa sp. nov., Stelletta hokuwanawana sp. nov., Stelletta apapaola sp. nov.) and one new species of Stryphnus (Stryphnus huna sp. nov.); all collected from the reef cryptofauna via the use of Autonomous Reef Monitoring Structures. Specimens were barcoded using 28S and COI molecular markers, providing insights into the phenotypic plasticity of sponges and the phylogenetic placement of these new species based on morphological characters. Using both molecular phylogeny and traditional taxonomy enhances the accuracy of species identification and classification, contributing to a broader understanding of sponge biodiversity within the Hawaiian archipelago.
Characteristics and Evolution of Cardiogenic Shock According to Gender in Latin America. LATIN Shock Registry Data
Authors: Castillo Costa Yanina , Delfino Flavio , Macías José , Quintana Miguel , Adamowski Mariano , Rodríguez Caballero Fabiola , Navarta Navarro Ma de los Ángeles , Velazco Gabriela , Mauro Víctor
Published: February 2025

Background: Cardiogenic shock (CS) as a complication of myocardial infarction is a condition with high mortality that, due to biological or equity differences, may have different characteristics according to gender.

Objectives: The aim of this study was to evaluate whether there are differences in the presentation, clinical evolution and treatment of patients with CS, according to gender.

Methods: We analyzed the patients of the LATIN Shock registry and evaluated whether there were differences according to gender.

Results: A total of 278 patients (30% women) were included. Seventy-five percent of patients presented ST-segment elevation acute coronary syndrome. Women were older and men were heavier smokers, and there were no differences in the prevalence of other cardiovascular risk factors, history, or comorbidities between genders. Revascularization was similar in men and women (86%) and there were no differences in the indication for pulmonary catheterization (11% vs. 20%, p=0.082). Women received less mechanical support with intra-aortic balloon counterpulsation (14% vs. 26%, p=0,032), while use of other mechanical support procedures was scarce, only in 1% of women and in 3% of men (p=0.678). Mortality in women was 48% vs. 54% in men, not reaching statistical significance (p=0.470).

Conclusions: Women with CS due to infarction are older and receive similar treatment except for mechanical supports, which are more frequently used in men. In our study there were no significant differences in mortality according to gender, which was high in both groups.
Evaluating the Adaptability of Hybrid Onions for Yield and Performance Analysis in Northwestern Tigray
Authors: Asgele Kiros
Published: February 2025

A field experiment was carried out in October 2019 in Tselemti District, North Western Zone of Tigray to assess the adaptability of seven registered hybrid onion varieties and one standard check for yield and yield attributing parameters of onion (Allium cepa L.). The tested hybrid onion varieties included MALBEC F1, NEPTUNE, RUSSET, JAMBAR, RED KING F1, RED COACH F1, ANKIN F1, and NASIK RED (Standard Check), and the experiment followed a Randomized Complete Block Design (RCBD) with three replications. The results indicated that the variety significantly impacted all characteristics except for neck thickness and bulb length. MALBEC F1 demonstrated the highest marketable bulb yield, followed by NEPTUNE, RUSSET, JAMBAR, and RED KING F1, yielding 49.81, 49.04, 48.02, 46.49, and 45.65 tons per hectare, respectively. Conversely, the lowest bulb yield was observed in NASIK RED (34.90) and ANKIN F1 (34.04 tons per hectare). Consequently, it is recommended that MALBEC F1, NEPTUNE, RUSSET, JAMBAR, and RED KING F1 hybrid onion varieties are the most adaptable and highest yielding options in the study area.
Mechanisms of Inflammation Associated with Chronic Diseases: A Brief Review
Authors: Gaikwad Vaishnavi V. , Gitaje Sameeksha R. , Joshi Saurabh D. , Kharmate Shrirang V. , Phalle Dipak R. , More Mrudula P. , Mali Mrunal A. , Shingade Pratibha P.
Published: February 2025

Inflammation is a vital immune response that protects the body from infections, damaged cells, and harmful stimuli. It can be acute (rapid and short-term, aiding tissue repair) or chronic (persistent, causing tissue damage and contributing to diseases like cancer and autoimmune disorders). Pattern recognition receptors activate inflammation through signaling pathways like JAK/STAT, MAPK, and NF-kB. Inflammatory mediators, such as cytokines, reactive oxygen species, and acute-phase proteins, attract immune cells (e.g., neutrophils and macrophages) to the damage site. Diagnostic markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) assess inflammation levels. Chronic inflammation is linked to conditions like rheumatoid arthritis and cardiovascular disease. NSAIDs, which block cyclooxygenase enzymes, are commonly used to manage inflammation. Understanding inflammation mechanisms is key to improving treatments and clinical outcomes.
Ontogenetic Changes in Feeding Behavior and Nutrient Allocation Patterns in Mexican Beetle (Zygogramma bicolorata) Pallister on Parthenium hysterophorus L
Authors: Kumar Anuj , Chaubey Ashok Kumar , Upadhyay Ankit
Published: February 2025

Parthenium hysterophorus L. (Asteraceae) is a noxious weed found in agricultural fields, pastures, and wastelands across tropical regions. It significantly reduces crop yields and poses serious health risks to humans. The Mexican beetle, Zygogramma bicolorata Pallister (Coleoptera: Chrysomelidae), has emerged as one of the most effective biological control agents against this weed. However, no previous research has examined the beetle's nutrient assimilation. This study evaluated the feeding behavior and nutrient assimilation in the larvae of Z. bicolorata when feeding on P. hysterophorus. The findings showed that the first instar larvae had the lowest food consumption rates and accumulated minimal amounts of glucose, proteins in their bodies. These larvae demonstrated compensatory feeding behavior, achieving the highest food utilization efficiency and developmental rates. In contrast, the fourth instar larvae exhibited the highest food consumption and conversion efficiency but had the slowest developmental rates. Notably, the fourth instar larvae accumulated the largest food reserves. These results provide valuable insights for laboratory-based mass-rearing programs for Z. bicolorata, though further field trials are necessary to validate these findings.
Accidental Childhood Death and the Role of the Pathologist
Authors: Byard Roger W.
Published: July 2002

The following study provides an overview of accidental childhood death. This study is based on a review of 369 cases of fatal childhood accidents taken from the records of the Department of Histopathology, Women's and Children's Hospital, Adelaide, Australia, over a 34-year period from 1963 to 1996. Data provide information on deaths due to motor vehicle accidents, drownings, accidental asphyxia, burns, poisonings, electrocution, and miscellaneous trauma. In addition, certain categories have undergone further examination, including asphyxial deaths due to unsafe sleeping environments and unsafe eating practices, drowning deaths, and deaths on farms, following identification of significant child safety problems in these areas as part of the “Keeping Your Baby and Child Safe” program. Previously unrecognized dangers to children detected through this program include mesh-sided cots, V-shaped pillows, and certain types of stroller-prams. The production of information pamphlets and packages for parents and the recall of certain dangerous products following recommendations made by pathologists demonstrate that pediatric and forensic pathologists have an important role to play in preventive medicine issues and in formulating public health strategies.
Use of Multicolor Spectral Karyotyping in Genetic Analysis of Pleuropulmonary Blastoma
Authors: Barnard Maja , Bayani Jane , Grant Ronald , Teshima Ikuko , Thorner Paul , Squire Jeremy
Published: July 2002

Pleuropulmonary blastoma (PPB) is a rare, malignant intrathoracic pediatric tumor. It arises from the lung, pleura, or mediastinum and its pathogenesis and relationship to other pediatric solid tumors is not well understood. In this study, a case of PPB in a 3-year-old girl was studied using a combination of molecular genetic methods and cytogenetics. Molecular analysis of the commonly encountered fusion translocation gene products of pediatric solid tumors failed to detect a rearrangement. Cytogenetic analysis, supplemented by multicolor spectral karyotyping (SKY), identified an unbalanced translocation between chromosomes 1 and X, resulting in additional copies of 1q, an extra copy of Xq, and loss of part of Xp. In addition, trisomy 8 was detected. The identification of new chromosomal alterations and confirmation of previously reported ones in this rare neoplasm helps to improve our understanding of its pathogenesis and association with other pediatric tumors.
Morphometric Assessment of Hirschsprung's Disease: Associated Hypoganglionosis of the Colonic Myenteric Plexus
Authors: Meier-Ruge William A. , Brunner Luzia A.
Published: July 2002

At present, there are no generally acceptable criteria for the evaluation of hypoganglionosis of the myenteric plexus. The aim of this morphometrical investigation was to examine the most important quantitative characteristics of hypoganglionosis. Colon specimens from 35 children with Hirschsprung's disease were assessed morphometrically. Twenty specimens with Hirschsprung's disease and proximal hypoganglionosis of the myenteric plexus were compared with 15 specimens with Hirschsprung's disease and normal innervation in the proximal myenteric plexus. All native surgical specimens were caudocranial coiled and sectioned in a cryostat. Nerve cells and ganglia were selectively stained with an enzyme-histochemical lactic dehydrogenase reaction. Morphometric measurements were done with an optic-electronic image analysis system. Hirschsprung's disease–associated hypoganglionosis of the myenteric plexus is characterized by a significant decrease in ganglion cross-sectional area (-56.2%) and in plexus area per mm colon (-53.5%). Together with these data, an increase in ganglion distance (+20%) was also determined, and the number of nerve cells per mm colon was decreased by −25.5%. The decrease in ganglion area and in the number of nerve cells per mm colon in the myenteric plexus proved to be the most characteristic parameters of a hypoganglionosis.
Pediatric Core Needle Biopsy: Strengths and Limitations in Evaluation of Masses
Authors: Willman Joseph H. , White Keith , Coffin Cheryl M.
Published: July 2002

Needle core biopsies (NCB) are widely used in adults but are less often used for the evaluation of pediatric tumors. To determine the diagnostic utility of NCB for pediatric tumors, we performed a retrospective analysis. Fifty NCB of masses from 1992 to 1998, subsequent pathologic specimens, and medical records were reviewed. All patients were less than 21 years of age. Of the NCB 78% (39/50) were diagnostic of a neoplasm, 8% (4/50) were nondiagnostic in cases where a tumor was subsequently diagnosed, and 14% (7/50) revealed inflammatory or reactive lesions, with no subsequent diagnosis of a neoplasm according to medical record review. In cases in which a neoplasm was present, NCB was diagnostic in 91% (39/43). For cases in which there was a previous diagnosis of a tumor, 100% (9/9) of NCB were diagnostic of a recurrence or metastasis. In cases of NCB for primary tumor diagnosis, 88% (30/34) were diagnostic. The most common problems encountered were related to specimen adequacy, such as insufficient tissue, crush artifact, and tumor necrosis. Tumor diagnoses were as follows: primitive neuroectodermal tumor (PNET)/Ewing sarcoma (12), malignant lymphoma/Hodgkin's disease (8), rhabdomyosarcoma (4), germ cell tumor (3), Wilms' tumor (3), neuroblastoma (1), sarcoma, not otherwise specified (4), and other neoplasms (8). There were no complications of the procedure. NCB of pediatric tumors is an effective diagnostic tool and can be used to obtain diagnostic material quickly and safely. NCB was diagnostic in 90% of cases in this series. When NCB provide sufficient material for immunohistochemical, cytogenetic, flow cytometric, and other ancillary studies, the diagnostic efficacy is enhanced. The major limitations in this series were related to sampling problems and specimen adequacy for comprehensive pathologic evaluation.
Large Granular Lymphocyte Leukemia: Case Report of Chronic Neutropenia and Rheumatoid Arthritis-like Symptoms in a Child
Authors: Blanchong Carol A. , Olshefski Randal , Kahwash Samir
Published: July 2002

Lymphoproliferative disorders of large granular lymphocytes (LGL) are heterogeneous, with a clinical/pathologic spectrum ranging from a benign polyclonal expansion to an aggressive clonal disease. Often these lymphoproliferative disorders are associated with autoimmune disease. The clonal form of the disorder, LGL leukemia, typically occurs in older adults with a median age of 55 years at diagnosis. Pediatric cases are referred to in review articles; however, no detailed reports of T-cell LGL leukemia in children exist. This report illustrates a case of a child who presented initially at age 2 and 1/2 years with psoriasis, juvenile rheumatoid arthritis-like symptoms, and neutropenia. Bone marrow examinations obtained throughout his course have demonstrated progressive hypercellularity with increased reticulin fibers and replacement of the normal marrow elements by lymphocytes, which were later identified as large granular lymphocytes. Further testing with immunophenotyping by flow cytometry and T-cell receptor gene rearrangement studies revealed a monoclonal proliferation of large granular lymphocytes and confirmed a diagnosis of LGL leukemia. Although rare, large granular lymphocyte leukemia should be included in the differential diagnosis of chronic neutropenia in children.
Central Nervous System Malformations in a Perinatal/Neonatal Autopsy Series
Authors: Pinar H. , Tatevosyants N. , Singer D.B.
Published: July 2002

Congenital malformations of the central nervous system (CNS) are among the most common anomalies, but data on the incidence of CNS malformations in autopsy populations are scant. We examined 4122 autopsies between the years 1958 and 1995. There were 363 cases (8.8%) with CNS malformations; 235 were neonates and 128 stillborns. The overall gender ratio was 1:1, although more male neonates and more female stillborns had malformations. The body weights ranged from 24 to 6440 g.

Neural tube defects were the most common types of malformations (45.5%) and included anencephaly, meningoencephalocele, meningocele/meningomyelocele, craniospinal rachischisis, and spina bifida occulta. The incidences of other malformations were: congenital hydrocephalus (12.4%), neuronal/glial proliferation disorders such as micro- and macrocephaly (8.8%), neuronal migration disorders (8.8%), prosencephalon growth disorders such as holoprosencephaly and arhinencephaly (8.5%), abnormalities of the midline structures such as agenesis of corpus callosum (4.1%), developmental cysts (3.3%), cerebellar malformations (3%), and vascular malformations (2%). Miscellaneous malformations (3%) consisted of acephalia in four cases with twin reversed arterial perfusion (TRAP), two cases of hydranencephaly, and four cases of rare degenerative and metabolic encephalopathies.
Bcl-2 Expression in Langerhans' Cell Histiocytosis
Authors: Savell Van H. , Sherman Todd , Scheuermann Richard H. , Siddiqui Abdul M. , Margraf Linda R.
Published: July 2002

Langerhans' cell histiocytosis (LCH) is an abnormal accumulation of dendritic histiocytes of unknown pathogenesis. It has recently been shown to be a clonal process. Bcl-2 is a proto-oncogene whose protein product is known to inhibit apoptosis. The overexpression of bcl-2 has been demonstrated in a number of neoplasms, presumably prolonging the survival of the neoplastic cells. We examined the expression of bcl-2 in normal Langerhans' cells in the skin and in LCH by immunohistochemistry for protein and in situ hybridization for mRNA to see if it could be implicated in the pathogenesis of this disorder. Additionally, we performed Southern analysis to determine if genomic rearrangement of the bcl-2 gene occurs in cases of LCH. Bcl-2 was not detected in normal skin Langerhans' cells. Eleven of thirteen cases of LCH demonstrated bcl-2 protein expression in the cytoplasm of the Langerhans' cells by immunohistochemistry, while 12 of 13 cases had evidence of bcl-2 mRNA by in situ hybridization. Southern analysis revealed a germ-line configuration of the bcl-2 gene in the five cases studied. These findings suggest that bcl-2 expression is present and up-regulated in pathologic Langerhans' cells, however, this overexpression does not appear to be due to genomic rearrangement.
Vimentin Immunohistochemistry in Human Fetal Brain: Methods of Standard Incubation versus Thermal Intensification Achieve Different Objectives
Authors: Sarnat Harvey B.
Published: July 2002

Vimentin is transiently expressed in many cells of neuroectodermal origin in the fetal central nervous system and may be demonstrated by immunohistochemistry in paraffin sections. Traditional methods incubate antibodies with tissue sections at room temperature, but boiling the incubating solution in a microwave oven enhances antigen retrieval and greatly intensifies immunoreactivity This study compares vimentin immunoreactivity using various dilutions of a commercial monoclonal antibody and various incubation conditions including room temperature, overnight at 4°C, and after heating to boiling either in a microwave oven or on a hot plate. Fifteen fetal brains and spinal cords were examined, ranging in age from 8 to 24 wk gestation. Normal brains of four term or near-term neonates and two with hypoxic/ischemic lesions were also studied. Hot plate and microwave heating were equivalent. No differences in immunoreactivity could be attributed to gestational age per se. Boiling for 10 min in a microwave oven at a dilution of 1:200 is recommended for the enhanced demonstration of fetal histological structures such as radial glial fibers, but it is not recommended for studies of maturational gradients of cellular vimentin that differ at each gestational age, as in fetal ependymal cells or during the conversion of radial glia to mature astrocytes. For semiquantitative developmental studies, vimentin incubation at room temperature or overnight in the refrigerator is recommended at a dilution of 1:25 or 1:50 to avoid misinterpretation of apparent excessive staining after thermal intensification. Recommendations of commercial suppliers focus on the identification of neoplastic cells and must be modified to demonstrate subtle developmental changes in fetal tissues.
Unique Desmoplastic Cerebral Tumor in a Patient with Complex Partial Seizures
Authors: Jay Venita , Edwards Vern , Rutka James , Mosskin Mikael , Hwang Paul , Resch Lothar
Published: July 2002

Primary brain tumors with prominent desmoplasia include the gliofibroma, desmoplastic infantile ganglioglioma (DIG), pleomorphic xanthoastrocytoma (PXA), and desmoplastic cerebral astrocytoma. In the present report, we describe unusual pathological appearances in two successive resections of a left temporal tumor in a patient with complex partial seizures. Both tumors showed focal astroglial and very prominent neuronal differentiation. In the first resection at age 11 years, the tumor showed only focal desmoplastic areas and prominent neuronal differentiation with bizarre atypical giant cells. In the second resection at age 14 years, the morphology was dramatically different. Now the tumor showed marked desmoplasia with tumor cells coexpressing neuronal and glial markers. Electron microscopy showed prominent neuronal differentiation in both resections and presence of basal lamina around tumor cells. Our case represents a unique example of an extraordinary degree of neuronal differentiation in a desmoplastic cerebral tumor. While cellular pleomorphism in a desmoplastic tumor traditionally suggests the diagnosis of PXA, we wish to underscore that many cells exhibiting marked cytologic atypia may in fact be of neuronal rather than of glial origin as in our case.
Histopathologic Approach to Metabolic Liver Disease: Part 2
Authors: Jevon Gareth P. , Dimmick James E.
Published: July 2002

In this, part 2 of the histopathologic approach to the diagnosis of metabolic disease of the liver, the steatotic, cirrhotic, and neoplastic groups are addressed. See the previous issue, Volume 1, Number 3, of Pediatric and Developmental Pathology for part 1 [1]. The perspective concludes with a tabulated assessment of the likelihood of diagnostic ascertainment.
Congenital Thyroid Teratoma: A Case with Persistent Neuroglial Involvement of Cervical Lymph Nodes
Authors: Keen C.E. , Said A.J. , Agrawal M. , Berry P.J.
Published: July 2002

A case of congenital thyroid teratoma with nodal spread is reported. Primary surgery was performed on a female infant on the 6th day of life. The thyroid mass was removed in toto, and an adjacent 1.2 cm lymph node was also removed. Histology showed solid and cystic teratoma with a variety of elements including prominent neuroglial tissue that was neuroblastoma-like in places. Residual compressed non-neoplastic thyroid tissue was identified in the subcapsular plane. The lymph node was largely replaced by neuroglial tissue that was cellular in some areas and showed intrasinusoidal growth and some mitotic activity. Recurrent cervical lymphadenopathy gradually developed, commencing a few months after surgery. Excision of cervical nodes was undertaken at 9 months of age. About 13 nodes up to 2 cm in diameter were excised. Most of the specimens consisted of reactive lymph nodes, but in three of the smaller nodes, there were subcapsular and sinusoidal masses of focally cellular neuroglial tissue, again with occasional mitoses. This tissue stained strongly for glial fibrillary acidic protein, in addition to expressing neural markers. The lymph node “deposits” were interpreted as “displaced” lesional tissue rather than metastases in the usual, aggressive sense. The girl remains well at 5 years of age.
Pediatric Germ Cell Tumors: Protocol Update for Pathologists
Authors: Perlman Elizabeth J. , Hawkins Edith P.
Published: July 2002

The therapy for pediatric germ cell tumors has historically been widely variable and institution dependent. The efforts to provide consistent, biology-driven therapy through Intergroup protocols has been a relatively recent phenomenon that has provided the framework for future protocol designs. The first Intergroup protocols confirmed that stage I malignant testicular germ cell tumors and immature teratomas at all sites in children could be treated with surgery alone followed by close observation. Future protocols currently in the planning stages may extend this low-risk category to stage I ovarian germ cell tumors of all histologic types. Low-stage extragonadal germ cell tumors may be placed in a new intermediate risk category. Particular pathologic issues that were raised and reported during the first protocols and that may impact on future protocol design include the presence and size of foci of endodermal sinus tumors within low-stage immature teratomas at all sites. Accurate staging will grow more critical in future protocols. The ability to recruit international cooperative groups will determine the success of chemotherapy tailored to specific subgroups that now must be lumped for statistical purposes. Lastly, companion biologic studies will be critical to defining the different subtypes of germ cell tumors and to determining predictors of biologic behavior.
Heterotopic Pancreas as Lead Point in Intussusception: New Variant of Vitellointestinal Tract Malformation
Authors: Abel Robin , Keen Charles E. , Bingham John B. , Maynard John , Agrawal Meena R. , Ramachandra Su
Published: July 2002

Two cases of intussusception are reported with heterotopic pancreatic tissue attached to and draining into the ileum. The first patient, a boy aged 16 months, presented with ileoileal intussusception. The diagnosis was confirmed on ultrasound scan. Laparotomy and resection were performed. A 12-mm nodule of heterotopic pancreatic tissue was identified in the ileal serosa at the apex of the intussusceptum, fully formed with acinar tissue, islets, and draining duct. The second patient, also a boy aged 16 months, presented with obstructed ileocolic intussusception in which the lead point at surgery resembled a Meckel's diverticulum. Histopathology revealed a similar 10-mm nodule of fully formed pancreatic tissue in the ileal serosal tissues, with some acinar tissue extending through the wall of the intestine alongside ductal structures. In both cases there was ectopic gastric mucosa either in the distal part of the draining duct or in the small intestine itself at the opening. Heterotopic pancreas is a rare cause of intussusception. We propose that this lesion is of vitellointestinal tract origin, conceptually similar to a Meckel's diverticulum but without a diverticulum as such. Heterotopic pancreatic tissue occurring alone is more common in the proximal small intestine, duodenum, and stomach than in the ileum, and it is often asymptomatic.
Cholesteryl Ester Storage Disease: Case Report during Childhood
Authors: Akçören Zuhal , Göğüş Safiye , Koçak Nurten , Gürakan Figen , Özen Hasan , Yüce Aysel
Published: July 2002

Cholesteryl ester storage disease (CESD) is rare and characterized by accumulation of cholesteryl esters and triglycerides in many tissues due to the deficiency of lysosomal acid lipase. We report a 3½-year-old child with CESD. The diagnosis was indicated by liver biopsy and confirmed by reduced acid lipase activity in leukocytes.
Legacy of Dr. Ewing
Authors: Jay Venita
Published: July 2002

For some years I have been encountering in material curetted from bone tumors a structure which differed markedly from that of osteogenic sarcoma, was not identical with any known form of myeloma, and which had to be designated by the vague term, “round cell sarcoma” of unknown origin and nature … this tumor is highly susceptible to radium…. The designation of the tumor as endothelioma, rather than as myeloma seems advisable.

—James Ewing
Possible role of H+—alkali cation countertransport in secretary granule swelling during exocytosis
Authors: Grinstein Sergio , Vander Meulen J. , Furuya W.
Published: July 2002

Studies in model systems, as well as observations in intact cells, suggest that osmotic swelling of secretory granules is an essential step in exocytosis. A model is proposed whereby the low pH recorded in most secretory organelles could provide the driving force for granule swelling. The model assumes that during stimulation an exchange of H+ for alkali cations is triggered across the granule membrane. The outgoing H+ are rapidly replaced by the internal buffering capacity with a concomitant osmotic gain. The exchange is independent of anions and could be triggered by cytoplasmic Ca2+. The H+‐pump is responsible for the ΔpH but independent of the exchange mechanism.
A fluorescent peptide model for the thioredoxin active site
Authors: Kishore R. , Mathew M.K. , Balaram P.
Published: July 2002

A synthetic model for the active site of the protein thioredoxin has been synthesized: corresponding to residues 31–35 of the protein and possessing the 14‒membered disulfide loop and a fluorescent chromophore. Dithiothreitol reduction of the disulfide bond results in a 50–60% enhancement of Trp fluorescence. The rate of reduction is solvent dependent, following the order 8 M urea » methanol > water. The spectral changes observed in the model peptide are compared with those reported for the native protein. Circular dichroism studies suggest a substantial change in peptide backbone conformation, on disulfide reduction.
Ethylene formation from 1‐aminocyclopropane‐1‐carboxylic acid in plant mitochondria
Authors: Vinkler Chana , Apelbaum Akiva
Published: July 2002

Mitochondria isolated from apical parts of etiolated pea seedlings convert ACC to ethylene. This conversion is heat‐sensitive and largely enhanced when the intact mitochondria are sonicated or when the ionophore nigericin is added to the reaction medium. When the sonicated submitochondiral particles are spun down, almost all of the activity is recovered in the pellet. The results suggest that the ethylene‐formation activity is associated with the inner mitochondrial membrane and that transport of ACC into the mitochondrial membrane is a rate limiting step for the reaction. The mechanism of ACC transport across the mitochondrial membrane is discussed.
Sodium‐dependent isoleucine transport in the methanogenic archaebacterium Methanococcus voltae
Authors: Jarrell Ken F. , Bird Sharon E. , Sprott G.Dennis
Published: July 2002

Methanococcus voltae possesses a Na+‐dependent transport system for isoleucine which requires for optimum rates a CO2/H2 atmosphere. The K
m for the system is 4.5 μM with a V
max of 1.5 nmol·min−1·mg dry wt−1. Approximately 75% of the label can be released from the cell pool following short‐term experiments with gradients of isoleucine reaching 100 (in/out). Transport is inhibited by ionophores and N‐ethyl maleimide. Only valine and leucine effectively compete with isoleucine for transport.
Human endothelial cells contain one type of plasminogen activator
Authors: Kristensen Peter , Larsson Lars-Inge , Nielsen Lars S. , Grøndahl-Hansen Jan , Andreasen Peter A. , Danø Keld
Published: July 2002

At least two types of animal plasminogen activating enzymes exist, differing in amino acid sequence, molecular mass and immunological reactivity: the urokinase‐type and the tissue‐type plasminogen activators. By affinity chromatography with monoclonal antibodies, we have purified the human activators of both types to homogeneity. Using immunocytochemistry with rabbit antibodies raised against these preparations, we now demonstrate that the plasminogen activator present in endothelium of veins and other blood vessels is of the tissue‐type. No urokinase‐type plasminogen activator immunoreactivity was detected in endothelial cells in the intact organism. These findings support the assumption that mobilization of plasmin for different purposes may involve different types of plasminogen activators, and that the plasminogen activator involved in thrombolysis is of the tissue‐type.
Protection against reactive oxygen species by NAD(P)H:quinone reductase induced by the dietary antioxidant butylated hydroxyanisole (BHA)
Authors: Wefers Heribert , Komai Toru , Talalay Paul , Sies Helmut
Published: July 2002

Menadione elicits low‐level chemiluminescence (λ >620 nm) associated with redox cycling of the quinone in mouse hepatic postmitochondrial fractions. This photoemission is suppressed when the animals are fed a diet containing the anticarcinogenic antioxidant, 2[3]‐(tert‐butyl)‐4‐hydroxyanisole (BHA), which leads to a 13‐fold increase in NAD(P)H:quinone reductase (EC 1.6.99.2). Inhibition of the enzyme by dicoumarol completely abolishes the protective effect of BHA treatment and leads to higher chemiluminescence, reaching similar photoemission for BHA‐treated and control animals. These findings indicate that the two‐electron reduction promoted by quinone reductase prevents redox cycling and that BHA protects against reactive oxygen species by elevating the activity of this enzyme.
Oxygen consumption by purified plasmalemma vesicles from wheat roots
Authors: Møller Ian M. , Bérczi Alajos
Published: July 2002

Plasmalemma vesicles from wheat (Triticum aestivum L.) roots consumed O2 and the addition of 1 mM NADH increased the rate ~ 3‐fold (to 15‐30 nmol O2·mg−1·min−1). The NADH‐dependent O2 uptake was abolished by catalase. In the presence of salicylhydroxamic acid (SHAM), an inhibitor of the alternative oxidase pathway in plant mitochondria, NADH‐dependent O2 consumption was stimulated 10–20‐fold (to 200–400 nmol·mg1̄·min−1). Catalase also abolished this stimulation, which was KCN‐sensitive but antimycin A‐insensitive, and the production of H2O2 during SHAM‐stimulated NADH‐dependent O2 uptake was demonstrated. Irrespective of the mechanism, SHAM‐stimulated respiration by root plasmalemma makes it difficult to interpret results on root respiration obtained using KCN and SHAM.
Oxyntomodulin (glucagon‐37) and its C‐terminal octapeptide inhibit gastric acid secretion
Authors: Jarrousse Claire , Audousset-Puech Marie-Pascale , Dubrasquet Marcelle , Niel Huguette , Martinez Jean , Bataille Dominique
Published: July 2002

Oxyntomodulin (OXM) is a peptide isolated from porcine intestine which consists of the whole glucagon sequence with a basic octapeptide (KA8) at its C‐terminal end. In this study, the effect of OXM and KA8 on pentagastrin‐stimulated gastric acid secretion has been studied in conscious rats and cats. In rats, OXM (25–450 pmol·kg−1) as well as KA8 (7.5–60 nmol·kg−1) inhibited pentagastrin‐stimulated gastric acid output in a dose‐dependent manner; KA8 was about 100‐times less potent than OXM. In cats, KA8 (90 nmol·kg−1) was also an inhibitor of acid secretion. We conclude that OXM, or a closely related peptide, could be a physiological modulator of gastric acid secretion, and that the C‐terminal octapeptide of OXM is implicated in this effect.
Thermodynamics of left‐handed helix formation
Authors: Klump H.H.
Published: July 2002

The thermodynamics of right‐ and left‐handed helix formation by poly[d(G‐C)]·poly[d(G‐C)] and by poly‐(dG‐m5dC)·poly(dG‐m5dC) were measured spectrophotometrically and calorimetrically. From the spectrophotometric measurements the thermal stabilities of the alternative helical conformations were evaluated as a function of counterion concentration. From the calorimetric measurements the enthalpies of either right‐handed or left‐handed helix formation were determined. The corresponding experimental ΔH values are −8.6 and −11.2 base pairs for the two conformations in poly[dG‐C)]·poly[d(G‐C)], and −9.0 and −12.7 base pairs, respectively, for poly(dG‐m5dC)·poly(dG‐m5dC).
Phosphorylation of phosphatidylinositols in isolated plant membranes
Authors: Sandelius Anna Stina , Sommarin Marianne
Published: July 2002

Lipid kinase
Phosphatidylinositol phosphorylation
Phosphoinositide
Polyphosphoinositide
Plant membrane
Plasma membrane
Monoclonal antibody detects Ag polymorphism of apolipoprotein B
Authors: Tikkanen Matti J. , Ehnholm Christian , Bütler Rene , Young Stephen G. , Curtiss Linda K. , Witztum Joseph L.
Published: July 2002

A monoclonal antibody (MB‐19) was used to investigate the polymorphism of apolipoprotein B in a large family and in unrelated subjects. Apolipoprotein B was shown to exhibit high‐, intermediate‐ or low‐affinitybinding to this antibody. Thus, MB‐19 bound strongly to the Ag(c) epitope, an Ag antigenic domain previously characterized by human antisera, while it bound only weakly to the allelic epitope Ag(g). It proved therefore useful for the detection of the two corresponding allelic apoB species designated apoBc (high‐affinity binding) and apoBg (low‐affinity binding), and for confirming their co‐dominant transmission. Intermediate binding resulted from the presence of a mixture of both apoB populations in heterozygous subjects.
A barley flour inhibitor of insect α‐amylase is a major allergen associated with baker's asthma disease
Authors: Barber Domingo , Sánchez-Monge Rosa , Gómez Luis , Carpizo José , Armentia Alicia , López-Otín Carlos , Juan Fernando , Salcedo Gabriel
Published: July 2002

A barley salt‐soluble protein of 14.5 kDa, which inhibits the α‐amylase from the insect Tenebrio molitor, has been identified as a major IgE‐binding component of sera from baker's asthma patients. The N‐terminal amino acid sequence of this protein indicates that it is a member of a previously described family of α‐amylase/trypsin inhibitors.
Identification of the cartilage α 1(XI) chain in type V collagen from bovine bone
Authors: Niyibizi Christopher , Eyre David R.
Published: July 2002

Type V collagen prepared from bovine bone was resolved into three distinct α‐chains by high performance liquid chromatography and gel electrophoresis. Peptide mapping established two chains as α 1(V) and α 2(V) as expected and the third as the cartilage α 1(XI) chain (previously thought to be unique to cartilage). In adult bone, the type V collagen fraction was richer in α 1(XI) chains than in fetal bone (about 1/3 of the chains in the adult). How these polypeptides are organized into native molecules is not yet clear, though the stoichiometry suggests cross‐type heterotrimers between the type V and XI chains.
Sequence and expression of human GABAA receptor α1 and β1 subunits
Authors: Schofield Peter R. , Pritchett Dolan B. , Sontheimer Harald , Kettenmann Helmut , Seeburg Peter H.
Published: July 2002

The deduced amino acid sequences of cDNA clones encoding human GABAA receptor α1 and β1 subunits are presented. The human subunits display very high levels of sequence identity with the corresponding bovine receptor subunits. The cloned human GABAA receptor subunits induce the formation of GABA‐gated chloride channels when expressed in mammalian cells.
Direct identification of the fluoroaluminate and fluoroberyllate species responsible for inhibition of the mitochondrial F1‐ATPase
Authors: Dupuis Alain , Issartel Jean-Paul , Vignais Pierre V.
Published: July 2002

In the presence of ADP, fluoroaluminate and fluoroberyllate inhibit irreversibly the soluble mitochondrial F1‐ATPase. We report here direct evidence that this inhibition is related to the tight binding of [3H]ADP, beryllium and fluoride to the enzyme. In the case of beryllium‐induced inhibition, the stoichiometry of bound species is 1 mol [3H]ADP, 1 mol beryllium and 2 or 3 mol fluoride depending on the initial fluoride concentration used, which indicates that both the combinations ADP1,Be1,F3 and ADP1,Be1,F3 are competent for inhibition. In the case of aluminium‐induced inhibition, the binding stoichiometry of 4 mol fluoride per mol [3H]ADP favours the following combination of bound species ADP1,Al1,F4. These results favour a model where fluorometals mimic phosphate and form an abortive complex with ADP in the catalytic site(s) of F1.
Different effects of sphingosine, R59022 and anionic amphiphiles on two diacylglycerol kinase isozymes purified from porcine thymus cytosol
Authors: Sakane Fumio , Yamada Keiko , Kanoh Hideo
Published: July 2002

Porcine thymus cytosol contains two immunologically distinct forms of diacylglycerol kinase (DGK) [Yamada, K. and Kanoh, H. (1988) Biochem. J. 255, 601–608]. These 2 DGK species, having apparent molecular masses of 80 and 150 kDa, were purified from the thymus cytosol. Upon sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, the 150‐kDa DGK gave 2 polypeptide bands of 50 and 75 kDa, whereas the 80‐kDa DGK yielded a single protein band. The 80‐kDa DGK was markedly activated by 10–20 μM sphingosine as well as by the known anionic activators such as phosphatidylserine and deoxycholate. In contrast, the 150‐kDa DGK was fully active in the absence of the anionic activators and was strongly inhibited by sphingosine (IC50, 20 μM). The putative DGK inhibitor R59022 inhibited the 80‐kDa DGK (IC50, 10 μM), but had little effect on the 150‐kDa form. It is therefore clear that in the thymus cytosol there are at least 2 DGK isozymes operating under different control mechanisms.
The dependence on intracellular ATP concentration of ATP‐sensitive K‐channels and of Na,K‐ATPase in intact HIT‐T15β‐cells
Authors: Niki Ichiro , Ashcroft Frances M. , Ashcroft Stephen J.H.
Published: July 2002

We have studied the effects of changes of intracellular ATP concentration ([ATP]i) on the activity of ATP‐sensitive K‐channels (I
K(ATP)) and of Na,K‐ATPase in intact cells of the insulin‐secreting cell‐line HIT‐T15. Pre‐exposure of HIT β‐cells to oligomycin caused a dose‐dependent reduction in [ATP]i. Marked activation of I
K(ATP) activity was found when ATP was lowered below 3 mM. Na,K‐ATPase was progressively inhibited as ATP was lowered to 1.5 mM. These data demonstrate that changes in intracellular ATP in the millimolar range markedly influence the activity of two β‐cell membrane proteins having affinities for ATP in the micromolar range. This suggests that submembrane [ATP] may be considerably below the measured bulk cytosolic concentration. The findings also support the proposed role of intracellular ATP in mediating effects of changes in glucose concentration on the activity of β‐cell I
K(ATP) and insulin secretion.
An architecture for the fusion site of Influenza hemagglutinin
Authors: Bentz Joe , Ellens Harma , Alford Dennis
Published: July 2002

The recent finding that more than one Influenza hemagglutinin (HA) is required at the fusion site for HA‐expressing fibroblasts [1], together with the crystal structure of HA at neutral pH [2], provide the basic elements of a plausible model for this fusion site. Within an aggregate of HA trimers at low pH, we propose fusion intermediates which are based upon a minimal alteration to the known neutral pH structure of HA and which should have reasonable activation energies. This is the first model of a glycoprotein‐mediated fusion site which explicitly accounts for the disposition of the lipids within these intermediates. While the fusion site created by HA will not be the same as that of eukaryotic fusion complexes [3], general characteristics could be shared.
Intra‐ and extraluminal sarcoplasmic reticulum membrane regulatory sites for Ca2+‐induced Ca2+ release
Authors: Nelson Thomas E. , Nelson Kenneth E.
Published: July 2002

A heavy skeletal muscle sarcoplasmic reticulum (SR) fraction was actively loaded stepwise with calcium until Ca2+‐induced Ca2+ release occurred. The total Ca2+ load, T1, at which release occurred is postulated to be regulated by an intraluminal, low‐affinity receptor. After obtaining T1, the critical concentration of Ca2+ required extraluminally (T2) was determined. T1 averaged 58.6 ± S.D., 6.9 nmol Ca2+/mg SR and T2 averaged 2.14 ± S.D., 0.24,μM. Both T1 and T2 were increased by Mg2+ and decreased by caffeine. Ruthenium red increased T2 more than T1 while ryanodine had no effect on T1 but markedly increased T2. The results suggest that two Ca2+ regulatory sites may be functional for Ca2+‐induced Ca2+ release from SR.
Interaction between the left‐handed Z‐DNA and polyamine The crystal structure of the d(CG)3 and N‐(2‐aminoethyl)‐1,4‐diamino‐butane complex
Authors: Ohishi Hirofumi , Kunisawa Shoko , van der Marel Gijs , van Boom Jacques H. , Rich Alexander , Wang Andrew H.-J. , Tomita Ken-ichi , Hakoshima Toshio
Published: July 2002

The DNA fragment d(CG)3 was co‐crystallized with N‐(2‐aminoethyl)‐1,4‐diaminobutane (PA(24)), a chemically synthesized polyamine. The complex crystal contained one polyamine, 3 magnesium cations and one sodium cation per duplex of d(CG)3, and well diffracted the X‐ray intensities up to 1.0 Å resolution. The d(CG)3 took a left‐handed Z‐DNA conformation, and the PA(24) molecule electrostatically interacted with the phosphate groups of the d(CG)3 duplex.