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Biomedical subjects

J Fischer

Publications and source records attributed to J Fischer.

At least 91 records · Page 5Linked to original sources
PubMed2001

Diagnosis and monitoring of murine histoplasmosis by a nested PCR assay.

A newly developed nested PCR assay was applied to murine models of histoplasmosis. ICR and BALB/c mice were intravenously infected with Histoplasma capsulatum and sacrificed up to 29 days later. Samples of blood, spleen, and lung homogenates were cultured and examined by the PCR assay. In the ICR mouse model, 265 of 319 organ samples showed concordant results. With 7 samples, the culture was positive and the PCR assay was negative whereas a positive PCR but a negative culture were obtained with 47 samples (P < 0.0001 according to McNemar's test). Organ homogenates and blood samples of either spontaneously cured or treated BALB/c mice were PCR negative. The nested PCR assay performs excellently in the monitoring of spontaneously and treatment-cured murine histoplasmosis. It limits the infection risks of the laboratory staff and might be of diagnostic value for humans.

Animals↗
PubMed2001

The suitability of hepatocyte culture models to study various aspects of drug metabolism.

Since the liver is the main organ involved in the metabolism and the toxicity of xenobiotics, isolated rat hepatocytes have been increasingly used in recent years as a model to identify pharmacological and toxicological responses of drugs. However, it is generally recognised that isolated hepatocytes retain most of their functions only for a short period. For this reason, numerous models and techniques have been developed to study and improve the metabolic capacity of hepatocytes in vitro over an extended time period and in application for drug metabolism studies. In the present study, we compared four different cell culture models to fulfill these requirements and have therefore harvested hepatocytes and cultured them in different culture systems over two weeks. In order to prove certain advantages or disadvantages of each model, we compared the metabolic capacity, albumin secretion, the release of cytosolic and mitochondrial enzymes, as well as the capacity to metabolise diclofenac (DF). We found that rat hepatocytes in all studied culture models (except the Unisyn Bioreactor) were able to metabolise DF to the same extent as found in vivo. However, the concentration of metabolites was found to decrease with culture time using the monolayer although the DF metabolite level in the collagen Sandwich culture was higher than that of the monolayer culture. The 3D-membrane bioreactor preserved the metabolic capacity for a prolonged period of time. The concentrations of DF metabolites in the Unisyn hollow fiber bioreactor were below the detection limit, which corresponded to other parameters such as albumin secretion and cytochrome P450 activity, disqualifying this culture system clearly for the use of in vitro primary hepatocyte cultures. The other three systems all have their place in drug metabolism with different advantages. However, our studies clearly showed that hepatocytes cultured within a collagen sandwich or in the 3D-membrane bioreactor qualify to study various aspects of drug metabolisms over a long time period. Further studies are needed to prove if the later two culture models may really help to reduce animal testing.

Alanine Transaminase↗
PubMed2001

Timing of analog research in medicinal chemistry.

Analog research plays an important role in medicinal chemistry. Having identified a new target in molecular biology many similar lead compounds are synthesized resulting in closely related products on the market. Another approach is the further optimising of an existing drug in order to improve on the original. In some cases these two approaches overlap. The question of timing and the importance of analog research are analyzed in this paper.

Animals↗
PubMed2001

Allogeneic bone marrow transplantation at Wilford Hall U.S. Air Force Medical Center: 1987-1999.

Wilford Hall Medical Center (WHMC), at Lackland Air Force Base in San Antonio, Texas, is the only center within the U.S. Department of Defense at which allogeneic bone marrow transplantation (BMT) is performed. From the inception of the BMT program in 1987 through February 1999, 286 military health care beneficiaries have undergone human leukocyte antigen-matched related donor allogeneic bone marrow transplantation for hematologic disorders. We conducted a retrospective chart review to analyze the outcomes of all allogeneic BMT procedures performed at WHMC through February 1999. Our analysis revealed that allogeneic BMT outcomes compared favorably with those reported by the International Bone Marrow Transplant Registry. The results of this study support the continued designation of the Fisher Bone Marrow Transplant Center at WHMC as a specialty treatment service within the Department of Defense.

Adult↗
PubMed2001

[Tamoxifen or tamoxifen in combination with chemotherapy in adjuvant therapy of breast carcinoma. Results of a multicenter randomized study].

UNLABELLED: Between April 1994 and May 1997 103 breast cancer patients (pts), pT1c-3a, pN0-1, M0, were randomised after surgery to adjuvant tamoxifen (20 mg per day) or to tamoxifen plus CMF (C 500 mg/m2, M 40 mg/m2 and F 600 mg/m2 on days 1st and 8th q 28 day) in 6 cycles. The median age (49-72 years, median 58), tumour size, number of involved lymphnodes (0-3), estrogens receptor status, grade (I-III) and type of operation were well balanced among the 50 pts on tamoxifen and the 53 pts on tamoxifen plus CMF pts, preferably postmenopausal. RESULTS: Grade of toxicity according to WHO criteria was not higher then two in both arms. Toxicity both haematological and non-haematological was higher in the group treated with chemotherapy (0 vs 32 resp. 20%) except weight gain (52% in both group). After median follow-up of 42 mos five recurrences in tamoxifen and seven in tamoxifen plus CMF pts were observed (p = NS). The projected 3-y DFS is 92% for tamoxifen and 88% for tamoxifen plus CMF (p = NS). The 3-y OS is 88% for tamoxifen and 80% for tamoxifen plus CMF pts (p = NS). CONCLUSIONS: Both regimens are equally effective with higher toxicity in the group with combined chemo- and hormonal therapy.

Aged↗
PubMed2000

Mechanical, thermal, and chemical analyses of the binary system Au-Ti in the development of a dental alloy.

Investigations in the binary system gold-titanium (Au-Ti) were performed in regard to the development of a universal dental alloy suited for inlays, for the conventional crown and bridge technique, as well as for the ceramic-fused-to-metal technique. With nine alloys with increasing Ti content from 0-10 atom %, microstructure, mechanical properties, thermal properties, and corrosion were determined in the as-cast state and after simulation of ceramic firing. The microstructure shows an increasing formation of a second phase with increasing Ti content, crystallizing dendritically, which, according to the binary phase diagram must be the intermetallic phase TiAu(4). The results of the measurements reveal that with increasing Ti content, hardness, Young's modulus, proof stress, and tensile strength strongly increase in the range of 2-6 atom % Ti and with higher Ti content remain constant. Elongation after fracture decreases with a Ti content above 2 atom %. The coefficient of thermal expansion decreases linearly with increasing Ti content. Thermal distortion decreases exponentially with increasing Ti content. The corrosion test showed an increasing release of Ti with increasing Ti content. Lowest corrosion was observed in the simulated state with intact oxide layer. Appropriate properties for dental application were found in the range of 6.5 at% Ti.

Ceramics↗
PubMed2000

Development of infant baboons' responses to graded bark variants.

We studied the development of infant baboons' (Papio cynocephalus ursinus) responses to conspecific 'barks' in a free-ranging population in the Okavango Delta, Botswana. These barks grade from tonal, harmonically rich calls into calls with a more noisy, harsh structure. Typically, tonal variants are given when the signaller is at risk of losing contact with the group or a particular individual ('contact barks'), whereas harsh variants are given in response to predators ('alarm barks'). We conducted focal observations and playback experiments in which we presented variants of barks recorded from resident adult females. By six months of age, infants reliably discriminated between typical alarm and contact barks and they responded more strongly to intermediate alarm calls than to typical contact barks. Infants of six months and older also recognized their mothers by voice. The ability to discriminate between different call variants developed with increasing age. At two and a half months of age, infants failed to respond at all, whereas at four months they responded irrespective of the call type that was presented. At six months, infants showed adult-like responses by responding strongly to alarm barks but ignoring contact barks. We concluded that infants gradually learn to attach the appropriate meaning to alarm and contact barks.

Animal Communication↗
PubMed2000

A brotherly donation.

Explore the source record for details and available documents.

Bone Marrow Transplantation↗
PubMed2000

Study of the adsorption behavior of the enantiomers of 1-phenyl-1-propanol on a cellulose-based chiral stationary phase.

Using single-step frontal analysis, we measured single-component and competitive adsorption isotherm data for the two enantiomers of 1-phenyl-1-propanol (PP). These experimental data were fitted to several competitive bi-Langmuir models (with 8, 6, 5 and 4 parameters) and to the competitive Langmuir model. The latter model accounted well for the behavior of both PP enantiomers on Chiracel OB (cellulose tribenzoate coated on silica gel). The parameters obtained were used in numerical calculations to predict the band profiles of the two single components and of their mixtures under overloaded conditions. The equilibrium-dispersive model provides satisfactory results, with minor differences between the calculated and the experimental profiles. These differences became negligible when a more complex kinetic model was used, with a concentration-dependent rate coefficient.

Adsorption↗
PubMed2000

Chiral "metallo-spiralenes": helical molecules conformationally stabilised by an organometallic scaffold

The synthesis of a series of chiral cyclomanganated 2-[(eta 6-phenyl)-Cr(CO)3]pyridine complexes derived from (-)-beta-pinene enables, by a "spirogenic transformation", the preparation of four different chiral helical heterobimetallic syn-facial complexes or Cr0/Mn1-spiralenes, among which two possess a right-handed P molecular helicity and two other a left-handed M one. These organometallic helical molecules are synthesised by applying two different methods to the chiral cyclomanganated (eta 6-arene)tricarbonylchromium substrates. The first method is the so-called "Fischer route" which involves a sequential addition of PhLi and MeOTf. The second method based on reaction of the cyclomanganated complex with diphenyldiazomethane which has been tested on achiral bimetallic substrates is a reasonable neutral alternative to the "Fischer methodology" for the synthesis of Cr0/Mn1-spiralenes. The crystal structure of one of these heterobimetallic chiral helical compounds serves as a starting point in the configurational and structural assessment of the synthesised chiral (eta 6-arene)tricarbonylchromium complexes. Application of the "Fischer route" to a cyclomanganated chiral 2-phenylpyridine generates a single chiral eta 3-benzylic complex--or Mn1-spiralene--bearing a left-handed M helicity which has been characterized by X-ray diffraction analysis. Circular dichroic spectroscopic measurements underline the predominant contribution of the chiral and chirally induced aromatic chromophores to the sign of the Cotton effects and confirm the helical configurations of the considered heterobimetallic species.

Journal Article↗