bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental Effects of Prenatal Cocaine Exposure on 5-HT1A Receptors in Male and Female Rat Offspring
Authors: Johns Josephine M. , Lubin Deborah A. , Lieberman Jeffrey A. , Lauder Jean M.
Published: April 2003

Prenatal cocaine exposure results in behavioral abnormalities throughout development in rats, but little is known regarding the biological mechanisms underlying these abnormalities. Pregnant rats received subcutaneous twice-daily injections (1 ml/kg) of normal saline or 15 mg/kg of cocaine hydrochloride throughout gestation (gestation days 1–20). Following delivery, pups were placed with untreated surrogates. Male and female pups were killed on postnatal days 30, 60 or 120 for assessment of 5-HT1A receptor development in the forebrain, diencephalon, midbrain and pons using radiolabel immunocytochemistry. Findings revealed gender and age differences in developmental regulation of 5-HT1A receptors, indicating that male rats are more susceptible to long-term consequences of prenatal cocaine exposure in comparison to females. This study also demonstrates gender-specific development of serotonin (5-HT1A) receptors across postnatal ages, demonstrating a fundamentally different pattern of development of 5-HT1A receptors between males and females.
Colonoscopy-Assisted ‘Trephine’ Sigmoid Colostomy
Authors: Parithivel Vellore S. , Schein Moshe , Gerst Paul H.
Published: April 2003

Fecal diversion is often required to treat complex traumatic, malignant or inflammatory anorectal conditions. In such circumstances, the formation of a proximal, ‘trephine’ sigmoid colostomy would avoid the need for, and the associated morbidity of, a formal laparotomy. We describe a technique which combines intraoperative colonoscopy with a diverting, ‘trephine’ sigmoid colostomy, thereby helping the surgeon to identify the correct loop of bowel, to avoid inadvertent maturing of the wrong end of the divided colon, and to exclude intracolonic lesions.
Mesenteric and Portal Vein Gas: Computerized Tomography Findings and Clinical Significance
Authors: Paran Haim , Epstein Tsvi , Gutman Mordechai , Shapiro Feinberg Myra , Zissin Rivka
Published: April 2003

Background: Gas in the mesenteric or portal veins (PVG) is an uncommon entity. It was first described only in patients with mesenteric ischemia and bowel gangrene. Later, several reports described other causes for PVG in which conservative treatment was successful. In the past, the diagnosis was made by vague signs in abdominal plain films. Since the era of computerized tomography (CT) scan the diagnosis became more objective, but nevertheless it is still an elusive entity. Our objective was to relate clinical and CT findings with outcome of patients with PVG, and to determine the indications for surgical treatment. Methods: Six-year records of patients from one general hospital with CT scan findings of gas in the mesenteric or portal veins were retrospectively studied, together with details of the clinical presentation, hospital course and outcome. Results: Between 1995 and 2000, 12 patients with findings of mesenteric and portal vein gas were identified. In 7 of 12 patients (58%) PVG developed secondary to ischemia of the small or large bowel, with mortality of 86%. Metabolic acidosis was the prominent laboratory finding. Pneumatosis intestinalis was present in all of these patients. Two patients with PVG had inflammatory bowel disease and both recovered with conservative management. Another 2 patients who were treated conservatively died. One patient had severe pancreatitis and died 2 weeks after PVG was diagnosed, from septic complications, while the other patient admitted with septic shock, died of multiorgan failure. In the last patient, PVG was diagnosed in a CT scan performed to investigate fever of unknown origin. She survived with no specific treatment. Conclusion: We suggest that patients in whom PVG is found by CT scan should be treated according to their clinical status, and underlying disease. Patients suspected of having an ischemic mesenteric event should be immediately explored.
Percutaneous Peripheral Neuromodulation in the Treatment of Fecal Incontinence
Authors: Shafik A. , Ahmed I. , El-Sibai O. , Mostafa R.M.
Published: April 2003

Background/Aims: To assess the results of peripheral neuromodulation for the treatment of fecal incontinence (FI) resulting from uninhibited rectal contraction (URC) or uninhibited anal sphincter relaxation (UASR). Methods: The work comprised 32 patients (age 38.2 ± 6.7 years; 22 women) with FI in whom conventional therapy had failed before enrollment in the study. Twenty-six had URC and 6 UASR. Peripheral neurostimulation was effected by posterior tibial nerve stimulation using a Stoller Afferent Nerve Stimulator (UroSurge, Coralville, lowa, USA). The needle was introduced into the skin cephalad to the medial malleolus. Stimulation (parameters: 0.5–10 mA, 200 µs, 20 Hz) was performed every other day for 4 weeks. Functional assessment was done by a questionnaire (incontinence score: 0–20) and physiologic studies. Results: Group 1: 17 patients (13 URC, 4 UASR) had FI improvement, recording a mean score of 1.7 of 20. Group 2: 10 patients (8 URC, 2 UASR) had fair improvement (score 8.6). Group 3: 5 patients had poor results (score 14.8). Rectometric recording showed improvement in groups 1 and 2. Recurrence of symptoms occurred in 8 patients; 6 improved after retreatment. Conclusions: A percutaneous access to the S3 spinal region was achieved through the posterior tibial nerve. Improvement of FI was achieved in 78.2%. The technique is simple, easy, without complications and cost-effective. It can be done as an outpatient procedure or by the patient at home. The results need to be reproduced on a large number of patients.
No Evidence of IFN-γ Increase in the Serum of HIV-Positive and Healthy Subjects after Subcutaneous Injection of a Non-Fermented Viscum album L. Extract
Authors: Stoss Matthias , Gorter Robert W.
Published: April 2003

Iscador®, an aqueous extract of Viscum album L., has been used for more than 80 years as an anticancer drug. Due to its immunomodulatory potential, since the onset of the AIDS epidemic it has also been applied in the treatment of HIV-positive and AIDS patients in the form of the preparation V. album QuFrF (VaQuFrF; Labor Hiscia, Arlesheim, Switzerland). In in vitro investigations, incubation of peripheral blood mononuclear cells with V. album L. extracts resulted in stimulation of lymphocyte activity with increased gene expression and release of various cytokines and also of interferon gamma (IFN-γ). In the latent phase, HIV positives exhibit only slightly elevated IFN-γ concentrations in serum in comparison with HIV negatives, but in the acute phase of AIDS, there is an increase in levels of IFN-γ. As the assay of cytokine levels in serum is a simple method of measuring immune system reactions, the aim of this trial was to determine whether increases in serum IFN-γ levels in HIV positives and HIV negatives can be detected using this method after repeated injections of VaQuFrF. Five healthy subjects and 13 HIV-positive patients were investigated. IFN-γ concentrations in serum were assayed using an ELISA test kit (ELISA test; ENDOGEN, Cambridge, Mass., USA). No drug-related elevation of serum IFN-γ was observed at any time point during the trial. It can thus be concluded that this method is not suitable for direct investigation of the immunomodulatory effects of VaQuFrF in vivo.
Natural Killer Cell Levels in Older Adult Mice Are Gender-Dependent: Thyroxin Is a Gender-Independent Natural Killer Cell Stimulant
Authors: Mahoney M.X. , Currier N.L. , Miller S.C.
Published: April 2003

The present study aimed to quantitatively analyze the effects of thyroxin on natural killer (NK) cells in the bone marrow and spleen of older adult (6 months) mice of both sexes. Five intraperitoneal injections of thyroxin were administered over 10 days in an attempt to stimulate the virtually negligible levels of NK cells in these older mice. Immunoperoxidase labeling of an NK cell surface marker, together with a tetrachrome hematologic counterstain, permitted morphological microscopic identification of mature NK cells, distinct from all other hemopoietic and immune (lymphoid) cells in the spleen and bone marrow. The results revealed that in spite of similar total cell content in both the spleen and bone marrow in both sexes at this age, there were significant, gender-based differences in NK cells and various other hemopoietic and immune cells. NK cells in the 6-month-old female mice are significantly more abundant than those of males at this age. Granulocytes in females were also significantly more numerous in both the spleen and bone marrow than in males. By contrast, monocytes and nucleated erythroid cells were significantly more numerous in males of this age. In both sexes, at this postbreeding age, the immunostimulant, thyroxin, had the common effect of significantly elevating the levels of NK cells. Our results underline the need for considering the two basic parameters of age and gender, as potentially confounding variables, prior to therapeutic administration of thyroxin, and possibly a host of hormones, cytokines and other regulators of hemopoietic and immune phenomena.
Autoantibody Level Modification in Adult Patients with Idiopathic Thrombocytopenic Purpura following Intravenous Immunoglobulin Treatment
Authors: Levy Yair , Sherer Yaniv , Ahmed Alaa , Fabbrizzi Fabrizio , Terryberry Jeff , Shen Guo Qiu , Peter James B. , Shoenfeld Yehuda
Published: April 2003

The aim of this study was to determine whether treatment of patients with immune thrombocytopenic purpura (ITP) with intravenous immunoglobulin (IVIg) is associated with a modification in the antiplatelet glycoprotein (GP) antibodies (Abs). Fourteen patients with ITP (11 females and 3 males, mean age 36.6 years, range 18–72) received one to four IVIg treatment courses. The preparation used was ISIVEN that was given in a dose of 2 g/kg body weight in a 5-day schedule and in monthly intervals. Levels of IgG, IgM and IgA isotypes of Abs to GPs IIb/IIIa and Ib/IX were measured before the treatment, and before and after each treatment course. Two patients did not respond to IVIg, 6 had a temporary response, 5 had a sustained response and 1 patient responded well to the treatment but was lost to follow-up. The patients had a high prevalence of serum Abs directed against GPs IIb/IIIa and Ib/IX before the treatment, and the mean IgG isotype levels of both Abs increased after each treatment course, and decreased again before the following course began. Whenever high Ab levels of either isotype (>10 U/ml) were detected before the treatment, they were significantly decreased before the last treatment course. The elevated levels of IgG Abs to IIb/IIIa and Ib/IX after every course are probably a result of displacement of these Abs from Fc receptors by the IVIg, rather than of exogenous infusion of these Abs contained within the IVIg, whereas the decrease in high Ab levels after a few treatment courses results from the immunomodulatory effects of IVIg: suppression of Ab formation, and the presence of anti-idiotypes.
Growth Arrest-Specific 2 Gene Expression during Patellar Tendon Healing
Authors: Lee K.K.H. , Cai D.Q. , Tang M.K. , Tsang K.F. , Kwong W.H. , Chow P.H.
Published: April 2003

We examined the cellular and molecular processes involved in patellar tendon healing following induced injury. A wound was surgically created at the center of the patellar tendon of adult rats. The wound site was examined at selected time intervals by immunohistochemical and in situ hybridization techniques. It was found that, between the 2nd and 7th day postoperation, fibroblast-like cells invaded the wound site. DiI-labelling experiments suggested that the majority of cells that occupied the wound originated from the edges of the wound. Furthermore, immunohistochemical studies revealed that at the wound site a meshwork of fibronectin developed that can support the migration of the DiI-labelled cells. We also examined the spatial and temporal expression patterns of the growth arrest specific 2 (gas2) gene during patellar tendon healing. Gas2 was found strongly expressed in the tenocytes of unoperated patellar tendons. The gene was also expressed in the intact regions of operated tendons but not in the fibroblast-like cells that occupied the wound site, when examined 2 days postoperation. In addition the strip of intact tendon directly opposite the wound site also did not express gas2. Examination of the experimental tendon at the 3rd month, when cells had completely occupied the wound site, revealed that Gas2 was expressed by all cells found in the wound. Bromodeoxyuridine (BrdU) incorporation analysis revealed that the presence of Brdu-positive cells in the wound indirectly correlated with the absence of Gas2 expression. We speculate that the gas2 gene might play a role in regulating tenocyte proliferation during tendon healing.
Effect of Altered Thyroid State on the in situ Mechanical Properties of Adult Cat Soleus
Authors: Roy R.R. , Zhong H. , Hodgson J.A. , Grossman E.J. , Edgerton V.R.
Published: April 2003

To determine the responsiveness of cat hindlimb muscles to thyroid manipulation, adult female cats were made hypothyroid (thyroidectomy plus tapazole treatment), hyperthyroid (synthroid pellets), or maintained euthyroid. After 4 months, the hypothyroid soleus had slower time-to-peak (TPT, 80%) and half-relaxation (HRT) times, whereas the hyperthyroid soleus had faster TPT (20%) and HRT than euthyroid cats. The tension at low stimulation frequencies (5–15 Hz) was higher in hypothyroid and lower in hyperthyroid cats compared to euthyroid cats. Muscle weight, maximum twitch and tetanic (Po) tensions, and maximum rates of shortening (Vmax) were similar across groups. The soleus of hypothyroid cats was more fatigable than normal. The myosin heavy chain (MHC) composition, based on gel electrophoresis, was unaffected by thyroid hormone manipulation. Based on the reaction of monoclonal antibodies for specific MHCs, some fast fibers in the hypothyroid cats coexpressed developmental MHC. These data indicate that 4 months of an altered thyroid state result in changes in the isometric twitch speed properties of the cat soleus, but not the tension-related or isotonic properties. Further, a chronic decrease in thyroid hormone had a greater impact than a chronic increase in thyroid hormone on the mechanical properties of the adult cat soleus.
Susceptibility of Young Adult and Old Rats to Noise-Induced Hearing Loss
Authors: Fraenkel Rachel , Freeman Sharon , Sohmer Haim
Published: April 2003

This study was designed to test whether old rats show signs of presbyacusis and whether they would be either similarly or more or less susceptible to noise-induced hearing loss than young adult rats. Old (24 months) and young adult (3–4 months) Wistar rats were exposed to a broad-band noise of 113 dB SPL for a duration of 1 h (producing temporary threshold shifts) or 3 days (12 h noise/12 h quiet; permanent shifts). Auditory brainstem response (ABR), distortion product otoacoustic emissions (DPOAEs) and transient evoked otoacoustic emissions (TEOAEs) were measured before and after exposure. At the initial recording (before exposure), old rats demonstrated a small mean ABR threshold elevation, a reduction in amplitude of wave I (WI), a shortening of WI latency and a prolongation of the interpeak interval between WI and WIV, as compared to the young rats. The old rats also demonstrated a small DPOAE amplitude reduction and a reduction of peak-to-peak amplitude in the TEOAE response 2 ms after stimulus, but no reduction in TEOAE energy content between 2 and 4 kHz. These are signs of presbyacusis in the old rats. The noise exposures caused elevations in ABR threshold and reductions in DPOAE amplitude and TEOAE energy content that were similar in both the old and young rats. Their recovery from the noise-induced loss was also similar. Thus, the results of this study show that old and young adult rats, at least when considering clinically relevant intensities and durations of noise exposure, are equally susceptible to the effects of the exposure.
Promoter Usage and Estrogen Regulation of Prolactin Receptor Gene in the Brain of the Female Rat
Authors: Pi Xiujun , Zhang Bo , Li Jun , Voogt James L.
Published: April 2003

Mechanisms underlying hormonal regulation of prolactin receptor (PRL-R) gene in the brain are unknown. The 5’-untranslated region of PRL-R mRNA in peripheral tissues contains at least three alternative first exons (1A, B, C) that are expressed as tissue-specific, suggesting the differential usage of PRL-R gene promoters. The present study aimed to investigate: (1) the possible regulation of PRL-R mRNA levels by estrogen in in vitro and in vivo tissues; (2) which exon (1A, or 1B, or 1C)-containing PRL-R mRNA transcript is expressed in the brain, and (3) how the specific exon 1-containing mRNA is affected by estrogen by using RT-PCR, Southern blot and 5’Race PCR techniques. The RT-PCR results showed that PRL-R mRNA was detected in the cerebral cortex and pons medulla in addition to the choroid plexus and hypothalamus in the female rat. The expression of PRL-R mRNA was up-regulated by estrogen treatment in the rat brain tissue and in the GT1-7 cell culture. Both exon 1A- and 1C-containing transcripts were expressed in all four regions, suggesting that promoters 1A and 1C for the PRL-R gene are utilized in the rat brain. Exon 1A-containing transcript was up-regulated by estrogen treatment in all four brain regions, whereas Exon 1C-containing transcript was up-regulated by estrogen treatment in 3 of the 4 brain regions, cerebral cortex being the exception. Exon 1B-containing transcript was neither detectable nor induced by estrogen treatment in any of the brain regions examined. The RT-PCR results were confirmed by partial isolation of 5′-untranslated regions of exon 1A- and 1C-containing PRL-R mRNA transcripts from brain tissue by using 5’Race PCR. The present result confirms the expression of PRL-R mRNA in the cerebral cortex and pons medulla in the female rat. The levels of PRL-R mRNA were up-regulated by estrogen in rat brain tissue and GT1-7 cell cultures. Detection of exon 1A- and 1C-containing transcripts implies that the promoter 1A and 1C are active in the female rat brain. Estrogen differentially regulates expression of the PRL-R mRNA in the different brain regions by increasing the utilization of PRL-R gene promoters 1A and 1C in the female rat.
Public Knowledge regarding the Role of Genetic Susceptibility to Environmentally Induced Health Conditions
Authors: Morris Jill , Gwinn Marta , Clyne Mindy , Khoury Muin J.
Published: April 2003

Objective: Diseases thought to be caused by exposure to environmental factors are also influenced by genetic susceptibility. It is not clear to what extent the public recognizes the role of genetics in causing these diseases. Methods: We asked 2,353 people in a national survey to indicate their level of agreement with statements about the genetic contribution to four health conditions typically considered to be environmentally induced. Results: 206 (9%) respondents believed that genetic susceptibility contributes to all four health conditions, while 751 (32%) believed that genetics plays no role in causing any of the conditions. Respondents were more likely to believe that genetics contributes to adverse drug reactions and smoking-related illnesses than to infectious diseases and diseases resulting from exposure to environmental agents. Conclusions: This study suggests that the public views genetic susceptibility as playing only a limited role in human disease induced by environmental factors. Increasing awareness of the role of genetic factors in these diseases will be necessary for translating gene discovery into effective personal and public health actions.
Membranous Glomerulonephritis Associated with Follicular B-Cell Lymphoma and Subepithelial Deposition of IgG1-κ Paraprotein
Authors: Evans David J. , Macanovic Momir , Dunn Michael J. , Pusey Charles D.
Published: April 2003

A case is described of B-cell lymphoma/chronic lymphocytic leukaemia associated with membranous glomerulonephritis in which the subepithelial deposits of immunoglobulin showed ĸ light chain restriction by immunofluorescence. Surface IgG-ĸ immunoglobulin was demonstrated on the malignant B cells, and a monoclonal protein of the same type was eluted from kidney. The mechanism of membranous glomerulonephritis in this type of lymphoid malignancy is clearly different from that in epithelial malignancies.
Cross-Talk between Two Organs: How the Kidney Responds to Disruption of Acid-Base Balance by the Lung
Authors: Madias Nicolaos E. , Adrogué Horacio J.
Published: April 2003

Hypoventilation increases PaCO2 (hypercapnia) and initiates the acid-base disorder known as respiratory acidosis. Hyperventilation decreases PaCO2 (hypocapnia) and initiates the acid-base disorder known as respiratory alkalosis. The impact on acidity of these primary changes in PaCO2 is ameliorated by secondary, directional changes in plasma bicarbonate concentration that occur in two stages. Acutely, modest changes in plasma bicarbonate originate from titration of the body’s nonbicarbonate buffers. In chronic hypercapnia and hypocapnia, larger changes in plasma bicarbonate occur that reflect adjustments in renal acidification mechanisms. As a result, the amelioration of systemic acidity is more pronounced in the chronic forms of the respiratory acid-base disorders.
Characterization of Temperature-Sensitive HVJ (Sendai Virus) Infection in Vero Cells: Inhibitory Mechanism of Viral Production at 41°
Authors: Hirayama Etsuko , Ishida Yo-ichi , Sugimoto Masao , Hiraki Akihiro , Kim Jeman
Published: April 2003

In a previous study, it was found that the synthesis of hemagglutinating virus of Japan (HVJ; Sendai virus)-specific proteins was inhibited at the transcriptional level at 41° in LLC-MK2 cells. During an investigation of the temperature sensitivity of HVJ production in other host cells, the synthesis of HVJ-specific proteins was recognized even at 41° in Vero cells. Viral production, however, was not detected, indicating the inhibition of steps after the synthesis of viral proteins. Hemadsorption activity was not detected at 41°, suggesting problems with the envelope proteins, especially hemagglutinin-neuraminidase (HN) protein, at the cell membrane. Immunofluorescent staining and surface immunoprecipitation showed that HN protein was not present on the surface in spite of its localization in the cytoplasm. Further, analysis of the cell membrane fraction suggested that fusion (F) protein was integrated into the cell membrane but HN protein was not at 41°. Electron microscopic observation showed that budding sites with spike structures formed and nucleocapsids assembled under the sites at 41° without HN protein, although budded HVJ virions were not detected. At this time, F protein was exposed to the cell membrane and interacted with matrix and nucleocapsid proteins. The results suggested that the suppression of HVJ production at 41° was due to the absence of HN protein in the membrane of Vero cells.
Effects of Multiple Virus Coinfections on Disease Progression in HIV-Positive Patients
Authors: Shieh Biehuoy , Chang Ming-Jen , Ko Wen-Chien , Chen Eng-Jun , Wu Jaw-Ching , Lee Chia-Fang , Chang Ting-Tsung , Li Ching
Published: April 2003

Objective: Since virus infections in AIDS patients are mostly inevitable and as they frequently cause disease deterioration and therapeutic failures, a comprehensive investigation was made of the influence of the coinfections of 9 well-known viruses on disease progression in patients infected with human immunodeficiency virus type 1 (HIV). Methods: A cross-sectional study of 62 HIV-positive patients was conducted to correlate the prevalence rates for the 9 viruses with the alanine aminotransferase (ALT) levels and CD4 cell counts of the patients. Results: The rates of HIV-positive patients infected with the 9 viruses are significantly higher than those of the control groups. Furthermore, almost one third of the patients in the studied group was coinfected with transfusion-transmitted virus (TTV) and manifested significantly higher ALT levels (p = 0.020), and these were raised further if coinfection with TTV and human hepatitis C virus had occurred (p = 0.010). By analyzing CD4 cell counts, the only significant effect on AIDS progression which could be detected was coinfection with human herpesvirus 8. Conclusion: This result confirmed that immune-suppressed persons are more vulnerable to common virus infections. Unlike hepatitis B or C virus, TTV seems to accelerate the progression of chronic hepatitis in HIV-infected patients.
Isolation, Identification, and Quantitation of Urinary Glycosaminoglycans
Authors: Lee Eun-Young , Kim Soo-Hyun , Whang Soo-Kyung , Hwang Kyu-Yoon , Yang Jong-Oh , Hong Sae-Yong
Published: April 2003

Background: Substantial amounts of glycosaminoglycans (GAGs) are present in the urine of healthy individuals, but the concentration in the serum is very low. This finding suggests that urinary GAGs come from the glomerulus and may reflect the turnover of GAGs in the glomerulus. Hypothesis: However, little is known about the physiologic regulation of the urinary GAGs in humans, and so investigations are needed to evaluate the effects of age and sex on urinary GAGs in normal individuals. Methods: Eighty-seven healthy subjects were included in this study. Urinary GAGs were isolated and quantified at the nanogram level by combined azure A-silver staining in agarose gels. Results: The level of urinary GAGs peaked at 10–19 years in both sexes. The proportion of chondroitin sulfate decreased with age, but the proportion of heparan sulfate increased with age. Conclusion: The total amount of GAGs and the proportions of chondroitin sulfate, heparan sulfate, and dermatan sulfate appear to change with age. Therefore, investigations in which urinary GAG is used as a parameter of glomerular GAG turnover should ensure that control groups are precisely matched for age. Changes in the proportions of each GAG may be more informative than their absolute levels.
Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets
Authors: Kufrin Dubravka , Eslin Don E. , Bdeir Khalil , Murciano Juan-Carlos , Kuo Alice , Kowalska M. Anna , Degen Jay L. , Sachais Bruce S. , Cines Douglas B. , Poncz Mortimer
Published: April 2003

Arterial occlusive disorders are a leading cause of human morbidity. We hypothesized that ectopic expression of fibrinolytic proteins in platelets could be used to favorably alter the hemostatic balance at sites of thrombosis. To test our hypothesis, we directed murine urokinase-type plasminogen activator transgene expression to platelets using a platelet factor 4 promoter. Urokinase was selectively expressed and stored in the platelets of these mice. These transgenic mice had altered platelet biology and a bleeding diathesis similar to that seen in patients with Quebec platelet disorder, affirming the role of ectopic urokinase expression as the etiology of this inherited disease. These mice were resistant to the development of occlusive carotid artery thrombosis in the absence of systemic fibrinolysis and displayed rapid resolution of pulmonary emboli. Moreover, transfusion of urokinase-expressing platelets into wild-type mice prevented formation of occlusive arterial thrombi. These studies show the feasibility of delivering fibrinolytic agents to sites of incipient thrombus formation through selective storage in platelets and offer a new strategy to prevent thrombosis and hemorrhage.
Patterns of Chemotherapy Use for Women With Ovarian Cancer: A Population-Based Study
Authors: Cress Rosemary D. , O’Malley Cynthia D. , Leiserowitz Gary S. , Campleman Sharon L.
Published: April 2003

Purpose: To evaluate adherence to published recommendations for chemotherapy for ovarian cancer patients in the general community and to identify factors associated with its use.

Patients and Methods: The study population consisted of 2,150 women residing in Northern California with a first diagnosis of primary epithelial ovarian cancer between January 1994 and December 1996. Patients were identified through the California Cancer Registry and their physicians were surveyed to supplement registry treatment information.

Results: Almost 89% of women younger than 75 years with International Federation of Gynecology and Obstetrics stage III or IV tumors received chemotherapy, with levels of treatment highest for women diagnosed at stage III. Patients 75 years of age and older were significantly less likely than younger women to receive chemotherapy (58.2% v 86.1%; P = .001) regardless of stage at diagnosis. Approximately 20% of patients younger than 55 years with early-stage (stage IC and II) cancer received no chemotherapy. Treatment in an American College of Surgeons hospital and treatment by a gynecologic oncologist increased the likelihood of receiving chemotherapy. Hospitalization for comorbid illness, race/ethnicity, census-based measures of socioeconomic status, and size or teaching status of hospital were all unrelated to probability of treatment after adjustment for other factors. Reasons reported most frequently by physicians for no treatment were lack of clinical indication and patient refusal.

Conclusion: The results of this study suggest that, despite scientific evidence and published guidelines that advocate chemotherapy for most women with ovarian cancer, some groups of women did not receive optimum treatment.
The Regulator of Sex-Limitation Gene, Rsl, Enforces Male-Specific Liver Gene Expression by Negative Regulation
Authors: Tullis Kathryn M. , Krebs Christopher J. , Leung Janet Y. M. , Robins Diane M.
Published: April 2003

Expression of a broad array of proteins is sexually dimorphic in rodent liver, dependent on sex-specific patterns of GH secretion. Mice carrying rsl (regulator of sex limitation) alleles, discovered as trans-acting loci affecting the mouse sex-limited protein (Slp) gene, reveal an additional axis in male-specific gene regulation. Slp expresses in adult males, but in rsl homozygous mice, Slp is also expressed in females. In this study, we examined congenic rsl strains to determine rsl’s site of action, breadth of targets, and interaction with hormonal induction. We show that rsl affects Slp in liver, but not kidney, and that Rsl acts on a spectrum of male-specific liver genes, including mouse urinary proteins and a cytochrome P450 expressed predominantly by males, Cyp 2d-9, but does not act on the female-prominent P450, Cyp 2a-4. Slp expression in hypophysectomized or Tfm/Y rsl mice reveals that Rsl action is independent of GH or androgen signaling. Further, parabiosis of Rsl and rsl mice does not alter expression patterns, consistent with rsl action being liver intrinsic. Finally, Slp expression initiates earlier in rsl mice, suggesting that Rsl operates before, as well as independently of, hormonal induction. This characterization suggests Rsl functions to repress transcription of a set of genes that have in common their hormonal induction in male liver, and thus accentuates sexual dimorphism of liver gene expression.
Agouti-Related Protein Stimulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis and Enhances the HPA Response to Interleukin-1 in the Primate
Authors: Xiao Ennian , Xia-Zhang Linna , Vulliémoz Nicolas R. , Ferin Michel , Wardlaw Sharon L.
Published: April 2003

α-MSH antagonizes many of the immune and neuroendocrine effects induced by inflammatory cytokines. Studies have shown that α-MSH attenuates the stimulatory effect of IL-1 on the hypothalamic-pituitary-adrenal (HPA) axis and plays a physiological role in limiting the HPA response to IL-1. Recently an α-MSH antagonist, agouti-related protein (AGRP), has been identified in the hypothalamus, which stimulates food intake by antagonizing the effects of α-MSH at specific melanocortin receptors. It is unknown whether AGRP can also modulate neuroendocrine responses to inflammatory cytokines. We have therefore examined the effects of AGRP on the HPA axis and on prolactin (PRL) at baseline and in response to stimulation by IL-1β in nine ovariectomized rhesus monkeys. In the first study, the effects of intracerebroventricular (icv) infusion of 20 μg (n = 6) and 50 μg (n = 4) of human AGRP (83–132)-NH2 were compared with icv saline infusion. There was a significant stimulatory effect of 20 μg AGRP on cortisol release over time (P < 0.001). The area under the hormone response curve (AUC) for cortisol increased by 29% after 20 μg AGRP vs. saline; the AUC for ACTH increased by 166% (P = 0.028); the AUC for PRL increased by 108% (P = 0.046). There was a significant stimulatory effect of 50 μg AGRP on ACTH (P < 0.001), cortisol (P < 0.001), and PRL (P < 0.001) release over time. The AUC for ACTH after 50 μg AGRP increased by 98%; the AUC for cortisol increased by 37%; the AUC for PRL increased by 161%. The effects of AGRP on ACTH, cortisol, and PRL release were prevented by α-MSH infusion. In the second study, animals received icv either 50 ng of human IL-1β or 20 μg of AGRP followed by 50 ng IL-1β. AGRP significantly enhanced the ACTH (P < 0.05) response to IL-1β. The peak ACTH response to IL-1β alone was 124 ± 55 pg/ml vs. 430 ± 198 pg/ml after IL-1β plus AGRP; the peak cortisol response was 70 ± 8.2 μg/dl vs. 77 ± 6.2 μg/dl, but this was not significantly different. In conclusion, AGRP stimulated ACTH, cortisol, and PRL release in the monkey and enhanced the ACTH response to IL-1β. These studies suggest that, in addition to its known orexigenic effects, AGRP may play a role in neuroendocrine regulation and specifically that AGRP may interact with α-MSH to modulate neuroendocrine responses to inflammation.
Antiproliferative Action of Calcitonin on Lactotrophs of the Rat Anterior Pituitary Gland: Evidence for the Involvement of Transforming Growth Factor β1 in Calcitonin Action
Authors: Wang Yong Qing , Yuan Ren , Sun Ya-Ping , Lee Tae-Jin , Shah Girish V.
Published: April 2003

Calcitonin-like pituitary peptide, which is synthesized and secreted by gonadotrophs of the rat anterior pituitary (AP) gland, is a potent inhibitor of prolactin biosynthesis and lactotroph cell proliferation. Because TGF-β1 is an autocrine inhibitor of lactotroph cell proliferation, we investigated a possibility that calcitonin (CT) interacts with TGF-β1 to inhibit lactotroph cell proliferation.

The actions of CT on GGH3 cell proliferation were examined in the absence or presence of anti-TGF-β1 serum. Subsequent experiments tested the effects of CT on TGF-β1 mRNA abundance as well as TGF-β1 synthesis. The studies also tested whether the stimulatory action of CT on TGF-β1 mRNA expression involves stabilization of TGF-β1 mRNA. Finally, the experiments investigated in vivo actions of CT on TGF-β1 synthesis in the AP gland. This was accomplished by studying the changes induced by iv administered CT in TGF-β1-immunopositive cell populations of adult female rat AP glands.

The results have shown that the inhibitory action of CT on proliferation of GGH3 cells was attenuated by rabbit anti-TGF-β1 serum. Moreover, CT stimulated TGF-β1 mRNA expression, as well as TGF-β1 synthesis, in a dose-dependent fashion. Stimulatory action of CT on TGF-β1 expression may be posttranscriptional, because it significantly increased TGF-β1 mRNA stability. When administered in vivo, CT significantly increased TGF-β1-immunopositive cell populations of adult female rat AP gland. Colocalization studies for prolactin and TGF-β1 suggest that CT increased TGF-β1 synthesis in lactotrophs, and possibly in nonlactotroph cell populations. These results suggest that antiproliferative action of CT on lactotrophs may, at least in part, be mediated by CT-induced TGF-β1 expression.
Porphyrin Supramolecules for Artificial Photosynthesis and Molecular Photonic/Electronic Materials
Authors: Kobuke Yoshiaki , Ogawa Kazuya
Published: April 2003

Porphyrin supramolecules were constructed by ligand coordination to central metal ions, hydrogen bonding, or chelate complexation to external metal ions. meso-N-Methyl-2-imidazolyl-substituted porphyrin afforded a special pair model and a light-harvesting antenna mimic by complementary coordination of imidazolyl to Zn and Mg, respectively. Characteristic splits of the Soret band in absorption spectra and large upfield shifts of imidazolyl and pyrrolic β protons in the 1H NMR spectra suggested the close proximity of two porphyrin π–π planes. Such upfield shifts in the 1H NMR spectra were also observed for coordination organization of 2,5-dihydroxyphenyl-substituted porphyrinatoMg. As an example of organization by hydrogen bonding, the supramolecular assembly between imidazolyl substituents afforded stacks of porphyrins with antenna function in solution and gave rise to the formation of stable antenna liposome without any lipid components such as lecitin. Mono- and bis(8-hydroxy-5-quinolyl) substituted porphyrins were coordinated with Ga(III) to afford tris(oxinato) chelate and poly(oxinato) chelate, respectively. The fluorescence intensity of each Ga complex was increased significantly compared with that of each starting monomer. At the same time, efficient excitation energy transfer among three porphyrins has been observed to realize the light-harvesting function. Novel bipyridylene-bridged bisporphyrin was synthesized by a nickel(0)-mediated homocoupling reaction of bromopyridyl-porphyrinatoZn. Spatial geometries of two porphyrins were regulated by reversible complexation of the bipyridyl part with PdCl2. Bis(imidazolylporphyrinatoZn), which was directly linked at meso-position, afforded a giant linear multi-porphyrin array by successive links of complementary coordination of imidazolyl to zinc having molecular weight of 105 at a distribution maximum corresponding to 80 bisporphyrin units and at the molecular length of 110 nm. On the other hand, the polyporphyrin can be dissociated to bisporphyrin unit and scrambled with monomeric imidazolylporphyrinatoZn in the presence of MeOH or pyridine to produce oligomers terminated by the monomeric porphyrin. This reorganization process could apply to the systems generating efficient photocurrents and large third-order optical nonlinearity.
Discotic Liquid Crystals of Transition Metal Complexes 33: Spontaneous Uniform Homeotropic Alignment and Unique Mesophase Transition Behavior of Bis[2,3,9,10,16,17,23,24-octakis(3,4-dialkoxyphenoxy)phthalocyaninato]lutetium(III) Complexes
Authors: Hatsusaka Kazuaki , Kimura Mutsumi , Ohta Kazuchika
Published: April 2003

Novel discotic liquid crystalline bis[2,3,9,10,16,17,23,24-octakis(3,4-dialkoxyphenoxy)phthalocyaninato]lutetium(III) complexes, {[(CnO)2PhO]8Pc}2Lu (n = 12: 5a and n = 13: 5b), were synthesized. Their mesomorphic properties were investigated using polarization microscopy, DSC, and temperature-dependent X-ray diffraction techniques. These Lu complexes exhibited a very unique mesophase transition sequence of Colh → Cub1 → Cub2 → Coltet. In Coltet, a monodomain spontaneous homeotropic alignment could be achieved. Moreover, they showed two Cub phases, which is the first example of phthalocyanine-based discotic liquid crystals. The electrochemical property of 5a was also estimated by cyclic voltummetry.
Novel Synthesis of P-Chiral Hydroxymethylphosphine–Boranes through Lipase-Catalyzed Optical Resolution
Authors: Shioji Kosei , Kurauchi Yoshimitsu , Okuma Kentaro
Published: April 2003

A novel approach toward the lipase-catalyzed acylation of alkyl(1-hydroxymethyl)phosphine–boranes was achieved. Up to 99% of enantiomerically enriched phosphine–boranes was obtained by using lipase AK and CAL.
Syntheses of Flavones via the Iodine-Mediated Oxidative Cyclization of 1,3-Diphenylprop-2-en-1-ones
Authors: Miyake Hideyoshi , Takizawa Eizo , Sasaki Mitsuru
Published: April 2003

The syntheses of flavones from 1,3-diphenylporp-2-ene-1-ones are described. When 1,3-diphenylprop-2-en-1-ones were heated with iodine in triethylene glycol, oxidative cyclization underwent to obtain flavones in good yields.
Infrared body temperature measurement of mice as an early predictor of death in experimental fungal infections
Authors: Warn P. A. , Brampton M. W. , Sharp A. , Morrissey G. , Steel N. , Denning D. W. , Priest T.
Published: April 2003

Temperatures of mice were measured using an infrared high performance non-contact thermometer, after the device had been calibrated using implantable microchips containing temperature transponders. Mice were infected with three species of Candida (isolates) and the resultant disseminated infections monitored. Mouse temperatures could be reliably measured using the infrared device and this measurement caused little distress to the mice. We were further able to demonstrate that mice rarely recovered if their body temperature dropped below 33.3°C (sensitivity 68%, specificity 97%). Adoption of a 33.3°C endpoint in fungal sepsis experiments measured by infrared non-contact thermometer would significantly reduce the suffering in the terminal stages of this type of infection model.
Price-Endings When Prices Signal Quality
Authors: Stiving Mark
Published: April 2003

This paper provides a theoretical explanation for why firms behave as though they use round prices to signal quality. By replacing the linear demand curve in Bagwell and Riordan's (1991) price as a signal of quality model with a kinked demand curve, and analyzing what price endings firms are most likely to use, the following observations can be made: (1) Firms that are using high prices to signal quality are more likely to set those prices at round numbers, and (2) price-endings themselves are not necessarily signals of quality. A simulation was conducted to demonstrate that these findings generally hold true even in the presence of demand spikes at 9-ending prices (e.g., Schindler and Kibarian 1996). Finally, empirical evidence is provided to demonstrate that firms tend to use more round prices for higherquality products, and that this relationship is even stronger for product categories where consumers are less able to detect the true level of quality prior to purchase.
The Optimal Choice of Promotional Vehicles: Front-Loaded or Rear-Loaded Incentives?
Authors: Zhang Z. John , Krishna Aradhna , Dhar Sanjay K.
Published: April 2003

We examine the key factors that influence a firm's decision whether to use front-loaded or rear-loaded incentives. When using price packs, direct mail coupons, FSI coupons or peel-off coupons, consumers obtain an immediate benefit upon purchase or a front-loaded incentive. However, when buying products with in-pack coupons or products affiliated with loyalty programs, promotion incentives are obtained on the next purchase occasion or later, i.e., a rear-loaded incentive. Our analysis shows that the innate choice process of consumers in a market (variety-seeking or inertia) is an important determinant of the relative impact of front-loaded and rear-loaded promotions. While in both variety-seeking and inertial markets, the sales impact and the sales on discount are higher for front-loaded promotions than for rear-loaded promotions, from a profitability perspective, rear-loaded promotions may be better than front-loaded promotions. We show that in markets with high variety-seeking it is more profitable for a firm to rear-load, and in markets with high inertia it is more profitable to front-load. Model implications are verified using two empirical studies: (a) a longitudinal experiment (simulating markets with variety-seeking consumers and inertial consumers) and (b) market data on promotion usage. The data in both studies are consistent with the model predictions.
Telecommunication Node Clustering with Node Compatibility and Network Survivability Requirements
Authors: Park Kyungchul , Lee Kyungsik , Park Sungsoo , Lee Heesang
Published: April 2003

We consider the node clustering problem that arises in designing a survivable two-level telecommunication network. The problem simultaneously determines an optimal partitioning of the whole network into clusters (local networks) and hub locations in each cluster. Intercluster traffic minimization is chosen as the clustering criterion to improve the service quality. Various constraints on the clustering are considered which reflect both the physical structures of local networks, such as the connectivity requirement, and the node compatibility relations such as community of interest or policy. Additional constraints may be imposed on the hub selection to ensure network survivability. We propose an integer programming formulation of the problem by decomposing the entire problem into a master problem and a number of column generation problems. The master problem is solved by column generation and the column generation problems by branch-and-cut. We develop and use strong cutting-planes for the cluster generation subproblems. Computational results using real data are reported.
Quantifying the Bullwhip Effect in a Simple Supply Chain: The Impact of Forecasting, Lead Times, and Information
Authors: Chen Frank , Drezner Zvi , Ryan Jennifer K. , Simchi-Levi David
Published: April 2003

An important observation in supply chain management, known as the bullwhip effect, suggests that demand variability increases as one moves up a supply chain. In this paper we quantify this effect for simple, two-stage supply chains consisting of a single retailer and a single manufacturer. Our model includes two of the factors commonly assumed to cause the bullwhip effect: demand forecasting and order lead times. We extend these results to multiple-stage supply chains with and without centralized customer demand information and demonstrate that the bullwhip effect can be reduced, but not completely eliminated, by centralizing demand information.
Organizing Distribution Channels for Information Goods on the Internet
Authors: Dewan Rajiv , Freimer Marshall , Seidmann Abraham
Published: April 2003

Rapid technological developments and deregulation of the telecommunications industry have changed the way in which content providers distribute and price their goods and services. Instead of selling a bundle of content and access through proprietary networks, these firms are shifting their distribution channels to the Internet. In this new setting, the content and Internet service providers find themselves in a relationship that is simultaneously cooperative and competitive. We find that proprietary content providers prefer the Internet channels to direct channels only if the access market is sufficiently competitive. Furthermore, maintaining a direct channel in addition to the Internet channels changes the equilibrium enough that the proprietary content providers prefer having the Internet channels, regardless of the level of competition in the access market. Telecommunications technology developments uniformly increase content providers' profit. On the other hand, the technology impact on Internet service provider profits is nonmonotonic: Their profits may increase or decrease as a result of lower telecommunication costs. While initially the ISP profit increases as more customers are drawn to the Internet, it eventually decreases as the spatial competition becomes more intense. We also show that proprietary content providers should benefit from having some free content available at the Internet service providers' sites to induce more customers to join the Internet.