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Biomedical subjects

B Gross

Publications and source records attributed to B Gross.

At least 19 recordsLinked to original sources

In vitro and in vivo comparison of two different light sources for topical photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is an effective and safe treatment option for the treatment of actinic keratosis (AK). Incoherent lamps are often used, matching the absorption maxima of ALA. OBJECTIVES: A comparative trial was performed to evaluate the efficacy of recently developed light-emitting diodes (LEDs). METHODS: Human epidermal keratinocytes were incubated for 24 h with ALA (100, 200, 300, 400 or 500 micromol L(-1)) and irradiated consecutively using either an incoherent halogen lamp (lambda(em) = 580-750 nm; 24 J cm(-2); 40 mW cm(-2)) or an LED system (lambda(em) = 633 +/- 3 nm; 3, 6, 12 or 24 J cm(-2); 40 mW cm(-2)). Topical ALA-PDT was performed on 40 patients with AK (n = 584) in a symmetrical distribution suitable for two-sided comparison. After incubation with ALA (20% in cream base) irradiation was performed with the incoherent lamp (100 J cm(-2); 160 mW cm(-2)) on one side and the LED system (40 J cm(-2); 80 mW cm(-2)) on the opposite side followed by re-evaluation up to 6 months. RESULTS: No significant differences between the LED system (3, 6, 12 or 24 J cm(-2)) and the incoherent light source (24 J cm(-2)) regarding cytotoxicity was found in vitro. The complete remission rate yielded in the in vivo investigation was also not significantly different at 6 weeks (P = 0.95), 3 months (P = 0.75) and 6 months (P = 0.61) following therapy. Six weeks following therapy complete remission rates of 84.3% (LED system) and 82.8% (incoherent lamp) were achieved. There was also no significant difference between both light sources regarding pain during light treatment (P = 0.67), patient satisfaction (P = 1.0) or cosmesis (P = 1.0) following therapy. CONCLUSIONS: These results show the efficacy of an LED system for ALA-PDT both in vitro and in vivo. ALA-PDT with the LED system showed a noninferiority regarding the clinical outcome in the treatment of AK compared with the incoherent lamp.

Adult↗

The presence of erythropoietin receptors in the human peripheral nervous system.

Erythropoietin (EPO) is a well-known hematopoietic factor and a major determinant of tissue oxygenation. EPO receptors have been identified on a wide variety of non-erythroid cell types including human central nervous system and peripheral nervous system of animal models. The presence or function of EPO receptors in human peripheral nervous system is unknown. By examining nerve segments from radicular and autonomic nerves using immunohistochemical methods, we demonstrated the presence of EPO receptors on myelin sheath of radicular nerves in the human peripheral nervous system.

Humans↗

["Gout tophi" and heart disease in the family].

A 35-year old man immigrated from Indonesia presented with "gout tophi" at his hands and lower extremities. Mother, aunt and uncle of this patient also suffered from "gout tophi" as well as a heart disease not exactly known to the patient. Clinical investigation was suspicious for tendon xanthomas and revealed arcus lipoides corneae of both eyes. Total cholesterol was 10.5 mmol/l and HDL cholesterol was 0.8 mmol/l. Genetic investigation showed heterozygous familial hypercholesterolemia, i.e., heterozygous mutation of the gene encoding the LDL receptor protein. The patient was treated with atorvastatin 20 mg daily and a low cholesterol diet. Total cholesterol decreased to 6.5 mmol/l and HDL cholesterol increased to 1.5 mmol/l within 2-month treatment. We recommended the determination of serum lipids in further members of this family and genetic evaluation of the patient's children with regard to the mutation identified.

Adult↗

[Management of primary intracerebral hemorrhage].

BACKGROUND: Primary intracranial hemorrhage (PICH) is responsible for about 10% of all strokes and is associated with a grave prognosis with high morbidity and mortality rates. OBJECTIVES: To familiarize the reader with new insights gained in the field of PICH over recent years. METHODS: The authors conducted a MEDLINE search on studies related to the diagnosis and therapy of PICH. The authors also formed an expert committee of the Israeli Neurological Society that discussed the epidemiology, prevention, diagnosis and therapy of PICH and present their conclusions herein. RESULTS AND DISCUSSION: PICH is a common and serious disorder with ominous prognosis. A large proportion of all PICH could theoretically be prevented if appropriate therapeutic interventions would be applied in advance. This holds especially true for lowering systolic and diastolic blood pressure. Conservative therapy continues to be the most appropriate therapy form to date although it only marginally improves patient outcome and survival. Surgical interventions have not proved to be superior to conservative therapy thus far, except for certain forms of PICH as detailed in the article. However, newer surgical techniques that are currently undergoing randomized studies could perceivably improve patients survival and outcome.

Cerebral Hemorrhage↗

Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis.

It is not known if a surgical lung biopsy is necessary in all patients for the diagnosis of idiopathic pulmonary fibrosis (IPF). We conducted a blinded, prospective study at eight referring centers. Initially, cases were evaluated by clinical history and examination, transbronchial biopsy, and high-resolution lung computed tomography scans. Pulmonologists at the referring centers then assessed their certainty of the diagnosis of IPF and provided an overall diagnosis, before surgical lung biopsy. The lung biopsies were reviewed by a pathology core and 54 of 91 patients received a pathologic diagnosis of IPF. The positive predictive value of a confident (certain) clinical diagnosis of IPF by the referring centers was 80%. The positive predictive value of a confident clinical diagnosis was higher, when the cases were reviewed by a core of pulmonologists (87%) or radiologists (96%). Lung biopsy was most important for diagnosis in those patients with an uncertain diagnosis and those thought unlikely to have IPF. These studies suggest that clinical and radiologic data that result in a confident diagnosis of IPF by an experienced pulmonologist or radiologist are sufficient to obviate the need for a lung biopsy. Lung biopsy is most helpful when clinical and radiologic data result in an uncertain diagnosis or when patients are thought not to have IPF.

Biopsy↗

Induction of the phospholipid transfer protein gene accounts for the high density lipoprotein enlargement in mice treated with fenofibrate.

Fibrate treatment in mice is known to modulate high density lipoprotein (HDL) metabolism by regulating apolipoprotein (apo)AI and apoAII gene expression. In addition to alterations in plasma HDL levels, fibrates induce the emergence of large, cholesteryl ester-rich HDL in treated transgenic mice expressing human apoAI (HuAITg). The mechanisms of these changes may not be restricted to the modulation of apolipoprotein gene expression, and the aim of the present study was to determine whether the expression of factors known to affect HDL metabolism (i.e. phospholipid transfer protein (PLTP), lecithin:cholesterol acyltransferase, and hepatic lipase) are modified in fenofibrate-treated mice. Significant rises in plasma PLTP activity were observed after 2 weeks of fenofibrate treatment in both wild-type and HuAITg mice. Simultaneously, hepatic PLTP mRNA levels increased in a dose-dependent fashion. In contrast to PLTP, lecithin:cholesterol acyltransferase mRNA levels in HuAITg mice were not significantly modified by fenofibrate despite a significant decrease in plasma cholesterol esterification activity. Fenofibrate did not induce any change in hepatic lipase activity. Fenofibrate significantly increased HDL size, an effect that was more pronounced in HuAITg mice than in wild-type mice. This effect in wild-type mice was completely abolished in PLTP-deficient mice. Finally, fenofibrate treatment did not influence PLTP activity or hepatic mRNA in peroxisome proliferator-activated receptor-alpha-deficient mice. It is concluded that 1) fenofibrate treatment increases plasma phospholipid transfer activity as the result of up-regulation of PLTP gene expression through a peroxisome proliferator-activated receptor-alpha-dependent mechanism, and 2) increased plasma PLTP levels account for the marked enlargement of HDL in fenofibrate-treated mice.

Animals↗

Syntheses of neoglycolipids with hexitol spacers between the saccharidic and the lipidic parts.

Four neoglycolipids having 2-amino-2-deoxy-D-glucose or D-galactose moieties linked to the lipidic part by a glucitol or a mannitol spacer-arm have been synthesized. The key step of the synthetic strategy was the regiospecific or regioselective beta-glycosylation of partially protected glucitol or mannitol acceptors by either 3,4,6-tri-O-acetyl-2-deoxy-2-iodo-alpha-D-mannopyranosyl azide or 2,3,4,6-tetra-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate donors.

Galactose↗

Impaired IgE response in SWAP-70-deficient mice.

Protein SWAP-70 was initially isolated from nuclei of activated B cells and was implicated in the immunoglobulin class switch process. After B cell activation the protein translocates from the cytoplasm to the nucleus, and may serve to signal nuclear processes. We have generated mice deficient in SWAP-70 and found three main differences when compared to wild-type mice: (i) their B lymphocytes are two- to threefold more sensitive to gamma-irradiation than B cells of wild type; (ii) SWAP-70-deficient mice developed autoantibodies at a much higher frequency; and (iii) the CD40 signaling pathway is compromised in the mutant mice. CD40-dependent switching to the IgE isotype is reduced five- to eightfold in vitro. In SWAP-70-deficient mice, IgE levels prior to immunization were six- to sevenfold lower than in wild-type mice, and after immunization three- to fourfold lower. CD40-induced proliferation was transiently increased in the mutant. LPS-induced switching to other isotypes, however, and LPS-induced proliferation were normal. We propose that SWAP-70 serves a specific role in the CD40 signaling pathway, in particular in the IgE response.

Animals↗

Novel meiosis-specific isoform of mammalian SMC1.

Structural maintenance of chromosomes (SMC) proteins fulfill pivotal roles in chromosome dynamics. In yeast, the SMC1-SMC3 heterodimer is required for meiotic sister chromatid cohesion and DNA recombination. Little is known, however, about mammalian SMC proteins in meiotic cells. We have identified a novel SMC protein (SMC1beta), which-except for a unique, basic, DNA binding C-terminal motif-is highly homologous to SMC1 (which may now be called SMC1alpha) and is not present in the yeast genome. SMC1beta is specifically expressed in testes and coimmunoprecipitates with SMC3 from testis nuclear extracts, but not from a variety of somatic cells. This establishes for mammalian cells the concept of cell-type- and tissue-specific SMC protein isoforms. Analysis of testis sections and chromosome spreads of various stages of meiosis revealed localization of SMC1beta along the axial elements of synaptonemal complexes in prophase I. Most SMC1beta dissociates from the chromosome arms in late-pachytene-diplotene cells. However, SMC1beta, but not SMC1alpha, remains chromatin associated at the centromeres up to metaphase II. Thus, SMC1beta and not SMC1alpha is likely involved in maintaining cohesion between sister centromeres until anaphase II.

Amino Acid Motifs↗

E. Coli MurG: a paradigm for a superfamily of glycosyltransferases.

MurG is an essential bacterial glycosyltransferase that is involved in the biosynthesis of peptidoglycan. The enzyme is found in all organisms that synthesize peptidoglycan and is a target for the design of new antibiotics. A direct assay to study MurG was reported recently, followed shortly by the crystal structure of E. coli MurG. This first MurG structure, combined with sequence data on other glycosyltransferases, has revealed that MurG is a paradigm for a large family of metal ion-independent glycosyltransferases found in both eukaryotes and prokaryotes. A better understanding of MurG could lead to the development of new drugs to combat antibiotic resistant infections, and may also shed light on a broad class of glycosyltransferases.

Amino Acid Sequence↗

[Choice of infusion site--differences in the references of staff (nurses and residents) and patients].

Insertion of an intravenous (i.v.) line is a common and routine procedure in hospitalized patients. The literature recommends not to insert an i.v. line in a limb fold, but other than that there are no guidelines regarding optimal locations for the i.v. line. In this study we attempted to elucidate whether there are other possible preferences and guidelines for choosing the location of an i.v. line. We studied four groups: patients at the time of hospitalization, hospitalized patients, nurses and surgical interns on a surgical ward. We found that 91.8% of the patients request to take part in choosing the location of their i.v. line. Moreover, we found that most patients have a hand preference for the i.v., whereas, the ward staff has little location preference. Despite these findings, we discovered that, in practice, most patients were not asked to participate in the decision making process regarding their i.v. line location. Analysis of the results showed that there is a need to include the patient's preference in choosing the location for the i.v. line, whenever possible. If the patient doesn't have a preference, the i.v. line should be inserted in the non-dominant hand or the hand in the bed which is more accessible to the medical & nursing staff.

Adult↗

Effect of sequential transdermal progesterone cream on endometrium, bleeding pattern, and plasma progesterone and salivary progesterone levels in postmenopausal women.

BACKGROUND: Transdermal progesterone is being used in some countries as a purported treatment for menopausal symptoms, either alone or prescribed in conjunction with estrogen, but little information exists regarding the biological activity and effectiveness of this method of delivery of progesterone in protecting the endometrium from excess proliferation. This study was designed to evaluate the use of sequential transdermal progesterone. End-points evaluated included endometrial cellular response and bleeding pattern as well as plasma hormone levels and salivary progesterone estimations. METHOD: Twenty-seven postmenopausal women were treated with continuous transdermal estrogen (28-day cycle) and a cream containing 16, 32 or 64 mg of progesterone in each 4-cm extrusion from a tube of Pro-Feme administered daily in a sequential (days 15-28 of cycle) regimen. Blood and endometrial samples were analyzed for progesterone response prior to therapy, after the first 14 days of unopposed transdermal estrogen and following 14 days of transdermal progesterone. Saliva samples were taken during the last 14 days of the 84-day study, when the final progesterone cream therapy was being applied. RESULTS: Hormone assay indicated that physiological levels of estradiol were achieved, but progesterone levels were insufficient to induce any detectable change in the endometrium. Only one patient experienced bleeding during the study period. Levels of salivary progesterone were so variable as to be considered completely unreliable in determining the potential influence on biological activity. INTERPRETATION: Pro-Feme transdermal progesterone administered in a 16-, 32- or 64-mg daily dose for 14 days in a sequential regimen does not appear to be effective in inducing a secretory change in a proliferative endometrium. Salivary progesterone levels were not of value in managing the therapy of postmenopausal women.

Administration, Cutaneous↗

Thymic size and lymphocyte restoration in patients with human immunodeficiency virus infection after 48 weeks of zidovudine, lamivudine, and ritonavir therapy.

Human immunodeficiency virus (HIV) infection is associated with progressive loss of circulating CD4+ lymphocytes. Treatment with highly active antiretroviral therapy (HAART) has led to increases in CD4+ T lymphocytes of naive (CD45RA+62L+) and memory (CD45R0+RA-) phenotypes. Thymic computerized tomography scans were obtained on 30 individuals with HIV disease to investigate the role of the thymus in cellular restoration after 48 weeks of HAART. Individuals with abundant thymic tissue had higher naive CD4+ T lymphocyte counts at weeks 2-24 after therapy than individuals with minimal thymic tissue. Individuals with abundant thymic tissue had significantly larger increases in naive CD4+ cells during the first 4 weeks of therapy. These individuals were also more likely to experience viral rebound despite comparable initial declines in plasma HIV-1 RNA. These findings suggest that there is a complex relationship among the thymus, viral replication, and lymphocyte restoration after application of HAART in HIV disease.

Adult↗

Association of mammalian SMC1 and SMC3 proteins with meiotic chromosomes and synaptonemal complexes.

In somatic cells, the heterodimeric Structural Maintenance of Chromosomes (SMC) proteins are involved in chromosome condensation and gene dosage compensation (SMC2 and 4), and sister chromatid cohesion and DNA recombination (SMC1 and 3). We report here evidence for an involvement of mammalian SMC1 and SMC3 proteins in meiosis. Immunofluorescence analysis of testis sections showed intense chromatin association in meiotic prophase cells, weaker staining in round spermatids and absence of the SMC proteins in elongated spermatids. In spermatocyte nuclei spreads, the SMC1 and SMC3 proteins localize in a beaded structure along the axial elements of synaptonemal complexes of pachytene and diplotene chromosomes. Both SMC proteins are present in rat spermatocytes and enriched in preparations of synaptonemal complexes. Several independent experimental approaches revealed interactions of the SMC proteins with synaptonemal complex-specific proteins SCP2 and SCP3. These results suggest a model for the arrangement of SMC proteins in mammalian meiotic chromatin.

Amino Acid Sequence↗

The implications of aging in place for community-based services for elderly people.

A study of 12 day care centers and luncheon clubs in London, England, found that, in response to changing client characteristics, many of the "clubs" were becoming formalized "centers." These agencies were expanding the number of days and hours of service, providing transportation, hiring professional staff, and renovating their premises to accommodate disabled individuals. The managers ascribed these changes to "aging in place" by the membership of the centers, and to new referrals of increasingly disabled people (who might once have been considered for institutionalization but who were now remaining in the community). These findings raise issues for providers of community-based services, and for case managers who are often the gatekeepers to these services.

Aged↗

Mammalian SMC3 C-terminal and coiled-coil protein domains specifically bind palindromic DNA, do not block DNA ends, and prevent DNA bending.

The C-terminal domains of yeast structural maintenance of chromosomes (SMC) proteins were previously shown to bind double-stranded DNA, which generated the idea of the antiparallel SMC heterodimer, such as the SMC1/3 dimer, bridging two DNA molecules. Analysis of bovine SMC1 and SMC3 protein domains now reveals that not only the C-terminal domains, but also the coiled-coil region, binds DNA, while the N terminus is inactive. Duplex DNA and DNA molecules with secondary structures are highly preferred substrates for both the C-terminal and coiled-coil domains. Contrasting other cruciform DNA-binding proteins like HMG1, the SMC3 C-terminal and coiled-coil domains do not bend DNA, but rather prevent bending in ring closure assays. Phosphatase, exonuclease, and ligase assays showed that neither domain renders DNA ends inaccessible for other enzymes. These observations allow modifications of models for SMC-DNA interactions.

Animals↗

A collagen-related peptide regulates phospholipase Cgamma2 via phosphatidylinositol 3-kinase in human platelets.

The collagen receptor glycoprotein VI (GPVI) induces platelet activation through a similar pathway to that used by immune receptors. In the present study we have investigated the role of phosphatidylinositol 3-kinase (PI 3-kinase) in GPVI signalling. Our results show that collagen-related peptide {CRP: [GCP*(GPP*)(10)GCP*G](n); P*=hydroxyproline}, which is selective to GPVI, induces formation of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] and phosphatidylinositol 3,4-bisphosphate [PI(3, 4)P(2)] in platelets. The increase in the two 3-phosphorylated lipids is inhibited completely by wortmannin and by LY294002, two structurally unrelated inhibitors of PI 3-kinase. The formation of inositol phosphates and phosphatidic acid (PA), two markers of phospholipase C (PLC) activation, by CRP are inhibited by between 50 and 85% in the presence of wortmannin and LY294002. This is associated with inhibition of elevation of intracellular Ca(2+) ([Ca(2+)](i)) and aggregation. Wortmannin and LY294002 also partially inhibit elevation of Ca(2+) by CRP in murine megakaryocytes. Microinjection of the pleckstrin-homology PH domain of Bruton's tyrosine kinase, which binds selectively to PI(3,4, 5)P(3), but not the R28C (Arg(28)-->Cys) mutant which binds to PI(3, 4,5)P(3) with low affinity, also inhibits elevation of [Ca(2+)](i) in megakaryocytes, suggesting that it is this lipid species which mediates the action of the PI 3-kinase pathway. Studies in platelets show that the action of wortmannin and LY294002 is not mediated through an alteration in tyrosine phosphorylation of PLCgamma2. These results demonstrate that PI 3-kinase is required for full activation of PLCgamma2 by GPVI in platelets and megakaryocytes.

Agammaglobulinaemia Tyrosine Kinase↗

Oxidative damage in rat tissue following excessive L-tryptophan and atherogenic diets.

Numerous reports were published on the connection between diets containing excessive L-tryptophan and the development of Eosinophilia Myalgia Syndrome. It has been also demonstrated that some cell functions depend on fatty acid composition which can result in increased lipid peroxidation in cells such as macrophages and other inflammatory cells. The purpose of the present study was to investigate the combined effects of an atherogenic diet enriched with tryptophan on lipid peroxidation in rats. 3-week-old CD-1 female rats were fed (3 weeks) control or atherogenic diets and the same diets supplemented with 0.4% or 1.0% L-tryptophan. Liver and skeletal muscle samples from all groups were taken for histology, autoradiography and for determination of lipid peroxidation. Infiltration of cells into fascia of muscle was observed following tryptophan or atherogenic diet consumption. However, no change in 3H-thymidine incorporation into DNA was observed by autoradiography. A significant increase of lipid peroxidation was detected in muscle following consumption of L-tryptophan-rich diets, with no significant difference from control in animals treated with atherogenic diets. Contrastly, a reduced lipid peroxidation was detected in liver of animals treated with excessive tryptophan as well as in animals fed on L-tryptophan and atherogenic diet or atherogenic diet alone. Our results indicated that excessive dietary tryptophan, when consumed with an atherogenic diet, increased lipid peroxidation in muscle but not in liver. Consumption of these feeding diets with or without supplementation of tryptophan resulted in reduced lipid peroxidation in muscle as well as in liver.

Animals↗