bluuebunny/crossref_metadata_2025_split huggingface dataset:
True hermaphroditism with ambiguous genitalia due to a complicated mosaic karyotype: Clinical features, cytogenetic findings, and literature review
Authors: Modan‐Moses Dalit , Litmanovitch Talia , Rienstein Shlomit , Meyerovitch Joseph , Goldman Boleslaw , Aviram‐Goldring Ayala 
Published: December 2002

AbstractAbnormal recombination between the X and Y chromosomes during meiosis, occurring outside the pseudoautosomal region, can result in translocation of the SRY gene from the Y to the X chromosome, and consequently in abnormal sexual differentiation, such as the development of 46,XX males or true hermaphroditism. In this report we present clinical, cytogenetic, and molecular‐cytogenetic data of a patient with ambiguous genitalia and true hermaphroditism, who had a unique mosaic karyotype, comprising three different cell lines: 46,XXSRY+, 45,XSRY+, and 45,X. The mosaic karyotype of our patient probably represents two different events: abnormal recombination between the X and Y chromosomes during paternal meiosis, and postzygotic loss of one of the X chromosomes. Replication studies demonstrated that in 80% of the XX cells, the SRY sequence was located on the active X chromosome. This finding suggests nonrandom X inactivation and, together with the presence of the SRY gene, explains the male phenotype of our patient. On the other hand, the presence of the 45,X cell line may have contributed to genital ambiguity. We conclude that fluorescence in situ hybridization (FISH) analysis with SRY probes is highly recommended and allows accurate diagnosis and optimal management in cases of 46,XX hermaphroditism and ambiguous genitalia. © 2002 Wiley‐Liss, Inc.
Hypertrichosis terminalis, gingival hyperplasia, and a characteristic face: A new distinct entity
Authors: Canún Sonia , Guevara‐Sanginés E.G. , Elvira‐Morales A. , Sierra‐Romero Ma. del C. , Rodríguez‐Asbun H. 
Published: December 2002

AbstractCongenital generalized hypertrichosis terminalis has been described in association with other features as gingival hyperplasia, osteochondrodysplasia, and a dysmorphic face. Bondeson and Miles [1993: Am J Med Genet 47:198–212] described a woman with universal congenital hypertrichosis terminalis associated with gingival hyperplasia; the face of this patient was coarse and different from other forms of hypertrichosis described before. We present an 11‐year, 6‐month‐old girl with universal congenital hypertrichosis terminalis, gingival hyperplasia, and a characteristic coarse face resembling the patient described by Bondeson and Miles [1993: Am J Med Genet 47:198–212]. We propose that this type of congenital generalized hypertrichosis terminalis, associated with gingival hyperplasia and a coarse face, is a distinctive new entity. © 2002 Wiley‐Liss, Inc.
Subcellular alteration of glyceraldehyde‐3‐phosphate dehydrogenase in Alzheimer's disease fibroblasts
Authors: Mazzola Jennifer L. , Sirover Michael A. 
Published: December 2002

AbstractThe regulation of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) has been implicated both in age‐related neurodegenerative disease and in apoptosis. Previous in vitro studies suggest an interaction between GAPDH and the β‐amyloid precursor protein (β‐APP), a protein directly involved in Alzheimer's disease (AD). New studies indicate that GAPDH is a multidimensional protein with diverse membrane, cytoplasmic, and nuclear functions; each is distinct from its role in glycolysis. The nuclear functions of GAPDH include a role in apoptosis that requires its translocation to the nucleus. Accordingly, β‐APP–GAPDH interactions, altering GAPDH structure in vivo, may affect energy generation, inducing hypometabolism, a characteristic AD phenotype. Because GAPDH is a multifunctional protein, pleiotropic effects may also occur in a variety of fundamental cellular pathways in AD cells. This may include unique GAPDH–RNA interactions. We report here the identification of a high‐molecular‐weight (HMW) GAPDH species present exclusively in the postnuclear fraction of AD cells. The latter is characterized by reduced GAPDH activity. The HMW GAPDH species was not detected in postnuclear age‐matched control (AMC) fractions nor in AD whole‐cell preparations. Each is characterized by normal GAPDH activity. By definition, the preparation of whole‐cell extracts entails the destruction of subcellular structure. The latter findings indicate that the dissociation of the GAPDH protein from the HMW species restores its enzymatic activity. Thus, these results reveal a new, unique intracellular phenotype in AD cells. The functional consequences of subcellular alteration in GAPDH structure in AD cells are considered. © 2002 Wiley‐Liss, Inc.
The aetiology of postpsychotic posttraumatic stress disorder following a psychotic episode
Authors: Shaw Katharine , McFarlane Alexander C. , Bookless Clara , Air Tracy 
Published: December 2002

AbstractThis paper examines the aetiology of postpsychotic posttraumatic stress disorder (PP/PTSD) symptoms in a sample of participants who had been hospitalized following a psychotic episode. Forty two people hospitalized for a psychotic illness were interviewed during recovery to investigate whether a psychotic episode was associated with PTSD symptomatology. All participants found psychosis and hospitalization highly distressing. PP/PTSD symptoms were not associated with demographic factors, previous trauma, treatment, or insight. The PP/PTSD group reported more distress and intrusive memories associated with illness and treatment experiences and had higher scores for anxiety and dissociative symptoms. The development of PP/PTSD phenomenology was associated with the psychological distress of the experience.
War exposure among children from Bosnia‐Hercegovina: Psychological adjustment in a community sample
Authors: Smith Patrick , Perrin Sean , Yule William , Hacam Berima , Stuvland Rune 
Published: December 2002

AbstractAs part of a United Nations Children's Fund (UNICEF) psychosocial programme during the war in Bosnia‐Hercegovina, data were collected from a community sample of 2,976 children aged between 9 and 14 years. Children completed standardized self‐report measures of posttraumatic stress symptoms, depression, anxiety, and grief, as well as a report of the amount of their own exposure to war‐related violence. Results showed that children reported high levels of posttraumatic stress symptoms and grief reactions However, their self‐reported levels of depression and anxiety were not raised. Levels of distress were related to children's amount and type of exposure. Girls reported more distress than boys, but there were few meaningful age effects within the age band studied. Results are discussed in the context of service development for children in war.
Diagnosis of Fructose‐1,6‐Bisphosphatase Deficiency Using Cultured Lymphocyte Fraction: A Secure and Noninvasive Alternative to Liver Biopsy
Authors: Kikawa Y. , Shin Y. S. , Inuzuka M. , Zammarchi E. , Mayumi M. 
Published: December 2002

AbstractWe report the result of enzymatic and molecular analyses, using cultured lymphocyte fractions (cultivated monocytes), of six Japanese patients (from five families) and one Italian patient with fructose‐1,6‐ bisphosphatase (FBPase) deficiency. Enzymatic analysis demonstrated FBPase deficiency in all seven patients, including the Italian patient whose fructose‐1,6‐bisphosphatase activity has been reported to be normal in leukocytes but deficient in liver. Molecular analysis of the FBPase gene identified pathogenic mutations in only 8 among the total 12 alleles of six families. We have thus demonstrated the validity of using cultured monocytes as a secure and noninvasive alternative to liver biopsy for accurate diagnosis of FBPase deficiency.
Tetrahydrobiopterin Responsiveness in Phenylketonuria. Two New Cases and a Review of Molecular Genetic Findings
Authors: Lässker U. , Zschocke J. , Blau N. , Santer R. 
Published: December 2002

AbstractWe report two new patients with tetrahydrobiopterin (BH4)‐responsive phenylketonuria and compare their phenylalanine hydroxylase (PAH) genotypes (A395P/IVS12+1g>a and R261Q/I65T, respectively) to those of previous cases from the literature. These case observations confirm earlier reports stating that BH4‐responsive patients are frequently carriers of a missense mutation within the DNA region coding for the catalytic domain of the enzyme. Interestingly, many of the PAH gene mutations detected in BH4‐responsive patients have been associated with an inconsistent phenotype in the past. Our case reports confirm that it is necessary to thoroughly examine individuals with increased phenylalanine levels, not only to detect BH4 deficiency, but also to identify patients with PAH deficiency who may benefit from BH4 treatment. In both of our patients, however, an effect of BH4 (7.5 mg/kg) on plasma phenylalanine levels was not seen in the newborn period. We therefore conclude that a normal neonatal BH4 test does not necessarily exclude BH4 responsiveness in all such patients.
Coping self‐efficacy perceptions as a mediator between acute stress response and long‐term distress following natural disasters
Authors: Benight Charles C. , Harper Michelle L. 
Published: December 2002

AbstractThe mediating effect of coping self‐efficacy (CSE) perceptions between acute stress responses (ASR) and 1 ‐year distress following two disasters was tested. Between 3 and 8 weeks after the second disaster and again at 1 year, 46 residents completed questionnaires. Posttraumatic Stress Disorder (PTSD) symptoms and global distress served as outcomes. Multiple regression demonstrated that ASR and Time 1 CSE were significant predictors of both Time 1 outcomes. Time 1 PTSD symptoms and Time 2 CSE were significant factors for Time 2 PTSD symptoms. Gender was significant for Time 2 PTSD symptoms, but not for Time 2 global distress. Longitudinally. Time 1 CSE predicted Time 2 PTSD symptoms, but not general distress. CSE mediated between ASR and both psychological outcomes at Time 2. Coping self‐efficacy perceptions provide a possible intervention target.
An Intergroup Phase III Comparison of Standard Radiation Therapy and Two Schedules of Concurrent Chemoradiotherapy in Patients With Unresectable Squamous Cell Head and Neck Cancer
Authors: Adelstein David J. , Li Yi , Adams George L. , Wagner Henry , Kish Julie A. , Ensley John F. , Schuller David E. , Forastiere Arlene A. 
Published: December 2002

Purpose: The Head and Neck Intergroup conducted a phase III randomized trial to test the benefit of adding chemotherapy to radiation in patients with unresectable squamous cell head and neck cancer. Patients and Methods: Eligible patients were randomly assigned between arm A (the control), single daily fractionated radiation (70 Gy at 2 Gy/d); arm B, identical radiation therapy with concurrent bolus cisplatin, given on days 1, 22, and 43; and arm C, a split course of single daily fractionated radiation and three cycles of concurrent infusional fluorouracil and bolus cisplatin chemotherapy, 30 Gy given with the first cycle and 30 to 40 Gy given with the third cycle. Surgical resection was encouraged if possible after the second chemotherapy cycle on arm C and, if necessary, as salvage therapy on all three treatment arms. Survival data were compared between each experimental arm and the control arm using a one-sided log-rank test. Results: Between 1992 and 1999, 295 patients were entered on this trial. This did not meet the accrual goal of 362 patients and resulted in premature study closure. Grade 3 or worse toxicity occurred in 52% of patients enrolled in arm A, compared with 89% enrolled in arm B (P < .0001) and 77% enrolled in arm C (P < .001). With a median follow-up of 41 months, the 3-year projected overall survival for patients enrolled in arm A is 23%, compared with 37% for arm B (P = .014) and 27% for arm C (P = not significant). Conclusion: The addition of concurrent high-dose, single-agent cisplatin to conventional single daily fractionated radiation significantly improves survival, although it also increases toxicity. The loss of efficacy resulting from split-course radiation was not offset by either multiagent chemotherapy or the possibility of midcourse surgery.
Defects of blastogenesis
Authors: Opitz John M. , Zanni Ginevra , Reynolds James F. , Gilbert‐Barness Enid 
Published: December 2002

AbstractEver more frequent and closer involvement by clinical geneticists and counselors in the prenatal assessment of development mandates a better understanding of all stages of human ontogeny, but especially those of earliest development during which most of the lethal and all of the gross, multiple and complex defects of morphogenesis arise. Because of the phenomenon of universality, i.e., identical molecular inductive mechanisms involved in the process of embryonic pattern formation in all vertebrates, experimental animals indeed are a most valuable approach to an understanding of the causal and formal aspects of development and are beginning to forge essential, strong bonds between molecular biologists and clinicians in a mutually supportive discipline of developmental biology. However, to grieving parents of a stillborn fetus with, say, Pentalogy of Cantrell, sirenomelia or otocephaly, mouse data offer little comfort or reassurance about recurrence; thus, it is imperative to make ever more effective a science of human teratology (sensu lato) with participating reproductive geneticists, obstetricians, neonatologists, ultrasonographers, pediatric/fetal pathologists, cytogeneticists and pediatric geneticists to generate the diagnostic, pathogenetic and causal data necessary to counsel and to comfort the parents. Few molecular data exist on causes of blastogenetic defects in humans; however, the phenomenon of parsimony, whereby the same “morphogenetic” molecule, say, sonic hedgehog (SHH), is “deployed” simultaneously or sequentially during the morphogenesis (and even the histogenesis) of several/many embryonic primordia, makes it likely that a genetic/epigenetic disturbance of such an inductive system will have multiple effects on blastogenetic, organogenetic and perhaps also histogenetic events in the embryo. If causally defined, such a pattern of anomalies constitutes pleiotropy, and the embryo/fetus can be said to have a syndrome. If cause is unknown, the presumption of pleiotropy is less certain, and the fetus/infant may be said to have an “association” with low empiric recurrence risk. © 2002 Wiley‐Liss, Inc.
Peripheral axotomy affects nicotinamide adenine dinucleotide phosphate diaphorase and nitric oxide synthases in the spinal cord of the rabbit
Authors: Lukáčová Nadežda , Čížková Dáša , Križanová Olga , Pavel Jaroslav , Maršala Martin , Maršala Jozef 
Published: December 2002

AbstractUsing nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry and nitric oxide synthase (NOS) immunocytochemistry combined with radioassay of calcium‐dependent NOS activity, we examined the occurrence of NADPHd staining and NOS immunoreactivity (NOS‐IR) in the dorsal root ganglia (DRG) neurons, dorsal root afferents, and axons projecting via gracile fascicle to gracile nucleus 14 days after unilateral sciatic nerve transection in the rabbit. Mild to moderate NADPHd staining and NOS‐IR appeared in a large number of small and medium‐sized to large neurons in the ipsilateral L4–L6 DRG, accompanied by enhanced NOS‐IR of thick myelinated fibers in the ipsilateral L4–L6 dorsal roots. A noticeable increase in the density of punctate NADPHd staining occurred throughout laminae I–IV in the ipsilateral medial part of the dorsal horn in L4–L6 segments. Concurrently, a statistically significant decrease in the number of small NADPHd‐exhibiting neurons in laminae I–II and, in contrast to this, a statistically significant increase of medium‐sized to large NADPHd‐stained somata in the ipsilateral laminae III–VI of L4–L6 segments were found. A detailed compartmentalization of L4–L6 segments into gray and white matter regions disclosed substantially increased catalytic NOS activity and inducible NOS mRNA levels in the dorsal horn and dorsal column ipsilaterally to the peripheral injury. A noticeable increase in the number of thick myelinated NADPHd‐exhibiting and NOS‐IR axons was noted in the ipsilateral gracile fascicle, terminating in dense, punctate NADPHd staining in the neuropil of the gracile nucleus. These observations indicate that the de novo‐synthesized NOS in the lesioned primary afferent neurons resulting after sciatic nerve transection may be involved in an increase in NADPHd staining and NOS‐IR in the ipsilateral dorsal roots and dorsal horn of L4–L6 segments, whence NOS could be supplied to ascending axons of the gracile fascicle. © 2002 Wiley‐Liss, Inc.
DNA repair gene O6‐methylguanine‐DNA methyltransferase: Promoter hypermethylation associated with decreased expression and G:C to A:T mutations of p53 in brain tumors
Authors: Yin Dong , Xie Dong , Hofmann Wolf‐Karsten , Zhang Wenxuan , Asotra Kamlesh , Wong Rex , Black Keith L , Koeffler H. Phillip 
Published: December 2002

AbstractThe DNA repair enzyme O6‐methylguanine‐DNA methyltransferase (MGMT) removes alkylating adducts from the O6 position of guanine and protects cells from cytotoxic and mutagenic effects. Expression of MGMT is decreased in some cancers, which may be the result of methylation of CpG islands of both the promoter and coding regions of the gene. We studied the methylation status of the MGMT promoter in a very large collection of brain tumors (85) using methylation‐specific polymerase chain reaction (PCR). Aberrant methylation occurred in 48% of 85 human brain tumor samples. Quantitative real‐time PCR showed that expression of MGMT mRNA levels was significantly decreased (P < 0.001) in those brain tumors that had methylation of the promoter region of their MGMT gene. MGMT can prevent G to A mutations by removing alkyl groups from the O6 position of guanine. We found a significantly increased frequency of G:C to A:T mutations of the p53 gene in brain tumors having a methylated MGMT promoter compared with those having an unmethylated MGMT promoter (P < 0.05), and all the non–CpG dinucleotide G:C to A:T mutations of p53 were in samples with a methylated MGMT promoter. © 2002 Wiley‐Liss, Inc.
Mid-Holocene Hydrologic Model of the Shingobee Watershed, Minnesota
Authors: Filby Sheryl K. , Locke Sharon M. , Person Mark A. , Winter Thomas C. , Rosenberry Donald O. , Nieber John L. , Gutowski William J. , Ito Emi 
Published: December 2002

AbstractA hydrologic model of the Shingobee Watershed in north-central Minnesota was developed to reconstruct mid-Holocene paleo-lake levels for Williams Lake, a surface-water body located in the southern portion of the watershed. Hydrologic parameters for the model were first estimated in a calibration exercise using a 9-yr historical record (1990–1998) of climatic and hydrologic stresses. The model reproduced observed temporal and spatial trends in surface/groundwater levels across the watershed. Mid-Holocene aquifer and lake levels were then reconstructed using two paleoclimatic data sets: CCM1 atmospheric general circulation model output and pollen-transfer functions using sediment core data from Williams Lake.Calculated paleo-lake levels based on pollen-derived paleoclimatic reconstructions indicated a 3.5-m drop in simulated lake levels and were in good agreement with the position of mid-Holocene beach sands observed in a Williams Lake sediment core transect. However, calculated paleolake levels based on CCM1 climate forcing produced only a 0.05-m drop in lake levels. We found that decreases in winter precipitation rather than temperature increases had the largest effect on simulated mid-Holocene lake levels. The study illustrates how watershed models can be used to critically evaluate paleoclimatic reconstructions by integrating geologic, climatic, limnologic, and hydrogeologic data sets.
Dendritic Cell-Based Vaccination in Solid Cancer
Authors: Stift A. , Friedl J. , Dubsky P. , Bachleitner-Hofmann T. , Schueller G. , Zontsich T. , Benkoe T. , Radelbauer K. , Brostjan C. , Jakesz R. , Gnant M. 
Published: December 2002

Purpose: Dendritic cell (DC)-based immunotherapy is rapidly emerging as a viable tool in cancer treatment. This approach has been used mostly in patients in the presence of defined tumor antigens such as melanoma. In this study, cancer patients with advanced disease that lacks defined tumor antigens were vaccinated with tumor lysate-pulsed DCs.Patients and Methods: Twenty patients (pancreatic, hepatocellular, cholangiocellular, and medullary thyroid carcinoma) with stage IV disease were enrolled in the study. In 3-week intervals, freshly isolated autologous CD14 magnetic bead-selected monocytes were cultured in granulocyte-macrophage colony-stimulating factor and interleukin-4 to obtain immature DCs. These cells were pulsed with autologous tumor lysate and matured with tumor necrosis factor alpha. Mature DCs were applied into a groin lymph node, under ultrasound guidance. Adjuvant interleukin-2 (20,000 U/kg) was given subcutaneously daily, for 12 days, after each vaccination. Toxicity, tumor marker profile, immune response, and clinical response were determined.Results: Vaccination was well tolerated. No physical signs of autoimmunity were detected. DC vaccination induced delayed-type hypersensitivity reactivity in 18 patients. Tumor marker responses were observed in eight patients. In addition, in three patients the generation of interferon gamma-positive T cells was induced during the vaccination. Objective changes in measurable lesions or tumor markers were evident in seven of 20 assessed patients. None of the patients was found to meet the criteria for partial or complete responses.Conclusion: These data indicate that vaccination with autologous tumor-pulsed DCs generated from peripheral blood is safe and can induce tumor-specific cellular cytotoxicity. Clinical responses are achievable, even in patients with advanced disease.
Differential Expression of S100A2 and S100A4 During Progression of Human Prostate Adenocarcinoma
Authors: Gupta Sanjay , Hussain Tajamul , MacLennan Gregory T. , Fu Pingfu , Patel Jigar , Mukhtar Hasan 
Published: December 2002

Purpose: To establish the clinical significance of calcium binding proteins S100A2 and S100A4 during progression of human prostate adenocarcinoma. Patients and Methods: Expression pattern of S100A2 and S100A4 was determined in normal human prostate epithelial cells (NHPE); virally transformed prostate epithelial cells (PZ-HPV-7); several human prostate carcinoma cells (22Rv1, DU145, LNCaP, and PC3); tissue samples obtained during transuretheral prostatic resection from patients with benign prostate hyperplasia (BPH), prostatitis, and adenocarcinoma; and paraffin-embedded sections from pair-matched benign and cancer specimens of different tumor grade. Results: High constitutive protein expression of S100A2 was observed in NHPE and PZ-HPV-7 cells, whereas its complete absence was observed in 22Rv1, DU145, LNCaP, and PC3 cells. Tissue samples of BPH and prostatitis exhibited higher mRNA and protein levels of S100A2 than low-grade cancer (Gleason score ≤ 6), whereas a complete loss was observed in high-grade cancer specimens (Gleason score > 6). Immunohistochemical analysis further confirmed high levels of S100A2 in benign tissues and a progressive loss with increasing tumor grade. The protein level of S100A4 was significantly higher in all carcinoma cells compared with NHPE and PZ-HPV-7 cells. The mRNA and protein level of S100A4 was significantly higher in high-grade cancer specimens compared with BPH, prostatitis, and low-grade cancer. The high levels of S100A4 observed in cancer tissue correlated with increasing tumor grade. Conclusion: Loss of S100A2 and increased expression of S100A4 may be an important event during progression of prostate cancer in humans.