bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of leukocyte cell adhesion molecules on gastric carcinomas: Possible involvement of lfa‐3 expression in the development of distant metastases
Authors: Mayer Barbara , Lorenz Claudia , Babic Rudolf , Jauch Karl W. , Schildberg Friedrich W. , Funke Ilona , Johnson Judith P.
Published: February 2007

Expression of the cell adhesion molecules ICAM‐1 (CD54) and LFA‐3 (CD58) was examined on primary gastric carcinomas, autologous benign mucosa and metastatic lesions. Although ICAM‐1 was never observed on benign gastric epithelium, even in the presence of chronic inflammation and a strong leukocyte infiltrate, 38% (26/69) of the primary tumors expressed this molecule. ICAM‐1 was restricted to differentiated tumors and correlated with the presence of leukocytes and the absence of vessel invasion. The ICAM‐1 expression pattern of metastatic lesions reflected that of the primary tumor, suggesting that most tumors retain the non‐inducible phenotype seen in normal mucosa while some become cytokine‐sensitive. ICAM‐1 expression showed no correlation with tumor relapse or survival. LFA‐3 was absent from 8% (4/49) of the primary tumors and reduced (e.g., ± 50% positive cells) in 33% (16/49). Expression of LFA‐3 by more than 50% of the tumor cells correlated with cellular dedifferentiation (G3, G4), histologically detectable vessel invasion, tumor recurrence and decreased survival time. Primary tumors and metastases in draining lymph nodes demonstrated a broad range of LFA‐3 expression. In contrast, distant metastases (liver and peritoneum) had uniformly high frequencies of LFA‐3‐positive cells, suggesting a selective advantage for these cells in the establishment of distant metastases. © 1995 Wiley‐Liss, Inc.
p53 protein accumulation and the presence of human papillomavirus dna in bronchiolo‐alveolar carcinoma correlate with poor prognosis
Authors: Nuorva Kyösti , Soini Ylermi , Kamel Dia , Pöllänen Raimo , Bloigu Risto , Vähäkangas Kirsi , Pääkkö Paavo
Published: February 2007

Accumulation of the tumour suppressor gene p53 product due to a gene mutation is frequently seen in human carcinomas, including lung carcinoma. Another indirect mechanism involving p53 in malignant growth relates to the E6 protein of the human papillomavirus (HPV), which is able to bind and degrade wild‐type p53 protein, thus eliminating its tumour suppressor activities. Bronchiolo‐alveolar carcinoma (BAC) is a rare type of lung carcinoma. The aim of our study was to examine the occurrence of p53 accumulation and the presence of HPV DNA in BAC. Sections of 22 BACs were immunohistochemically stained using a p53 antibody, CM‐1. The presence of HPV DNA in BACs was verified by in situ hybridisation for HPV types 6, 11, 16, 18, 31 and 33 and confirmed by PCR. Thirty‐six percent of the tumours showed abnormal p53 nuclear accumulation, and HPV DNA, revealed by in situ hybridisation, was found in 36%. Unexpectedly, only 13% of the type 1 BACs were positive for p53, whereas 45% of the type 2 BACs were positive. During a follow‐up of 12‐176 months, only 10% of the patients with BACs negative for both p53 and HPV died of the disease, compared with 42% of the patients with either p53 or HPV positivity. No inverse relationship between abnormal p53 protein accumulation and the presence of HPV DNA was found. © 1995 Wiley‐Liss, Inc.
Genetic alterations distinguish different types of ovarian tumors
Authors: Pieretti Maura , Cavalieri Cristina , Conway Pamela S. , Gallion Holly H. , Powell Deborah E. , Turker Mitchell S.
Published: February 2007

Seventy‐four sporadic ovarian tumors were studied for loss of heterozygosity (LOH) and microsatellite instability (MI) with 20 polymorphic markers on chromosome 17 and at least I marker on every other chromosome. Additionally, activation of the K‐ras oncogene was examined through mutation analysis of codon 12. A majority of the tumors analyzed were low grade and/or of the mucinous histologic type. A negative correlation between LOH on chromosome 17 and K‐ras activation was observed, with the former alteration present in the majority of high grade serous and endometrioid tumors and the latter most commonly found in the mucinous and low malignant potential (LMP) tumors. In 60% of cases where LOH on chromosome 17 was present, it was observed at all informative markers, indicating chromosome loss. In these cases, frequent events of LOH were observed on the other chromosomes. When confined events of LOH were observed on chromosome 17, fewer events of LOH were observed on the other chromosomes. In the absence of LOH on chromosome 17, LOH on other chromosomes was rare. K‐ras activation was most commonly observed in tumors with no LOH events. Two endometrioid tumors and 2 mucinous tumors demonstrated MI. Our data support the involvement of different molecular pathways in the development of different types of ovarian tumors. © 1995 Wiley‐Liss, Inc.
α subunit partners to β1 and β2 integrins during IL‐4‐induced foreign body giant cell formation
Authors: McNally Amy K. , MacEwan Sarah R. , Anderson James M.
Published: February 2007

As β1 and β2 integrins were previously found to mediate adhesion during IL‐4‐induced foreign body giant cell (FBGC) formation, we pursued the identities of the α integrin partners of these adhesion receptors using our in vitro system of human monocyte‐derived macrophage fusion. Immunoprecipitation with β1 and immunoblotting reveal the presence of α5 and αV, as well as α2 and α3. αM and αX immunoprecipitate with β2 but not with β1. Immunocytochemistry coupled with confocal microscopy indicates that α5 and αX are poorly expressed on day 0. However, following the induction of fusion by IL‐4 on day 3, they are each readily detectable in fusing macrophages/FBGC on day 7. In contrast, αM and αV are present throughout the culture period, with very strong αM expression on day 7. We also demonstrate expression and colocalization of α3, α5, or αV with β1 on fusing macrophages/FBGC at this time point as well as strong colocalization of αM and αX with β2 in FBGC and at fusion interfaces. Therefore, IL‐4‐induced FBGC are characterized by the expression of αMβ2, αXβ2, α5β1, αVβ1, α2β1, and α3β1, which indicates potential interactions with fragments of complement C3, fibrin(ogen), fibronectin, Factor X, and vitronectin, and possibly with certain collagens, laminin, and thrombospondin at sites of biomaterial implantation. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Retracted: Overexpression HERG K+ channel gene mediates cell‐growth signals on activation of oncoproteins SP1 and NF‐κB and inactivation of tumor suppressor Nkx3.1
Authors: Lin Huixian , Xiao Jiening , Luo Xiaobin , Wang Huizhen , Gao Huanhuan , Yang Baofeng , Wang Zhiguo
Published: February 2007

The long QT syndrome gene human ether‐a‐go‐go related gene (HERG) encodes a K+ channel critical to cardiac repolarization. It peculiarly overexpresses in cancer cells of different histogenesis and promotes tumorigenesis. To decipher the molecular mechanisms for HERG overexpression, we identified and characterized the promoter region of the HERG gene, which contains cis‐elements for multiple oncoproteins and tumor suppressors. Oncoprotein Sp1 was found to be essential to driving the HERG promoter thereby transcription. Another oncoprotein NF‐κB transactivated, while tumor suppressor Nkx3.1 repressed HERG promoter activity and endogenous HERG transcription. Loss‐of‐function mutations in the corresponding cis‐elements rendered a loss of the ability of the oncoproteins Sp1 and NF‐κB to transactivate, and of the tumor repressor Nkx3.1 to repress, HERG transcription. Either activation of Sp1 and NF‐κB or silencing of Nkx3.1 promoted tumor cell growth, and the effects were abrogated by HERG inhibition or knockdown, but facilitated by overexpression of HERG, indicating that HERG mediates the cell growth signals generated by activation of oncoproteins or inactivation of tumor suppressors. Binding of Sp1, NF‐κB, and Nkx3.1 to their respective cis‐elements in the HERG promoter in vitro and their presence on the HERG promoter in vivo were confirmed. Therefore, the HERG promoter region is characterized by multiple Sp1 binding sites that are responsible for transcription initiation of the HERG gene and by binding sites for multiple other oncogenes and tumor suppressor genes being important for regulating HERG expression. The HERG K+ channel is likely a mediator of growth‐promoting processes induced by oncoproteins and/or by silencing of tumor suppressors. J. Cell. Physiol. 212: 137–147, 2007. © 2007 Wiley‐Liss, Inc.
Flt‐1, but not Flk‐1 mediates hyperpermeability through activation of the PI3‐K/Akt pathway
Authors: Vogel Carsten , Bauer Alexander , Wiesnet Marion , Preissner Klaus T. , Schaper Wolfgang , Marti Hugo H. , Fischer Silvia
Published: February 2007

Vascular endothelial growth factor (VEGF), a potent mediator of endothelial proliferation and migration, has an important role also in brain edema formation during hypoxia and ischemia. VEGF binds to the tyrosine kinase receptors Flt‐1 and Flk‐1. Yet, their relative importance for hypoxia‐induced hyperpermeability is not well understood. We used an in vitro blood‐brain barrier (BBB) model consisting of porcine brain microvascular endothelial cells (BMEC) to determine the role of Flt‐1 in VEGF‐induced endothelial cell (EC) barrier dysfunction. Soluble Flt‐1 abolished hypoxia/VEGF‐induced hyperpermeability. Furthermore, selective antisense oligonucleotides to Flt‐1, but not to Flk‐1, inhibited hypoxia‐induced permeability changes. Consistent with these data, addition of the receptor‐specific homolog placenta‐derived growth factor, which binds Flt‐1 but not Flk‐1, increased endothelial permeability to the same extent as VEGF, whereas adding VEGF‐E, a viral VEGF molecule from the orf virus family activating Flk‐1 and neuropilin‐1, but not Flt‐1, did not show any effect. Using the carcinoma submandibular gland cell line (CSG), only expressing Flt‐1, it was demonstrated that activation of Flt‐1 is sufficient to induce hyperpermeability by hypoxia and VEGF. Hyperpermeability, induced by hypoxia/VEGF, depends on activation of phosphatidylinositol 3‐kinase/Akt (PI3‐K/Akt), nitric oxide synthase (NOS) and protein kinase G (PKG). The activation of the PI3‐K/Akt pathway by hypoxia was confirmed using an in vivo mice hypoxia model. These results demonstrate that hypoxia/VEGF‐induced hyperpermeability can be mediated by activation of Flt‐1 independently on the presence of Flk‐1 and indicate a central role for activation of the PI3‐K/Akt pathway, followed by induction of NOS and PKG activity. J. Cell. Physiol. 212: 236–243, 2007. © 2007 Wiley‐Liss, Inc.
Soft substrate induces apoptosis by the disturbance of Ca2+ homeostasis in renal epithelial LLC‐PK1 cells
Authors: Chiu Wen‐Tai , Wang Yao‐Hsien , Tang Ming‐Jer , Shen Meng‐Ru
Published: February 2007

Different rigidities of adhesive collagen substrate affect cellular functions with unclear mechanisms. Here, we cultured a renal epithelial cell line (LLC‐PK1) and a tumor cell line (HeLa) on substrates of different rigidities and compared the cell type‐specific responses. The culture dish was coated with a very thin layer of collagen gel (control group) or overlaid with collagen gel (soft substrate). LLC‐PK1 cells contracted as they grew on collagen gel and the apoptotic bodies obviously appeared with time. The protein levels of procaspase‐12 and its downstream target procaspase‐3 were decreased when LLC‐PK1 cells cultured on collagen gel. µ‐calpain was activated on collagen gel. Collage gel also induced the cleavage of α‐spectrin which resulted in the disorganization of actin cytoskeleton. In contrast, there was no significant change in cytochrome c revelation, mitochondrial membrane potential, and the protein levels of procaspase‐8 and procaspase‐9. Moreover, soft substrate caused elevated cytosolic Ca2+, Ca2+ overload in ER and upregulation of capacitative calcium entry. Ca2+ chelator or channel blocker partially rescued the collagen‐gel induced apoptosis by inhibiting µ‐calpain activation. In contrast, for HeLa cells cultured either on collagen gel or on gel‐coated dish, there was no significant change in positive Annexin V staining, no activation of procaspase‐12 and no cleavage of µ‐calpain. Thus, soft substrate induces apoptosis in LLC‐PK1 cells by the disturbance of Ca2+ homeostasis. J. Cell. Physiol. 212: 401–410, 2007. © 2007 Wiley‐Liss, Inc.
Apoptosis of human neutrophils induced by protein phosphatase 1/2A inhibition is caspase‐independent and serine protease‐dependent
Authors: Park Hae‐Young , Song Min‐Gyu , Lee Jun‐Sik , Kim Ja‐Woong , Jin Jun‐O , Park Joo‐In , Chang Young‐Chae , Kwak Jong‐Young
Published: February 2007

Protein phosphatase (PP) activity is associated with the regulation of apoptosis in neutrophils. However, the underlying regulatory mechanism(s) in apoptosis remain unclear. The type of cell death induced by okadaic acid (OA), the inhibitor of PP1 and PP2A, is characterized by apoptotic morphological changes of the cells and annexin V‐positive staining without DNA fragmentation. The apoptotic effects of OA and calyculin A on neutrophils were observed at concentrations ranging from 50 to 200 nM, or 10 to 50 nM, respectively. Cyclosporine A (a PP2B specific inhibitor), however, did not exhibit any pro‐apoptotic effects. OA and calyculin A, but not cyclosporine A, exhibited significant effects on protein levels and on the electrophoretic mobility of Mcl‐1. zVAD‐fmk, a pancaspase inhibitor, failed to inhibit the effect of OA on the caspase‐3 activity, procaspase‐3 processing, and the apoptotic rate of neutrophils. However, 4‐(2‐aminoethyl) benzenesulfonylfluoride (AEBSF), a general serine protease inhibitor, significantly abrogated the OA‐induced mobility shift in procaspase‐3, caspase‐3 activation, and the apoptotic morphological changes in neutrophils. Moreover, OA enhanced the serine protease activity of the neutrophils. The addition of the proteinase‐3 protein increased the rate of neutrophil apoptosis, which was also blocked by AEBSF but not by zVAD‐fmk. These results suggest that OA induces procaspase‐3 processing but that OA‐induced apoptosis is caspase‐independent and serine protease‐dependent. J. Cell. Physiol. 212: 450–462, 2007. © 2007 Wiley‐Liss, Inc.
The adjuvant effects of co‐stimulatory molecules on cellular and memory responses to HBsAg DNA vaccination
Authors: Du Xiaogang , Zheng Guoxing , Jin Huali , Kang Youmin , Wang Junpeng , Xiao Chong , Zhang Shuo , Zhao Lin , Chen Aoshuang , Wang Bin
Published: February 2007

Because DNA vaccines on their own tend to induce weak immune responses in humans, adjuvant methods are needed in order to improve their efficacy. The co‐stimulatory molecules 4‐1BBL, OX40L, and CD70 have been shown to induce strong T cell activities; therefore, in this study, we investigated whether they may be used as molecular adjuvants for a hepatitis B surface antigen (HBsAg) DNA vaccine (pcDS2) in eliciting strong cellular and memory responses. Compared to mice immunized with pcDS2 alone, addition of the co‐stimulatory molecules increased T cell proliferation and an HBsAg‐specific antibody response that was marked with a higher ratio of IgG2a/IgG1. Importantly, pcDS2 plus these co‐stimulatory molecules elicited a higher level of IFN‐γ and IL‐4 in CD4+ T cells and a higher level of IFN‐γ in CD8+ T cells. In addition, a significantly robust antigen‐specific cytotoxic T lymphocyte (CTL) response and the production of long‐term memory CD8+ T cells were also observed in the groups immunized with pcDS2 plus 4‐1BBL, OX40L, or CD70. Consistently, as late as 100 days after immunization, upregulated expressions of BCL‐2, Spi2A, IL‐7Ra, and IL‐15Ra were still observed in mice immunized with pcDS2 plus these co‐stimulatory molecules, suggesting the generation of memory T cells in these groups. Together, these results suggest that the co‐stimulatory molecules 4‐1BBL, OX40L, or CD70 can enhance the immunogenicity of HBsAg DNA vaccines, resulting in strong humoral, cellular, and memory responses. This approach may lead to an effective therapeutic vaccine for chronic hepatitis B virus (HBV) infection. Copyright © 2007 John Wiley & Sons, Ltd.
Molecular epidemiological studies show that hepatitis A virus is endemic among active homosexual men in Europe
Authors: Stene‐Johansen Kathrine , Tjon Grace , Schreier Eckart , Bremer Viviane , Bruisten Sylvia , Ngui Siew‐Lin , King Mike , Pinto Rosa M. , Aragonès Lluis , Mazick Anne , Corbet Sylvie , Sundqvist Lena , Blystad Hans , Norder Helene , Skaug Kjell
Published: February 2007

Large outbreaks of hepatitis A have occurred in Denmark, Germany, the Netherlands, Norway, Spain, Sweden, and the United Kingdom during the period 1997–2005 affecting homosexual men. A collaborative study was undertaken between these countries to determine if the strains involved in these hepatitis A outbreaks were related genetically. The N‐terminal region of VP1 and the VP1/P2A region of the strains were sequenced and compared. The majority of the strains found among homosexual men from the different European countries formed a closely related cluster, named MSM1, belonging to genotype IA. Different HAV strains circulated among other risk groups in these countries during the same period, indicating that specific strains were circulating among homosexual men exclusively. Similar strains found among homosexual men from 1997 to 2005 indicate that these HAV strains have been circulating among homosexual men for a long time. The homosexual communities are probably too small within the individual countries to maintain HAV in their population over time, whereas the homosexual communities across Europe are probably sufficiently large to sustain continued circulation of homologous HAV strains for years resulting in an endemic situation among homosexual men. J. Med. Virol. 79:356–365, 2007. © 2007 Wiley‐Liss, Inc.
Epstein Barr virus genotypes and LMP‐1 variants in HIV‐infected patients
Authors: Correa Rita Mariel , Dolores Fellner María , Durand Karina , Redini Liliana , Alonio Virginia , Yampolsky Claudio , Colobraro Antonio , Sevlever Gustavo , Teyssié Angélica , Benetucci Jorge , Picconi María Alejandra
Published: February 2007

Two Epstein Barr virus (EBV) genotypes: EBV‐1 and EBV‐2 have been described. A 30‐bp deletion in latent membrane protein‐1 gene (del‐LMP‐1) has been identified in various pathologies. The aim of this study was to determine EBV genotypes and 30‐bp deletion frequency in HIV‐infected patients from Argentina. The study was performed on 258 individuals: Cases: 144 HIV‐infected patients that included: (a) 7 AIDS patients with primary central nervous system lymphoma (PCNSL), (b) 62 AIDS patients, and (c) 75 asymptomatic HIV‐infected patients. Controls: 114 HIV‐negative individuals. EBV genotypes and variants in LMP‐1 gene were detected by polymerase chain reaction (PCR)‐Southern blot on DNA extracted from peripheral blood mononuclear cells and brain biopsies. In PCNSL, the presence of EBV was confirmed by EBER RNA in situ hybridization, and DNA sequencing of 3′ end LMP‐l gene of PCR products was performed. In HIV‐infected patients, EBV‐1 was detected in 48.6%, EBV‐2 in 18.8%, and co‐infection with both genotypes in 32.6%. In control group, EBV‐1 was present in 74.3%, EBV‐2 in 12.4%, and co‐infection in 13.3%. Del‐LMP‐1 was found in 44.4% of HIV‐infected patients samples (20.7% alone and 23.7% co‐infection with non‐deleted form) while it was found in 25.3% (6.3% alone and 19% with co‐infection) in HIV‐negative individuals. In HIV‐infected patients EBV‐2, co‐infection and 30‐bp deletion are more prevalent than in control group. In all, PCNSL brain biopsies samples, del‐LMP‐1 always was detected with EBV‐2, but more cases would have to be included to draw definitive conclusions. J. Med. Virol. 79:401–407, 2007. © 2007 Wiley‐Liss, Inc.
Presence, quantitation and characterization of JC virus in the urine of Italian immunocompetent subjects
Authors: Rossi Andrea , Delbue Serena , Mazziotti Romina , Valli Marilena , Borghi Elisa , Mancuso Roberta , Calvo Maria G. , Ferrante Pasquale
Published: February 2007

Human polyomavirus JC (JCV) infects the worldwide population, remains latent in the kidney, and is excreted in the urine. A longitudinal study was performed in order to evaluate JCV excretion, to characterize molecularly the virus and to determine if its presence in urine is a consequence of viral reactivation or merely of epithelial squamous cell shedding. The presence of cellular sediment and the JCV genome were examined in 333 urine samples collected periodically for 3 months from 17 healthy subjects; molecular characterization, and quantitation of the virus were also undertaken. JCV DNA was detected in 40.2% of the samples, with a significant difference (P < 0.001) observed between males and females. JCV shedding was independent of the presence of cellular sediment in every individual. JCV genotype 1 was the genome detected most frequently, while all of the amplified strains showed archetypal organization of the transcriptional control region (TCR). No clinical symptoms have been associated with JCV excretion and no microbial load was detected in the urine samples. The lack of correlation between JCV DNA detection and the presence of squamous cells in urine sediment indicates that viruria is regulated by the life cycle of JCV. Thus, the virus is eliminated as consequence of its reactivation. J. Med. Virol. 79:408–412, 2007. © 2007 Wiley‐Liss, Inc.
Matrix metalloproteinase‐9 and tissue inhibitor of matrix metalloproteinase‐1 in the respiratory tracts of human infants following paramyxovirus infection
Authors: Elliott Matthew B. , Welliver Robert C. , Laughlin Todd S. , Pryharski Karin S. , LaPierre Natisha A. , Chen Tong , Souza Victor , Terio Nicole B. , Hancock Gerald E.
Published: February 2007

Respiratory syncytial (RSV) and parainfluenza (PIV) viruses are primary causes of acute bronchiolitis and wheezing illnesses in infants and young children. To further understand inflammation in the airways following infection, we tested for the presence of matrix metalloproteinases (MMP) and natural tissue inhibitors of MMP (TIMP) in primary and established human cell lines, and in the nasopharyngeal secretions (NPS) of human infants infected with RSV or PIV. Using ELISA and multiplex‐based assays, MMP‐9 and TIMP‐1 proteins were, respectively, detected in 66/67 and 67/67 NPS. During PIV or RSV infection TIMP‐1 concentrations were associated with hypoxic bronchiolitis. TIMP‐1 amounts were also negatively correlated with O2 saturation, and positively correlated with IL‐6, MIP‐1α, and G‐CSF amounts following RSV infection. IL‐6, MIP‐1α, and G‐CSF were negatively correlated with O2 saturation during RSV infection. Acute respiratory tract disease was not associated with MMP‐9 protein/protease activity. Additional studies using real‐time quantitative PCR suggested that MMP‐9 mRNA copy numbers were elevated in normal human bronchial epithelial (NHBE) cells infected with RSV, while TIMP‐1 and TIMP‐2 were not increased. However, ELISA did not reveal MMP‐9 protein in the NHBE cell culture supernatants. Hence, the data implied that airway epithelial cells were not the primary source of MMP or TIMP following paramyxovirus infection. Taken together, the data suggested that paramyxovirus infection perturbs MMP‐9/TIMP‐1 homeostasis that in turn may contribute to the severity of respiratory tract disease. J. Med. Virol. 79:447–456, 2007. © 2007 Wiley‐Liss, Inc.
Hypophysectomy for disseminated prostatic carcinoma
Authors: Murphy G. P. , Boctor Z. N. , Gailani S. , Belmusto L.
Published: February 2007

A series of 15 patients with disseminated prostatic carcinoma were treated with open or cryosurgical hypophysectomy, following relapse from conventional forms of hormonal therapy. Six of 15 patients (40%) had objective and subjective signs of clinical and chemical response. To date, however, patients in remission have not demonstrated a significant prolongation in survival. Human growth hormone (HGH) levels were used to test the degree of functional suppression of pituitary function posthypophysectomy. Cryosurgical hypophysectomy, although an admittedly anatomically incomplete procedure, can induce marked reduction in activity of the anterior pituitary as judged by the HGH responses. The levels of plasma growth hormone suggested some residual pituitary tissue (hypofunction) rather than complete ablation. The decreased operative mortality and present results with cryosurgical hypophysectomy for disseminated prostatic carcinoma are encouraging and may permit the application of this form of therapy to a greater number of patients.
Purified roswell park cultured antilymphocytie globulin RPMI‐CALG: Preparation and clinical trial
Authors: Moore G. E. , Murphy G. P. , Papermaster B. W. , Amiraian K. , Kenny G. M. , Moore R. H.
Published: February 2007

Purified human antilymphocytic globulin (RPMI‐CALG) has been prepared in bulk quantities by immunization of horses with purified normal lymphocytes maintained in continuous cell culture at the Roswell Park Cell Plant. The characterization studies herein described reveal RPMI‐CALG to be purified, nontoxic, and nonpyrogenic with specific in vitro immunosuppressive activity. Contamination with hemolysins and hemagglutinins is minimal and in marked contrast to other available preparations. Initial clinical trials with a lyophilized preparation reveal that it can be safely administered intravenously to humans without untoward effects. Comparison of hematological data was made on patients receiving RPMI‐CALG pretransplant without other immunosuppressive agents to the same patients post‐transplant receiving RPMI‐CALG plus azathioprine and prednisone. No significant depressive hematological effect was apparent. Platelets were not depressed. Eosinophilia was not seen acutely or on follow‐up examination. Urticaria was not evident. Follow‐up studies up to 6 months after allografting failed to reveal any specific toxicity in the measured hematological parameters. This purified preparation merits further clinical trial.
The effects of uremia on erythropoietin activity
Authors: Mirand Edwin A. , Murphy Gerald P.
Published: February 2007

Erythropoietin (ESF) activity was determined during acute and chronic uremic states with and without evidence of excretory renal function in humans. These observations demonstrated that detectable endogenous levels of ESF were absent in humans during an acute and chronic uremic state. Unlike the humans, the experimental animals produced ESF at a diminished rate. Also, in experimental animals, factors appear by 48–60 hr which make the bone marrow and spleen less responsive to exogenous ESF. Therefore, the human and nonhuman data show that the anemia of the uremic state can be explained by two factors: (1) an initial inhibition of end‐organ ESF responsiveness, and (2) a failure in ESF production. The temporal difference in the effect of these two aspects of erythropoietin activity is perhaps the basis for the variability in measured ESF activity in acute and chronic uremic states.
Simultaneous bilateral radical neck dissection following high‐level radiation therapy
Authors: Mooney Charles S. , Jewell William , Greenlaw Robert , Rush Benjamin F.
Published: February 2007

Twenty‐two patients with advanced cancer in the area of the head and neck were treated by combining major curative radiation (5000‐8000 rads) and a composite operation including excision of the primary lesion and bilateral radical neck dissection. The mortality and morbidity of combining these two treatment methods was quite acceptable and did not exceed mortality and complication rates for this type of operation done without prior radiation.
Exaggerated cold‐pressor response in hypertensive patients with superimposed arteriosclerosis
Authors: Voudoukis Ignatios J.
Published: February 2007

A series of 172 hypertensive patients with excessive cold‐pressor response (elevation of systolic blood pressure more than 30 mm Hg above basal) and 65 hypertensive patients with normal cold‐pressor response (elevation of systolic blood pressure less than 20 mm Hg above basal) was studied. A correlation of the pressor response with various parameters pertaining to the cardiovascular system was made. A highly significant correlation between retinal arteriosclerosis and exaggerated cold‐pressor response was seen. In addition, there was an excellent correlation between the latter and calcification of the aorta and/or its branches. Arteriosclerotic heart disease was much more prevalent among the hyperreactors than among the normoreactors. Elevation in serum cholesterol was also more frequent in the hyperreactors, but it was only seen in a small percentage of cases. The incidence of diabetes mellitus and established diastolic hypertension was also higher in the hyperreactors than in the normoreactors. Obesity was found twice as often in the patients with excessive cold‐pressor response than with normal cold‐pressor response. The results would seem to suggest that exaggerated cold‐pressor response may be related to superimposed systemic vascular sclerosis rather than to hypertension per se.
Supravesical urinary diversion: A comparison between cutaneous ureterostomy and heal conduit
Authors: Kursh Elroy D. , Albert David J. , Persky Lester
Published: February 2007

In an effort to compare objectively the two most commonly employed methods of supravesical urinary diversion, the cutaneous ureterostomy and the ileal conduit, this study was designed to compare functionally each technique in the experimental animal. Sixteen female mongrel dogs underwent ligation of the distal right ureter. One week later, diversion of the right ureter was performed by either cutaneous ureterostomy or ileal conduit in two groups of animals. One month following diversion, the function of the diverted right kidney was compared to the control left kidney in all dogs and radiological evaluation was done. In the groups of dogs diverted by the ileal conduit, renal function studies were significantly better and radiologic interpretation revealed a more nearly normal collecting system. The data strongly support the position that the ileal conduit is the preferred route for urinary diversion in the dog. The clinical application is discussed.
Value of electrophysiologic tests for peripheral nerve neuromas
Authors: Kline David G. , Hackett Earl R.
Published: February 2007

Management of a peripheral nerve neuroma can be improved by the use of electro‐physiologic tests. The relative value of these tests and their possible applications are discussed in some detail. Nerve stimulation either preoperatively or at the operating table remains the simplest and best test for early regeneration. Electromyography can document denervation, although similar conclusions can usually be reached by a careful clinical examination. Nascent muscle action potentials or decreased numbers of fibrillations can be recorded by electromyography and sometimes herald return of function. Conduction velocity tests are most useful for neuropathies of nontraumatic origin, while muscle stimulation tests are of limited value because they tell the investigator little about the quantity or quality of reinnervation. Evoked nerve action potentials (NAP) can be recorded at the operating table and are helpful in documenting a partial lesion or relatively early regeneration.
Free urinary amino acid excretion in patients with familial polyposis of the colon
Authors: Sachatello Charles R. , Tritsch George
Published: February 2007

The free urinary amino acids excretion per 24 hr of the neutral and acidic amino acids did not reveal any diagnostic abnormality in five patients with familial polyposis of the colon with or without associated desmoid tumors and osteomas. One patient with Klinefelter's syndrome and familial polyposis had a urinary acid excretion pattern indistinguishable from his brother, who had familial polyposis and normal chromosomes. It is suggested that patients with familial polyposis deserve intensive biochemical study as this represents a prototype hereditary malignant disease.
Delayed wound closures based on bacterial counts
Authors: Robson Martin C. , Heggers John P.
Published: February 2007

There exists a quantitative relationship between bacterial contamination and clinical infection. Because of this relationship, delayed wound closure can be performed based on the number of viable bacteria present in the incision at the time of closure. This principle was applied to 95 delayed wound closures in a prospective series. Ninety‐three cases were closed when the bacterial estimate was 105 bacteria or fewer per gram of tissue. This resulted in a 96% successful closure rate. The method of bacterial quantification on a tissue biopsy from the wound requires 1 hr from time of culture to quantitative report to the surgeon so that closure can be effected.
The incidence of ‘leukovirus’ in cultured human hematopoietic cells
Authors: Moore George E. , Kitamura Hajime , Minowada Jim
Published: February 2007

A majority of cell lines derived from peripheral blood samples of patients with leukemia, lymphomas, and other malignancies and of normal individuals have a herpes‐like virus (or EBV). This virus seems to be identical with one found in Burkitt lymphoma cell lines. The virus has biological activity to the extent of destroying some cells of the affected cell line, but is seemingly incapable of infecting some noninfected cell lines. No strong evidence of alteration of biological activity of the cells or their chromosomes by leukovirus was noted.
An evaluation of the mechanism of action of pentamidine isethionate
Authors: Bornstein Richard S. , Yarbro J. W.
Published: February 2007

The effect of pentamidine on DNA, RNA, phospholipid, and protein synthesis was evaluated in 6C3HED ascites tumor of C3H mice by incorporation in vitro of 3H‐thymidine, 3H‐uridine, 3H‐algal protein hydrolysate, and 32P‐orthophosphate. Inhibition of all parameters measured was observed, suggesting that pentamidine does not, as has been suggested, selectively inhibit DNA synthesis or act as an antifol. A reduced incorporation of 32P into charcoal adsorbable acid soluble phosphate was observed, suggesting that pentamidine may impair nucleotide formation.
The radioisotope skeletal survey
Authors: Volpe Joseph A.
Published: February 2007

The radionuclides presently available for bone imaging include Sr87m, Sr85, and F18. With any of these, the entire skeleton can be surveyed for localized bone disease by profile scanning, whole body counting, rectilinear scanning, or with the Mark II whole body scanner and positron scintillation camera. Whole body counting and profile scanning rapidly eliminate normal areas and focus attention on suspicious sites which must then be studied with a conventional scantier. Rectilinear scanning requires considerable time. The Mark II whole body scanner can survey the skeleton rapidly but not so accurately as the positron scintillation camera. The positron camera is accurate but slow. The ideal method for accurately and rapidly surveying the entire skeleton would utilize F18 as the radioactive agent and a large‐crystal positron scintillation camera as the imaging device.
Tissue adhesives and pelvic hemostasis: An evaluation of isobutyl 2‐cyanoacrylate
Authors: O'Leary James A.
Published: February 2007

A tissue adhesive, isobutyl cyanoacrylate, was studied in 17 mongrel dogs. The hemostatic properties of the drug were good, but the tissue tensile strength was inadequate. The exothermic activity of the preparation caused some tissue distortion. The aerosol study group was associated with an increase in sepsis. The clinical usefulnesses of the preparation are numerous and remain to be explored.
Variation in tumor doubling time in patients with pulmonary metastatic disease
Authors: Joseph William L. , Morton Donald L. , Adkins Paul C.
Published: February 2007

Recent experience has shown that the tumor doubling time (TDT) is an easily measurable, uniform, and accurate method for judging the progression of pulmonary metastatic disease in patients. Forty‐five patients with multiple pulmonary metastatic foci present had their TDTs measured. In 37, the calculated TDTs for each individual were similar and allowed the patients to be placed in particular groups based on their growth rates. In eight patients, there was particularly wide variation in TDTs such that placement of these patients into a particular category was impossible. Prognosis in these individuals appeared to be determined by the more rapid TDT. Nevertheless, in the majority of instances, calculated TDTs appear to be similar in each patient, and this confirms the accuracy of measurement of TDT in patients with multiple metastatic foci. Reasons for the wide variations in TDTs seen in some patients are suggested.
The metabolism and pharmacology of 5‐fluorouracil
Authors: Miller Edward
Published: February 2007

5‐Fluorouracil (5‐FU) is a chemotherapeutic agent, which is administered systemically for the palliative treatment of certain neoplastic diseases. Because 5‐FU is a potent antimetabolite, it is recommended that the drug be given only by physicians experienced in the use of antimetabolites. Now that 5‐FU is being applied topically for the treatment of skin neoplasms, it would be useful to review the metabolism and pharmacology of this compound. In this paper, the metabolic pathways, the antineoplastic mechanism of action, and the effects on normal tissues are discussed.
Occurrence of simian virus 40 (SV40)‐reacting antibodies in sera of some patients with prostatic cancer
Authors: Shah K. V. , Weismann M. , Murphy G. P.
Published: February 2007

SV48‐neutralizing antibodies were found in four of 77 sera from patients with pgostatic carcinoma. T antibodies were not detected in any of the sera. The antibody prevalence and the titers of positive sera in prostatic cancer patients were similar to those in sera of bladder cancer patients and of non‐cancerous individuals.
Gardner's syndrome, colon cancer, and sarcoma
Authors: Johnson Jerome G. , Gilbert Enid , Zimmermann Bernard , Watne Alvin L.
Published: February 2007

Soft tissue involvement is a major component of Gardner's syndrome. While these are frequently skin inclusion cysts, some patients exhibit fibrous dysplasias. These can vary from severe fibrosis, frequently intra‐abdominal and causing bowel obstruction, to desmoid tumors and fibrosarcomas, both of which can be progressive and life threatening. This aspect of the syndrome is poorly understood, but must be carefully evaluated in selecting treatment for the associated polyposis coli.
Radiotherapy in advanced prostatic carcinoma
Authors: Varkarakis M. J. , Webster J. , Bhanalaph T. , Murphy G. P.
Published: February 2007

Twenty‐two patients with advanced stages of prostatic carcinoma were treated with‐Cobalt‐60 teletherapy. Local control of the prostatic lesion was obtained in five out of eight patients with stage C. and in 2 out of 14 patients with stage D of the disease. However, survival of these irradiated patients was not better than other similar patients treated with orchiectomy and stilbestrol. Following radiotherapy, pain relief was obtained in almost all the patients without serious complications. Nevertheless in available post mortem material the histological appearance of the primary tumor was unchanged before and after radiotherapy. A randomized controlled clinical trial of radiotherapy in prostatic cancer is needed before final decisions can be made on its primary role in the treatement of this disease.
The management of patients with gestational trophoblastic neoplasia based on the antigenic properties of human chorionic gonadotropin
Authors: Goldstein Donald P. , Nudemberg Franklin , Lymeburner Nancy , Levesque Linda , Shore Christine
Published: February 2007

The use of a rapid, solid‐phase RIA for the quantitative measurement of serum LH‐HCG activity is described for use in the management of patients with GTN. The five‐hour test period permits more precise monitoring of drug therapy without compromising therapeutic effectiveness. The future implications of this new method in redesigning therapeutic regimens according to tumor cell kinetics is discussed.
Hemangioendothelioma of the penis with late appearing metastases: Report of a case with review of the literature
Authors: Deutsch Melvin , Leen Raymond L. S. , Mercado Raul
Published: February 2007

A case of hemangioendothelioma of the penis is presented. It was treated initially by excision and postoperative irradiation to the primary site. Systemic chemotherapy and radiotherapy to the thoracic spine was administered in the belief that the patient had osseous metastases in the spine. The patient was subsequently free of disease for more than five years at which time metastases appeared almost simultaneously in the extradural spinal column, right 12th rib, and lungs. A possible explanation for the peculiar distribution of these metastases is presented.

A review of the literature reveals no more than 30 other cases, none of which showed a similar clinical course, namely later appearing metastases after a five‐year disease‐free interval.
Fudr as an adjuvant to surgery in cancer of the large bowel
Authors: Dwight Richard W. , Humphrey Edward W. , Higgins George A. , Keehn Robert J.
Published: February 2007

In a controlled trial the Veterans Administration Surgical Adjuvant Group studied 735 patients with carcinoma of the large bowel in an effort to determine the possible benefits of using FUDR as an adjuvant to surgical resection. Patients randomized to treatment received a reduced course of the drug on the first, second, and third postoperative days, and a second standard therapeutic course approximately six weeks later. There was no significant difference in postoperative complications or 30 day mortality. The second course of chemotherapy was an apparent contributory factor in the death of six patients. Long term follow‐up studies showed no difference in survival between patients receiving the drug and those treated by surgery alone.
Serum lactic dehydrogenase and isoenzyme changes in clinical cancer
Authors: Wood Don C. , Varela Virginia , Palmquist Michele , Weber Frank
Published: February 2007

Total LDH and LDH isoenzyme values were measured in serum collected from patients at the time of hospital admission. Changes in isoenzyme values were not necessarily found to depend upon elevated total serum LDH levels. Many patients with normal levels of serum LDH had abnormal isoenzyme patterns usually related to a disease process. A large percentage of patients with neoplastic disease had statistically increased LDH 5 values. Many other patients with either acute and/or chronic disease failed to reflect changes in the isoenzyme values.
Esophageal cancer in california 1942‐1969: The California tumor registry experience
Authors: Krain Lawrence Stirling
Published: February 2007

An analysis of the 3,319 cases of esophageal cancer (ICD No. 150), 1942‐1969, from the California Tumor Registry was performed, and related data are examined. Esophageal cancer predominates in the Negro race, urban areas in California, and the lower socio‐economic classes. Esophageal cancer occurs at a median age of 63.8 years and has a male‐female sex ratio of 2.84:1. Despite an increase in the percentage of cases localized at the time of diagnosis, the five‐year survival rate (localized cases) for esophageal cancer patients has remained constant at 7%. The mean survival from the time of diagnosis for all stages of the disease was 5.2 months. Although there has been a slight increase in incidence of esophageal cancer, the mortality rate has remained constant at 2.4/100,000 (age‐adjusted). While more patients have been treated with surgery and/or radiation, this has had a negligible effect on the relative survival rates for esophageal cancer.
Cross‐classification and survival characteristics of 5,000 cases of cancer of the pancreas
Authors: Baylor Stephen M. , Berg John W.
Published: February 2007

Over 5,000 histologically confirmed cases of cancer of the pancreas from the End Results Group of cancer registries have been examined for differences in behavior by epidemiologic and pathologic variables. Thirteen percent had a specific histologic diagnosis other than “adenocarcinoma,” “carcinoma,” or “cancer.” The 92 cases of islet cell carcinoma were unique, having a much younger age at diagnosis (two‐thirds instead of one‐third diagnosed under the age of 60), a locational preference for the body and/or tail (only 40% instead of 70% occurring in the head of the pancreas), and a very favorable survival experience (15 year relative survival of 14%). Of cancers of the exocrine pancreas, the 64 cases with papillary histology were most distinct, two‐thirds being found in women, 18% instead of 10% being localized, and having relatively favorable survival (30% one‐year survival, 5% three‐year survival). Patients whose tumors revealed squamous metaplasia occurred in general at older ages and had unusually poor survival. Analysis by anatomic location showed an increasing percentage of carcinomas occurring in the head of the pancreas with increasing age. Analysis of “adenocarcinomas” by histologic grade indicated that grade may carry some prognostic information not explained by difference in stage. A striking gradient of decreasing survival with increasing age did not explain, and was not explained by survival gradients in other variables.
Control of erythropoietin production during hypoxic hypoxia
Authors: Harvey S. R. , Mirand E. A. , Back N. , Murphy G. P.
Published: February 2007

The control of erythropoietin (ESF) production in rats subjected to hypoxic hypoxia was investigated by studying the inhibition of endogenous ESF production by inhibitors affecting proteases and protein synthesis. The study revealed that the production of endogenous ESF was inhibited by protease inhibitors, Trasylol and epsilon amino caproic acid (EACA) and inhibitors affecting protein synthesis such as actinomycin–D, puromycin, and cycloheximide. The inhibitory effect of actinomycin–D on ESF production was dose dependent and markedly dimiished (threefold) in hepatectomized rats, whereas the inhibitory effects of Trasylol, EACA, and Step–I ESF (used as feedback inhibitor) were enhanced. These preliminary findings suggest that, during hypoxic stress, the control of ESF production may involve the interaction of a protease‐globulin substrate to produce ESF as well as the de novo synthesis of a protein or proteins involved in ESF production.
Extracranial meningioma
Authors: Farr Hollon W. , Gray George F. , Vrana Mark , Panio Michael
Published: February 2007

Meningioma can be a diagnostic problem for the head and neck surgeon and the surgical pathologist by reason of extracranial manifestation and the varying histological patterns seen in small biopsy specimens submitted from various extracranial sites. During the thirty year period 1940–1970, 405 cases of meningioma were seen at the New York Hospital and the Memorial Hospital and the clinical findings have been reviewed together with recent pertinent literature. Thirty‐four cases were spinal in origin: 9 cervical, 22 dorsal, and 2 lumbar. An external mass was present in 20% of the intracranial tumors: the orbit was involved in 30 patients, the outer table and scalp in 25, the paranasal sinuses and nasal cavity in 10, and the parotid and parapharyngeal region in 5. Three cases are documented primary extracranial meningiomas arising is soft parts; one free in the orbit and two in the neck masquerading as deep lobe parotid gland tumors. The pathological features of extra‐cranial meningioma were identical with the intracranial variety and a standard classification of the main histological types is outlined. A variety of differential diagnoses were entertained before the true nature of the neoplasm was established. The necessity for sophisticated radiographic studies and neurosurgical attention to the intracranial component of the tumor is emphasized.