bluuebunny/crossref_metadata_2025 huggingface dataset:
Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is essential for spermatid development and completion of spermatogenesis
Authors: Tsai-Morris Chon-Hwa , Sheng Yi , Lee Eric , Lei Ke-Jian , Dufau Maria L.
Published: April 2004

Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25), a member of the DEAD-box protein family, is a testis-specific gonadotropin-regulated RNA helicase that is present in Leydig cells and germ cells (meiotic spermatocytes and spermatids). In this study, we observed that GRTH is present in the nucleus, cytoplasm and chromatoid body of germ cells, and is an integral component of messenger ribonuclear protein particles. Male mice with a null mutation in the GRTH gene displayed normal gonadotropin and androgen profiles. However, they were sterile, with azoospermia caused by a complete arrest of spermiogenesis at step 8 of round spermatids and failure to elongate. Round spermatids of the null mice showed marked diminution in the size of chromatoid bodies. The transcription of relevant messages was not altered, but their translation was abrogated in a selective manner. Protein expression of transition proteins 1 and 2 and angiotensin-converting enzyme was completely absent, whereas that of the transcriptional activator cAMP responsive element modulator was intact. These findings indicate that GRTH participates in translational-associated events during germ cell development. Although significant apoptosis was present at the metaphase of meiosis in the GRTH-null mice, spermatogenesis proceeded to step 8 of spermiogenesis when complete arrest occurred. This progression may relate to compensatory gene function(s) and/or the observed up-regulation of DNA repair proteins Rad51 and Dmc1. This study (
i
) demonstrates that GRTH is essential for completion of spermatogenesis, (
ii
) provides insights into intrinsic requirements for spermiogenesis, and (
iii
) establishes a model for studies of male infertility and contraception.
ZIP kinase is responsible for the phosphorylation of myosin II and necessary for cell motility in mammalian fibroblasts
Authors: Komatsu Satoshi , Ikebe Mitsuo
Published: April 2004

Reorganization of actomyosin is an essential process for cell migration and myosin regulatory light chain (MLC20) phosphorylation plays a key role in this process. Here, we found that zipper-interacting protein (ZIP) kinase plays a predominant role in myosin II phosphorylation in mammalian fibroblasts. Using two phosphorylation site-specific antibodies, we demonstrated that a significant portion of the phosphorylated MLC20 is diphosphorylated and that the localization of mono- and diphosphorylated myosin is different from each other. The kinase responsible for the phosphorylation was ZIP kinase because (a) the kinase in the cell extracts phosphorylated Ser19 and Thr18 of MLC20 with similar potency; (b) immunodepletion of ZIP kinase from the cell extracts markedly diminished its myosin II kinase activity; and (c) disruption of ZIP kinase expression by RNA interference diminished myosin phosphorylation, and resulted in the defect of cell polarity and migration efficiency. These results suggest that ZIP kinase is critical for myosin phosphorylation and necessary for cell motile processes in mammalian fibroblasts.
The role of Cdc6 in ensuring complete genome licensing and S phase checkpoint activation
Authors: Oehlmann Maren , Score Alan J. , Blow J. Julian
Published: April 2004

Before S phase, cells license replication origins for initiation by loading them with Mcm2-7 heterohexamers. This process is dependent on Cdc6, which is recruited to unlicensed origins. Using Xenopus egg extracts we show that although each origin can load many Mcm2-7 hexamers, the affinity of Cdc6 for each origins drops once it has been licensed by loading the first hexamers. This encourages the distribution of at least one Mcm2-7 hexamer to each origin, and thereby helps to ensure that all origins are licensed. Although Cdc6 is not essential for DNA replication once licensing is complete, Cdc6 regains a high affinity for origins once replication forks are initiated and Mcm2-7 has been displaced from the origin DNA. We show that the presence of Cdc6 during S phase is essential for the checkpoint kinase Chk1 to become activated in response to replication inhibition. These results show that Cdc6 plays multiple roles in ensuring precise chromosome duplication.
Long-term modulation of mitochondrial Ca2+ signals by protein kinase C isozymes
Authors: Pinton Paolo , Leo Sara , Wieckowski Mariusz R. , Di Benedetto Giulietta , Rizzuto Rosario
Published: April 2004

The modulation of Ca2+ signaling patterns during repetitive stimulations represents an important mechanism for integrating through time the inputs received by a cell. By either overexpressing the isoforms of protein kinase C (PKC) or inhibiting them with specific blockers, we investigated the role of this family of proteins in regulating the dynamic interplay of the intracellular Ca2+ pools. The effects of the different isoforms spanned from the reduction of ER Ca2+ release (PKCα) to the increase or reduction of mitochondrial Ca2+ uptake (PKCζ and PKCβ/PKCδ, respectively). This PKC-dependent regulatory mechanism underlies the process of mitochondrial Ca2+ desensitization, which in turn modulates cellular responses (e.g., insulin secretion). These results demonstrate that organelle Ca2+ homeostasis (and in particular mitochondrial processing of Ca2+ signals) is tuned through the wide molecular repertoire of intracellular Ca2+ transducers.
Explicit formulation of different receptor–G-protein interactions and effector regulation
Authors: Kukkonen Jyrki P.
Published: April 2004

Motivation: G-protein-coupled receptors (GPCRs) can create different intracellular signals depending on which G-proteins they couple to and which intracellular signal-integrators, such as adenylyl cyclases, are expressed in the cell. One and the same GPCR can activate multiple G-protein species, generating signals, which either inhibit or amplify each other. Because of this complexity, extraction of mechanistic information from concentration–response curves is not straightforward.

Results: To tackle this problem, I describe in this paper explicit equations for GPCR-interaction with two G-protein species by different possible mechanisms, and also an equation for the regulation of an effector enzyme by the activated G-proteins or their effectors. Arithmetic solutions to these equations are presented, which resulted in the equations being applicable in a spreadsheet program environment. These equations are useful in simulations to analyze results, to design experiments and to test hypotheses. Some examples of this are presented in this study.
Molecular Genetic Testing for Malignant Hyperthermia Susceptibility
Authors: Girard Thierry , Treves Susan , Voronkov Evgueni , Siegemund Martin , Urwyler Albert
Published: April 2004

Background

For more than 30 yr, the in vitro contracture test (IVCT) was the only appropriate diagnostic tool for malignant hyperthermia (MH). After the introduction of molecular genetics into MH research, guidelines for molecular genetic diagnosis of MH susceptibility were published. The aim of this study was to establish applicability of the guidelines, sensitivity, and specificity of genetic testing in MH and advantages for studied patients.

Methods

The IVCT was performed following the guidelines of the European MH Group. Mutation analyses were performed by amplification of genomic DNA by polymerase chain reaction and restriction enzyme digestion.

Results

Two hundred eight individuals underwent MH testing between January 2001 and April 2003. In 32 of 67 initially genetic-tested patients, the familial mutation was identified, and they were diagnosed as MH susceptible. The IVCT followed negative genetic test results in 20 patients, and all but one had negative IVCT results. Three patients were scheduled to undergo elective surgery, and IVCT and genetic testing were performed simultaneously. All three had positive IVCT results and were carriers of their familial mutation.

Conclusions

In families with known MH mutations, there is a 50% chance of reliably confirming MH susceptibility by noninvasive testing. The authors found the negative predictive value of genetic testing to be 0.95 (95% confidence interval, 0.75-0.99), but for patient safety, they still recommend following the guidelines for genetic testing in MH and therefore performing an IVCT in case of negative genetic results.
Altered Cell-mediated Immunity and Increased Postoperative Infection Rate in Long-term Alcoholic Patients
Authors: Spies Claudia D. , von Dossow Vera , Eggers Verena , Jetschmann Gesine , El-Hilali Ratiba , Egert Julia , Fischer Marc , Schröder Torsten , Höflich Conny , Sinha Pranav , Paschen Christian , Mirsalim Parwis , Brunsch Ralf , Hopf Jürgen , Marks Christian , Wernecke Klaus-D. , Pragst Fritz , Ehrenreich Hannelore , Müller Christian , Tonnesen Hanne , Oelkers Wolfgang , Rohde Wolfgang , Stein Christoph , Kox Wolfgang J.
Published: April 2004

Background

Preoperative alteration of T cell-mediated immunity as well as an altered immune response to surgical stress were found in long-term alcoholic patients. The aim of this study was to evaluate perioperative T cell-mediated immune parameters as well as cytokine release from whole blood cells after lipopolysaccharide stimulation and its association with postoperative infections.

Methods

Fifty-four patients undergoing elective surgery of the aerodigestive tract were included in this prospective observational study. Long-term alcoholic patients (n = 31) were defined as having a daily ethanol consumption of at least 60 g and fulfilling the Diagnostic and Statistical Manual of Mental Disorders for either alcohol abuse or alcohol dependence. The nonalcoholic patients (n = 23) were defined as drinking less than 60 g ethanol/day. Blood samples to analyze the immune status were obtained on morning before surgery and on the morning of days 1, 3, and 5 after surgery.

Results

Basic patient characteristics did not differ between groups. Before surgery, the T helper 1:T helper 2 ratio (Th1: Th2) was significantly lower (P < 0.01), whereas plasma interleukin 1beta and lipopolysaccharide-stimulated interleukin 1ra from whole blood cells were increased in long-term alcoholic patients. After surgery, a significant suppression of the cytotoxic lymphocyte ratio (Tc1:Tc2), the interferon gamma:interleukin 10 ratio from lipopolysaccharide-stimulated whole blood cells, and a significant increase of plasma interleukin 10 was observed. Long-term alcoholics had more frequent postoperative infections compared with nonalcoholic patients (54%vs. 26%; P = 0.03).

Conclusions

T helper cell-mediated immunity was significantly suppressed before surgery and possibly led to inadequate cytotoxic lymphocyte and whole blood cell response in long-term alcoholic patients after surgery. This altered cell-mediated immunity might have accounted for the increased infection rate in long-term alcoholic patients after surgery.
Effect of Hypertonic Saline Infusion on Postoperative Cellular Immune Function
Authors: Kølsen-Petersen Jens A. , Nielsen Jens-Ole D. , Tonnesen Else M.
Published: April 2004

Background

Previous studies found hypertonicity to affect immune responses in intact laboratory animals and in human blood cell cultures. In this study, the authors investigated the cellular immune response to surgery after preoperative infusion of hypertonic saline in humans.

Methods

Sixty-two women scheduled to undergo abdominal hysterectomy were randomly assigned to single-blinded infusion of 4 ml/kg NaCl, 7.5%; 4 ml/kg NaCl, 0.9%; or 32 ml/kg NaCl, 0.9%, over 20 min. Blood was collected at baseline, during surgery, and 1, 24, and 48 h after surgery for the determination of leukocyte and differential counts, flow cytometric phenotyping of mononuclear cells, and natural killer cell activity against K 562 tumor cells. Phytohemagglutinin-induced lymphocyte proliferation, plasma elastase, and neutrophil chemotaxis were measured at the same time points except during surgery. The authors tested cell-mediated immune function in vivo by delayed-type hypersensitivity reaction in the skin.

Results

Surgery induced well-known changes in the cellular immune response, which were unrelated to the tonicity or volume of the infused fluids.

Conclusion

Infusion of a clinically relevant dose of hypertonic saline did not seem to modify the postoperative cellular immune response after elective abdominal hysterectomy.
Development and Psychometric Evaluation of the Pediatric Anesthesia Emergence Delirium Scale
Authors: Sikich Nancy , Lerman Jerrold
Published: April 2004

Background

Emergence delirium has been investigated in several clinical trials. However, no reliable and valid rating scale exists to measure this phenomenon in children. Therefore, the authors developed and evaluated the Pediatric Anesthesia Emergence Delirium (PAED) scale to measure emergence delirium in children.

Methods

A list of scale items that were statements describing the emergence behavior of children was compiled, and the items were evaluated for content validity and statistical significance. Items that satisfied these evaluations comprised the PAED scale. Each item was scored from 1 to 4 (with reverse scoring where applicable), and the scores were summed to obtain a total scale score. The degree of emergence delirium varied directly with the total score. Fifty children were enrolled to determine the reliability and validity of the PAED scale. Scale validity was evaluated using five hypotheses: The PAED scale scores correlated negatively with age and time to awakening and positively with clinical judgment scores and Post Hospital Behavior Questionnaire scores, and were greater after sevoflurane than after halothane. The sensitivity of the scale was also determined.

Results

Five of 27 items that satisfied the content validity and statistical analysis became the PAED scale: (1) The child makes eye contact with the caregiver, (2) the child's actions are purposeful, (3) the child is aware of his/her surroundings, (4) the child is restless, and (5) the child is inconsolable. The internal consistency of the PAED scale was 0.89, and the reliability was 0.84 (95% confidence interval, 0.76-0.90). Three hypotheses supported the validity of the scale: The scores correlated negatively with age (r = -0.31, P <0.04) and time to awakening (r = -0.5, P <0.001) and were greater after sevoflurane anesthesia than halothane (P <0.008). The sensitivity was 0.64.

Conclusions

These results support the reliability and validity of the PAED scale.
Unanticipated Difficult Airway in Anesthetized Patients
Authors: Combes Xavier , Le Roux Bertrand , Suen Powen , Dumerat Marc , Motamed Cyrus , Sauvat Stéphane , Duvaldestin Philippe , Dhonneur Gilles
Published: April 2004

Background

Management strategies conceived to improve patient safety in anesthesia have rarely been assessed prospectively. The authors undertook a prospective evaluation of a predefined algorithm for unanticipated difficult airway management.

Methods

After a 2-month period of training in airway management, 41 anesthesiologists were asked to follow a predefined algorithm for management in the case of an unanticipated difficult airway. Two different scenarios were distinguished: "cannot intubate" and "cannot ventilate." The gum elastic bougie and the Intubating Laryngeal Mask Airway (ILMA) were proposed as the first and second steps in the case of impossible laryngoscope-assisted tracheal intubation, respectively. In the case of impossible ventilation or difficult ventilation, the IMLA was recommended, followed by percutaneous transtracheal jet ventilation. The patient's details, adherence rate to the algorithm, efficacy, and complications of airway management processes were recorded.

Results

Impossible ventilation never occurred during the 18-month study. One hundred cases of unexpected difficult airway were recorded (0.9%) among 11,257 intubations. Deviation from the algorithm was recorded in three cases, and two patients were wakened before any alternative intubation technique attempt. All remaining patients were successfully ventilated with either the facemask (89 of 95) or the ILMA (6 of 95). Six difficult-ventilation patients required the ILMA before completion of the first intubation step. Eighty patients were intubated with the gum elastic bougie, and 13 required a blind intubation through the ILMA. Two patients ventilated with the ILMA were never intubated.

Conclusion

When applied in accordance with a predefined algorithm, the gum elastic bougie and the ILMA are effective to solve most problems occurring during unexpected difficult airway management.
Effects of Isoflurane Versus Fentanyl–Nitrous Oxide Anesthesia on Long-term Outcome from Severe Forebrain Ischemia in the Rat
Authors: Elsersy Hazem , Sheng Huaxin , Lynch John R. , Moldovan Maria , Pearlstein Robert D. , Warner David S.
Published: April 2004

Background

This study examined long-term outcome from severe forebrain ischemia in the rat, as a function of anesthetic given during the ischemic injury.

Methods

Rats were subjected to 10 min of near-complete forebrain ischemia while anesthetized with either 1.4% isoflurane or 70% nitrous oxide-fentanyl. Neurologic and histologic outcomes were measured at 5 days, 3 weeks, or 3 months after ischemia.

Results

At 5 days, isoflurane-anesthetized rats had less damage than did fentanyl-nitrous oxide-anesthetized rats (mean +/- SD, percent alive hippocampal CA1 neurons = 58+/-29 vs. 20+/-16, respectively; P = 0.011). This was accompanied by improved motor function in the isoflurane group (P = 0.002). At 3 weeks, there was no difference between groups for either outcome variable (percent alive CA1 neurons = 35+/-26 and 36+/-28 for isoflurane and fentanyl-nitrous oxide, respectively). Similarly, at 3 months, there was no difference between groups (percent alive CA1 neurons = 56+/-27 and 60+/-27 for isoflurane and fentanyl-nitrous oxide, respectively). Morris water maze performance at 3 months was similar between anesthetic groups and was also similar to sham performance. The percent alive CA1 neurons in the fentanyl-nitrous oxide group increased with duration of recovery (P = 0.004). There were no differences among isoflurane groups over time (5 days vs. 3 weeks, P = 0.26; 5 days vs. 3 months, P = 0.99; 3 week vs. 3 months, P = 0.32).

Conclusions

This study found no change in the percent alive CA1 hippocampal neurons as a function of duration of recovery from severe forebrain ischemia in isoflurane anesthetized rats. In contrast, the percent alive CA1 neurons in fentanyl-nitrous oxide-anesthetized rats tripled over 3 months of recovery. The natural history of long-term responses to forebrain ischemia requires further study before conclusions can be drawn with respect to the permanence of isoflurane neuroprotection.
Folding mechanism of the (H3–H4)2histone tetramer of the core nucleosome
Authors: Banks Douglas D. , Gloss Lisa M.
Published: April 2004

To further understand oligomeric protein assembly, the folding and unfolding kinetics of the H3–H4 histone tetramer have been examined. The tetramer is the central protein component of the core nucleosome, which is the basic unit of DNA compaction into chromatin in the eukaryotic nucleus. This report provides the first kinetic folding studies of a protein containing the histone fold dimerization motif, a motif observed in several protein–DNA complexes. Previous equilibrium unfolding studies have demonstrated that, under physiological conditions, there is a dynamic equilibrium between the H3–H4 dimer and tetramer species. This equilibrium is shifted predominantly toward the tetramer in the presence of the organic osmolyte trimethylamine‐N‐oxide (TMAO). Stopped‐flow methods, monitoring intrinsic tyrosine fluorescence and far‐UV circular dichroism, have been used to measure folding and unfolding kinetics as a function of guanidinium hydrochloride (GdnHCl) and monomer concentrations, in 0 and 1 M TMAO. The assignment of the kinetic phases was aided by the study of an obligate H3–H4 dimer, using the H3 mutant, C110E, which destabilizes the H3–H3′ hydrophobic four‐helix bundle tetramer interface. The proposed kinetic folding mechanism of the H3–H4 system is a sequential process. Unfolded H3 and H4 monomers associate in a burst phase reaction to form a dimeric intermediate that undergoes a further, first‐order folding process to form the native dimer in the rate‐limiting step of the folding pathway. H3–H4 dimers then rapidly associate with a rate constant of ≥107M−1sec−1to establish a dynamic equilibrium between the fully assembled tetramer and folded H3–H4 dimers.
The NMR solution structure of the 30S ribosomal protein S27e encoded in gene RS27_ARCFU of Archaeoglobus fulgidis reveals a novel protein fold
Authors: Herve du Penhoat Catherine , Atreya Hanudatta S. , Shen Yang , Liu Gaohua , Acton Thomas B. , Xiao Rong , Li Zhaohui , Murray Diana , Montelione Gaetano T. , Szyperski Thomas
Published: April 2004

The Archaeoglobus fulgidis gene RS27_ARCFU encodes the 30S ribosomal protein S27e. Here, we present the high‐quality NMR solution structure of this archaeal protein, which comprises a C4 zinc finger motif of the CX2CX14‐16CX2C class. S27e was selected as a target of the Northeast Structural Genomics Consortium (target ID: GR2), and its three‐dimensional structure is the first representative of a family of more than 116 homologous proteins occurring in eukaryotic and archaeal cells. As a salient feature of its molecular architecture, S27e exhibits a β‐sandwich consisting of two three‐stranded sheets with topology B(↓), A(↑), F(↓), and C(↑), D(↓), E(↑). Due to the uniqueness of the arrangement of the strands, the resulting fold was found to be novel. Residues that are highly conserved among the S27 proteins allowed identification of a structural motif of putative functional importance; a conserved hydrophobic patch may well play a pivotal role for functioning of S27 proteins, be it in archaeal or eukaryotic cells. The structure of human S27, which possesses a 26‐residue amino‐terminal extension when compared with the archaeal S27e, was modeled on the basis of two structural templates, S27e for the carboxy‐terminal core and the amino‐terminal segment of the archaeal ribosomal protein L37Ae for the extension. Remarkably, the electrostatic surface properties of archaeal and human proteins are predicted to be entirely different, pointing at either functional variations among archaeal and eukaryotic S27 proteins, or, assuming that the function remained invariant, to a concerted evolutionary change of the surface potential of proteins interacting with S27.
Structural and stability effects of phosphorylation: Localized structural changes in phenylalanine hydroxylase
Authors: Miranda Frederico Faria , Thórólfsson Matthías , Teigen Knut , Sanchez‐Ruiz Jose M. , Martínez Aurora
Published: April 2004

Phosphorylation of phenylalanine hydroxylase (PAH) at Ser16 by cAMP‐dependent protein kinase increases the basal activity of the enzyme and its resistance to tryptic proteolysis. The modeled structures of the full‐length phosphorylated and unphosphorylated enzyme were subjected to molecular dynamics simulations, and we analyzed the energy of charge–charge interactions for individual ionizable residues in the final structures. These calculations showed that the conformational changes induced by incorporation of phosphate were localized and limited mostly to the region around the phosphoserine (Arg13–Asp17) and a region around the active site in the catalytic domain that includes residues involved in the binding of the iron and the substrate L‐Phe (Arg270 and His285). The absence of a generalized conformational change was confirmed by differential scanning calorimetry, thermal‐dependent circular dichroism, fluorescence spectroscopy, and limited chymotryptic proteolysis of the phosphorylated and unphosphorylated PAH. Our results explain the effect of phosphorylation of PAH on both the resistance to proteolysis specifically by trypsin‐like enzymes and on the increase in catalytic efficiency.
Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia
Authors: Leren TP
Published: April 2004

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is at a locus for autosomal dominant hypercholesterolemia, and recent data indicate that the PCSK9 gene is involved in cholesterol biosynthesis. Mutations within this gene have previously been found to segregate with hypercholesterolemia. In this study, DNA sequencing of the 12 exons of the PCSK9 gene has been performed in 51 Norwegian subjects with a clinical diagnosis of familial hypercholesterolemia where mutations in the low‐density lipoprotein receptor gene and mutation R3500Q in the apolipoprotein B‐100 gene had been excluded. Two novel missense mutations were detected in the catalytic subdomain of the PCSK9 gene. Two patients were heterozygotes for D374Y, and one patient was a double heterozygote for D374Y and N157K. D374Y segregated with hypercholesterolemia in the two former families where family members were available for study. Our findings support the notion that mutations in the PCSK9 gene cause autosomal dominant hypercholesterolemia.
Prejudice From Thin Air
Authors: DeSteno David , Dasgupta Nilanjana , Bartlett Monica Y. , Cajdric Aida
Published: April 2004

Two experiments provide initial evidence that specific emotional states are capable of creating automatic prejudice toward outgroups. Specifically, we propose that anger should influence automatic evaluations of outgroups because of its functional relevance to intergroup conflict and competition, whereas other negative emotions less relevant to intergroup relations (e.g., sadness) should not. In both experiments, after minimal ingroups and outgroups were created, participants were induced to experience anger, sadness, or a neutral state. Automatic attitudes toward the in- and outgroups were then assessed using an evaluative priming measure (Experiment 1) and the Implicit Association Test (Experiment 2). As predicted, results showed that anger created automatic prejudice toward the outgroup, whereas sadness and neutrality resulted in no automatic intergroup bias. The implications of these findings for emotion-induced biases in implicit intergroup cognition in particular, and in social cognition in general, are considered.
The Agony of Victory and Thrill of Defeat
Authors: Larsen Jeff T. , Peter McGraw A. , Mellers Barbara A. , Cacioppo John T.
Published: April 2004

Because of counterfactual comparisons, good outcomes that could have been better (i.e., disappointing wins) and bad outcomes that could have been worse (i.e., relieving losses) elicit relatively middling ratings on bipolar emotion scales. We conducted two experiments with gambles to examine whether such outcomes elicit neutral emotions, sequentially mixed emotions of positive and negative affect, or simultaneously mixed emotions. In Experiment 1, static unipolar measures of positive and negative affect revealed that disappointing wins and relieving losses elicit mixed emotions, rather than relatively neutral emotions. In Experiment 2, participants provided continuous unipolar measures of positive and negative affect by pressing one button whenever they felt good and another button whenever they felt bad. Results revealed that disappointing wins and relieving losses elicit positive and negative affect simultaneously, rather than in alternation.
Clinical, biochemical and imaging‐verified regression of hepatitis B‐induced cirrhosis
Authors: Massarrat S. , Fallahazad V. , Kamalian N.
Published: April 2004

Abstract: In a 65‐year‐old patient with ascites, jaundice and positive hepatitis B surface antigen (HBsAg), the histological diagnosis of cirrhosis with knodell total score 13 was made in 1995. The patient was followed up for 8 years. Spontaneous seroconversion of HBsAg appeared. Except for slight hyperbilirubinemia, all pathologic, clinical laboratory data remained normal from the second year of diagnosis till 8 years of follow‐up. In the last follow up, the markers of liver fibrosis were all normal. The portal vein diameter was decreased and the esophageal varices disappeared. The imaging of liver by sonography and CT‐scan did not reveal any abnormality.
Preoperative assessment of liver function: a comparison of 99mTc‐Mebrofenin scintigraphy with indocyanine green clearance test
Authors: Erdogan Deha , Heijnen Bob H.M. , Bennink Roelof J. , Kok Mariël , Dinant Sander , Straatsburg Irene H. , Gouma Dirk J. , Van Gulik Thomas M.
Published: April 2004

Background/aims: The indocyanine green (ICG) clearance test is the most frequently used test for preoperative assessment of liver parenchymal function but has its limitations. The aim of this study was to investigate the correlation between ICG clearance test and the liver uptake of 99‐Technetium‐labelled (99mTc)‐Mebrofenin (99mTc‐Mebrofenin) as measured with hepatobiliary scintigraphy.

Methods: Fifty‐four patients were diagnosed as hepatocellular carcinoma (n=9), hilar tumours (n=20) and 25 patients with non‐parenchymal tumours including colorectal metastasis (n=15) and miscellaneous tumours (n=10). One day prior to operation, hepatobiliary 99mTc‐Mebrofenin scintigraphy was performed after intravenous injection of 85 MBq and the 15‐min clearance rate of ICG (ICG‐C15) was measured.

Results: The mean ICG‐C15 was 86.86±1.19% (SEM). The mean 99mTc‐Mebrofenin uptake rate was 12.87±0.52%/min. A significant correlation was obtained between 99mTc‐Mebrofenin uptake rate by scintigraphy and ICG‐C15 (r=0.73, P<0.0001). The mean clearance capacity of the right liver segments (79.83±1.63, range 47.75–95.97%) was larger than that of the left segments (20.24±1.55, range 6.51–52.51%).

Conclusion: 99mTc‐Mebrofenin uptake rate as assessed by scintigraphy is an efficient method for determining liver function and correlates well with ICG clearance. At the same time, 99mTc‐Mebrofenin scintigraphy provides information of segmental functional liver tissue, which is of additional use when planning liver resection.
Therapeutic effect of photodynamic therapy using PAD‐S31 and diode laser on human liver cancer cells
Authors: Date Masataka , Fukuchi Kazuhide , Namiki Yoshihisa , Okumura Akihiko , Morita Shosuke , Takahashi Hiroshi , Ohura Kiyoshi
Published: April 2004

Abstract:  Background/aims: Photodynamic therapy (PDT) is an effective local cancer treatment which a photosensitizer is administered and the tumor is irradiated with light. We examined the effect of PDT using PAD‐S31 as the photosensitizer, and the 670 nm diode laser on human hepatocellular carcinomas (HCCs).

Methods: Huh‐7, HepG2 and Hep3B cell lines were used in the all experiments. Cell viability was determined by a modified MTT assay. Two methods were used for the determination of apoptosis: terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick‐end labeling assay and detection of fragmented mono‐ and oligo‐nucleosomes by enzyme‐linked immunosorbent assay. The caspase activity was measured by fluorometric assay. Cytochrome c in cytosolic fraction was determined using a human cytochrome c immunoassay. Xenografts of human oral HCC cells were generated in KSN S1c nude mice.

Results: In vitro PDT showed excellent cytotoxicity that was a function of laser energy, drug concentration and time to the hepatoma cell lines. The combined use of PAD‐S31 and laser irradiation showed excellent anti‐tumor activity without severe side‐effect against human hepatoma xenografts in nude mice. PDT‐mediated cell death occurred predominantly by apoptosis in vitro and in vivo. Furthermore, this treatment initiates early cytochrome c release, followed by late caspase‐3 and ‐9 activation.

Conclusion: Our study demonstrates that PDT using PAD‐S31 and the diode laser induces apoptosis that is mediated by cytochrome c release and caspase activation in human liver cancer cell lines. It is expected that this therapy will be clinically useful for the treatment of patients with HCC.
Serum levels of tumor necrosis factor‐α correlate with severity of hepatic encephalopathy due to chronic liver failure
Authors: Odeh M. , Sabo E. , Srugo I. , Oliven A.
Published: April 2004

Background: Several studies have shown that serum levels of tumor necrosis factor‐α (TNF) are significantly elevated in patients with acute and chronic liver diseases, where these elevations are independent of the etiology of the underlying disease. Serum levels of TNF are significantly higher in patients with cirrhosis than in those without cirrhosis, reaching the highest levels in decompensated cirrhosis. It has also been shown that plasma levels of TNF correlate with the severity of hepatic encephalopathy (HE) in fulminant hepatic failure. However, still there are no published data regarding the relationship between blood levels of TNF and the presence or severity of HE in patients with chronic liver failure.

Aim: The aim of this study is to determine the relationship between serum levels of TNF and clinical grades of HE in patients with liver cirrhosis.

Methods: Using a commercially available high‐sensitivity enzyme‐linked immunosorbent assay kit, serum levels of TNF were measured in 74 patients with liver cirrhosis in various clinical grades of HE (grades 0–4).

Results: The mean±SEM values of serum levels of TNF at presentation in patients with grade 0 of HE (n=23), grade 1 (n=12), grade 2 (n=14), grade 3 (n=16), and grade 4 (n=9) were 4.50±0.46, 9.10±1.0, 12.98±1.22, 21.51±2.63, and 58.26±19.7 pg/ml, respectively. A significant positive correlation was found between serum levels of TNF and the severity of HE (P<0.0001).

Conclusion: Serum levels of TNF correlate positively with the severity of HE in patients with chronic liver failure.
Evidence for a rhesus monkey model of asymptomatic tuberculosis
Authors: Gormus Bobby J. , Blanchard James L. , Alvarez Xavier H. , Didier Peter J.
Published: April 2004

Abstract:  Rhesus monkeys (RM) were inoculated intrabronchially with graded doses of Mycobacterium tuberculosis (MTB) strains Erdman and H37Rv in an effort to produce a model of asymptomatic tuberculosis infection. Erdman strain produced active disease within 7–11 weeks regardless of dose. Low doses of H37Rv resulted in asymptomatic infections; high doses produced active disease within 11 weeks. Over a 4‐month period of post‐inoculation study, MTB culture‐filtrate protein (CFP)‐stimulated bronchoalveolar lavage cells (BALC) and blood mononuclear cells (PBMC) from monkeys with active disease (30 cfu Erdman‐inoculated) or asymptomatic infection (200 cfu H37Rv‐inoculated) produced similar significant quantities of mRNA encoding for IFN‐γ or TNF‐α, but insignificant quantities of IL‐4 mRNA. Differences were observed in antigen‐induced in vitro blastogenic responses and serum anti‐lipoarabinomannan (LAM) antibody responses in animals with active compared with asymptomatic MTB infections. The results indicate that RM are a good model for the study of asymptomatic tuberculosis infections using low doses of H37Rv.
Effect of carnosine on runt‐related transcription factor‐2/core binding factor α‐1 and Sox9 expressions of human periodontal ligament cells
Authors: Ito‐Kato Emi , Suzuki Naoto , Maeno Masao , Takada Tsuyoshi , Tanabe Natsuko , Takayama Tadahiro , Ito Koichi , Otsuka Kichibee
Published: April 2004

Background:  Previous studies have reported that β‐alanyl‐l‐histidine (carnosine) enhanced the process of wound healing by stimulating effusion at the initial stage of inflammation, and also enhanced runt‐related transcription factor‐2/core binding factor α‐1 (RUNX2/Cbfa1), Sox9, bone morphogenetic protein‐2 (BMP‐2) and BMP‐7 expressions of human periodontal ligament cells.

Objectives:  In order to clarify the relationship between RUNX2/Cbfa1 or Sox9 expressions and BMP‐2 or BMP‐7 expressions enhanced by carnosine, we determined the effect of carnosine on the expression of BMP receptors and activation of their downstream signaling molecules in human periodontal ligament cells.

Material and methods:  Human periodontal ligament cells were cultured with α‐minimum essential medium containing 10% fetal bovine serum with or without 10−4 or 10−5 m carnosine for up to 10 days. The gene expression of BMP receptors, RUNX2/Cbfa1 and Sox9 was measured using semiquantitative reverse transcription‐polymerase chain reaction. Phosphorylation of Smad1 was determined using a western blot analysis.

Results:  Alkaline phosphatase activity increased in cultures with carnosine. Among the BMP receptors, expression of ActR‐I and BMPR‐II increased in cultures with carnosine, whereas expression of BMPR‐IA, BMPR‐IB, ActR‐IIA and ActR‐IIB was not affected. Culture with carnosine increased phosphorylation of Smad1, a signal‐transducing molecule for BMP‐2 and BMP‐7. Noggin reduced carnosine‐induced up‐regulation of RUNX2/Cbfa1 and Sox9 mRNA, suggesting that BMPs were responsible for up‐regulating RUNX2/Cbfa1 gene expression in human periodontal ligament cells.

Conclusion:  These results suggest that carnosine enhance RUNX2/Cbfa1 and Sox9 expression of human periodontal ligament cells via the autocrine action of BMP‐2 or BMP‐7 produced by the cells.
A New Approach to Explaining Fertility Patterns: Preference Theory
Authors: Hakim Catherine
Published: April 2004

Preference theory is a new approach to explaining current and future patterns of employment and fertility among women in modern societies. Although economists usually claim that preferences cannot be measured, methods for identifying women's and men's lifestyle preferences were developed and applied in British (and Spanish) national surveys, confirming the results of previous British and American studies showing three distinct lifestyle preference groups. The results confirm the heterogeneity of women's preferences and suggest that preferences are the primary determinant of fertility and employment decisions. The implications for policies to raise fertility are discussed.
Some Thoughts on Causation as It Relates to Demography and Population Studies
Authors: Smith Herbert L.
Published: April 2004

The counterfactual account of causality defines an effect as the difference, for some unit, between an outcome under an observed treatment and an outcome under a hypothetical alternative. When units are heterogeneous in a population, there is no single causal effect. The micro‐level account of causation is complicated when units interact with one another, as they do in human populations. The search for causation requires manipulation. But key micro‐level demographic variables—age, race, sex—are not easily manipulated. What are subject to manipulation are the social rules, policies, or choice sets available to individuals within populations. Thus causes are best conceptualized at the macro level, even if their effects are observed at the micro level.
Conflicting Preferences: A Reason Fertility Tends to Be Too High or Too Low
Authors: Voas David
Published: April 2004

Fertility has often seemed to be too high or too low, relative not only to social and economic goals, but also to reproductive preferences. In developing countries actual fertility has often been higher than desired family size, while in developed societies fertility tends to be below replacement level even though people generally say that they want at least two children. In explanations of fertility extremes, or of the discrepancies between desired and actual fertility, the effect of partners' holding different preferences has tended to be overlooked. Individual preferences expected to lead to replacement‐level reproduction may in combination generate substantially higher or lower fertility. In explaining such outcomes, a crucial question is what happens when spousal preferences diverge. Given that personal practices or social norms may systematically favor high or low preferences in the event of disagreement, chance alone will ensure that desired and actual fertility do not coincide.
When Numbers Began to Count for Health Policy: A Review Essay*
Authors: Johansson Sheila Ryan
Published: April 2004

Books reviewed in this article:

Jack M. Hollander, The Real Environmental Crisis: Why Poverty, Not Affluence, Is the Environment's Number One Enemy

Glenn Firebaugh, The New Geography of Global Income Inequality

Nancy E. Riley and James Mccarthy, Demography in the Age of the Postmodern

Catherine Campbell, ‘Letting Them Die’: Why HIV/AIDS Intervention Programmes Fail

Konstantinos Kapparis, Abortion in the Ancient World
Obligation or Opportunity: How Can Could-Be Heirs Assess Their Position?
Authors: Rogal Keith H.
Published: April 2004

Potential heirs can make informed choices about whether or not to accede to leadership positions by entering into a pre-decision period consisting of systematic and rigorous self-examination aimed at evaluating the personal and professional implications of accession for themselves, their families and their families' firms.
The Development of Organization Structure in the Family Firm
Authors: Barry Bernard
Published: April 2004

Where the family does play an important part in business it is often a reflection of the economic immaturity of the population, the absence of a tradition of impersonal service in industry and the vulnerability of employees who have no kinship ties to the firm.1

—United Nations

There has always been, and there will always be, a place for smaller companies and for the family business.2

—Sir Frederick Catherwood
Who's the Boss? Responsibility and Decision Making in Copreneurial Ventures
Authors: Ponthieu Louis D. , Caudill Helene L.
Published: April 2004

The study reports the dispositions towards responsibility and decision making of 80 male and 104 female copreneurs in jointly owned and managed ventures. While the husband still tends to be the boss, the wife is an equal partner, since such relationships are based on a clear division of responsibilities and on mutual trust and confidence.
Is Rugged Individualism the Whole Story? Public and Private Accounts of a Firm's Founding
Authors: Cramton Catherine Durnell
Published: April 2004

This article compares public and private accounts of the creation of a retail sales business. The two sets of accounts are examined from the perspectives of literature on entrepreneurial activity and literature on family systems theory. The two theoretical perspectives explain the salience of different facts regarding the founding of the business. The article also questions the legitimacy of privileging certain types of accounts of business foundings over other types.
The Chinese Family Firm: A Model
Authors: Wong Siu-lun
Published: April 2004

Three aspects of Chinese economic familism are distinguished: nepotism, paternalism, and family ownership. This essay is mainly concerned with the last aspect and the resultant phenomenon of the prevalence of family firms among privately owned Chinese commercial and industrial enterprises. It is argued that such firms are not necessarily small, impermanent, and conservative, because they tend to behave differently at various stages of their developmental cycle. Four phases of development—emergent, centralized, segmented, and disintegrative—are identified and discussed. This Chinese pattern is then compared with its Filipino and Japanese counterparts.
Home-Based Family Business
Authors: Rowe Barbara R.
Published: April 2004

I OFFER special thanks to Barbara Rowefor organizing and editing this topical issue on home-based family business. Often, our attention is captured by the large, mature family firms. However, the much larger numbers of businesses, and the leading edge of social trends, are on the boundary of entrepreneurship and family business. Many of those businesses are-operated out of the owners’ homes. This issue takes advantage of an opportunity to present the findings of the most comprehensive study of home-based enterprise to date. Barbara and her colleagues raise provocative questions in these articles. We look forward to further empirical and conceptual work in this area in future issues of FBR.—Kelin Gersick, Editor
Non-Market-Based Transfers of Wealth and Power: A Research Framework for Family Business
Authors: Churchill Neil C. , Hatten Kenneth J.
Published: April 2004

Family businesses are basically owner-managed enterprises with the family involved within the business. When, to family ties within the business, is added the biological inevitability of an eventual transfer of power, family succession becomes an alternative to selling the business—a transfer based on non-market considerations. A framework for studying family businesses is proposed which has succession as its anchor. The succession process is where changes in management, in strategy, and in control are planned for and executed. The framework is built upon stages of the family enterprise which emanate from the biological reality of parent and offspring being separated by age and business experience, but wedded together by “blood” and a shared family experience.
East Meets West: Innovative Forms of Foreign Trade Finance Between Italian Family Enterprises and Emerging SMEs in Romania
Authors: McKibbin Paul , Pistrui David
Published: April 2004

The collapse of the USSR has created an opportunity for the rebirth of entrepreneurship and family business. Unfortunately, the transition economies of the former Soviet Bloc often lack the financial resources required to upgrade operations. This paper examines how an innovative form of finance, with historical roots in East-West European trade, helps drive the expansion of transition enterprises in the emerging markets of Eastern Europe, and at the same time provides export-led growth particularly for family-based small and medium-sized enterprises (SMEs) in the more developed nations of Western Europe.

The technique, called forfaiting, allows businesses to control some of the risks that are inherent in dealing with emerging markets. We present a forfaiting model that demonstrates the way in which these singular transactions divide localized (transaction-oriented) risks from those risks that are associated with political instability, macroeconomic changes, environmental volatility, and force majeure. We follow this with presentations of actual examples of how forfaiting is being used between Italian family businesses and newly emerging private enterprises in Romania.
Women Entrepreneurs in Family Business: The Hungarian Case
Authors: Hisrich Robert D. , Fülöp Gyala
Published: April 2004

Although in many countries throughout the world a large percentage of firms are family businesses that directly impact the well-being of an economy, research in the field, particularly on the role of women, has been very sparse. By exploring the role of women in family business within a Hungarian context, this paper provides an indication of the similarities and differences of women entrepreneurs in family businesses and how this reflects their social structure. Since owning and running a family business requires a lifestyle that deeply impacts the women's role in society and in the family, governments need to address some fundamental issues that will help women in this process.
A Resource-Based Framework for Assessing the Strategic Advantages of Family Firms
Authors: Habbershon Timothy G. , Williams Mary L.
Published: April 2004

The Resource-Based View (RBV) of competitive advantage provides a theoretical framework from the field of strategic management for assessing the competitive advantages of family firms. The RBV isolates idiosyncratic resources that are complex, intangible, and dynamic within a particular firm. The bundle of resources that are distinctive to a firm as a result of family involvement are identified as the “familiness” of the firm. This approach provides a research and practice method for assessing the specific behavioral and social phenomena within a firm that provide an advantage. Using a familiness model for assessing competitive advantage overcomes many of the problems associated with the generic claim that family companies have an advantage over nonfamily companies. It also provides a unified systems perspective of family firm performance.