bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and assignment of the human NIMA-related protein kinase 7 gene (NEK7) to human chromosome 1q31.3
Authors: Kimura M. , Okano Y.
Published: April 2003

Neks (NIMA-related kinase) are a group of protein kinases sharing high amino acid sequence identity with NIMA which controls initiation of mitosis in Aspergillus nidulans. We have identified and characterized human NEK7, a novel human gene structurally related to NIMA. Its open reading frame encodes a 302-amino acid protein and is 77% identical to human NEK6 protein. Phylogenetic analysis suggests that NEK6, NEK7, and Caenorhabditis elegans F19H6.1 constitute a subfamily within the NIMA family of protein kinases. Tissue distributions of NEK7 and NEK6 were studied by RT-PCR. NEK7 expression was restricted to a subset of tissues containing lung, muscle, testis, brain, heart, liver, leukocyte, and spleen, but NEK6 transcripts were detected in all tissues studied. The human NEK7 gene was assigned to human chromosome 1 by somatic cell hybrids and 1q31.3 by radiation hybrid mapping.
Compaction, stainability and methylation of the late replicating X chromosome in mouse female fibroblasts
Authors: Bernardino-Sgherri J. , Dutrillaux B.
Published: April 2003

In metaphases from female mouse fibroblasts, successive stainings by Giemsa and DAPI and immunolabeling of 5-methylcytosine were performed with or without bromodeoxyuridine pretreatment. It was shown that, compared to all other chromosomes, the late replicating X is the least methylated, the most compacted, and the most intensely stained by DAPI and Giemsa.
Human and mouse orthologs of a new ATP-binding cassette gene, ABCG4
Authors: Annilo T. , Tammur J. , Hutchinson A. , Rzhetsky A. , Dean M. , Allikmets R.
Published: April 2003

We characterized a new ATP-binding cassette (ABC) transporter gene from human and mouse that is highly expressed in the brain. The gene, ABCG4, produces several transcripts that differ at the 5′ end and encode proteins of various lengths. The ABCG4 protein is closely related to the Drosophila white and human ABCG1 genes, and belongs to the ABCG subfamily several members of which are involved in cholesterol transport. All representatives of this “reverse transporter” subfamily, including ABCG4, have a single ATP-binding domain at the N-terminus and a single C-terminal set of transmembrane segments. ABCG4 maps to human chromosome 11q23, between the markers D11S939 and D11S924, and Abcg4 to a conserved syntenic region on mouse chromosome 9. The abundant expression of this gene in the brain and close evolutionary relationship to the other members of the subfamily suggests a potential role for ABCG4 in cholesterol transport processes in this tissue.
A new balanced autosomal reciprocal translocation in cattle revealed by banding techniques and human-painting probes
Authors: Iannuzzi L. , Molteni L. , Di Meo G.P. , Perucatti A. , Lorenzi L. , Incarnato D. , De Giovanni A. , Succi G. , Gustavsson I.
Published: April 2003

Three hundred and twenty-two (264 males and 58 females), randomly sampled Grey Alpine cattle individuals from Northeastern Italy, were investigated cytogenetically by both conventional chromosome staining and R-banding. Two hundred and eighty-one (87%) individuals had a normal karyotype and 41 (13%) carried chromosomal aberrations such as (a) rob(1;29) in two individuals, (b) rob(26;29) in 36 individuals, (c) XX/XY-chimerism in two individuals, and (d) an abnormally long chromosome in one individual. All these aberrations except (d) have been described before. GBG-, RBG-, CBA-banding and sequential GBG/CBA- and RBG/CBA-banding techniques revealed that the abnormally long chromosome was the result of a reciprocal translocation between chromosomes 1 (q21→qter) and 5 (q11→q33), as confirmed also by chromosome painting with human chromosome 3 and 12 probes. The dam of the carrier bull carried the same translocation, while the grandam showed a normal karyotype. Since the sire of the dam was not available for study, no conclusion about the origin of the chromosome translocation could be drawn. The carrier bull was eliminated because of poor fertility. The dam had three other calves, which all were chromosomally normal. On average the dam had to be served 2.5 times (breed average was 1.2) to be in calf.
Epidemiological Aspects of Irritable Bowel Syndrome in Europe and North America
Authors: Müller-Lissner Stefan A. , Bollani Simona , Brummer Robert-Jan , Coremans George , Dapoigny Michel , Marshall John K. , Muris Jean W.M. , Oberndorff-Klein Wolthuis Ardi , Pace Fabio , Rodrigo Luis , Stockbrügger Reinhold , Vatn Morten H.
Published: April 2003

The epidemiology of irritable bowel syndrome (IBS) in Europe and North America was analyzed from published material. The percentage of the population of Western civilisation with IBS symptoms is between 10 and 15% in most studies. The proportion of a Western population visiting a doctor for IBS symptoms is around 5%. The prevalence of IBS and the proportion of consulters do not seem to depend on age in an adult population. The female-to-male ratio of IBS in the population is close to 2. It is higher in IBS consulters in primary care and may be as high as 3 or 4 in tertiary referral centers. At least in patients from these centers, the number of physician visits and colonoscopies is considerable. Most of the consulters get a drug prescription.
Second-Line Helicobacter pylori Eradication with a Furazolidone-Based Regimen in Patients Who Have Failed a Metronidazole-Based Regimen
Authors: Sotoudehmanesh Rasoul , Malekzadeh Reza , Vahedi Homayoon , Dariani Nasser Ebrahimi , Asgari Ali Ali , Massarrat Sadegh
Published: April 2003

Background/Aim: In developing countries the standard quadruple therapy containing metronidazole results in suboptimal eradication rates of Helicobacter pylori (<75%). In a retrospective study, we undertook to evaluate efficacy and tolerability of a furazolidone-based regimen (omeprazole, furazolidone, bismuth, and tetracycline) in patients who had previously failed the standard metronidazole-based regimen (omeprazole, metronidazole, bismuth, and amoxicillin). Methods: The records of H. pylori infected patients who were referred to outpatient clinic (from March 1999 to August 1999) and who underwent previous eradication regimens were studied. A total of 320 cases were noted to have received a metronidazole-based quadruple regimen. From these 320 patients, 80 were noted to have failed this regimen based on a urea breath test. These 80 patients were enrolled in the study and given the furazolidone-based regimen. Side effects were assessed at follow-up visits. At least 2 months after the end of each therapy regimen, a 14C-urea test was performed in each subject to document the cure of the patients. Results: A total of 80 patients (39 males and 41 females) with a mean age of 43.8 ± (SD) 13.3 years were studied. The H. pylori eradication rate was 90% with the furazolidone-based regimen. The side effects of this regimen were minor. Conclusions: A furazolidone-based regimen is effective in patients who do not achieve cure of H. pylori infection with the metronidazole-based quadruple therapy. In areas where the metronidazole resistance is high, initial therapy with a furazolidone-based regimen is recommended.
Adverse Drug Reactions: Mechanisms and Assessment
Authors: Ring Johannes , Brockow Knut
Published: April 2003

Adverse drug reactions (ADR) are an important clinical problem. They account for about 5% of all hospital admissions and cause death in approximately 0.01% of surgical patients. The mechanisms leading to ADR beyond IgE-mediated allergy are still poorly understood. The importance of chemically reactive drug metabolites and the involvement of T-lymphocytes in many drug hypersensitivity reactions have been highlighted in recent years. ADR are diagnosed on clinical grounds and the temporal relation between drug intake and the appearance of the symptoms. Allergy tests are required in the further assessment of the reaction. By means of skin tests, in vitro tests and provocation tests information about the culprit drug, the mechanism involved and possible alternatives can be obtained.
Searching the Ideal Inhaled Vasodilator: From Nitric Oxide to Prostacyclin
Authors: Kemming G. , Habler O. , Kleen M. , Kisch-Wedel H. , Welte M. , Zwissler B.
Published: April 2003

Today, the technique to directly administer vasodilators via the airway to treat pulmonary hypertension and to improve pulmonary gas exchange is widely accepted among clinicians. The flood of scientific work focussing on this new therapeutic concept had been initiated by a fundamental new observation by Pepke-Zaba [1]and Frostell in 1991 [2]: Both scientists reported, that inhalation of exogenous nitric oxide (NO) gas selectively dilates pulmonary vessels without a concomittant systemic vasodilation. No more than another decade ago NO was identified as an important endogenous vasodilator [3]while having merely been regarded an environmental pollutant before that time. Although inhaled NO proved to be efficacious, alternatives were sought-after due to NO’s potential side-effects. In search for the ideal inhaled vasodilator another group of endogenous mediators – the prostanoids – came into the focus of interest. The evidence for safety and efficacy of inhaled prostanoids is – among a lot of other valuable work – based on a series of experimental and clinical investigations that have been performed or designed at the Institute for Surgical Research under the guidance and mentorship of Prof. Dr. med. Dr. h.c. mult. K. Messmer [4-19]. In the following, the current and newly emerging clinical applications of inhaled prostanoids and the experimental data which they are based on, will be reviewed.
Adenine Nucleotide and Creatine Phosphate Pool in Adult and Old Rat Heart during Immobilization Stress
Authors: Davydov V.V. , Shvets V.N.
Published: April 2003

Background: Disturbances in the heart energy provision is important in the stress-induced injury of myocardium. In order to learn the causes of age-dependent differences in myocardial sensitivity to stress, we determined the level of adenylates, creatine and creatine phosphate in adult and old rat heart during an immobilization stress. Methods: Fifty male Wistar rats were used to study the myocardial adenine nucleotides, creatine and creatine phosphate pool and creatine kinase activity during an immobilization period. Results: The concentration of adenine nucleotides in old and adult rat hearts was similar. The total concentration of adenylate pool, ATP and ADP in the heart of both age groups was reduced during stress. However, in old rats under stress the concentration of ATP in a less measure and ADP in a greater measure is decreased against that observed in adult animals. The level of inorganic phosphate in old rat heart remains the same as in adult rats. Conclusion: The creatine kinase system may be important in stabilizing the ATP level in myocardium of adult rats during stress. The role of this system in heart energy metabolism during stress is decreased in old rats. Disturbances of isoenzyme creatine kinase activity are responsible for these disorders.
Vasopeptidase Inhibitors: A New Class of Drugs
Authors: Corti Roberto , Ruschitzka Frank , Hürlimann David , Lüscher Thomas F. , Noll Georg
Published: April 2003

The human cardiovascular system is regulated by hemodynamic, neurohumoral and structural mechanisms. The endothelium and the neurohumoral system play a key role in modulating both vascular tone and structure by producing vasoactive substances as well as influencing the modulation of blood cell adhesion. Although the neurohormonal systems are essential in the vascular homeostasis, they become maladaptive in conditions such as hypertension, coronary disease and heart failure. The clinical success of blocking the renin-angiotensin system by angiotensin-converting enzyme (ACE) inhibitors and the sympathetic nervous system by β-blockers demonstrates the importance of neurohumoral blockades. The inadequate effect of ACE or neutral endopeptidase (NEP) inhibitor monotherapy seen in some patients treated for hypertension or congestive heart failure (CHF) and the promising effect seen after their combination led to the development of drugs that simultaneously inhibit both enzyme systems. NEP, like ACE, is an endothelial cell surface zinc metallopeptidase with a similar structure and catalytic site to ACE. NEP is the major enzymatic pathway for the degradation of natriuretic peptides. Natriuretic peptides can be viewed as endogenous inhibitors of the renin-angiotensin system. The dual metalloprotease inhibitors of ACE and NEP, called vasopeptidase inhibitors, represent a new class of drugs and an attractive therapeutic strategy for the treatment of cardiovascular diseases such as hypertension and CHF.
Surgical Management of Postinfarction Ventricular Septal Rupture
Authors: Prêtre René , Turina Marko I.
Published: April 2003

Purpose: To evaluate our results based on rapid closure of a postinfarction ventricular septal defect, myocardial revascularization and ventricular remodeling. Patients: Retrospective analysis of 54 consecutive patients (30 with a posterobasal and 24 with an antero-apical rupture) operated between 1979 and 1998. Twenty-five patients were in shock. Twenty-six patients had a coronary disease limited to the culprit artery, and 28 a multivessel disease. Results: Early mortality was 26% (21% during the last decade). Two patients died peroperatively and 12 postoperatively, mostly due to cardiac failure. Ten patients had a residual septal defect requiring reoperation in 5. Survival was 78, 65 and 40% at 1, 5 and 10 years, respectively. Three years after the operation, the great majority of patients (17 out of 18) were in NYHA class I or II. Conclusions: Although surgery is the only chance for most patients with postinfarction ventricular septal rupture, it carries a significant early mortality. Survival rate with a good quality of life can, however, be achieved in the majority of the patients.
Coincident Nonlinear Changes in the Endocrine and Immune Systems due to Low-Frequency Magnetic Fields
Authors: Marino Andrew A. , Wolcott R. Michael , Chervenak Robert , Jourd’heuil Frances , Nilsen Erik , Frilot II Clifton , Pruett Stephen B.
Published: April 2003

Objective: The characteristic biological effects of low-frequency electromagnetic fields (EMFs) appear to be functional changes in the central nervous, endocrine and immune systems. For unapparent reasons, however, the results of similar studies have often differed markedly from one another. We recognized that it had generally been assumed, in the studies, that EMF effects would exhibit a dose-effect relationship, which is a basic property of linear systems. Prompted by recent developments in the theory on nonlinear systems, we hypothesized that there was a nonlinear relationship between EMFs and the effects they produced in the endocrine and immune systems. Methods: We developed a novel analytical method that could be used to distinguish between linear and nonlinear effects, and we employed it to examine the effect of EMFs on the endocrine and immune systems. Results: Mice exposed to 5 G, 60 Hz for 1–175 days in 7 independent experiments reliably exhibited changes in serum corticosterone and lymphoid phenotype when the data were analyzed while allowing that the field exposure and the resulting effects could be nonlinearly related. When the analysis was restricted to linear relationships, no effects due to the field were found. Conclusions: The results indicated that transduction of EMFs resulted in changes in both the endocrine and immune systems, and that the laws governing the changes in each system were not the type that govern conventional dose-effect relationships. Evidence based on mathematical modeling was found suggesting that the coincident changes could have been causally related.
Serotonin and Immune Response: Effect of the Amine on in vitro Proliferation of Rat Lymphocytes
Authors: Stefulj Jasminka , Cicin-Sain Lipa , Schauenstein Konrad , Jernej Branimir
Published: April 2003

Objective: The effect of serotonin (5-hydroxytryptamine; 5HT) on the in vitro proliferation of mitogen-stimulated lymphocytes was studied in primary cultures of rat spleen cells. Methods: 5HT was added to the cultures 1 h prior to the mitogen, at final concentrations from 10–13 up to 10–2M. T and B cell mitogens (concanavalin A, pokeweed mitogen and lipopolysaccharide) were used at suboptimal and optimal concentrations. The cell proliferation was measured 24–72 h after the addition of mitogen. The effect of each 5HT concentration was studied on a group of 6–12 animals and was expressed as a percentage of the control values obtained with mitogen alone. Results: No significant effect of 5HT at concentrations from 10–13 to 10–5M was found. At concentrations of ≧10–4M, a regular dose-dependent inhibition of the lymphocyte proliferation appeared, the concentration producing the half-maximal effect being 6 × 10–4M. The observed suppression was not due to 5HT cytotoxicity toward spleen cells. Conclusion: With the experimental system used, we failed to confirm an immunostimulatory effect of 5HT in the range of concentrations of its receptor sensitivities or lower, but found a clear-cut immunoinhibitory effect at higher concentrations.
Anti-Inflammatory Effects of Somatostatin Analogs on Zymosan-Induced Earlobe Inflammation in Mice: Comparison with Dexamethasone and Ketoprofen
Authors: Kurnatowska Ilona , Pawlikowski Marek
Published: April 2003

The aim of the present study was the estimation of the anti-inflammatory effects of the somatostatin analogs, octreotide (OCT) and vapreotide (RC-160), in zymosan-induced mice ear inflammation and to compare their effects with those of the glucocorticoid dexamethasone (DX) and the non-steroid anti-inflammatory drug ketoprofen (KP), which are the well-known and potent suppressors of the inflammatory reaction. The inflammation was induced by injecting 20 µl of 1% suspension of zymosan intradermally into one of the earlobes of the mouse. The control animals received a vehicle 0.9% NaCl. The zymosan-treated animals were injected subcutaneously with one of the following substances: 0.9% NaCl, OCT, RC-160, DX, KP or with OCT plus DX and OCT plus KP. The edema of earlobes, the area of inflammatory focus and the area of vascular profiles in the inflamed tissues were estimated. A reduction of the ear edema in the mice treated with OCT, DX, KP, OCT + DX and OCT + KP was observed. The administration of all drugs caused the decrease of the area of the inflammatory focus and of the area of vascular profiles. The antiphlogistic activity was more pronounced in the OCT-treated animals in comparison to those treated with RC-160. The joint treatment with either OCT plus DX or OCT plus KP almost totally inhibited the zymosan-induced inflammatory reaction. In summary, the somatostatin analog OCT possesses antiphlogistic activity roughly comparable with classical anti-inflammatory drugs such as DX and KP. The somatostatin analogs may constitute a new promising group of anti-inflammatory agents.
The Reductions in Sweetened Milk Intake Induced by Interleukin-1 and Endotoxin Are Not Prevented by Chronic Antidepressant Treatment
Authors: Dunn Adrian J. , Swiergiel Artur H.
Published: April 2003

Administration of interleukin-1 (IL-1) and endotoxin (lipopolysaccharide, LPS) to rodents can decrease food intake, a behavioral response resembling the diminution of appetite observed in human depression. IL-1 and LPS are known to affect cerebral neurotransmission involving norepinephrine and serotonin, both of which have been implicated in feeding behavior and in the pharmacotherapy of depression in man. The ability of chronic antidepressant treatment to attenuate LPS-induced depressed feeding in rats has been cited as evidence that cytokines may be involved in human depression. Thus, we studied the effects of chronic treatment with the tricyclic antidepressant, imipramine, and the novel antidepressant, venlafaxine, on the sweetened milk intake challenged with intraperitoneally injected IL-1β and LPS. Chronic (from 2 to 8 weeks) treatment of the mice with imipramine (10 mg/kg once or twice daily) or venlafaxine (10 and 20 mg/kg/day) did not significantly alter the decreases in milk intake in response to mIL-1β or LPS. In some experiments, chronic imipramine slightly decreased body weight and slightly increased milk intake, but not food pellet intake. Venlafaxine had none of these effects. Analysis of variance did not indicate any significant interactions between the antidepressant and IL-1 or LPS treatments. These results indicate that chronic treatment with antidepressants does not significantly alter the responses to IL-1 or LPS in the mouse sweetened milk model of sickness behavior.
Cyclosporin A: Effects on the Secretory Process and Noradrenergic Activity in the Submandibular Gland of the Rat
Authors: Giglio Juan M. , Vatta Marcelo S. , Bianciotti Liliana G. , Lomniczi Alejandro , Elverdin Juan C.
Published: April 2003

Objectives: The aim of the present work was to study the effect of long-term cyclosporine (CSA) administration on norepinephrine (NE) metabolism and adrenergic-evoked secretion in the rat submandibular gland (SMG). Methods: Dose-response curves to adrenergic agonists (methoxamine, isoproterenol, NE) were performed in control and CSA (10 and 30 mg/kg every 2 days for 1 month)-treated rats after SMG duct cannulation. In SMG tissue neuronal NE uptake, release, synthesis and endogenous content were determined. In addition phosphoinositide intracellular signaling was also investigated. Results: CSA administration caused an increase in salivary secretion evoked by methoxamine (α-adrenergic agonist) and NE but failed to modify salivation evoked by β-adrenergic stimulation (isoproterenol). Long-term CSA administration decreased NE release and synthesis whereas it enhanced the amine uptake and phosphoinositide hydrolysis in the SMG. Conclusions: The administration of CSA for 30 days induced salivary gland sensitization likely mediated by diminished adrenergic input. Present results suggest that the decreased sympathetic activity evoked by long-term CSA administration in the rat SMG may lead to sensitization of the gland supported by increased phosphoinositide hydrolysis and enhanced adrenergic-evoked salivation.
Tumor Necrosis Factor and Motoneuronal Degeneration: An Open Problem
Authors: Ghezzi Pietro , Mennini Tiziana
Published: April 2003

Tumor necrosis factor (TNF) has been implicated in the pathogenesis of various central nervous system diseases with an inflammatory component. Elevated TNF levels were observed in animal models of motor neuron disease (MND), and activation of the TNF system has been reported in patients with amyotrophic lateral sclerosis (ALS). The easy availability of scientific reports to the layman through the web, often based only on the abstracts, has prompted many patients to ask whether anti-TNF therapy might be beneficial in ALS. This review discusses the possible role of TNF in motoneuronal degeneration. Although TNF is mostly regarded as neurotoxic cytokine, there are reports of a neuroprotective and neurotrophic action. Studies with animal models of ALS are not sufficient to show whether TNF has a pathogenic or a protective role in MND though anti-TNF antibodies have shown protective effects in experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). On the other hand, while TNF-deficient mice are protected from EAE, anti-TNF antibodies worsen the disease in MS patients, suggesting caution in extrapolating preliminary basic studies to the patient.
Impaired Activity of Phagocytic Cells in Candida albicans Infection after Exposure to Chronic Varied Stress
Authors: Rodriguez-Galán María Cecilia , Correa Silvia Graciela , Cejas Hugo , Sotomayor Claudia Elena
Published: April 2003

Objective: Candidiasis is a prototypic opportunistic fungal disease that may follow severe modulations of the immune system of the host. The purpose of this study was to evaluate which innate immune mechanisms involved in the protection against fungal invasion are impaired under stress conditions. Methods: Wistar rats were infected intraperitoneally with Candida albicans and immediately exposed to chronic varied stress (CVS) over 10 days (CVS; Ca-S); the fungal burden (CFU), histopathological lesion and ACTH levels were evaluated. Additionally, functional assessment of peritoneal cells (PC) included the phagocytic and anticandidacidal activities and the production of H2O2 and NO. Results: In the only infected animals (Ca), C. albicans colonization stimulated an efficient inflammatory response, while in Ca-S rats poor tissue reactions were associated with increased CFU in livers and kidneys (p < 0.05, Ca vs. Ca-S). Whereas the phagocytic process was not modified, the candidacidal activity of PC was significantly decreased after the application of CVS (p < 0.001, Ca vs. Ca-S). The H2O2 production by macrophages and neutrophils was downregulated by the infection, and while at early intervals these cells possessed a residual oxidative capacity, by day 10, the production of this metabolite was blocked. Spontaneous NO production by macrophages was significantly increased in both Ca and Ca-S animals (p < 0.001), but in stressed rats, this reactive nitrogen intermediate was noticeably downregulated (p < 0.05, Ca vs. Ca-S). The hyperactivity of hypothalamus-pituitary-adrenal axis after exposure to stress was confirmed by an increase in baseline plasma ACTH levels. Conclusion: These results show that during infection with C. albicans, the exposure to CVS contributes to the spread of the fungus and downregulates critical functions of phagocytic cells involved in the control of this opportunistic pathogen.
Functional Asymmetry of Thymus and the Immune Response in Mice
Authors: Abramov Valery V. , Gontova Irina A. , Kozlov Vladimir A.
Published: April 2003

We have studied the capability of the mouse thymus for asymmetrical formation. Concanavalin A (Con A)-stimulated proliferation of thymocytes from the right and left lobes of the thymus appeared to be significantly different. The direction of the differences depends on the dominance of the brain hemispheres with regard to motor asymmetry. In mice with right-dominant hemispheres, thymocytes from the left lobe of the thymus demonstrate a higher level of Con A-stimulated proliferation than those from the right lobe. In mice with left-dominant hemispheres, we found the opposite dependence. The in vivo experiments showed that the properties of cells from the contralateral lobes of the thymus proved to be a deciding factor that defines the differences at the level of the immune response in recipient mice with left-dominant hemispheres. This effect was less pronounced in mice with right-dominant hemispheres. Further analysis showed that left and right-dominant hemisphere mice differ according to the immune response only if mice from both groups received cells from the left but not from the right lobe of the thymus. That is, in the formation of the immune response to sheep red blood cells, the functional asymmetry of both the brain and thymus is of great importance. The experiments show that brain hemispheres and cells from different lobes of the thymus are able to interact in the regulatory effect on the immune response. The injection of cells from the thymus lobe ipsilateral to the dominant hemisphere, results in a significant excess of the immune response in left-dominant hemisphere mice in comparison with the response of right-dominant hemisphere mice. It can be concluded that this work demonstrates, for the first time, the asymmetrical function of a bilateral immune organ – the thymus. The asymmetry is shown not only at the level of Con A-induced proliferative activity but also at the level of the influence on the humoral T-dependent immune response in mice. Besides, we have found the interaction of brain hemispheres and thymus lobes in the regulation of the immune response.
Effect of Hyperoxaluria on the Inhibitory Activity of a 45-kD Urinary Protein
Authors: Selvam Ramasamy , Balakrishnan Selvakumar , Kalaiselvi Periandavan
Published: April 2003

Proteins are thought to play a major role in stone formation and structurally abnormal proteins have been reported to be present in the urine of stone formers. This study was aimed to determine whether hyperoxaluria modifies the kinetic properties of urinary inhibitory proteins. Hyperoxaluria was induced by feeding 1% ethylene glycol to rats. Oxalate, uric acid and calcium excretion were increased progressively during hyperoxaluria, while magnesium level was decreased. Urinary proteins were separated on a DEAE-cellulose column by eluting with stepwise increasing salt concentration in 0.05 M Tris-HCl buffer (pH 7.0). Each protein fraction was studied for its crystallization inhibitory potential by the spectrophotometric method. The protein eluted in 0.3 M NaCl containing buffer had the maximal nucleation as well as inhibitory activity. The protein had a molecular weight of 45 kD. In hyperoxaluria, the urinary excretion of this protein significantly increased. In the crystal growth assay, the control rat 45-kD protein inhibited nucleation by 75% and aggregation by 100%. In contrast, it is very interesting to note that the protein derived from 28th day hyperoxaluric urine, behaved as a promoter of nucleation (–113%, percentage inhibition) and weak inhibitor of aggregation (28%). A significantly high negative correlation (r = –0.97) between oxalate excretion and the inhibitory activity of the 45-kD protein was observed suggesting a modification of the protein by oxalate.
A Rare Cause of Focal Segmental Glomerulosclerosis: Sarcoidosis
Authors: Altiparmak Mehmet Rıza , Oygar Deren , Bilir Muammer , Kiliçarslan Işın , Serdengeçti Kamil
Published: April 2003

A 58-year-old female patient diagnosed as having sarcoidosis 23 years ago developed nephrotic syndrome. No pathology was found which could explain this, so it was attributed to her sarcoidosis. Renal biopsy showed global and segmental sclerosis. The occurrence of focal segmentary glomerulosclerosis in a case of sarcoidosis is rare. In systemic sarcoidosis it is thought that T-cell dysfunction may play a role in the pathogenesis of glomerulonephritis. When treatment is considered, corticosteroid therapy may be used according to the clinical status at diagnosis as well as on follow-up of the patient.
Angiotensin II Type 1 Receptor Antagonist, Losartan, Causes Regression of Left Ventricular Hypertrophy in End-Stage Renal Disease
Authors: Shibasaki Yasunobu , Masaki Hiroya , Nishiue Takashi , Nishikawa Mitsushige , Matsubara Hiroaki , Iwasaka Toshiji
Published: April 2003

Left ventricular hypertrophy (LVH) commonly occurs in patients with end-stage renal disease (ESRD) and is an independent risk factor for cardiovascular events. Angiotensin II type 1 receptor (AT1-R) antagonists may be able to reverse LVH independent to the hypotensive effect in the ESRD setting. Thirty chronically hemodialyzed uremic patients with hypertension were randomly assigned to receive the AT1-R antagonist losartan (n = 10), the angiotensin-converting enzyme (ACD) inhibitor enalapril (n = 10), or calcium antagonist amlodipine (n = 10). Left ventricular mass (LVM) index was measured by echocardiography before and 6 months after treatment. The baseline demographic and clinical characteristics did not differ between the three groups. The mean baseline LVM index also did not differ in the three groups. After 6 months of treatment, losartan treatment significantly reduced the LVM index (–24.7 ± 3.2%) than amlodipine (–10.5 ± 5.2%) or enalapril (–11.2 ± 4.1%) therapy. All three groups had a similar decrease in the mean blood pressure with treatment. The plasma angiotensin II concentration increased 5-fold with losartan treatment. In contrast, the plasma angiotension II concentration did not change with enalapril and only increased 2-fold with amlodipine. Thus, the present study indicates that losartan more effectively regresses LVH in patients with ESRD than do enalapril and amlodipine despite a comparable depressor effect between the three drugs.
Protein Phosphatase 2A Isotypes Regulate Cell Surface Expression of the T Cell Receptor
Authors: Lauritsen Jens Peter H. , Menné Charlotte , Kastrup Jesper , Dietrich Jes , Geisler Carsten
Published: April 2003

The mechanisms underlying T cell receptor (TCR) down-regulation have been extensively studied during the last decade. Whereas the importance of phosphorylation in this process has been established, it is less certain whether dephosphorylation plays a role in TCR down-regulation. In this study, we show that inhibition of the serine/threonine protein phosphatase PP2A family had a biphasic effect on TCR expression. Thus, low concentrations of PP2A inhibitors induced TCR down-regulation, whereas higher concentrations of PP2A inhibitors induced TCR up-regulation. The effect of PP2A inhibition was independent of phosphorylation of the CD3γ endocytosis motif. Whereas TCR down-regulation was caused by a partial inhibition of exocytosis, TCR up-regulation was caused by an inhibition of endocytosis. The effects on exocytosis and endocytosis were not restricted to the TCR, indicating a more general regulatory role for PP2A in both exocytosis and endocytosis.
Benefit and Safety of Enhanced External Counterpulsation in Treating Coronary Artery Disease Patients with a History of Congestive Heart Failure
Authors: Lawson William E. , Kennard Elizabeth D. , Holubkov Richard , Kelsey Sheryl F. , Strobeck John E. , Soran Ozlem , Feldman Arthur M.
Published: April 2003

Enhanced external counterpulsation (EECP) is used to noninvasively treat refractory angina patients, including those with a history of heart failure. The International EECP Patient Registry was used to examine the benefit and safety of EECP treatment, including a 6-month follow-up, in 1,957 patients, 548 with a history of heart failure. The heart failure cohort was older, with more females, a greater duration of coronary artery disease, more prior infarcts and revascularizations. Significantly fewer heart failure patients completed the course of EECP, and exacerbation of heart failure was more frequent, though overall major adverse cardiac events (MACE, i.e. death, myocardial infarction, revascularization) during treatment were not significantly different. The angina class improved in 68%, with comparable quality of life benefit, in the heart failure cohort. At 6 months, patients with congestive heart failure maintained their reduction in angina but were significantly more likely to have experienced a MACE end point.
Effects of Spironolactone and Fosinopril on the Spontaneous and Chronic Ventricular Arrhythmias in a Rat Model of Myocardial Infarction
Authors: Beck Lionel , Blanc-Guillemaud Vanessa , Cherif Ouafiya K. , Jover Bernard , Davy Jean-Marc
Published: April 2003

We documented chronic ventricular arrhythmias in a first group of 58 rats after myocardial infarction (MI), then assessed the effects of spironolactone and fosinopril on morphological indexes and arrhythmias in a second group (n = 33). Rats underwent Holter monitoring at 2 months after MI. Treatment was randomly given from 1 until 4 months after MI: placebo in 12 rats (P), fosinopril in 9 (F) and spironolactone + fosinopril in 12 (SF). The score of ventricular premature beats (VPBs) was related to the MI size and the delay from MI (p < 0.01). VPB’s reduction/increase required to demonstrate anti/pro-arrhythmic effects were 55 and 59%. Mass indexes were lower in F and SF (p = 0.01). VPB’s difference (4 months vs. 1) was positive in P, significantly lower in F and negative in SF (p = 0.04). In this relevant model of spontaneous and chronic ventricular arrhythmias, SF association did not increase mortality but lowered the arrhythmic score.
What Dental Diseases Are We Facing in the New Millennium: Some Aspects of the Research Agenda
Authors: ten Cate J.M.
Published: April 2003

The next decades will show a shift in the attention given to diseases of the dental hard tissues. Clinical evidence on how to prevent dental caries is now available. More emphasis should be given to optimising the rational use of schemes of prevention. Caries still shows epidemic patterns in many countries while in some developed countries a high prevalence of the disease is limited to a small group. Increased attention is needed for new manifestations of pathology such as dental erosion, and for caries in special high-risk groups. New methods of presenting caries prevalence and incidence data should be implemented to ensure that the diseases of the dental hard tissues continue to have an important place on the political and research agendas.
How to Measure the Effects of Fluoride Treatments in Clinical Trials?
Authors: Angmar-Månsson B.
Published: April 2003

In recent years there has been a pronounced change in the epidemiology and disease pattern of dental caries. In the current context, traditional methods of caries assessment, discriminating lesions at cavitation, are clinically inappropriate, and obsolete for research requiring detection of a very early phase of mineral loss. Modern prospective caries studies require sensitive methods permitting the measurement of small changes in tooth mineral content, and objective, quantitative measurements of such changes are now possible in a single caries lesion. For longitudinal studies there are noninvasive methods for assessment of new lesions as well as quantitative changes (progression or regression) in existing lesions. Among as yet unresolved issues are improved methods to assess the current activity of a lesion, methods for detection and quantification of secondary caries and root caries, calibration of methodologies between different research institutes, and methods capable of assessment of the whole continuum in the development of a caries lesion, from initial loss of mineral to cavitation.
Carotid Angioplasty and Stenting: Are They Therapeutic Alternatives?
Authors: Brown Martin M.
Published: April 2003

Clinical trials have shown that carotid surgery prevents stroke, but also has a significant risk of morbidity. Percutaneous transluminal angioplasty and stenting (endovascular treatment) can also be used to treat carotid stenosis and have the advantage of avoiding general anaesthesia, cranial nerve injury and the discomforts of surgery. However, there are several potential complications of endovascular treatment, including intimal dissection and plaque rupture, and the long-term consequences of restenosis. More embolic signals are detected during and immediately after carotid angioplasty than during carotid surgery, although a randomised comparison showed no difference in neuropsychological outcomes. The large published case series of carotid endovascular treatment suggest a similar major morbidity rate to surgery, but a small single centre randomised trial reported very poor results in stented patients. Trial data from the much larger Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) has been more encouraging. Results are available from 504 patients with carotid stenosis randomised to surgery or endovascular treatment. Endovascular treatment was carried out by percutaneous transluminal angioplasty using balloon catheters with the adjunct use of stents in 22%. Audited safety analysis by intention to treat showed no difference in the outcome measure of disabling stroke or death within 30 days of treatment, but the rate of treatment related death or stroke lasting more than seven days was relatively high in both groups (endovascular treatment 10%, surgery 9.9%). Minor complications, particularly cranial nerve palsy and haematoma were significantly less frequent in the endovascular group, but restenosis was significantly more common. Both treatments appeared equally effective at preventing stroke recurrence with no difference in the rates of stroke during follow-up for up to 3 years. Techniques of carotid angioplasty and stenting improved over the course of CAVATAS, and new designs of stents, filters and protection devices are being developed. Further large, multicentre randomised trials are therefore being started which will evaluate primary stenting of carotid artery stenosis in patients with cerebrovascular disease. Until the results are available, it will remain uncertain whether angioplasty and stenting are safe and effective therapeutic alternatives to surgery.
Antiproliferative Effect of Somatostatin and Analogs
Authors: Bousquet Corinne , Puente Elena , Buscail Louis , Vaysse Nicole , Susini Christiane
Published: April 2003

Over the past decade, antiproliferative effects of somatostatin and analogs have been reported in many somatostatin receptor-positive normal and tumor cell types. Regarding the molecular mechanisms involved, somatostatin or analogs mediate their action through both indirect and direct effects. Somatostatin acts through five somatostatin receptors (SSTR1–5) which are variably expressed in normal and tumor cells. These receptors regulate a variety of signal transduction pathways including inhibition of adenylate cyclase, regulation of ion channels, regulation of serine/threonine and tyrosine kinases and phosphatases. This review focuses on recent advances in biological mechanisms involved in the antineoplastic activity of somatostatin and analogs.
Management of Breast Cancer: Is There a Role for Somatostatin and Its Analogs?
Authors: Boccardo Francesco , Amoroso Domenico
Published: April 2003

Somatostatin and related peptides are a family of peptides which are ubiquitous and function as endogenous growth inhibitors. Analogs have been developed through the introduction of a D-amino acid in the position 8 of somatostatin moiety which is more resistant to the action of endogenous peptidases than the parental moiety. Both somatostatin and its analogs interact with specific receptors on the cell surface. The five receptor subtypes, SSTR-1 to SSTR-5, which have been characterized so far, have a different affinity for somatostatin and its analogs. This and the fact that receptors are not homogeneously expressed in tissues account for the different activity of these compounds, all of which have demonstrated tumoristatic properties both in vitro and in vivo. The interaction of somatostatin and of somatostatin analogs with specific SSTR receptors is crucial to the antiproliferative mechanisms exerted by these compounds in vitro and in some animal models and the various pathways have been reviewed in detail. However, inhibition of angiogenesis and suppression of lactogenic hormones might represent alternative mechanisms, in particular in breast cancer. The rationale for the use of somatostatin and its analogs in breast cancer patients and to combine these peptides with antihormones, like antiestrogens or prolactin-lowering drugs, or cytotoxics has been reviewed together with the results obtained in phase II and comparative trials. The reasons for the limited efficacy shown by these compounds either when used alone or when used in combination with other drugs have also been critically reviewed in the perspective of new trials.
Octreotide for Cancer of the Liver and Biliary Tree
Authors: Kouroumalis Elias A.
Published: April 2003

Inoperable liver tumors have an unfavorable natural course despite various therapeutic modalities. Octreotide, a somatostatin analog, has shown considerable antitumor activity on animal models of various hepatic tumors and on isolated cell culture lines. In this paper, a review of the experimental evidence is presented. Moreover clinical papers of case reports of uncontrolled studies of patients are also reviewed. The majority of clinical studies provide evidence of a clinical and biochemical response of liver endocrine tumors while regression of tumor size is a rare event. A randomized controlled trial of octreotide in the treatment of advanced hepatocellular carcinoma has shown a significant survival benefit in the treated patients. Literature reports indicate a stimulatory effect of octreotide on Kupffer cells as a possible antitumor mechanism, but other antiproliferative actions of octreotide have been suggested but not proved. Finally the question of the presence and affinity of somatostatin receptors on liver tumor tissue is discussed. In conclusion, according to our experience, octreotide administration is the best available treatment for advanced inoperable hepatocellular carcinoma and future better patient selection, based on receptor subtypes, might further improve the results.
Optimal Treatment Strategies for Community-Acquired Pneumonia: Non-Responders to Conventional Regimens
Authors: File Jr. Thomas M.
Published: April 2003

When patients with community-acquired pneumonia (CAP) fail to respond after initiation of empirical therapy, it is necessary for the physician to consider a number of possibilities. The diagnosis should be reviewed, with consideration given to both non-infectious and infectious illnesses. If the diagnosis is correct, the failure may relate to three areas: host-related problems, including overwhelming infection and empyema, pathogen-related problems, including infection caused by an unusual or resistant pathogen, and drug-related problems, including inappropriate dose of drug, poor compliance, malabsorption, and drug interactions. A systematic therapeutic approach including a microbiological evaluation to identify the causative pathogen and its susceptibility will help to ensure that an appropriate antimicrobial agent is used.
Solutions for Difficult Diagnostic Cases of Acute Exacerbations of Chronic Bronchitis
Authors: Tsang Kenneth W.T.
Published: April 2003

Acute exacerbation of chronic bronchitis (AECB) is a very common condition, which presents with deteriorating sputum production and dyspnoea in a patient with pre-existing COPD or chronic bronchitis. As these symptoms are relatively non-specific and also the presenting feature of a wide range of other conditions, the physician should carefully consider the differential diagnosis before deciding on whether or not a patient indeed has AECB. The differential diagnosis can be summarised as pneumonia, pneumothorax, cardiac failure/cor pulmonale, bronchiectasis, asthma, tuberculosis, sinusitis and other forms of upper respiratory tract sepsis, diffuse panbronchiolitis, lung cancer, gastro-oesophageal reflux, the presence of a foreign body in the airway, melioidosis, and lung abscess. This article aims to discuss these conditions, with brief presentation of clinical cases, in the evaluation of differential diagnosis of AECB.
An Aberrant Form of CD59 Derived from HeLa Cells
Authors: Davies A. , Vannais D. , Fernie B.A. , Wilson A.B. , Gustafson D. , Willers C. , Waldren C.
Published: April 2003

We isolated a CD59 cDNA from a HeLa cell library which encoded a mutated form of CD59, having a single base substitution (G to T) that changed Arg55 to Met. Since this mutation occurred in the vicinity of the putative active site of CD59, we expressed the aberrant form of the protein in Chinese hamster ovary cells in order to test for effects upon function. We found that the mutation did not influence complement inhibitory activity of CD59. However, the epitopes recognised by the function-blocking CD59 monoclonal antibodies BRIC229 and YTH 53.1 were significantly affected. The G to T substitution caused loss of an Mnl I restriction site which permitted PCR-RFLP analysis. All of 52 human subjects studied, and our in-house HeLa cells, were homozygous for the normal CD59 sequence, indicating that the altered sequence was not due to normal variation in the general population. Therefore this mutation probably arose spontaneously in the HeLa cell line used to generate the commercially obtained cDNA library.