bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of MAGE‐1, MAGE‐2, MAGE‐3/‐6 and MAGE‐4A/‐4B genes in ovarian tumors
Authors: Yamada Akira , Kataoka Akio , Shichijo Shigeki , Kamura Toshiharu , Imai Yasuhisa , Nishida Takashi , Itoh Kyogo
Published: February 2007

MAGE genes encoding tumor‐rejection antigens recognized by cytotoxic T lymphocytes are expressed at the mRNA level in various malignant tumors. We have investigated the expression of genes MAGE‐1, ‐2, ‐3/‐6 and ‐4a/‐4b at the mRNA level in malignant and non‐malignant ovarian tumors as well as in normal ovaries by reverse transcription‐polymerase chain reaction. MAGE‐1, ‐2, ‐3/‐6 and ‐4a/‐4b were expressed in 12, 5, 11 and 4 of 58 malignant tumors, respectively. The majority of these MAGE‐mRNA‐positive tumors were histologically surface‐epithelial‐stromal tumors, in particular serous adenocarcinomas. They mostly consisted of either advanced‐stage or recurrent tumors. In contrast, neither benign tumors nor normal ovaries expressed any of the MAGE genes investigated. A 46‐kDa MAGE‐1 protein was identified in MAGE‐1‐mRNA‐positive serous adenocarcinomas by immunoblot analysis with polyclonal anti‐MAGE‐1 antibody. These results provide important information for specific immunotherapy of ovarian serous adenocarcinomas with MAGE gene products. © 1995 Wiley‐Liss, Inc.
In vitro osteogenesis on a highly bioactive glass‐ceramic (Biosilicate®)
Authors: Moura João , Teixeira Lucas Novaes , Ravagnani Christian , Peitl Oscar , Zanotto Edgar Dutra , Beloti Márcio Mateus , Panzeri Heitor , Rosa Adalberto Luiz , de Oliveira Paulo Tambasco
Published: February 2007

One of the strategies to improve the mechanical performance of bioactive glasses for load‐bearing implant devices has been the development of glass‐ceramic materials. The present study aimed to evaluate the effect of a highly bioactive, fully‐crystallized glass‐ceramic (Biosilicate®) of the system P2O5–Na2O–CaO–SiO2 on various key parameters of in vitro osteogenesis. Surface characterization was carried out by scanning electron microscopy and Fourier transform infrared spectroscopy. Osteogenic cells were obtained by enzymatic digestion of newborn rat calvarial bone and by growing on Biosilicate® discs and on control bioactive glass surfaces (Biosilicate® parent glass and Bioglass® 45S5) for periods of up to 17 days. All materials developed an apatite layer in simulated body fluid for 24h. Additionally, as early as 12 h under culture conditions and in the absence of cells, all surfaces developed a layer of silica‐gel that was gradually covered by amorphous calcium phosphate deposits, which remained amorphous up to 72 h. During the proliferative phase of osteogenic cultures, the majority of cells exhibited disassembly of the actin cytoskeleton, whereas reassembly of actin stress fibers took place only in areas of cell multilayering by day 5. Although no significant differences were detected in terms of total protein content and alkaline phosphatase activity at days 11 and 17, Biosilicate® supported significantly larger areas of calcified matrix at day 17. The results indicate that full crystallization of bioactive glasses in a range of compositions of the system P2O5–Na2O–CaO–SiO2 may promote enhancement of in vitro bone‐like tissue formation in an osteogenic cell culture system. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Tenascin cytotactin epidermal growth factor‐like repeat binds epidermal growth factor receptor with low affinity
Authors: Iyer Anand Krishnan V. , Tran Kien T. , Borysenko Christopher W. , Cascio Michael , Camacho Carlos J. , Blair Harry C. , Bahar Ivet , Wells Alan
Published: February 2007

Select epidermal growth factor (EGF)‐like (EGFL) repeats of human tenascin cytotactin (tenascin C) can stimulate EGF receptor (EGFR) signaling, but activation requires micromolar concentrations of soluble EGFL repeats in contrast to subnanomolar concentrations of classical growth factors such as EGF. Using in silico homology modeling techniques, we generated a structure for one such repeat, the 14th EGFL repeat (Ten14). Ten14 assumes a tight EGF‐like fold with truncated loops, consistent with circular dichroism studies. We generated bound structures for Ten14 with EGFR using two different approaches, resulting in two distinctly different conformations. Normal mode analysis of both structures indicated that the binding pocket of EGFR exhibits a significantly higher mobility in Ten14–EGFR complex compared to that of the EGF–EGFR complex; we hypothesized this may be attributed to loss of key high‐affinity interactions within the Ten14–EGFR complex. We proved the efficacy of our in silico models by in vitro experiments. Surface plasmon resonance measurements yielded equilibrium constant KD of 74 µM for Ten14, approximately three orders of magnitude weaker than that of EGF. In accordance with our predicted bound models, Ten14 in monomeric form does not bind EGFR with sufficient stability so as to induce degradation of receptor, or undergo EGFR‐mediated internalization over either the short (20 min) or long (48 h) term. This transient interaction with the receptor on the cell surface is in marked contrast to other EGFR ligands which cause EGFR transit through, and signaling from intracellular locales in addition to cell surface signaling. J. Cell. Physiol. 211: 748–758, 2007. © 2007 Wiley‐Liss, Inc.
Interleukin‐1β induces MMP‐9 expression via p42/p44 MAPK, p38 MAPK, JNK, and nuclear factor‐κB signaling pathways in human tracheal smooth muscle cells
Authors: Liang Kao‐Chih , Lee Chiang‐Wen , Lin Wei‐Ning , Lin Chih‐Chung , Wu Chou‐Bin , Luo Shue‐Fen , Yang Chuen‐Mao
Published: February 2007

Matrix metalloproteinases (MMPs) are responsible for degradation of extracellular matrix and play important roles in cell migration, proliferation, and tissue remodeling related to airway inflammation. Interleukin‐1β (IL‐1β) has been shown to induce MMP‐9 production in many cell types and contribute to airway inflammatory responses. However, the mechanisms underlying MMP‐9 expression induced by IL‐1β in human tracheal smooth muscle cells (HTSMCs) remain unclear. Here, we investigated the roles of p42/p44 MAPK, p38 MAPK, JNK, and NF‐κB pathways for IL‐1β‐induced MMP‐9 production in HTSMCs. IL‐1β induced production of MMP‐9 protein and mRNA in a time‐ and concentration‐dependent manner determined by zymographic, Western blotting, and RT‐PCR analyses, which was attenuated by inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), JNK (SP600125), and NF‐κB (helenalin), and transfection with dominant negative mutants of MEK1/2, p38 and JNK, respectively. IL‐1β‐stimulated phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK was attenuated by pretreatment with U0126, SB202190, SP600125, or transfection with these dominant negative mutants of MEK, ERK, p38 and JNK, respectively. Furthermore, IL‐1β‐stimulated translocation of NF‐κB into the nucleus and degradation of IκB‐α was blocked by helenalin. Finally, the reporter gene assay revealed that MAPKs and NF‐κB are required for IL‐1β‐induced MMP‐9 luciferase activity in HTSMCs. MMP‐9 promoter activity was enhanced by IL‐1β in HTSMCs transfected with MMP‐9‐Luc, which was inhibited by helenalin, U0126, SB202190, and SP600125. Taken together, the transcription factor NF‐κB, p42/p44 MAPK, p38 MAPK, and JNK that are involved in MMP‐9 expression in HTSMCs exposed to IL‐1β have now been identified. J. Cell. Physiol. 211: 759–770, 2007. © 2007 Wiley‐Liss, Inc.
Defining the involvement of proteinases in pemphigus vulgaris: Evidence of matrix metalloproteinase‐9 overexpression in experimental models of disease
Authors: Cirillo Nicola , Lanza Michele , Rossiello Luigi , Gombos Fernando , Lanza Alessandro
Published: February 2007

Pemphigus vulgaris (PV) acantholysis represents a complex phenomenon wherein a number of factors cooperates. PV serum is known to modulate important cellular events, including kinase activity, transcriptional regulation, and proteinase expression. Indeed, transduction of signals to the cell triggered by PV serum may induce proteinase up‐regulation potentially responsible for disruption of epidermal adhesion and, ultimately, blister formation. Here, we sought to investigate this hypothesis by using both in vivo and in vitro models of PV. Microarray analysis on mouse skin tissues suggested that the equilibrium between extracellular proteinases and their inhibitors moved towards enhanced proteolytic activity in PV neonatal mouse model, at least on the transcriptional level. Conversely, genes codifying cell adhesion proteins were dramatically down‐regulated. The effects of PV serum on the protein level were then studied in vitro both in keratinocyte monolayers and skin organ cultures focusing on matrix metalloproteinase (MMP) 9 expression and activity. By means of Western blotting, zymography, and living cell immunofluorescence studies, we showed that MMP‐9 was early overexpressed in keratinocytes exposed to PV serum, and subsequently secreted in the culture medium. However, we failed to demonstrate extracellular activation of MMP‐9, since it was found in its 92 kDa inactive form in serum‐free culture supernatants. Taken together, our data demonstrated that proteinase expression, particularly of MMP‐9, is modulated by PV serum and associated with PV acantholysis. J. Cell. Physiol. 212: 36–41, 2007. © 2007 Wiley‐Liss, Inc.
Fibroblast growth factor receptor‐induced phosphorylation of STAT1 at the golgi apparatus without translocation to the nucleus
Authors: Citores Lucía , Bai Ling , Sørensen Vigdis , Olsnes Sjur
Published: February 2007

STAT transcription factors signal from the plasma membrane to the nucleus in response to growth factors and cytokines, but little is known about activation of STAT1 from intracellular sites. Here we show that transient transfection of COS cells with fibroblast growth factor receptors (FGFRs) led to ligand‐independent phosphorylation of the receptors, including intracellular immature forms. FGF‐independent activation of STAT1 was demonstrated at the Golgi apparatus where it was colocalized with FGFRs. Both FGFR1 and FGFR2 induced strong phosphorylation of STAT1 causing redistribution of the Golgi apparatus, while FGFR3 and FGFR4 induced less phosphorylation of STAT1 and little or no redistribution of the Golgi apparatus. Upon expression of a cytosolic mutant of FGFR4 lacking the transmembrane as well as the extracellular region (CytR4), STAT1 was phosphorylated and transferred to the nucleus. The results indicate that immature forms of FGFRs form incomplete signaling complexes on Golgi membranes trapping phospho‐STAT1 on this organelle. J. Cell. Physiol. 212: 148–156, 2007. © 2007 Wiley‐Liss, Inc.
Growth factors improve gene expression after lentiviral transduction in human adult and fetal hepatocytes
Authors: Selden Clare , Mellor Neil , Rees Myrddin , Laurson Joanna , Kirwan Mike , Escors David , Collins Mary , Hodgson Humphrey
Published: February 2007

Background

Lentiviral vectors may be vectors of choice for transducing liver cells; they mediate integration in quiescent cells and offer potential for long‐term expression. In adult liver, hepatocytes are generally mitotically quiescent. There has been controversy as to the necessity for lentiviral vector target cells to be in the cell cycle; currently, there is consensus that effective transduction can be achieved in quiescent hepatocytes, by using virus at high titre. However, transduction approaches which reduce the multiplicities of infection (MOIs) required provide potential benefit of cost and safety for therapeutic use.

Methods

We used two late‐generation HIV‐based lentiviral vector systems (pHR‐SIN‐cppT SGW and pRRLSIN.cPPT.PGK.WPRE) encoding LacZ/GFP reporter genes to transduce adult and fetal human hepatocytes in vitro + /− growth factors, hepatocyte growth factor (HGF) and epidermal growth factor (EGF). Green fluorescent protein (GFP) expression was observed microscopically, and quantified by fluorescence spectrometry for protein expression, fluorescence‐activated cell sorting (FACS) analysis to identify the proportion of cells expressing GFP, and real‐time quantitative polymerase chain reaction (PCR) for number of integrations.

Results

Gene expression following lentiviral transduction of human liver cells in vitro was markedly enhanced by the growth factors HGF and EGF. In adult cells growth factors led to a greater proportion of cells expressing more GFP per cell, from more integration events. In human fetal cells, the proportion of transduced hepatocytes remained identical, but cells expressed more GFP protein.

Conclusions

This has implications for the design of regimes for liver cell gene therapy, allowing marked reduction of MOIs, and reducing both cost and risk of viral‐mediated toxicity. Copyright © 2007 John Wiley & Sons, Ltd.
Genomic diversity of human papillomavirus genotype 53 in an ethnogeographically closed cohort of white European women
Authors: Kocjan Boštjan J. , Seme Katja , Močilnik Tina , Jančar Nina , Vrtačnik‐Bokal Eda , Poljak Mario
Published: February 2007

Human papillomavirus (HPV) genotype 53 is classified taxonomically in alpha HPV genus–species 6, together with HPV‐30, HPV‐56, and HPV‐66 and is considered to be one of three “probable high‐risk” HPV genotypes. Recent worldwide comparison of 44 isolates of HPV‐53 showed the existence of nine long control region (LCR) genomic variants, which formed a phylogenetic tree with two deep dichotomic branches. In order to investigate further the genomic diversity of HPV‐53, a total of 94 isolates of HPV‐53 obtained from an ethnogeographically closed cohort of 70 white European women was analyzed. The identification and characterization of HPV‐53 genomic variants was based on analysis of three different HPV genomic regions: LCR, E6 and E7. A higher genomic diversity of HPV‐53 was identified in the ethnogeographically closed cohort of white European women than has been reported previously on isolates collected worldwide. Altogether, 19 HPV‐53 genomic variants, composed of 13 LCR, 13 E6, and 5 E7 genomic variants, were identified. Eleven out of 13 LCR, all E6, and four out of five E7 genomic variants were described for the first time. The present study confirmed dichotomic phylogeny of HPV‐53 described previously and, in addition, showed for the first time that after a dichotomic split, both groups of HPV‐53 genomic variants formed star‐like phylogenetic clusters. In women with persistent HPV‐53 infection, HPV‐53 genomic variants remained unchanged for up to 51 months. In rare cases, infection with multiple HPV‐53 genomic variants is possible. Taking into account the results of this and previous studies, at least 26 different HPV‐53 genomic variants exist today. J. Med. Virol. 79:431–438, 2007. © 2007 Wiley‐Liss, Inc.
Distinctive distribution of HPV16 E6 D25E and E7 N29S intratypic Asian variants in Korean commercial sex workers
Authors: Choi Byeong‐Sun , Kim Sung Soon , Yun Haesun , Jang Dae Ho , Lee Joo‐Shil
Published: February 2007

The distribution of HPV16 sequence variations differs geographically and specific HPV16 E6 and E7 variants might carry a high risk for development of invasive cervical cancer and cervical intraepithelial neoplasia in a given population. To investigate the genetic variation of HPV 16 E6 and E7 genes, genomic DNAs from 56 HPV16‐infected commercial sex workers were extracted from their cervical swabs by using DNA isolation kit. The E6 and E7 coding region (34–880) with HPV16 E6/E7 specific PCR were amplified and analyzed by using the DNAstar software. At the nucleotide level, 26 variants of the HPV16 E6 and E7 genes were identified including 12 silent mutations. At the amino acid level, the isolates showed 14 variants including E6 Q14H, E6 D25E, E6 I27R, E6 H78Y, E6 L83V, and E7 N29S. The dominant HPV16 E6 and E7 variants were HPV16 E6 D25E (68%) and HPV16 E7 N29S (73%), respectively, which belong to Asian lineage. Although this study has some limitations such as a small sample size and not enough clinical data, these finding suggests that the distinctive distribution of HPV 16 As‐variant E6 D25E and E7 N29S might be associated with geographical dependence rather than disease progression. Further study is needed to determine the clinical and biological effects of these variants. J. Med. Virol. 79:426–430, 2007. © 2007 Wiley‐Liss, Inc.
Genetic characterization of hepatitis C virus strains in Estonia: Fluctuations in the predominating subtype with time
Authors: Tallo Tatjana , Norder Helene , Tefanova Valentina , Krispin Tõnu , Schmidt Jelena , Ilmoja Madis , Orgulas Karen , Pruunsild Kaije , Priimägi Ludmilla , Magnius Lars O.
Published: February 2007

During the last decade, there has been a dramatic increase in intravenous drug use in young adults in Estonia with an increased incidence of both hepatitis B and C as a consequence. Since genetic data are limited regarding hepatitis C virus (HCV) strains in Estonia, the aim of the study was to characterize HCV strains in different risk groups to determine their relatedness to strains from other geographical regions. Three hundred fifty‐three anti‐HCV positive sera collected during 1994–2004 from hospitalized patients, blood donors and health care workers were used as source of HCV RNA. Two hundred nine (59%) of the sera were positive for HCV RNA by PCR directed to the 5′‐UTR region. For 174 strains the HCV subtype was determined by analyses of the NS5B and/or the 5′UTR‐core regions. 1b (71%) was the most common subtype followed by 3a (24%), 2c (2%), 1a (1%), and 2a (1%). The 1b and 3a strains were similar to strains from other regions of the former USSR. Within genotype 1b there were several HCV lineages. However, for 3a there seemed to be two separate introductions into Estonia. There was a relative shift from subtype 1b to 3a in 1999–2000 with a further replacement of 3a with 1b in intravenous drug users in 2001 and onwards (P < 0.05). However, both subtypes were found to co‐circulate in the community independent of risk factors. One patient was infected with the 2k/1b recombinant presumed to originate from St. Petersburg being the first isolate of this recombinant recovered outside Russia. J. Med. Virol. 79:374–382, 2007. © 2007 Wiley‐Liss, Inc.
Effects of post‐hepatectomized rat sera on cultured cells
Authors: Gentile John M. , Ali Elizabeth , Grace James T.
Published: February 2007

These experiments suggest that serum obtained subsequent to partial hepatectomy of rats is capable of stimulating the growth of and enhancing the final population and cell viability achieved in antibiotic‐free suspension cultures of L929 cells. Preliminary enzymatic inhibition of post‐hepatectomy serum suggests that one of the humoral factors involved may be RNA.
A computer approach to cancer patient follow‐up
Authors: Graham Thomas D. , Ausman Robert K.
Published: February 2007

A computer based system to follow until death all discharged patients with a malignant diagnosis has been implemented at Roswell Park Memorial Institute. The automated system has relieved the follow‐up clerks of tedious clerical procedures and the human decision‐making that was prevalent in its manual predecessor. The system automatically prepares letters based on the patient's condition and, when the patient expires, a physician letter is generated to obtain details of the death (autopsy, mechanism of death, etc.). All correspondence is stored on magnetic tape for patient as well as system evaluation. Less than one percent of the cases registered has been lost to follow‐up. The system has shown that the family physician contact is most desirable. The system is economically feasible.
Lack of effect of diphenylhydantoin ingestion on vesical transitional epithelium in the rat
Authors: McDonald D. F.
Published: February 2007

Seizure‐prone patients may be chronically treated with diphenylhydantoin, a mitogenic agent excreted in the urine. Chronic ingestion of diphenylhydantoin by 64 rats failed to demonstrate vesical epithelial tumor formation under conditions which demonstrate the tumorigenicity of other vesical carcinogens. Vesical neoplasms occurring in patients chronically ingesting diphenylhydantoin are probably co‐incidental.
Truncated left hepatic lobe: A significant liver scan abnormality
Authors: Johnston Gerald S. , Jones A. Eric
Published: February 2007

Three patients with truncated left hepatic lobe on scintiscan of the liver have been presented to illustrate this diagnostic finding. This scintiscan finding should evoke more definitive study.
Successful long‐term coumadin anticoagulation of mice with prothrombin time monitoring
Authors: Ryan James J. , Orme S. Kirby , Wexler Hilda , Ketcham Alfred S.
Published: February 2007

Animal studies involving prolonged anticoagulation have been few in number. In such studies the level of anticoagulation has infrequently been monitored and hemorrhagic complications have been common. A regimen of long‐term sodium warfarin anticoagulation was studied in several strains of mice using, with slight modification, the Miale micromethod of prothrombin time determination. The degree and course of the prothrombin time alteration with several warfarin dosages was determined over a 4‐week period. The method proved very sensitive to changes in warfarin dosage, and results obtained were reproducible to a degree sufficient to permit the selection of optimal warfarin dosages for normal and tumor‐bearing mice. On these dosages the mean prothrombin time remained within the range of 2–3 times the average normal value and hemorrhagic complications were entirely avoided. In studies with small animals these methods could facilitate the use of prolonged anticoagulation, permit accurate monitoring of the level of anticoagulation, and diminish the incidence of hemorrhagic complications.
The influence of zinc gluconate and casein hydrolysate on the fluid and tissue kinetics of zinc‐65 in the baboon prostate
Authors: Schoonees R. , De Klerk J. N. , Johnston G. S. , Murphy G. P.
Published: February 2007

The clearance of 65Zn from the bloodstream following an intravenous injection of 65ZnCl2 was significantly delayed by the intravenous administration of stable zinc gluconate 15 min before and the addition of 5% casein hydrolysate to the 65ZnCl2. This resulted in a higher blood 65Zn concentration maintained for a longer period than was the case when only the 65ZnCl2 was injected. The uptake of 65Zn by a number of organs, especially the liver, pancreas, spleen, adrenal, kidney, and caudal prostate, was suppressed by the addition of zinc gluconate and Amigen (5% casein hydrolysate) to the 65ZnCl2. The 65Zn uptake by the skin, testis, epididymis, bladder, and aorta was enhanced by adding zinc gluconate and Amigen to the 65ZnCl2. This also resulted in a raised pancreas/liver ratio. The caudal prostatic 65Zn uptake was significantly suppressed by the use of stable zinc gluconate prior to injection of 65ZnCl2. In both groups the caudal portion of the prostate responded much better to exogenous testosterone than the cranial portion. Zinc gluconate treatment, in general, prevented the rise in prostatic 65Zn uptake observed between the fourth hour and sixth day following the injection of 65ZnCl2. The higher blood 65Zn radioactivity and perhaps the blocking of 65Zn uptake sites in the kidney by stable zinc gluconate resulted in a much higher output of 65Zn in the urine than was the case when only 65 ZnCl2 was used. By the second day, however, the blood and urine concentration of 65Zn had returned to almost ‘normal’ values. The results obtained in this study, using baboons, assume great significance by virtue of their easier application to man than is the case in studies involving rats and dogs. The use of stable zinc gluconate in addition to 65ZnCl2 partially blocked the liver uptake of 65Zn. This may assist in successful pancreatic scanning. The stable zinc gluconate partially blocked the uptake by the prostate of subsequently injected 65Zn.
Prostatic carcinoma: Reflections on its natural history, diagnosis, and therapy
Authors: Schirmer Horst K. A.
Published: February 2007

The natural history of prostatic cancer is reviewed in brief with emphasis on transitions in cellular differentiation. Diagnostic features are appraised in conjunction with prognostication of the clinical course. Radical prostatectomy is considered the best form of treatment for the isolated prostatic nodule with preserved cellular differentiation. Endocrine therapy should be withheld until manifestations of cancer spread are evident.
Studies on the chemistry, antitumor activity, and pharmacology of ethyl Di‐(2,2 ‐dimethyl)ethylenamido phosphate (AB‐163)
Authors: Munson A. E. , Babbitt H. , Chmielewicz Z. F. , Bardos T. J. , Ambrus J. L.
Published: February 2007

AB‐163, a new alkylating agent containing the 2,2‐dimethylaziridine moiety, was found to be active against a number of transplanted and virus‐induced tumor systems in mice. This compound hydrolyzes in water at 37 C. The hydrolysis product was isolated and identified as ethanol and amino‐tert‐butyl phosphate. The compound was shown to react with the model nucleophile 4‐(p‐nitrobenzyl) pyridine (NBP) comparably to previously studied alkylating agents. The intravenous LD50 was 198 mg/kg and the intraperitoneal LD50 was 159 mg/kg in ICR/Ha male mice. In mice carrying Ehrlich ascites tumor (E‐2), 30 mg/kg of AB‐163 resulted in 95% tumor inhibition. In Sarcoma‐180 inoculated mice, 15 mg/kg caused a 20–30% apparent cure rate and a 62% tumor inhibition of the animals having tumors. Against Adenocarcinoma 755, 40 mg/kg exhibited a 60% cure rate and 50% tumor inhibition of the animals with tumors. Leukemia L1210 treated on days 1–11 was cured in 20–30% of the animals receiving 30 mg/kg of AB‐163 and there was a 76–170% increase in survival time in the remaining animals. In animals infected with Friend virus, a 40 mg/kg dose resulted in 65% reduction of splenic weight as compared to controls. Studies in dogs indicated that the main toxicity is hematopoietic depression. Terminally, depression of liver functions was observed. High doses produced central nervous system effects which manifested themselves in loss of appetite, vomiting, increased salivation, lethargy, and convulsions.
Histopathological changes in autotransplanted baboon kidneys after 24‐hour hyperbaric, hypothermic preservation perfusion
Authors: Weber H. W. , Van Zyl J. J. W. , Groenewald J. H. , Brede H. D. , Murphy G. P.
Published: February 2007

Baboon kidneys were preserved at 4 C and 3 atm for 24 hr. Thirty‐two kidneys were perfused with G.S.H. replacement solution or Plasmalyte B during preservation. Fifteen kidneys were flushed with the same solution prior to preservation but not perfused during preservation. Twenty‐six kidneys were flushed with serum prior to preservation and also not perfused during preservation. The preserved kidneys were autotransplanted to the iliac fossa. Histopathological studies of the kidneys were undertaken between the second and twenty‐fourth day after reinsertion. It was found that preservation perfusion was frequently accompanied by glomerular thrombosis, glomerular and interstitial fibrosis as well as endarteritis in many kidneys. These changes were rarely observed in unperfused preserved kidneys. The observed renal alterations are similar to those described in the literature as chronic pyelonephritis in long‐term studies of preserved dog kidneys.
Splenectomy in Felty's syndrome
Authors: Elias E. G. , Mittelman Arnold , Wieckowska Wanda , Shapiro S. , Jones Ralph
Published: February 2007

The syndrome of rheumatoid arthritis, splenomegaly, leukopenia, and neutropenia is rare. When it occurs, it could become complicated by infection that does not respond to antibiotics and steroid therapy. We feel that splenectomy should be carried out once the diagnosis of Felty's syndrome is made. In the presence of infection, prompt splenectomy should be done, even if the patient shows signs of systemic toxicity. Splenectomy is the most beneficial treatment and may prevent a fatal outcome in these cases. Splenectomy is usually followed by immediate hematologic response. Steroid therapy may alter the arthritic symptoms but has no effect in altering or controlling the infection in these cases, even if accompanied by antibiotic therapy. Radiation of the spleen may reduce its size, but does not prevent or control the infections in patients with Felty's syndrome.
Cytochemical study on the nature of nucleic acids in Epstein—Barr virus (EBV)
Authors: Chai L. S. , Horoszewicz J. S. , Grace J. T.
Published: February 2007

The nature of nucleic acids present in the nucleoids of Epstein‐Barr virus (EBV) was investigated with cytochemical methods. EBV infected cell cultures were embedded in glycol‐methacrylate and thin sections were exposed to DNase and RNase and examined in the electron microscope. The results showed disappearance of viral nucleoids after DNase treatment, which provided evidence that EBV contains DNA, as do other herpes viruses.
The effect of depostat (SH 582) on the baboon prostate
Authors: Schoonees R. , De Klerk J. N. , Murphy G. P.
Published: February 2007

The 4‐hr tissue Zn65 uptake, the prostatic, seminal vesicular, and testicular weight ratios, and the caudal prostatic radioisotopic blood flow rate were employed to determine the effect of norhydroxyprogesterone caproate (Depostat, Schering A.G., Berlin) on intact adult male Chacma baboons. The metabolism of the intravenously injected Zn65Cl2 is markedly altered by Depostat treatment. Depostat inhibits prostatic and seminal vesicular growth and/or function, as indicated by a statistically significant reduction of the Zn65 uptake and weight ratios of these organs. The testicular weight ratio is statistically significantly suppressed by Depostat treatment. This indicates that Depostat inhibits testicular function. The caudal prostatic radioisotopic blood flow rate is not significantly altered by Depostat treatment.
The false positive technetium‐99m hepatic scintiscan
Authors: Volpe J. A. , Morita E. T. , Johnston G. S.
Published: February 2007

Instances of false positive technetium‐99m hepatic scintiscans resulting from objects in a right jacket pocket, the interposition of an arm between the liver and the detector, the presence of deeply indented rib margins, and the presence of kidney shadows on the posterior scan are presented. Such false positive scans are caused by the easily shielded 140 kev gamma photon of technetium‐99m. The problem may be accentuated by the tomographic effect of the various focused rectilinear scanners currently in use. By anticipating these problems and by promptly repeating scans following corrective measures, misinterpretation of the technetium‐99m hepatic scintiscan may be avoided.
Ureteral obstruction following treatment of cervical carcinoma
Authors: Schoonees Rikus , Kenny Gerald M. , Moore Robert H. , Murphy Gerald P.
Published: February 2007

Benign ureteral obstruction is a significant cause of uremia in patients treated for cervical carcinoma. In the present study, the records of 250 randomly selected patients treated for cervical carcinoma at Roswell Park Memorial Institute during the past 5 years were reviewed. The incidence of ureteral obstruction increased with the apparent clinical extent of the disease. This was associated with a rising BUN level. Following therapy there was a marked increase in the incidence of radiological hydronephrosis and a significantly raised BUN level. The importance of careful urological follow‐up of patients treated for cervical carcinoma in order to prevent renal damage from benign ureteral strictures is stressed.
Needle biopsy versus open perineal biopsy for the detection of carcinoma of the prostate
Authors: Lilien O. M.
Published: February 2007

The significance of prostatic carcinoma as a primary cause of death is presented; the concept that prostatic carcinoma is omnipresent in elderly males is challenged; the incidence of prostatic carcinoma is reviewed and discrepancies in published reports are analyzed. A comparison is made between the yield of positive diagnoses using open perineal biopsy and needle biopsy techniques. Contraindications in the use of needle biopsy for the diagnosis of operable carcinoma of the prostate are discussed.
Tissue protein‐bound fucose in carcinoma of the female breast (tumor fucose in breast carcinoma)
Authors: Seltzer Murray H. , Rosato Francis E.
Published: February 2007

A positive relationship between serum protein‐bound fucose levels and carcinoma of the female breast has been demonstrated in previous reports. In this study, breast tissue fucose levels were determined and the value of a ratio between malignant tumor and control tissue levels was found to correlate directly with serum fucose levels. This evidence is presented as further confirmation of a relationship between the sugar l‐fucose and breast carcinoma.
A reappraisal of primary gallbladder carcinoma
Authors: Neel Iii H. B. , , Neel H. B. , Hammond W. G.
Published: February 2007

A 10‐year experience with 14 patients with primary carcinoma of the gallbladder encountered in a typical community hospital has been reviewed. Abdominal discomfort in its many manifestations occurred in all patients, with chronic pain of long duration frequently being noted. Six patients were jaundiced. Twelve had documented cholelithiasis. Histologic examination revealed adenocarcinoma in all instances. One patient is alive and well at 3 years; survival of the remaining patients was from 9 days to 25 months. Primary carcinoma of the gallbladder occurs in more than 1% of surgically removed gallbladders. The disease is largely one of elderly persons with chronic calculous cholecystitis. Not only will it be seen with increasing frequency as life expectancy increases, but also it is preventable. Improvement in treatment can thus be initiated by prophylactic removal of diseased gallbladders in otherwise healthy persons. Malignancy may be obscured in those patients presenting with acute cholecystitis eluding surgeon and pathologist alike. These cases, as well as all early malignancies, are diagnosed only by careful histologic examination. Therefore, all gallbladders should be opened and examined by the surgeon in the operating room. Suspicious areas should be evaluated histologically by frozen section so that extension of the operation to include removal of adjacent hepatic parenchyma and performance of an extensive regional lymphadenectomy can be undertaken if cancer is found. By routinely considering every older patient who comes to cholecystectomy as suspect of harboring gallbladder cancer, survival may well be improved.
The effect of cinanserin (antiserotonin agent) on canine renal allografts
Authors: Murphy G. P. , Brede H. D. , Weber H. W. , Groenewald J. H. , Mirand E. A.
Published: February 2007

A new compound, cinanserin, which possesses antiserotonin as well as immunosuppressive properties, was tested in dog renal allografts. Increased survival rates were noted at a dose level of 40 mg/kg/day. Increasing drug therapy above this level was associated with hepatotoxicity. There was no evidence of bone marrow toxicity. Histologically, characteristic features of allograft rejection were generally unmodified. Serological alterations seen in untreated renal allografts were generally suppressed to a limited degree.
A new regional perfusion system
Authors: Wilson Samuel E. , Passaro Edward
Published: February 2007

The development of an in situ perfusion system utilizing a new pulsatile pneumatic pump (Starling‐Fields pump) is described. Experiments with dogs demonstrated that kidneys perfused in situ for 4–6 hr by this system maintained life when transplanted into bilaterally nephrectomized recipients. The pump is automatic and incapable of pumping a gas. A technician is not required for its operation. Hemolysis is less than with roller or peristaltic pumps. The pulsatile flow provided is in the physiologic range. Chemotherapeutic agents may be added easily and directly into the pump. The pump's small size, inability to pump air emboli, autoregulation, low hemolysis, and ease of operation offer advantages that make it especially suitable for regional perfusion use.
Colostral leukocytes
Authors: Mohr John A. , Leu Richard , Mabry Wynn
Published: February 2007

Leukocytes of human colostrum were studied for their phagocytic activity and ability to migrate in vitro. Samples were collected from healthy females in the first 2 weeks after delivery. Leukocytes were found with great regularity in concentrations of 2200–4100/mm3. These colostral leukocytes displayed glass adhesiveness, amoeboid movement, and the ability to migrate in capillary tubes. The phagocytic activity of colostral leukocytes against nonencapsulated Cryptococcus neoformans approached the normal values of peripheral blood leukocytes. The colostral leukocytes reacted to specific antigen similar to the donors' peripheral blood leukocytes and correlated with the dermal reactivity of the donor. The finding that these leukocytes are in relatively large numbers and possess phagocytic activity supports the concept that this is a naturally occurring in vivo phenomenon and that these cells may protect the breast against invading microorganisms; also, since these cells demonstrate the presence of cell‐mediated hypersensitivity and are normally ingested by the neonate, they may play a role in the development and/or induction of cellular immunity in the neonate.
The direct effects of metolazone diuresis on the isolated bloodless perfused canine kidney
Authors: Murphy G. P. , Groenewald J. H. , Kenny G. M. , Reynoso G. F.
Published: February 2007

Renal bloodless perfusions under normothermic, normobaric conditions with oxygen or helium gas equilibrations were conducted in 14 canine kidneys. A new diuretic, metolazone (SR‐720—22), a quinazolinone compound, was evaulated for possible direct renal effects. Metolazone exerts direct renal effects with or without oxygen characterized by (1) fall in renal resistance; (2) rise in urine flow rate and osmolar clearance; (3) no change in GFR, in inulin extraction, or in the proximal tubular reabsorption of sodium. The agent at low doses is thus a potent and direct active diuretic. Lack of alteration in renal acidification processes as well as activity under anoxic conditions may indicate future usefulness in renal insufficiency states.
Responsiveness of uroepithelium to estrogens as an indication of dose response in prostatic carcinoma
Authors: Silk Mark R.
Published: February 2007

Diethylstilbestrol was administered to patients with prostatic carcinoma to establish the relationship between tumor response and urethral cytological response. In the majority of patients the dose of diethylstilbestrol necessary to induce an estrogen effect in the urethral cytology was the same as that necessary for tumor response.
The effects of phytohemagglutinin in treated and untreated dog renal allografts
Authors: Murphy G. P. , Groenewald J. H. , Brede H. D. , Williams P. D. , Grace J. T.
Published: February 2007

Dogs undergoing renal allografts were treated with phytohemagglutinin‐M (PHA‐M) with and without azathioprine before and after transplantation. PHA‐M treatment was associated with histological evidence of decreased renal allograft rejection and minimal azotemia. PHA‐M‐treated animals had marked leukocytosis postoperatively and, unlike untreated control animals or azathioprine‐treated dogs, had sustained elevations in total lymphocyte levels. However, PHA‐M treatment did not decrease survival due to associated drug toxicity manifested by a distemper‐like syndrome not observed in other concurrently evaluated animals.
The role of starvation, hypoglycemia, and adrenergic blockade on growth hormone secretion in obesity
Authors: Herrold Joyce N. , Tzagournis Manuel
Published: February 2007

The effects of starvation and refeeding on the circulating levels of human growth hormone (HGH) of seven obese subjects were studied with and without alpha and beta adrenergic blockade during an insulin tolerance test (ITT). The tests were performed during baseline, total fast, and refeeding periods. Autonomic blockade during starvation was not performed. The degrees of hypoglycemia produced during the mean baseline ITT before and after blockade and in the fasting period were comparable and associated with HGH levels of similar response. During refeeding, mean fasting glucose levels before and after blockade were higher than in control and fasting periods. The insulin‐induced hypoglycemia effect was comparable in percentage decrease, although absolute levels of hypoglycemia were less. There was correspondingly less response of HGH to this stimulus. This indicates that HGH secretion is normal in obesity provided sufficient hypoglycemia is produced a not apparently affected by circulating catecholamine levels.
Role of pinealectomy on Walker 256 carcinoma in rats
Authors: Barone Robert M. , Gupta Tapas K. Das
Published: February 2007

After years of investigation, today it is generally agreed that mammalian pineal is a functioning organ with endocrine‐like properties. Several investigators in the past have shown that pinealectomy possibly alters the growth and spread of tumors in rodents. An experimental system has been devised in this laboratory to study the effects of pinealectomy on the growth and spread of Walker 256 carcinoma in rats. One hundred and ten inbred Holtzman male rats weighing 40–60 g were used. Thirty‐nine rats were pinealectomized. Thirty‐five rats were subjected to a comparative trauma and bleeding but the pineal was left intact (sham‐operated). Thirty‐six rats served as controls. Five weeks after operation all the rats were inoculated with 500,000 tumor cells. The rats were observed for 23 days after tumor inoculation. Autopsies were performed on the twenty‐fourth day. Results showed the tumor volumes were 149.37 ± 26.46 ml in pinealectomized rats, 104.79 ± 19.97 ml in the sham‐operated group, and 103.59 ± 19.61 ml in the control group. This was statistically significant (p = 0.01). Metastatic tumor involvement of the mediastinal lymph nodes occurred in 82% of the pinealectomized rats versus 38% of the controls and 46% of sham‐operated animals. Metastatic tumor involvement occurred in 79% of the lungs in pinealectomized rats versus 31% in the sham‐operated and 36% in the control animals.
Cancer of the colon in California, 1945–1966: The California tumor registry experience
Authors: Krain Lawrence S.
Published: February 2007

Appropriate data from the California Tumor Registry (1945–1966) and the Alameda County Tumor Registry were analyzed with specific reference to colon cancer (excluding rectal cancer) I.C.D.A. No. 153. The high incidence of colon cancer in the Chinese population (33.8 per 100,000) requires further epidemiologic study to ascertain its significance. The sigmoid colon is the location of the highest percentage of colonic tumors. The 5‐year relative survival rate for all stages of colon cancer has increased from 24% in 1945 to 43.2% in 1966. For cases localized at the time of diagnosis, the 5‐year relative survival rate was 71.3%. An inverse relationship between age and survival was noted for both sexes, except for those under 45, who had a poorer survival experience. An appreciable difference was seen in the lessened survival of patients with upper colonic versus lower colonic lesions. Part of the increase in survival over time appeared to be due to an increasing percentage of patients who received surgery in contrast to other modalities. Part of the female's better survival experience was due to the fact that more women in proportion to men with colon cancer underwent surgery. The physician should take these characteristics, among others, into account when advising his patient on his chances of survival (and when considering treatment modality), and be alert to the high risk of this entity in certain racial, sex, and age groups as noted.
A ‘transmissible entity’ in the control of cancer in mice
Authors: Strong Leonell C. , Matsunaga Henry
Published: February 2007

The paper is divided into three sections. Section 1 consists of an account of the historical development of a biological concept for cancer control in mice by the senior author. Section 2 presents new data on the effect of a liver‐derived inhibitor of spontaneous tumors of mammary gland origin in mice in inducing a ‘transmissible entity’ that has been passed down through nine generations. The entity affects the biological characteristics of spontaneous tumors in mice and increases in potency in controlling cancer in mice of succeeding generations. The possibility of whether a genetic or a nongenetic transmission is involved in the passage of a ‘transmissible entity’ from generation to generation cannot be determined by the existing data. Section 3 lists the conclusions that have been reached concerning the biological and biochemical characteristics of the tumor inhibitor.
Acquired Pelger‐Huet anomaly in erythroleukemia
Authors: Phillips Bruce A. , Yarbro John W. , Konior Geraldine S.
Published: February 2007

The Pelger‐Huet anomaly was found in association with erythroleukemia in a 62‐year‐old female who was known to have had normal granulocyte morphology 9 months previously. This is the third reported case of the coexistence of Pelger‐Huet anomaly with erythroleukemia and the first case in which normal morphology was known to have been present prior to the development of erythroleukemia. Although the pseudo‐Pelger‐Huet anomaly has been reported in association with numerous neoplastic and non‐neoplastic hematologic diseases, its pathogenesis and the clinical significance of its presence remain to be elucidated.
B16 melanoma in C57BL/6J mice: Kinetics and effects of heterologous serum
Authors: Hill George J. , Littlejohn Kathrine
Published: February 2007

B16 melanoma was studied in syngeneic C57BL/6J mice as a therapeutic model of melanoma. The irregular behavior of tumor after trochar passage was eliminated by serial intraperitoneal passage, but abundant melanin production was maintained. Mean viability of dispersed suspensions was 56%. Median survival time after injection of 107 cells intraperitoneally was 11‐16 days (average 13.20). In vivo doubling time was estimated at 3.24 days. Tenfold increase time was approximately 10.75 days. Preliminary studies with rabbit antiserum demonstrated possible enhancement after incubation with tumor in vitro, and a possible therapeutic effect after administration in vivo.
Kinetic studies of hyperimmune 7s globulins in allogenic rats bearing walker 256 tumors
Authors: Jewell W. R. , Hunter L.
Published: February 2007

Kinetic studies of I131‐labeled rat anti‐Walker 256 antibodies are described. The anti‐tumor antibody is a 7S globulin. The presence of tumor diminishes the level of circulating antibody. When the tumor is removed, the antibody level rises to a measurable amount. Ouchterlony in‐gel diffusion studies as well as I131‐globulin uptake data on subcellular tumor fractions indicate that the antigen is probably located on the cell membrane. Whether the antigen studied is a transplantation rather than tumor‐specific type was not determined. It is felt that the techniques described are useful for studying the human patient with autochthonous tumor as well as the cross‐immunotherapy patient.
Urinary pseudouridine excretion following hypophysectomy for prostatic carcinoma in man
Authors: Schoonees Rikus , Mittelman Arnold , Chheda Girish B. , Murphy Gerald P.
Published: February 2007

Urinary pseudouridine excretion, which may be used as a good index of RNA turnover in the body, was measured in 25 patients who underwent hypophysectomy for advanced prostatic carcinoma. The excretion of pseudouridine was markedly elevated during the first 4 postoperative days in 9 patients who underwent open surgical hypophysectomy, but it remained essentially unchanged after stereotactic cryohypo‐physectomy in 16 patients. No correlation existed between the urinary pseudouridine excretion and the degree of ablation of pituitary function or the duration of the symptomatic remission of the disease. The body turnover of RNA was apparently not affected by gross ablation of pituitary function (plus cortisone replacement) but was moderately increased by the trauma associated with an open surgical hypophysectomy.