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PubMed2003

New findings in the study on the intercalation of bisdaunorubicin and its monomeric analogues with naked and nucleus DNA.

DNA is a target molecule for anthracycline anticancer drugs. We have used new anthracycline derivatives, bisdaunorubicin (WP631) and its monomeric analogues (WP700 serie), and look if there was a relation between the drug binding affinity to naked DNA and to cell nucleus in the cell with its cytotoxicity. Circular dichroism (CD) and fluorescence were used to follow the interaction of anthracycline derivatives with naked DNA and cell nuclei. WP631 interacts with DNA at two distinct stoichiometries, 6:1 and 3:1 base pair (bp)/WP631 molecule (3:1 and 1.5:1 per anthracycline rings). Monomeric daunorubicin (DNR) with its amino sugar N-bound to amino- and nitro-substituted benzyl moiety, representing p-xylenyl linker present in WP631 bisintercalator, is much more binding to DNA than DNR or WP631. These findings are supported by the study of drug binding by nuclei of K562 cells. Around 70% of WP700 intercalate to nucleus DNA in the steady-state, while only 45% of DNR intercalate DNA in the cell. The binding of WP631 by K562 cells is even less effective ( approximately 20%). WP 700 compounds, which are very similar to each other in their binding to DNA, self-association and cell accumulation, differ very distinctly in their cytotoxicity power. The most effective compounds are amino-benzyl derivatives of WP 700 series. The nitro-benzyl compounds have very low toxicity, even if they bind to DNA with similar power with that of the amino derivatives. The comparison of the all data clearly indicates no relation between cytotoxicity of the drug and its ability to intercalate DNA.

Antibiotics, Antineoplastic↗
PubMed1993

New findings in the treatment of panic disorder.

Research conducted during the past decade has resulted in a range of options for treating panic disorder. Favorable responses to tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and high-potency benzodiazepines have been reported. When costs and benefits are taken into account, the selective serotonin uptake inhibitors currently seem to be the treatment of choice. Studies with serotonin agonists and antagonists are as of yet disappointing. The introduction of cholecystokinin antagonists has opened up intriguing new areas of research. This paper reviews those findings and developments.

Antidepressive Agents, Tricyclic↗
PubMed2002

Re-annotation of genome microbial coding-sequences: finding new genes and inaccurately annotated genes.

BACKGROUND: Analysis of any newly sequenced bacterial genome starts with the identification of protein-coding genes. Despite the accumulation of multiple complete genome sequences, which provide useful comparisons with close relatives among other organisms during the annotation process, accurate gene prediction remains quite difficult. A major reason for this situation is that genes are tightly packed in prokaryotes, resulting in frequent overlap. Thus, detection of translation initiation sites and/or selection of the correct coding regions remain difficult unless appropriate biological knowledge (about the structure of a gene) is imbedded in the approach. RESULTS: We have developed a new program that automatically identifies biologically significant candidate genes in a bacterial genome. Twenty-six complete prokaryotic genomes were analyzed using this tool, and the accuracy of gene finding was assessed by comparison with existing annotations. This analysis revealed that, despite the enormous effort of genome program annotators, a small but not negligible number of genes annotated within the framework of sequencing projects are likely to be partially inaccurate or plainly wrong. Moreover, the analysis of several putative new genes shows that, as expected, many short genes have escaped annotation. In most cases, these new genes revealed frameshifts that could be either artifacts or genuine frameshifts. Some entirely unexpected new genes have also been identified. This allowed us to get a more complete picture of prokaryotic genomes. The results of this procedure are progressively integrated into the SWISS-PROT reference databank. CONCLUSIONS: The results described in the present study show that our procedure is very satisfactory in terms of gene finding accuracy. Except in few cases, discrepancies between our results and annotations provided by individual authors can be accounted for by the nature of each annotation process or by specific characteristics of some genomes. This stresses that close cooperation between scientists, regular update and curation of the findings in databases are clearly required to reduce the level of errors in genome annotation (and hence in reducing the unfortunate spreading of errors through centralized data libraries).

Computational Biology↗
PubMed2003

New findings about endocrine therapy for breast cancer.

For over a decade, the selective estrogen receptor modulator, tamoxifen, has been the primary agent for adjuvant endocrine therapy for steroid receptor-positive breast cancer. New data over the last 2 years now suggest that its primacy may be challenged by strategies that lower circulating and/or intratumoral estrogens. Recent trials support the use of ovarian suppression approaches with or without tamoxifen in place of chemotherapy in premenopausal women. A large randomized trial has also established the short-term efficacy and safety of the aromatase inhibitor, anastrozole, in postmenopausal women. How and when to integrate these new approaches into standard practice are topics of debate. Ongoing research is focused on choice of endocrine approach, duration and sequencing of endocrine treatment, identification of better predictive markers for hormone response, and assessment of long-term risks and benefits.

Anastrozole↗
PubMed2003

Basilar artery duplication associated with pituitary duplication: a new finding.

Pituitary duplication is a rare malformation, reported previously in approximately 18 patients. It is usually unsuspected before imaging, although it occurs most commonly in association with complicated midline and skull base anomalies. It is easily shown by MR imaging. Five new cases of pituitary duplication were diagnosed by using MR imaging studies reviewed at the Hospital for Sick Children. Among the many associated midline abnormalities, partial basilar artery duplication is a previously undescribed finding that we observed in all our cases. Cases of basilar artery duplication or fenestration are associated with altered flow dynamics, leading to a higher incidence of aneurysms. Periodic surveillance for this potential complication may be warranted.

Basilar Artery↗
PubMed1998

Iron metabolism and human ferritin heavy chain cDNA from adult brain with an elongated untranslated region: new findings and insights.

Ferritin is a ubiquitous protein which plays a major role in iron sequestration, detoxification and storage. In this paper we highlight the role of ferritin in iron homeostasis and describe factors and diseases that affect its expression. We also describe new studies which further characterize the structure and expression of a novel form of ferritin heavy (H) chain mRNA that was identified in brain and discuss possible implications of these findings. Human fetal and adult brain cDNA libraries previously were screened with cDNA for well-characterized liver ferritin H. In addition to 'liver-like' brain ferritin H cDNA, novel ferritin H cDNAs with an additional 279 nucleotide sequence at the 3'untranslated region (UTR) were identified in both libraries (see refs. 1 and 2; Dhar, M., Chauthaiwale, V., and Joshi, J. G., Gene, 1993, 126, 275 and Dhar, M., and Joshi, J. G., J. Neurochem., 1993, 61, 2140). However, relative to liver ferritin H cDNA, these novel cDNAs were incomplete at their 5'ends [see ref. 3; Joshi, J. G., Fleming, J. T., Dhar, M. S., and Chauthaiwale, V., J. Neurol Sci., 1995, 134, (Suppl.), 52]. In the present paper, by sequencing of cDNAs using reverse transcriptase polymerase chain reaction, we show that the 279 nt 3'UTR sequence, a coding sequence identical to that in human liver ferritin H, and a full-length 5'UTR that includes one mRNA regulatory iron-response element sequence, co-exist in at least one species of ferritin H transcript in six normal human adult and six late-onset, sporadic Alzheimer disease (AD) brains. This sequence is the same in the normal and AD brains. Dot-blot analysis of poly A+ RNAs from different human tissues indicates that relative to the coding sequence of ferritin H, expression of the 279 nt 3'UTR sequence varies among different tissues, is highest in the adult brain, and is very low in fetal brain. In normal adult hippocampus, ferritin H RNA with the novel 279 nt sequence localizes strongly to small non-neuronal cells, capillary endothelial cells, and to selected populations of neurons (granule cells of the dentate gyrus). Significant homology was observed between a region in the 279 nt 3'UTR segment of ferritin H RNA and the 3'UTR of cyclooxygenase-2 mRNA (an inducible iron-containing enzyme involved in prostaglandin synthesis). Possible functions for ferritin H protein derived from the novel message and for the elongated 3'UTR and 5'UTR are discussed.

Adult↗
PubMed2005

HCV-hepatocellular carcinoma: new findings and hope for effective treatment.

We present here a comprehensive review of the current literature plus our own findings about in vivo and in vitro analysis of hepatitis C virus (HCV) infection, viral pathogenesis, mechanisms of interferon action, interferon resistance, and development of new therapeutics. Chronic HCV infection is a major risk factor for the development of human hepatocellular carcinoma. Standard therapy for chronic HCV infection is the combination of interferon alpha and ribavirin. A significant number of chronic HCV patients who cannot get rid of the virus infection by interferon therapy experience long-term inflammation of the liver and scarring of liver tissue. Patients who develop cirrhosis usually have increased risk of developing liver cancer. The molecular details of why some patients do not respond to standard interferon therapy are not known. Availability of HCV cell culture model has increased our understanding on the antiviral action of interferon alpha and mechanisms of interferon resistance. Interferons alpha, beta, and gamma each inhibit replication of HCV, and the antiviral action of interferon is targeted to the highly conserved 5'UTR used by the virus to translate protein by internal ribosome entry site mechanism. Studies from different laboratories including ours suggest that HCV replication in selected clones of cells can escape interferon action. Both viral and host factors appear to be involved in the mechanisms of interferon resistance against HCV. Since interferon therapy is not effective in all chronic hepatitis C patients, alternative therapeutic strategies are needed to treat chronic hepatitis C patients not responding to interferon therapy. We also reviewed the recent development of new alternative therapeutic strategies for chronic hepatitis C, which may be available in clinical use within the next decade. There is hope that these new agents along with interferon will prevent the occurrence of hepatocellular carcinoma due to chronic persistent hepatitis C virus infection. This review is not inclusive of all important scientific publications due to space limitation.

Antiviral Agents↗
PubMedDate not supplied

[New findings in the field of pediatric tuberculosis].

The Authors explain the news about pediatric tuberculosis; they underline the problems related to microepidemics, to immigration and AIDS increase, and to atypical mycobacteria infections. They also indicate the new diagnostic possibilities in Tb.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Right colonic diverticulitis: US and CT findings--new insights about frequency and natural history.

PURPOSE: To evaluate how the use of ultrasonography (US) and computed tomography (CT) has changed insights on the frequency and natural history of right colonic diverticulitis. MATERIALS AND METHODS: Clinical findings, US and CT images, and clinical and surgical records in 44 patients with a final diagnosis of right colonic diverticulitis seen over 11 years were retrospectively studied. RESULTS: Of the 44 patients, three underwent diverticulectomy, and 41 were successfully treated conservatively. Follow-up US demonstrated a consistent change in the pattern of the findings of diverticulitis over time, with eventual spontaneous evacuation of the contents of the inflamed diverticulum into the colonic lumen. Five patients had recurrent symptoms; two of them underwent elective surgery. The frequency of right colonic diverticulitis was one in 34 appendectomies, which is nine times higher than that reported to date. CONCLUSION: Right colonic diverticulitis is more common than has been previously reported. US and CT findings are characteristic and show a consistent pattern of changes over time. The natural history is benign, and surgical intervention can be avoided in the vast majority of patients.

Abdomen, Acute↗
PubMed1984

[New findings on the organization of retinal projections in the Scyliorhinus canicula shark. Radioautographic study].

The retinal projections of the shark Scyliorhinus canicula were re-examined using the radioautographic method following the intraocular injection of tritiated tracers. New primary visual centers were identified. Overall 12 distinct sites of termination of contralateral optic endings were found distributed within five levels of the brain (hypothalamus, thalamus, pretectum, tectum and mesencephalic tegmentum). Furthermore the presence of a small ipsilateral retinal projection was demonstrated attaining the hypothalamic thalamo:pretectal and tectal levels. These new data broaden our understanding of the organization of the primary visual system in Scyliorhinus as defined previously using the degeneration technique.

Animals↗
PubMed2005

[New findings on the influence of body weight on mortality].

The link between obesity/adipositas and excess mortality has been a prominent topic in medical literature for some time. The epidemic increase in obesity in the western world is going to confront the medical profession with a new problem, particularly with regard to life expectancy trends and appropriate prophylactic measures. Swiss Reinsurance Company (Swiss Re), which has a large portfolio of life reinsurance business, has conducted a follow-up study over an observation period of 25 years (1976 - 2001) to investigate the correlation between body weight and mortality. The findings indicate that the lifestyle-related risks of obesity and adipositas, especially in combination with other risk factors such as high blood pressure and smoking, contribute to a significantly elevated mortality risk.

Adiposity↗
PubMed2005

Invasive aspergillosis in the hematologic and immunologic patient: new findings and key questions in leukemia.

Patients suffering from acute leukemia are at high risk for invasive aspergillosis and a large review and a recent clinical trial have shown that they represent the largest group of patients developing the disease. New host groups such as patients with multiple myeloma or low-grade lymphoproliferative disorders have contributed to an increase in the incidence of invasive aspergillosis over recent years. There are substantial differences in the diagnostic strategy and therapeutic outcome of disease between patients with a hematological malignancy and other host groups such as allogeneic hematopoietic stem cell transplant patients. Galactomannan detection ELISA test is more specific in adult patients with hematological malignancies than in hematopoietic stem cell transplantation recipients. As a result of possible improvement of the underlying immune deficiency upon recovery from neutropenia, survival is higher in leukemic patients with invasive aspergillosis than in other host groups. However, there is currently no evidence of an effective antifungal prophylaxis strategy against aspergillosis in leukemic patients. As these patients account for a majority of the aspergillosis cases, clinical trials on prophylaxis should not only be focused on allogeneic stem transplant recipients but also be designed for the patient with leukemia.

Aspergillosis↗
PubMed1984

New findings on the proteins of sebaceous glands.

In order to understand the distribution and concentration of proteins with -SH groups or S-S linkages in sebaceous cells during differentiation and holocrine secretion of sebaceous glands, skin specimens from the inner side of ears of New Zealand white rabbits were examined histochemically and ultrastructurally. DACM (N-[7-dimethylamino-4-methyl-3-coumarinyl] maleimide) staining method showed that proteins containing -SH groups were present in the cells (cytoplasm and nuclei) in all layers from the peripheral to the terminally differentiated cells of sebaceous glands and that proteins containing S-S linkages were present in the terminally differentiated cells and their pyknotic nuclei but not in the peripheral and differentiating cells of sebaceous glands. Lipid droplets in all sebaceous cells contained neither -SH groups nor S-S linkages. Ultrastructurally, the terminally differentiated cells were very electron dense and seemed to be abruptly formed from the differentiating cells that were producing lipid droplets. These findings indicate that the conversion of -SH groups to S-S linkages of proteins also occurs in sebaceous glands as in epidermis and hair.

Animals↗
PubMed2004

Sex differences in developmental reading disability: new findings from 4 epidemiological studies.

CONTEXT: An influential article published in 1990 claimed that the increased rate of reading disability in boys was a consequence of referral bias. OBJECTIVES: To summarize the history of research on sex differences in reading disability and to provide new evidence from 4 independent epidemiological studies about the nature, extent, and significance of sex differences in reading disability. DESIGN, SETTING, AND PARTICIPANTS: The Dunedin Multidisciplinary Health and Development Study comprised 989 individuals (52.1% male) in a cohort born between April 1972 and March 1973 in Dunedin, New Zealand, and followed up from age 3 years; reading performance and IQ were assessed at ages 7, 9, and 11 years using the Burt Word Reading Test and the Wechsler Intelligence Scale for Children-Revised (WISC-R), respectively. The Christchurch Health and Development Study comprised 895 individuals (50% male) in a prospectively studied cohort born in the Christchurch, New Zealand, region during a 4-month period in 1977; reading performance and IQ were assessed at ages 8 to 10 years using the Burt Word Reading Test and the WISC-R. The Office for National Statistics (ONS) Study comprised a UK nationally representative sample of 5752 children (50.1% male) aged 9 to 15 years in 1999; reading was assessed on the British Ability Scales II and IQ on the British Picture Vocabulary Scales II. The Environmental Risk Longitudinal Twin Study (E-Risk) comprised 2163 twin children from England and Wales (49.1% male) identified at birth in 1994 and 1995 and included administration of the Test of Word Reading Efficiency at age 7 years and the Wechsler Preschool and Primary Scale of Intelligence-Revised as a test of IQ at age 5 years. MAIN OUTCOME MEASURE: Reading performance by sex in the lowest 15% of the distribution for all 4 studies, with and without taking IQ into account. RESULTS: In all 4 studies, the rates of reading disability were significantly higher in boys. For non-IQ-referenced reading disability: Dunedin study, 21.6% in boys vs 7.9% in girls (odds ratio [OR], 3.19; 95% confidence interval [CI], 2.15-4.17); Christchurch study, 20.6% in boys vs 9.8% in girls (OR, 2.38; 95% CI, 1.62-3.50); ONS study, 17.6% in boys vs 13.0% in girls (OR, 1.43; 95% CI, 1.23-1.65); and E-Risk, 18.0% in boys vs 13.0% in girls (OR, 1.39; 95% CI, 1.04-1.86). The rates for IQ-referenced reading disabilities were similar. CONCLUSION: Reading disabilities are clearly more frequent in boys than in girls.

Aptitude Tests↗
PubMed2004

Molecular basis of Diamond-Blackfan anemia: new findings from the Italian registry and a review of the literature.

BACKGROUND AND OBJECTIVES: Diamond-Blackfan anemia (DBA) is a rare, pure red blood cell aplasia of childhood caused by an intrinsic defect in erythropoietic progenitors. Malformations occur in about 40% of patients. More than half of patients respond to steroids; non-responders need chronic transfusions or stem cell transplantation (SCT). Mutations in the gene encoding ribosomal protein S19 are found in 25% of patients, but the link with erythropoiesis is unclear. A second DBA locus has been found on chromosome 8p22-p23; analysis of genes of the region is in progress. METHODS AND INFORMATION SOURCES: We present clinical and molecular data from 97 Italian DBA patients and a review of the literature. RESULTS AND STATE OF THE ART: We describe five new RPS19 gene mutations: four point mutations and one unbalanced chromosomal translocation. Hematologic findings, malformations and outcome are similar in the RPS19 mutated and the non-mutated groups. No genotype-phenotype correlation has been found so far in RPS19 mutated patients. Our data, however, and a thorough review of literature show a worse outcome (expressed as transfusion dependence) in patients with mutations that completely abolish one allele, i.e. gross chromosomal rearrangements and mutations at the initiation codon. The association of mental retardation with large deletions at the 19q locus points to a contiguous gene syndrome. A recurrent missense mutation (Arg62Trp) is associated with transfusion dependence in eight of the nine reported cases. PERSPECTIVES: Nationwide collaboration and population-based registries recording molecular data are essential for the further dissection of this rare heterogeneous disease and the definition of new therapeutic trials.

Anemia, Diamond-Blackfan↗