bluuebunny/crossref_metadata_2025 huggingface dataset:
Histopathological Features of Acral Melanocytic Nevi in Children: Study of 21 Cases
Authors: Evans Margaret J. , Gray Elizabeth S. , Blessing Karen
Published: July 2002

Benign melanocytic lesions in children may give cause for some concern histologically. This is because they represent a specific entity, or they reflect the state of evolution of the lesion or the anatomical location. This latter phenomenon has been poorly documented in children. In this study, we address the problem of atypical features frequently seen in benign nevi from acral sites in a group of patients aged 18 years or less. Twenty-one cases (12 female, 9 male) were identified from the Department of Pathology files during the years 1975–1988. All were Caucasian. Histological examination revealed that 6 cases were congenital and 15 were aquired; of these, 19 cases (90%) had a junctional component and all of these exhibited architecture atypia in the form of either lentiginous proliferation (84%) or confluence of junctional nests (84%). Forty-two percent (8/19) showed a mixture of both. Thirty-seven percent (7/19) exhibited transepidermal elimination of melanocytic nests, with 13/19 (68%) showing single cell infiltration of the epidermis. Atypical size, shape, and location of the junctional nests were present in 10/19 cases (53%). Within this group there appears to be no relationship between the age of the patient and the degree of architectural atypia. Mild cytological atypia was common. This report stresses the importance of anatomic subsite in the assessment of melanocytic lesions in children as well as in adults.
Gonadoblastoid Testicular Dysplasia in Walker-Warburg Syndrome
Authors: Hung Noelyn A. , Silver Meredith M. , Chitayat David , Provias John , Toi A. , Jay Venita , Becker Laurence E.
Published: July 2002

Two male fetuses (18 and 22 weeks gestation) and a 3-month-old male infant (full sibling of the younger fetus) who were diagnosed with Walker-Warburg syndrome (WWS) on the basis of neuropathologic autopsy findings in brain, eyes, and muscle also had micro-orchia and, microscopically, diffuse gonadoblastoid dysplasia in the testes. Both fetuses also had a miniature left ureter and cystic dysplastic left kidney. Testes from control fetuses of 17–24 weeks gestation with normal karyotype and no central nervous system abnormalities (group A, n = 50), a variety of central nervous system abnormalities (group B, n = 50), or an autosomal aneuploidy syndrome with or without central nervous system abnormalities (group C, n = 30) had no diffuse dysplasia, although a single gonadoblastoid seminiferous tubular profile was present in three controls. Testicular morphology was normal in older fetuses and infants with a wide variety of central nervous system malformations (group D, n = 50). We found no evidence of hypogonadotrophic hypogonadism in the three WWS cases to account for the small penis and incompletely descended testes commonly reported in this condition. We concluded that the apparent specificity of the gonadoblastoid testicular dysplasia to WWS suggests that the gene defect directly affects testicular development.
Mitral and Aortic Atresia Associated with Hypoplastic Right Lung, Crossover Segment of Right Lower Lobe, and Anomalous Scimitar-like Right Pulmonary Venous Connection with Inferior Vena Cava: Clinical, Angiocardiographic, and Autopsy Findings in a Rare Case
Authors: Bartram Ulrike , Van Praagh Stella , Keane John F. , Lang Peter , van der Velde Mary E. , Van Praagh Richard
Published: July 2002

A newborn female infant was found to have a unique and previously unreported group of anomalies: ( 1) mitral and aortic atresia with a highly obstructive atrial septum; ( 2) hypoplasia of the right lung with a crossover segment involving the right lower lobe; ( 3) normally connected pulmonary veins, two from the left lung and one from the right; and ( 4) a large anomalous branch of the right pulmonary vein of scimitar configuration that anastomosed with the normally connected right pulmonary vein and with the inferior vena cava (IVC). The scimitar vein appeared obstructed at its junction with the right pulmonary vein and at its junction with the inferior vena cava within the hepatic parenchyma. To our knowledge, this is the first report of a scimitar-like vein coexisting with mitral and aortic atresia and connecting both with the right pulmonary vein and with the inferior vena cava. The highly obstructed left atrium was partially decompressed by retrograde blood flow via the normally connected right pulmonary vein to the anomalous scimitar venous pathway and thence to the inferior vena cava via a pulmonary-to-IVC collateral vein.
Epstein-Barr Virus Polymerase Chain Reaction and Serology in Pediatric Post-Transplant Lymphoproliferative Disorder: Three-Year Experience
Authors: Rogers Beverly Barton , Sommerauer John , Quan Albert , Timmons Charles F. , Dawson D. Brian , Scheuermann Richard H. , Krisher Karen , Atkins Carolyn
Published: July 2002

To assess whether the semiquantitative peripheral blood Epstein-Barr virus (EBV) polymerase chain reaction (PCR) test correlates with post-transplant lymphoproliferative disorder (LPD), we compiled the results of the test done over a 3-year period ending July 1997. Six hundred seventy-six tests were done on 185 patients. Four hundred-thirty tests (63%) were negative, 167 (25%) were weak positive, 67 (10%) were moderate positive, and 12 (2%) were strong positive. Twelve of the patients developed a lymphoproliferative disorder (LPD) during this time. The EBV PCR tests proximate to the diagnosis of LPD in the 12 patients with EBV-positive LPD were 6 strong positive, 5 moderate positive, 1 weak positive. No patient with LPD had a negative result at diagnosis. Stated another way, 6/12 (50%) of strong-positive PCR tests, 5/67 (7%) moderate-positive tests, and 1/167 (.6%) of weak-positive tests correlated with LPD. Serologic evaluation for EBV done on 7 patients at the time of LPD showed low serologic responses in 5 of the 7 patients. The EBV PCR temporally associated with the serology indicated moderate to large viral burdens. In each patient evaluated serially, the EBV PCR test rose before the diagnosis of LPD and fell with treatment for the disorder. In conclusion, the EBV PCR test may be used as an adjunct to the diagnosis of patients with LPD and may be used to monitor response to therapy for the disorder.
Methotrexate-Resistant Form of Dihydrofolate Reductase Protects Transgenic Murine Embryos from Teratogenic Effects of Methotrexate
Authors: Sutton Cari , McIvor R. Scott , Vagt Micki , Doggett Barbara , Kapur Raj P.
Published: July 2002

Methotrexate, a potent inhibitor of the ubiquitously expressed enzyme dihydrofolate reductase, induces limb and facial anomalies that resemble vascular disruptions in their evolution and final outcome. Previous studies suggest that inhibition of dihydrofolate reductase is responsible for methotrexate-induced embryopathy, although specific sites of methotrexate activity have not been well defined. In this report, we show that constitutive expression of a methotrexate-resistant form of dihydrofolate reductase in transgenic embryos and their placentas ameliorates methotrexate teratogenicity. However, expression of the transgene in maternal tissues had no significant protective effect. The results confirm the role of dihydrofolate reductase inhibition in the pathogenesis of methotrexate-induced birth defects and provide a foundation for future studies of targeted transgene expression in select embryonic or placental cell populations.
Intergroup Rhabdomyosarcoma Study: Update for Pathologists
Authors: Qualman Stephen J. , Coffin Cheryl M. , Newton William A. , Hojo Hiroshi , Triche Timothy J. , Parham David M. , Crist William M.
Published: July 2002

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood, and 75% of such cases in the United States are reviewed at the Pathology Center for the Intergroup Rhabdomyosarcoma Study Group (IRSG). The first four generations of IRSG therapeutic trials (IRS I–IV) and supportive pathologic studies have generated a new International Classification of Rhabdomyosarcoma (ICR) that offers new morphologic concepts to the practicing pathologist. The objective of this report is to clearly define emerging histopathologic categories of RMS as defined by the ICR, and to emphasize correlative immunohistochemical or molecular studies. Emerging ICR variants of RMS place the patient in widely divergent prognostic categories (superior, botryoid or spindle cell variants; poor, solid alveolar or diffusely anaplastic variants). The cardinal histopathologic features of the ICR combined with results of studies of fusion genes seen with t(1;13) and t(2;13) will help delineate therapeutic subgroups of RMS for the fifth generation (IRS V) of IRSG studies. Consequently, it is imperative for the practicing pathologist to be familiar with the practical workup and diagnosis of RMS in childhood.
Peripheral Neuroepithelioma with Ganglion Cells: Report of Two Cases and Review of the Literature
Authors: Williams Susan , Parham David M. , Jenkins Jesse J.
Published: July 2002

Peripheral neuroepitheliomas, also known as peripheral primitive neuroectodermal tumors, are by definition primitive embryonal lesions generally composed of poorly differentiated neuroectodermal elements. We have examined two cases that paradoxically contain extensive foci of ganglionic differentiation similar to that of ganglioneuroblastoma, in addition to primitive elements. One tumor arose from the chest wall of an 8-year-old male and the other from the abdominal wall of a 15-year-old male. Differentiation into a mature ganglionic phenotype was confirmed by immunohistochemistry in one case. Rare peripheral neuroepitheliomas have a capacity for maturation that is not generally appreciated. These lesions should not be confused with ganglioneuroblastomas, which are genotypically unrelated neoplasms.
Cervical Ribs: Useful Marker of Monosomy X in Fetal Hydrops
Authors: Keeling Jean W. , Kjaer Inger
Published: July 2002

Cervical ribs were observed in six hydropic fetuses with 45X karyotype. To test the usefulness of this observation in the macerated hydropic fetus where chromosome culture is problematic, a group of 36 hydropic fetuses was examined. Cases were chosen to include fetuses with several karyotypic and pathological abnormalities known to be associated with fetal hydrops. Whole-body anteroposterior radiographs were evaluated without knowledge of the fetal karyotype or pathological findings. Twenty-five fetuses had an abnormal karyotype, seven had a normal karyotype and in four culture failed. In the last group, the number of X, 21 and 18 chromosomes per nucleus was estimated using FISH. Radiographic analysis demonstrated that among the 16 fetuses with 45,X karyotype or a single copy of X and female phenotype, 12 had a pair of cervical ribs. Three other fetuses had a single cervical rib. Only one fetus had no cervical ribs. The last fetus had tubular hypoplasia of the aortic arch and persistent mesocolon. Twelve of the sixteen 45,X fetuses had tubular hypoplasia of the aortic arch. Seven had other cardiovascular anomalies, five had renal anomalies, and five had anomalies of intestinal rotation. Cervical rib appears to be more common than other frequently recorded associations of 45,X. It is a useful and easily demonstrated mark in the evaluation of the macerated hydropic fetus.
Abnormalities in Central Nervous System Development in Osteogenesis Imperfecta Type II
Authors: Emery Shawn Clark , Karpinski Nancy C. , Hansen Lawrence , Masliah Eliezer
Published: July 2002

Osteogenesis imperfecta (OI) type II is a perinatally lethal condition resulting from mutations in type I collagen genes. In addition to characteristic skeletal anomalies, OI type II has recently been shown to be associated with neuropathological alterations, specifically perivenous microcalcifications, and impaired neuroblast migration. In light of these findings, and because type I collagen promotes neuritic maturation both in vitro and in vivo, we sought to determine if additional central nervous system (CNS) developmental anomalies could be found in previously autopsied OI type II cases, and if specific abnormalities correlate with OI subtypes. We retrospectively studied brains of nine patients diagnosed with OI. Of these, seven were OI type II: five were OI type IIA, one was type IIB, and one was type IIC. One OI type I specimen and one OI type III brain were included for comparison, as well as five controls. The IIC brain showed hippocampal malrotation, agyria, abnormal neuronal lamination, diffuse hemorrhage, and peri-ventricular leukomalacia (PVL). The IIB brain had white matter gliosis, PVL, and perivascular calcifications, but was normally developed. Of the five type IIA brains, two showed migrational defects with coexisting PVL and gliosis, two were normally developed with similar white matter injuries, and one was grossly normal. These findings support the contention that collagen mutations might negatively impact CNS development.
Malignant Peripheral Nerve Sheath Tumor of Bone in Children and Adolescents
Authors: Wesche W. Allen , Khare Vivek , Rao Bhaskar N. , Bowman Laura C. , Parham David M.
Published: July 2002

Malignant peripheral nerve sheath tumor (MPNST) of bone is a rare entity. We have examined three lesions that fit standard histopathologic criteria for MPNST of soft tissues but that arose in the skeleton of three children aged 6 to 13 years. None was affected by neurofibromatosis 1 (NF1). Histologic features typical of MPNST included spindle cells with comma-shaped nuclei, tactoid bodies, nuclear palisading, hyaline bands, and schwannoma-like and curlicue foci. Epithelioid foci were seen in two cases, and heterologous differentiation in one. Immunohistochemistry revealed positivity for S-100 (1 positive/3 tested), vimentin (3/3), glial fibrillary acidic protein (2/3), CD34 (1/1), and CD68 (1/2). Studies for CD99 (0/3), epithelial membrane antigen (0/3), cytokeratin (0/3), CD57 (0/3), and HMB-45 (0/2) were negative. Ultrastructural findings in one of two cases examined included interlacing, attenuated cytoplasmic processes, microtubules, and rare dense-core granules. We conclude that MPNST may arise as a primary bone neoplasm in children without NF1.
Unusual Case of Tracheal Agenesis
Authors: O'Neill David , Morecroft James A. , Gibson Alan T. , Bull Peter D. , Walker Jenny
Published: July 2002

We describe the clinical presentation and pathological features of an unusual case of tracheal agenesis. The axial derivatives of the primitive foregut between the larynx and stomach were represented by a single structure featuring sequential segmentation into regions showing exclusively tracheal or esophageal differentiation in a pattern that is not easily classified by existing nosologic systems nor explained by the conventional hypothesis of dysontogenesis.
Fibrous Hamartoma of Infancy: Current Review
Authors: Dickey Glenn E. , Sotelo-Avila Cirilo
Published: July 2002

This review examines 197 cases of fibrous hamartoma of infancy (FHI) described in the literature and provides a detailed clinicopathologic analysis of what is known to date of this peculiar lesion of the subcutis and lower dermis. The vast majority of these cases occurred within the first year of life (91%). Twenty-three percent were congenital. There was a predilection for boys with a male/female ratio of 2.4. Males and females had similar anatomic distribution with the most common locations being the axillary region, upper arm, upper trunk, inguinal region, and external genital area. Most cases presented as solitary masses, but four cases of multiple separate synchronous lesions have been reported.

Most lesions presented as a painless nodule, sometimes with rapid growth. A few cases had overlying skin changes, including alteration in pigmentation, eccrine gland hyperplasia, and increased hair. No lesions were reported to have familial or syndromic association, or to occur in combination with other hamartomas. Spontaneous regression has not been reported. The treatment of choice is local excision. Even with incomplete excision, FHI has a low recurrence rate. Criteria for histologic diagnosis include the presence of well-defined bundles of dense, uniform, fibrous connective tissue projecting into fat, primitive mesenchyme arranged in nests, concentric whorls or bands, and mature adipose tissue intimately admixed with the other components.

Flow-cytometric and conventional cytogenetic studies have not been reported; these may clarify any relationship to other fibroblastic/myofibroblastic proliferations in children, resulting in better classification and terminology of this unique lesion.
Takayasu's Arteritis Coexisting with Wegener's Granulomatosis in a Teenager with Renal Insufficiency: Case Report
Authors: Mejia-Hernandez Carmen , Alvarez-Mendoza Antonio , DeLeon-Bojorge Beatriz
Published: July 2002

A case of Wegener's granulomatosis (WG) coexisting with Takayasu's arteritis (TA) in a 12-year-old girl is presented. She presented with fulminant and severe renal insufficiency due to crescentic glomerulonephritis. At autopsy, aortic lesions of Takayasu's arteritis coexisted with pulmonary and renal findings of WG, and the patient's serum at autopsy had an elevated level of antineutrophil cytoplasmic antibodies (ANCA). Both forms of vasculitis have been thought to be triggered by infectious agents and it is postulated that this occurrence accounts for the coexistence of the two forms of vasculitis in this case.
Composition of the Pulmonary Interstitium during Normal Development of the Human Fetus
Authors: Wright Christopher , Strauss Susanne , Toole Kieran , Burt Alastair D. , Robson Stephen C.
Published: July 2002

Normal lung development is dependent on epithelial–mesenchymal interactions. This study was undertaken to examine the structure of the interstitium of the developing human fetal lung, concentrating particularly on the first and second trimesters. Lung tissue was obtained at autopsy from nonmalformed, nonmacerated cases of spontaneous abortion ( n = 15), stillbirth ( n = 9), and very early neonatal death ( n = 5) (range of gestations, 10–42 weeks). Paraffin-embedded tissue sections were examined using immunohistochemical methods to determine expression of collagens I, III, IV, V, and VI; the glycoproteins fibronectin and laminin; and the intermediate filaments vimentin, α-smooth muscle actin (αSMA), and desmin. Collagens III and VI and cells expressing αSMA were present consistently at points of airway branching and secondary crest formation, indicating a role for these components in the initiation and stabilization of airway branches in the developing lung. Desmin expression by stromal cells succeeded αSMA temporally, and may represent a marker of terminal smooth muscle differentiation within the airway; it was not detected in the vascular tree. Other components were widely expressed throughout the extracellular matrix, including basement membranes, at all gestations. The spatial and temporal patterns of expression of components of the lung interstitium provide clues to the mechanisms underlying normal human lung development and possible insights into the pathogenesis of fetal and neonatal lung disease.
Extralobar Sequestration with Frequently Associated Congenital Cystic Adenomatoid Malformation, Type 2: Report of 50 Cases
Authors: Conran Richard M. , Stocker J. Thomas
Published: July 2002

Extralobar pulmonary sequestration (ELS) represents a mass of pulmonary parenchyma separate from the normal lung. The coexistence of congenital cystic adenomatoid malformation (CCAM) in ELS has been reported. To define this association, the clinical, gross, and histologic features of 50 ELS cases were analyzed.

The age at diagnosis varied from birth to 65 years with 24% of cases diagnosed prenatally and 61% (23/38) diagnosed within the first 3 months of life. Fifty-two percent of cases were in females and 48% in males. Forty-eight percent of ELS(s) were located in the left hemithorax, 20% in the right hemithorax, 8% in the anterior mediastinum, 6% in the posterior mediastinum, and 18% beneath the diaphragm. The blood supply to the sequestration in 77% of cases was directly from the aorta. Grossly, the lung, though hypoplastic in some cases, was otherwise unremarkable.

Fifty percent (23/46) of ELS cases were associated with a coexistent CCAM. In contrast to the series as a whole, 92% (11/12) of the ELS/CCAM cases, excluding those prenatally diagnosed, were diagnosed within the first 3 months and 57% occurred in females. ELS/CCAM lesions, while randomly distributed, were more frequently seen on the left side. Gross features of the ELS/CCAM cases were similar to those cases with ELS alone. All CCAM cases had a type 2 pattern on histologic examination with 48% of those cases also displaying rhabdomyomatous dysgenesis.

Our findings indicate that the occurrence of CCAM in ELS is more frequent than reported in the literature and differs in presentation from ELS cases not associated with CCAM.
Solitary Unilocular Cyst of the Lung with Features of Persistent Interstitial Pulmonary Emphysema: Report of Four Cases
Authors: Cohen Marta C. , Drut Rosa M. , Drut Ricardo
Published: July 2002

Neonatal interstitial pulmonary emphysema (IPE) is a well-characterized lesion usually presenting in preterm newborns as a complication of respiratory distress syndrome and/or assisted ventilation. Occasionally, IPE may occur spontaneously in infants with no underlying pulmonary disease. Persistence of IPE (PIPE) may be diffuse or localized. Localized PIPE usually presents as multiple cysts 0.3 to 3 cm in one or more lobes of the lung. In this report, we describe four cases of unilocular large cysts (up to 5 cm in diameter) partially lined by uni- and multinucleated histiocytes in a foreign body type reaction and showing gas dissection of the surrounding parenchyma (present in case 1). These histological features favored the diagnosis of PIPE and the cases were interpreted as such, since no other clear-cut diagnosis could be defined. However, because the lesion was limited to one lobe, and the children were full term, asymptomatic at birth and without history of respiratory distress or assisted ventilation, differential diagnosis with other pulmonary cystic lesions of infancy is mandated.
Congenital Sacrococcygeal Teratomas: Effect of Gestational Age on Size, Morphologic Pattern, Ploidy, p53, and ret Expression
Authors: Herrmann Marille E. , Thompson Karen , Wojcik Eva M. , Martinez Robert , Husain Aliya N.
Published: July 2002

Prognosis of infants born with sacrococcygeal teratomas (SCTs) correlates with gestational age (GA). The survival rate after 30 weeks of gestation is 75%, compared to 7% before 30 weeks of gestation. Studies correlating GA with size, morphologic composition of teratomas, ploidy or expression of cell cycle control proteins such as p53, and ret [a tyrosine kinase receptor of the GDNF (glial cell line–derived neurotrophic factors)] receptor family may provide information explaining differences in survival. Seven SCTs (GA 21 to 41 weeks), ranging in size from 5 to 15 cm, were evaluated for morphologic composition. DNA ploidy was assessed in mature and immature neural elements. Immunohistochemical reactivity with monoclonal antibodies recognizing p53, and ret was quantitated and correlated with morphological pattern and GA. Relative size of teratomas to infants' weight and content of immature neural tissues correlated inversely with advancement of GA. Yolk sac tumor (YST) and immature tissues showed aneuploid cell populations. Nuclear p53 reactivity was apparent in the teratoma with YST in the microcystic patterns, the neuroectodermal rosettes, and the glandular patterns. Ret reactivity was seen in osteoclasts adjacent to bone formation surrounding developing teeth in an immature teratoma, and in rare mature neural cells of one SCT of 35 weeks GA. The rapid growth of SCT (GA <30 weeks) correlates with increase in immature neural tissues. Our study confirms aneuploidy in YST and suggests aneuploid populations within immature tissues. p53 accumulates in a variety of patterns of YST and may be seen in immature components of SCTs. To understand the possible role of ret, further studies comparing ret expression in immature human tissues are needed.
Nijmegen Breakage Syndrome-associated T-cell-rich B-cell Lymphoma: Case Report
Authors: Paulli Marco , Viglio Alessandra , Boveri Emanuela , Pitino Antonio , Lucioni Marco , Franco Carla , Riboni Roberta , Rosso Renato , Magrini Umberto , Marseglia Gian Luigi , Marchi Antonietta
Published: July 2002

In 1981 Weemaes et al. first described the Nijmegen breakage syndrome (NBS), a rare autosomal recessive disorder characterized by stunted growth, microcephaly, immunodeficiency, spontaneous chromosome instability, and a peculiar predisposition to cancer development. Most NBS-related malignancies are lymphomas, but their pathologic features have rarely been specified. We report here the case of a northern Italian 8-year-old child who, 2 years after the diagnosis of NBS, developed a diffuse large B-cell lymphoma (T cell–rich B-cell lymphoma variant). The histological and immunobiological features of the lymphoma population are analyzed and discussed in detail.
Extensive Gastric Heterotopia of the Small Intestine Resulting in Massive Gastrointestinal Bleeding, Bowel Perforation, and Death: Report of a Case and Review of the Literature
Authors: Lambert Michele P. , Heller Debra S. , Bethel Colin
Published: July 2002

Gastric heterotopia of the small intestine is a rare occurrence outside of Meckel's diverticulum and intestinal duplication. The vast majority of cases of gastric heterotopia occur as polypoid or tumorous lesions in the duodenum. These lesions have been associated with clinical symptoms including diarrhea, obstruction, dyspepsia, ulceration, and gastrointestinal bleeding. We present a case of gastric heterotopia that is unique because the lesions occurred as multiple, carpet-like, nonpolypoid areas throughout a large portion of the small intestine. A review of the literature is included.
Sturge-Weber Syndrome
Authors: Jay Venita
Published: July 2002

I have no intention of going into the difficult question of the pathology of port-wine mark. The point to which I wish to call particular attention is the probable relationship between the mark and the fits …. From the nature of the fits, and from their mode of onset, I think there can be no doubt that they are due to some cause external to the nerve-tissue … and this external cause is in all probability to be found in the presence of a “port-wine mark” on the surface of the right side of the brain, just as we have found it in the skin, mucous membranes, and retina of that side.

William Allen Sturge, 1879
Persistent Interstitial Pulmonary Emphysema-like Cyst Associated with Metastatic Synovial Sarcoma
Authors: Cohen Marta C. , Drut Ricardo
Published: July 2002

Interstitial pulmonary emphysema is characterized by the presence of gas dissecting the interstitial tissues of the lung. Clinically, it may be acute or persistent, and the latter can be further categorized as localized or diffuse. Usually, it appears in preterm neonates with a history of assisted ventilation or respiratory distress. Although far from frequent, the localized variety of persistent interstitial pulmonary emphysema (PIPE) can develop spontaneously in full-term babies or infants without any obvious underlying pulmonary disease. Histologically, PIPE is characterized by the presence of uni- and multinucleated histiocytes lining the inner surface of the cysts. In this report, we describe a 15-year-old male with synovial sarcoma (SS) of the right ankle diagnosed 4 years previously who developed pulmonary metastasis, one of which presented cystic changes with features of PIPE.
Volkensin, the toxin of Adenia volkensii (kilyambiti plant)
Authors: Barbieri Luigi , Falasca Anna Ida , Stirpe Fiorenzo
Published: July 2002

A toxic protein, volkensin, has been purified from the roots of Adenia volkensii. This toxin is a galactose‐specific lectin with M
r 62000, consisting of two subunits with M
r 36000 and 29000. Volkensin inhibits protein synthesis by a lysate of rabbit reticulocytes and by HeLa cells, and is highly toxic to mice (LD
50 1.38 μg/kg body wt).
The phospholipid organisation in the membranes of McLeod and Leach phenotype erythrocytes
Authors: Kuypers Frans A. , van Linde-Sibenius Trip Margreet , Roelofsen Ben , Op den Kamp Jos A.F. , Tanner Michael J.A. , Anstee David J.
Published: July 2002

The phospholipid composition, the distribution of phospholipids over the two membrane layers as well as the phosphatidylcholine‐specific transfer protein‐mediated exchangeability of phosphatidylcholine from the membrane, has been investigated in two types of abnormal erythrocytes ‐ the McLeod phenotype and the Leach phenotype. The acanthocytic McLeod cells appeared to have a normal phospholipid composition and distribution, but the exchangeability of phosphatidylcholine was found to be markedly enhanced. Unlike control erythrocytes, in which 75% of all of the phosphatidylcholine can be exchanged during an 8 h incubation, the McLeod cell showed a complete exchange of this phospholipid within the same time period. This obviously indicates an enhanced transbilayer mobility of phosphatidylcholine in the membrane of McLeod cells. Erythrocytes of the Leach phenotype showed an elliptocytic shape and increased osmotic fragility, but no abnormalities were observed as to the composition and organisation of the phospholipid complement of their membranes.
Sequence‐dependent hydrolysis of RNA using modified oligonucleotide splints and RNase H
Authors: Inoue Hideo , Hayase Yoji , Iwai Shigenori , Ohtsuka Eiko
Published: July 2002

We found that, in the presence of chimeric oligonucleotides containing complementary deoxyribo‐ and 2′‐O‐methylnucleosides, a nonaribonucleotide, [5′‐32 pACUUACCUG, was cleaved specifically upon treatment with RNase H. When 3′m(UG)d(AATG)m(GAC)5′ was used as a hybridization strand, *pACUUACCUG was cleaved between C6 and C7 to yield *pACUUAC. In the presence of 3′m(UGAA)d(TGGA)m(C)5′, the nonaribonucleotide was hydrolyzed, mainly between U8 and C9, to give *pACUUACCU. This method will have a variety of applications in the field of RNA engineering.
A dicarboxylate transporter on the peribacteroid membrane of soybean nodules
Authors: Udvardi Michael K. , Price G.Dean , Gresshoff Peter M. , Day David A.
Published: July 2002

Using preparations of peribacteroid membrane (PBM)‐enclosed bacteroids from soybean root nodules, we show here that the PBM possesses a dicarboxylate transporter capable of mediating a rapid flux of dicarboxylate anions, such as malate and succinate, to the bacteroids inside the nodule. The transporter has a higher affinity for the monovalent malate anion than for the succinate anion (K
m = 2 and 15 μM, respectively) although the V
max for malate− appears to be lower than for succinate− (V
max = 11 and 30 nmol·min−1·mg protein−1, respectively).
Biosyntheses and processing of lysosomal cysteine proteinases in rat macrophages
Authors: Kominami Eiki , Tsukahara Toshifumi , Hara Kenji , Katunuma Nobuhiko
Published: July 2002

The intracellular processing and release of three lysosomal cysteine proteinases, cathepsin B, H and L, by rat peritoneal macrophages were investigated by pulse‐chase experiments. Newly synthesized procathepsins B (39 kDa), H(41 kDa) and L (39 kDa) after 15 min labeling were processed to the mature, single‐chain enzymes within 1 h. The single‐chain forms of cathepsin B, H and L were further processed to two‐chain forms at different rates: conversion of cathepsin L to the two‐chain form was rapid, whereas the conversions cathepsin B and H took at least 6 h. Macrophages released 30% of the procathepsins B and L, and 10% of the procathepsin H.
Backbone folding of the polypeptide cardiac stimulant anthopleurin‐A determined by nuclear magnetic resonance, distance geometry and molecular dynamics
Authors: Torda Andrew E. , Mabbutt Bridget C. , van Gunsteren Wilfred F. , Norton Raymond S.
Published: July 2002

The solution conformation of the cardiac stimulatory sea anemone polypeptide anthopleurin‐A has been characterised using distance geometry and restrained molecular dynamics calculations. A set of 253 approximate interproton distance restraints and 14 peptide backbone torsion angle restraints derived from two‐dimensional 1H‐NMR spectra at 500 MHz were used as input for these calculations. 13 structures generated by either metric matrix or variable target function distance geometry calculations were refined using energy minimisation and restrained molecular dynamics. The resulting structures contain a region of twisted antiparellel β‐sheet to which two separate regions of unordered chain are linked by three disulphide bonds. Two loops, one including Pro‐41 and the other encompassing residues 10–18, are poorly defined by the NOE data.
Formation of an ion transport supercomplex in Escherichia coli An experimental model of direct transduction of energy
Authors: Bagramyan K.A. , Martirosov S.M.
Published: July 2002

Within this supercomplex direct transduction of energy is accomplished via oxidation of 2 SH to S‐S.
Heat and cold denaturation of phosphoglycerate kinase (interaction of domains)
Authors: Griko Yu.V. , Venyaminov S.Yu. , Privalov P.L.
Published: July 2002

It has been shown that the denaturation of phosphoglycerate kinase (PGK) can be observed not only when the solution is heated above 30°C, but also when it is cooled below this temperature. The disruption of the native PGK structure upon cooling and the subsequent formation of this structure upon heating both proceed in two distinct stages which correspond to the independent disruption or reformation of each of its domains. In contrast, the heat denaturation of PGK proceeds in one stage, showing that the two domains of the molecule are associated into a single complex which figures in the denaturation process as a cooperative unit. It follows that, at elevated temperature, there is a positive interaction between the domains, which disappears at lower temperatures. This might be due to hydrophobic interactions, which are known to be temperature dependent. The temperature decrease leads to a decrease in inter‐ and intradomain interactions, which results in an increase of the independence of the domains and a decrease in their stability.
A synthetic peptide substrate specific for casein kinase‐1
Authors: Agostinis Patrizia , Pinna Lorenzo A. , Meggio Flavio , Marin Oriano , Goris Jozef , Vandenheede Jackie R. , Merlevede Wilfried
Published: July 2002

The synthetic peptide, Asp‐Asp‐Asp‐Glu‐Glu‐Ser‐Ile‐Thr‐Arg‐Arg, derived from the phosphorylation site of casein kinase‐1 (CK‐1) in β‐casein A2, is readily phosphorylated by CK‐1, but not by casein kinase‐2 (CK‐2), cyclic AMP‐dependent protein kinase, protein kinsae C, phosphorylase kinase and protein kinase Fa. Phosphorylation by CK‐1 occurs only at Ser‐6, Thr‐8 being unaffected. The K
m for the peptide is higher (1 mM) than for β‐casein A2 (40 μM), while the V
maxis quite comparable. This is the first synthetic peptide substrate for CK‐1 described so far, and can be used for the rapid and specific estimation of CK‐1 activity in crude extracts.
A type 2A protein phosphatase dephosphorylates the elongation factor 2 and is stimulated by the phorbol ester TPA in mouse epidermis in vivo
Authors: Gschwendt Michael , Kittstein Walter , Mieskes Gottfried , Marks Friedrich
Published: July 2002

Mouse epidermal cytosol contains a protein phosphatase with M
r, 38000, which dephosphorylates the elongation factor 2 (EF‐2) of protein biosynthesis and is stimulated after topical application of TPA to mouse skin [(1988) Biochem. Biophys. Res. Commun. 153, 1129‐1135], Dephosphorylation of EF‐2 by this phosphatase is inhibited by okadaic acid at concentrations as low as 10−8 M, but not by heparin up to concentrations of 600 . The catalytic subunit of protein phosphatase 2A (PP2Ac) with EF‐2 as a substrate exhibits the same sensitivity towards okadaic acid and insensitivity towards heparin as the EF‐2 phosphatase of epidermal cytosol. The catalytic subunit of protein phosphatase 1 (PP1c) is strongly suppressed by heparin and less sensitive towards okadaic acid than PP2Ac. PP2Ac is around 50 times more efficient in dephosphorylating EF‐2 than PP1c. These data indicate that the TPA‐stimulated EF‐2 phosphatase in epidermal cytosol is a type 2A protein phosphatase.
Reversible ADP‐ribosylation of the 78 kDa glucose‐regulated protein
Authors: Leno Gregory H. , Ledford Barry E.
Published: July 2002

Starvation of Mouse hepatoma cells for essential amino acids or glucose results in the mono‐ADP‐ribosylation of the 78 kDa glucose‐regulated protein, GRP78. Here we show that the ADP‐ribosylated and non‐ADP‐ribosylated forms of GRP78 are interconvertible during tryptophan starvation and refeeding. In addition, the ADP‐ribosylation of GRP78 was shown to be reversible even during nutritional stress. The overexpressed pool of non‐ADP‐ribosylated GRP78 synthesized during tunicamycin treatment was available for ADP‐ribosylation during subsequent amino acid starvation, especially in the absence of tunicamycin. The reversible ADP‐ribosylation of GRP78 could be part of a metabolic control mechanism in operation during nutritional stress.
Modeling by homology of RNA binding domain in A1 hnRNP protein
Authors: Ghetti Andrea , Bolognesi Martino , Cobianchi Fabio , Morandi Carlo
Published: July 2002

Eukaryotic nuclear RNA binding proteins share a common sequence motif thought to be implicated in RNA binding. One of the two domains present in A1 hnRNP protein, has been modelled by homology in order to make a prediction of the main features of the RNA binding site. Acyl‐phosphatase (EC 3.6.1.7) was selected as template for the modeling experiment. The predicted RNA binding site is a β‐sheet containing the two RNP consensus sequences as well as lysines and arginines conserved among the family.
Primary structure and functional expression of a high voltage activated calcium channel from rabbit lung
Authors: Biel Martin , Ruth Peter , Bosse Eva , Hullin Roger , Stühmer Walter , Flockerzi Veit , Hofmann Franz
Published: July 2002

The complete amino acid sequence of the receptor for organic calcium channel blockers (CaCB) from rabbit lung has been deduced by cloning and sequence analysis of the cDNA. Synthetic RNA derived from this cDNA induces the formation of a functional CaCB‐sensitive high voltage activated calcium channel in Xenopus oocytes.
NMR studies of the lipid metabolism of T47D human breast cancer spheroids
Authors: Ronen S.M. , Stier A. , Degani H.
Published: July 2002

The in vivo 31P NMR spectrum of T47D human breast cancer cells grown as spheroids shows changes in the phosphomonoester lipid precursors as a function of spheroid size. The ratio of phosphorylethanolamine (PE) to phosphorylcholine (PC) was 1.0±0.3 for 3‐day‐old, 150 μm spheroids. This ratio increased to 2.4±0.4 for spheroids 7 days and older and which were at least 300 μm in diameter. To investigate the phosphatidylethanolamine to phosphatidylcholine (PdyIE/Pdy1C) ratio in the membranes, chloroform/methanol extracts of spheroids were performed. The 31P spectrum of these extracts showed no change with spheroid size, namely the PdyIE/Pdy1C ratio was 0.5±0.06 for spheroids of all ages suggesting that membrane composition is strongly regulated at the precursor level.
Influence of the steric barrier activity of amphipathic poly(ethyleneglycol) and ganglioside GM1 on the circulation time of liposomes and on the target binding of immunoliposomes in vivo
Authors: Mori Atsuhide , Klibanov Aleksander L. , Torchilin Vladimir P. , Huang Leaf
Published: July 2002

A series of dioleoyl N‐(monomethoxy polyethyleneglycol succinyl)phosphatidylethanolamine (PEG‐PE) of different polymer chain length was used in this study. Both the activity of PEG‐PE in prolonging the circulation time of liposomes and the relative steric barrier activity of amphipathic polymer, measured by a liposome agglutination assay, were found to be directly proportional to the chain length of PEG‐PE (PEG5000‐PE > PEG2000‐PE > PEG750‐PE). However, PEG5000‐PE caused a reduced target binding of immunoliposomes in mice due to its overly strong steric barrier activity. The best PEG‐PE species supporting the target binding of immunoliposomes was PEG2000‐PE, the activity of which was compatible to that of ganglioside GM1. However, GM1 only showed a weak steric barrier activity, suggesting a different mechanism for this glycolipid.
New mouse 5‐HT2‐like receptor Expression in brain, heart and intestine
Authors: Loric Sylvain , Launay Jean-Marie , Colas Jean-François , Maroteaux Luc
Published: July 2002

A novel member of the family of G protein‐coupled receptors has been isolated from a mouse brain cDNA library by screening with polymerase chain reaction (PCR) generated fragment of mouse genomic DNA amplified using degenerated primers. Sequence comparison demonstrates that the encoded protein sequence shows the highest homology to the 5‐HT2 family of receptors. The pharmacological profile of membranes from COS cells transfected with this cDNA, corresponds to a new 5‐HT2‐like receptor that we propose to call 5‐HT2C. Its major sites of expression are in the mouse intestine and heart, also with detectable expression in brain and kidney. We speculate that it could account at least in part for the ‘atypical’ functions attributed to the 5‐HTIC/5‐HT2 receptors.
Characterization of a spinach psbS cDNA encoding the 22 kDa protein of photosystem II
Authors: Kim Sunyoung , Sandusky Peter , Bowlby Neil R. , Aebersold Ruedi , Green Beverley R. , Vlahaskis Sari , Yocum Charles F. , Pichersky Eran
Published: July 2002

An intrinsic 22 kDa polypeptide is found associated with the oxygen‐evolving photesytem II (PSII) core complex in all green plants and cyanobacteria so far examined, although it does not appear to be required for oxygen evolution. Amino acid sequence information obtained from the purified 22 kDa protein was used to construct a probe that was employed to isolate a full‐length cDNA clone encoding the 274‐residue precursor of the 22 kDa protein. Hydropathy plot analysis predicts the existence of four membrane‐spanning helices in the mature protein. The two halves of the approximattely 200‐residue mature protein show high sequence similarity to each other, suggesting that the psbS gene arose from an internal gene duplication. The 22 kDa protein has some sequence similarity to chlorophyll a/b‐binding, proteins.
K+‐driven sinusoidal efflux of glutathione disulfide under oxidative stress in the perfused rat liver
Authors: Masuda Yasusuke , Ozaki Masanobu , Aoki Shouko
Published: July 2002

Tert‐butyl hydroperoxide (BHP), hydrogen peroxide and diamide caused a rapid and simultaneous release of glutathione disulfide (GSSG) and K+ in the isolated perfused rat liver. Both BHP‐induced effluxes were suppressed by prior depletion of hepatic glutathione, but not by co‐infusion of desferrioxamine which prevented lipid peroxidation and cell death. High K+ media decreased the GSSG efflux even though hepatic GSSG levels remained high. The GSSG and K+ effluxes were repeatable if cellular K+ recovered after a short BHP exposure. Ouabain inhibited the K+ re‐uptake and decreased the response to repeated BHP challenge. Thus, sinusoidal efflux of GSSG under oxidative stress may be driven by a K+ gradient.
Cloning of an Arabidopsis histidine transporting protein related to nitrate and peptide transporters
Authors: Frommer Wolf B. , Hummel Sabine , Rentsch Doris
Published: July 2002

In plants, many of the proteins involved in transport of nitrogenous compounds have not been identified so far. The use of heterologous complementation in yeast mutants has enabled the isolation of a gene family encoding amino acid permease (AAP). A highly sensitive selection procedure was used to identify other proteins capable of transporting amino acids. In addition to members of the AAP gene family, an integral membrane protein (NTR1) that shows significant similarities to the low affinity nitrate transporter from Arabidopsis and to peptide transporters from yeast and rabbit was identified. NTR1 seems to be involved in the supply of reproductive organs with nitrogen as it is expressed at low levels in leaves and highly in developing pods.
Human glucose‐6‐phosphate dehydrogenase Lysine 205 is dispensable for substrate binding but essential for catalysis
Authors: Bautista JoséM. , Mason Philip J. , Luzzatto Lucio
Published: July 2002

By site‐directed mutagenesis of the cloned human glucose‐6‐phosphate dehydrogenase cDNA, lysine 205 (the residue that after reacting with pyridoxal‐5′‐phosphate renders inactive enzyme) was mutated to threonine (K205T) to remove the amino group, or to arginine (K205R) to displace the position of the amino group, in order to analyze the role of its nucleophilic group in position ϵ. Compared to the wild‐type enzyme, the K205T and K205R mutants retain a specific activity of 2.6 and 11.4%, respectively; their catalytic specificity (K
cat/K
m) is drastically decreased, whereas the K
m values for both substrates are only slightly increased. These findings in the light of the 3D structure of G6PD suggest that the ϵ‐amino group of lysine 205 can favour a hydrogen bond within the active pocket essential for catalysis.
High‐specific binding of Fe(II) at the Mn‐binding site in Mn‐depleted PSII membranes from spinach
Authors: Semin B.K. , Ivanov I.I. , Rubin A.B. , Parak F.
Published: July 2002

The interaction of Fe(II) and Fe(III) with the ‘high‐affinity Mn‐binding site’ in Mn‐depleted photosystem II (PSII) was investigated using diphenilcarbazide (DPC)/2, 6‐dichlorophenol‐indophenol (DCIP) inhibition assay. Fe(III) was ineffective in the inhibition of DPC‐DCIP reaction while Fe(II) decreased the rate of DCIP photoreduction supported by DPC in the same concentration range as Mn(II). The effectivity of the interaction of Fe(II) with the high affinity Mn‐binding site depends on different anions in the same manner as for Mn(II) and coincides with hierarchy observed for the stimulation of O2 evolution. The Fe(II) binding is accompanied by its oxidation. By using reductants it was shown that the high affinity site contains a redox‐active component and the reduction of this component totally prevents the binding of Fe(II).
The assessment and management of treatment-resistant schizophrenia in perspective
Authors: Meltzer HY , Hippius H
Published: July 2002

Consensus was reached on the five following points: (1) “Treatment resistance” is a term which is widely used, but not adequately defined. In particular, definitions of “responders” and “non-responders” need to be more precise. (2) There is a need to extend the assessment of the results of treatment to include factors such as quality of life and the subjective evaluation by the patient and relatives. (3) Clozapine (Clozaril®/Leponex®) has become the standard for atypical antipsychotic drugs. The adjective “atypical” is not an exact descriptor. The vague nature of the term leads to confusion with other drugs that are putative atypical antipsychotic agents but have different properties. D2 dopamine receptor antagonism is the single factor common to all antipsychotic drugs. Antagonism at a specific D2-like receptor may underlie the atypical antipsychotic actions of clozapine. Drugs described as being atypical antipsychotics share a relatively low incidence of extrapyramidal side effects. (4) Clozapine is the only drug that produces antipsychotic (therapeutic) effects at doses that do not result, in significant extrapyramidal side effects. This may be due to the fact that antipsychotic efficacy is obtained with clozapine in doses that result in significantly less striatal D2 occupancy. Other factors including concomitant 5-HT2 antagonism, may contribute to the lack of motor side effects observed with clozapine treatment. (5) Clozapine is the only drug currently well proven in therapy-resistant schizophrenia, and there is a case for its earlier use in patients who can be anticipated to become therapy resistant. Other antipsychotic therapies remain unproven in this group of patients.