Biomedical subjects

H Lazar

Publications and source records attributed to H Lazar.

15 recordsLinked to original sources

PubMed2006

Inflexal V--the influenza vaccine with the lowest ovalbumin content.

The antigen used in influenza vaccines is directly derived from influenza viruses. It is produced in embryonated chicken eggs for both inactivated and live attenuated influenza vaccines. As a consequence, all influenza vaccines contain varying amounts of residual egg proteins, depending on the specific manufacturing process of the vaccine. The degree of purity of influenza vaccines can be assessed by quantifying the total amount of protein in relation to the amount of specific antigen. Alternatively, ovalbumin can be used as surrogate marker, representing the amount of egg-derived proteins present in the vaccine. Egg proteins, such as ovalbumin, are classified as sensitising agents. Their presence in a vaccine may be linked to adverse reactions. Such a vaccine is not suitable for subjects with a known history of egg-allergy. This population is currently excluded from influenza vaccination programs. Influenza vaccines are intended for annual re-immunisation. This repeated administration may lead to an immunity against ovalbumin and other egg proteins, which in turn may provoke increased local and systemic reactions and a reduced tolerability profile of the product. Comparing several influenza vaccines present on the market, ELISA and Western blot analysis showed clearly a very low level of ovalbumin in Inflexal V. Furthermore, data showed, that Inflexal V is the influenza vaccine with the lowest ovalbumin content.

Blotting, Western↗

PubMed2001

The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data.

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

Mouse mammary gland involution is associated with cytochrome c release and caspase activation.

At weaning, milk producing mammary epithelial cells undergo apoptosis and are removed by phagocytosis. Here, we show that mouse mammary gland involution is associated with mitochondrial cytochrome c release and processing of numerous caspases, including caspase-1, -3, -7, -8 and -9. Induction of caspase-3-like activity paralleled cleavage of poly-(ADP--ribose) polymerase. Dexamethasone inhibited processing of caspase-3, -7 and -8 and apoptosis, but had no effect on caspase-1 accumulation and cytochrome c release. In Bcl-2 transgenic animals, cytochrome c release, caspase activation and apoptosis were impaired. Thus, the pro-apoptotic signaling pathway in mammary epithelial cells during involution involves the release of cytochrome c and activation of caspases. It is inhibited by Bcl-2 at the mitochondrial level and by dexamethasone at a post-mitochondrial level.

Animals↗

PubMed2000

Over-expression of erbB-2/neu is paralleled by inhibition of mouse-mammary-epithelial-cell differentiation and developmental apoptosis.

The erbB-2/neu oncogene is frequently over-expressed in many different tumors in humans, including those of breast and ovary. The oncogene encodes a receptor tyrosine kinase closely related to the epidermal-growth-factor receptor. We studied effects on differentiation and cell death of erbB-2/neu during mammary-gland development in transgenic mice expressing an activated, oncogenic rat erbB-2/neu gene controlled by the mammary-gland-specific promoter from mouse-mammary-tumor virus (MMTV-LTR). Transgenic animals develop mammary cancer after repeated pregnancies and lactation. We present evidence that over-expression of erbB-2/neu in these mice is restricted to tumor cells. Tumor cells fail to differentiate and express milk proteins such as beta-casein and whey acidic protein (WAP) during lactation. Epithelial-cell apoptosis during normal involution is characterized by non-random DNA degradation into oligonucleosomal fragments. Tumor cells were mostly refractory to this developmentally controlled programmed cell death. Distinct areas within tumors, however, showed spontaneous cell death as measured by in situ TUNEL staining that co-localized with caspase-3-like activity. Our results indicate that the control of developmental cell death during involution is disturbed in erbB-2/neu-induced tumors although cell death and caspase activation can take place.

Animals↗

PubMed2000

Caspases: decoders of apoptotic signals during mammary involution. Caspase activation during involution.

At weaning most of the alveolar epithelial cells in the mammary gland die by apoptosis and are removed by phagocytosis. Caspases are a family of aspartate specific cysteine proteases. Activation of caspases is generally thought to represent a major and irreversible event in the apoptotic process. We analyzed caspase expression and activation during mammary gland involution. A quantitative RT-PCR based approach revealed that levels of mRNA expression of several caspases are induced during involution. Using an antibody that specifically recognizes activated caspases we measured a transient induction of caspase activity in situ and found a maximal activation at days two and three of involution. These data were corroborated by monitoring caspase-3 like activity in mammary extracts with a synthetic DEVD-afc peptide as caspase-3 substrate. Using Fas-deficient mice we present evidence that the Fas signaling pathway is not essential for caspase activation and apoptosis during mammary gland involution. In summary, signaling pathways during involution seem to involve activation of caspases as intraepithelial triggers of mammary epithelial cell apoptosis.

Animals↗

PubMed1999

Transcription factor activities and gene expression during mouse mammary gland involution.

Maintenance of mammary epithelial differentiation and milk production during lactation is a consequence of milk removal and the presence of lactogenic hormones, particularly glucocorticoids, insulin and prolactin. After weaning the fall in lactogenic hormones and milk stasis lead to involution, a process that is mainly characterized by three events: (i) downregulation of milk protein gene expression, (ii) loss of epithelial cells by apoptosis and, (iii) tissue remodeling and preparation of the gland for a new pregnancy. Each of these processes is likely to depend on the activity of specific sets of transcription factors in the mammary epithelium and stroma that ensure the timely and spatially coordinated expression of critical gene products such as mediators of apoptosis (e.g., caspase-1 and regulators of tissue remodeling events (e.g., matrix metalloproteinases). Here we describe signal transduction events such as activation of protein kinase A and JNK and changes in the activity of several transcription factors including Stat5, Stat3, NF1, Oct-1, and AP-1 during the early and late phases of mammary gland involution. We discuss their possible role in regulating and coordinating involution with emphasis on the apoptotic process of involution.

Animals↗

PubMed1992

Bacillus cereus endocarditis: report of a case and review.

Bacillus cereus is a ubiquitous organism that infrequently causes serious infections. We report a patient with B. cereus endocarditis involving a mechanical aortic valve. Data for 10 cases of B. cereus endocarditis reported in the literature are summarized. B. cereus is resistant to many commonly used antibiotics, a finding that has clinical significance for empirical antibiotic selection in patients with suspected endocarditis. Infection in patients with valvular heart disease in the few cases reported is associated with significant mortality and morbidity.

Adult↗

PubMed1986

Hematocrit as a risk factor for vascular disease.

Besides the classical risk factors for vascular diseases, markedly elevated or reduced hematocrit values may also affect the course of circulatory disturbances. To find out an appropriate hematocrit for sufficient oxygen perfusion of the tissues, several studies have been conducted. Most of the surveys indicate that a hematocrit between 35% and 40% is the best solution. To achieve this aim by iso- and hypervolumetric hemodilution, a clinical double-blind trial with three substances, dextran 40, middle-molecular hydroxyethyl starch and isotonic saline solution was carried out. With regard to clinical results and the possible side effects of dextran middle molecular hydroxyethyl starch seems to be the best choice for hemodilution.

Animals↗

PubMed1984

The hematocrit-electrolyte-concentration-apparatus (HECA).

An instrument was developed which can simultaneously determine the hematocrit and the total electrolyte concentration in blood and plasma respectively. It is possible to correct the hematocrit value for fluctuations of the total electrolyte concentration. Pilot studies of this device have been conducted on physiological and rigid erythrocyte suspensions and on plasma with various total electrolyte concentration. In the future, this device will be employed in analyzing blood and plasma of patients undergoing hemodialysis.

Electrolytes↗

PubMed1984

The hematocrit-erythrocyte-disaggregation-apparatus (HEDA).

We have developed a device for the determination of the minimum shear force necessary to maintain complete disaggregation of erythrocytes and to simultaneously determine the hematocrit of blood samples (red cells in autologous plasma). A functional relationship between this shear force and the hematocrit was determined. The first derivative of the (measured) gamma Tmin as a function of the hematocrit was found to be identical (within limits) for all normal blood samples tested.

Equipment Design↗

PubMed1979