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Biomedical subjects

R Weiss

Publications and source records attributed to R Weiss.

At least 73 records · Page 4Linked to original sources
PubMed2001

Slip sliding away: a journey from professional to consumer.

Although I am primarily known in my local mental health community for my professional advocacy and consumer satisfaction work, my consumer status has never been a secret. This article briefly details what has happened as I see and feel the effectiveness of my medications decrease along with my professional credibility and self-respect. Despite my diligence to my mental health and recovery practices, I, nonetheless, feel I am decompensating. The article explores some thoughts and lessons I am learning, along with my fellow consumers/professionals, as I find myself straddling the fence between these two groups of my colleagues.

Anecdotes as Topic↗
PubMed2001

Diabetic embryopathy in C57BL/6J mice. Altered fetal sex ratio and impact of the splotch allele.

Maternal diabetes (types 1 and 2) induces a broad array of congenital malformations, including neural tube defects (NTDs), in humans. One of the difficulties associated with studying diabetic embryopathy is the rarity of individual malformations. In an attempt to develop a sensitive animal model for maternal diabetes-induced NTDs, the present study uses chemically induced diabetes in an inbred mouse model with or without the splotch (Sp) mutation, a putatively nonfunctional allele of Pax3. Pax3 deficiency has been associated with an increase in NTDs. Female C57BL/6J mice, either with or without the Sp allele, were injected intravenously with alloxan (100 mg/kg), and plasma glucose was measured 3 days later. A wide range of hyperglycemia was induced, and these diabetic mice were bred to C57BL/6J males, some carrying the Sp allele. Gestational-day-18 fetuses were examined for developmental malformations. Fetuses from matings in which either parent carried the Sp allele were genotyped by polymerase chain reaction. Maternal diabetes significantly decreased fetal weight and increased the number of resorptions and malformations, including NTDs. A significant correlation was found between the level of maternal hyperglycemia and the malformation rate. The sex ratio for live fetuses in diabetic litters was significantly skewed toward male fetuses. Matings involving the Sp allele yielded litters with significantly higher percentages of maternal diabetes-induced spina bifida aperta but not exencephaly, and this increase was shown to be associated with the presence of a single copy of the Sp allele in affected fetuses. Thus, Pax3 haploinsufficiency in this murine model of diabetic embryopathy is associated with caudal but not cranial NTDs.

Alleles↗
PubMed2001

Adenocarcinoma of the stomach in an adolescent presenting as pneumoperitoneum: a brief report.

BACKGROUND: Adenocarcinoma of the stomach is rare in children and adolescents. A unique case, presenting as an acute abdomen with pneumoperitoneum, is discussed. METHODS: Case presentation and literature review. RESULTS: A 13-year-old girl with perforated gastric adenocarcinoma treated by wedge resection developed metastatic disease within two months and died within six months despite chemotherapy. CONCLUSION: Frozen section of all perforated gastric ulcers, with resection/postoperative chemotherapy for adenocarcinoma. SUMMARY: A 13-year-old girl with gastric adenocarcinoma presented with pneumoperitoneum. Within two months of wedge resection widespread metastatic disease was documented by computerized tomography scan and laparoscopy and despite chemotherapy, the patient died within six months. Frozen section of all perforated gastric ulcers, even in children, and definitive formal gastrectomy with postoperative chemotherapy, offer the only chance of cure.

Adenocarcinoma↗
PubMed2001

[Prevalence of the Salmonella plasmid virulence gene "spvD" in Salmonella strains from animals].

Strains of Salmonella isolated from animals in Germany (n = 878) were analysed for the presence of the spvD gene ("Salmonella plasmid virulence gene D") by DNA-DNA hybridization. The spvD gene was only detected in strains of serovars Typhimurium (93.3%), Enteritidis (97.1%), and Dublin (100%) as well as in two rough strains of Salmonella enterica. Salmonella isolates from mammals carried the gene more frequently (cattle 94.0%, horses 92.6%, pigs 73.7%) than those from birds (33.3%) or reptiles (4.5%). Due to its high prevalence in epidemiologically relevant salmonellae, the virulence factor spvD may represent a sensitive and specific target in various serovars for diagnostic or immunization strategies.

Animals↗
PubMed2001

Reduction of 1-methyl-1-nitrosourea-induced mammary gland carcinoma by in vivo application of immunostimulatory CpG motifs in Sprague-Dawley rats.

In the present work the role of 13-cis retinoic acid and CpG oligodeoxynucleotides (CpG-ODN) in a 1-methyl-1-nitrosourea (MNU)-induced mammary gland carcinoma animal model was investigated. Treatment with both components, applied either alone or in combination, induced a significant decrease of the tumour burden and the volume of tumours only in rats that received CpG-ODN (p = 0.046, compared to the MNU control group). The data indicate that the Th-1 biased immunostimulatory capacities of CpG motifs may play a significant role in induction of protective immune responses against mammary gland tumours in Sprague-Dawley rats.

Alkylating Agents↗
PubMed2000

Intermediates in the reaction of substrate-free cytochrome P450cam with peroxy acetic acid.

Freeze-quenched intermediates of substrate-free cytochrome 57Fe-P450(cam) in reaction with peroxy acetic acid as oxidizing agent have been characterized by EPR and Mossbauer spectroscopy. After 8 ms of reaction time the reaction mixture consists of approximately 90% of ferric low-spin iron with g-factors and hyperfine parameters of the starting material; the remaining approximately 10% are identified as a free radical (S' = 1/2) by its EPR and as an iron(IV) (S= 1) species by its Mossbauer signature. After 5 min of reaction time the intermediates have disappeared and the Mossbauer and EPR-spectra exhibit 100% of the starting material. We note that the spin-Hamiltonian analysis of the spectra of the 8 ms reactant clearly reveals that the two paramagnetic species, e.g. the ferryl (iron(IV)) species and the radical, are not exchanged coupled. This led to the conclusion that under the conditions used, peroxy acetic acid oxidized a tyrosine residue (probably Tyr-96) into a tyrosine radical (Tyr*-96), and the iron(III) center of substrate-free P450(cam) to iron(IV).

Camphor 5-Monooxygenase↗
PubMed2000

DNA immunization in vivo down-regulates nuclear all-trans retinoic acid receptors in mouse spleen cells.

Nuclear retinoid receptors - retinoic acid inducible transcription factors - participate in pathways influencing many components of the immune system. In the present study in vivo effects of DNA-based immunization of mice on binding parameters of all-trans retinoic acid receptors (RARs) in spleen cell nuclei was investigated. A eucaryotic expression vector encoding the gene for the model enzyme beta-galactosidase of Escherichia coli (pCMV-beta) was used for intradermal injection. Furthermore, immunostimulatory CpG motifs, which stimulate the expression of various cytokines and may serve as a 'danger signal' for the mammalian immune system, were coinjected as oligodeoxynucleotides. The results demonstrate that the concentration of RARs was significantly reduced in the late phase of the primary immune response (21 days after injection of plasmid DNA-indicated by high affinity IgG antibodies and IFN-gamma expression). Coinjection of CpG motifs did not change the course of the humoral response but enhanced and accelerated the proliferative response and expression of IFN-gamma, which correlated with the reduced RARs concentration.

Animals↗
PubMed2000

Increased baseline occupancy of D2 receptors by dopamine in schizophrenia.

The classical dopamine hypothesis of schizophrenia postulates a hyperactivity of dopaminergic transmission at the D(2) receptor. We measured in vivo occupancy of striatal D(2) receptors by dopamine in 18 untreated patients with schizophrenia and 18 matched controls, by comparing D(2) receptor availability before and during pharmacologically induced acute dopamine depletion. Acute depletion of intrasynaptic dopamine resulted in a larger increase in D(2) receptor availability in patients with schizophrenia (19% +/- 11%) compared with control subjects (9% +/- 7%, P = 0.003). The increased occupancy of D(2) receptors by dopamine occurred both in first-episode neuroleptic-naive patients and in previously treated chronic patients experiencing an episode of illness exacerbation. In addition, elevated synaptic dopamine was predictive of good treatment response of positive symptoms to antipsychotic drugs. This finding provides direct evidence of increased stimulation of D(2) receptors by dopamine in schizophrenia, consistent with increased phasic activity of dopaminergic neurons.

Adult↗
PubMed2000

Generation of oxoiron (IV) tetramesitylporphyrin pi-cation radical complexes by m-CPBA oxidation of ferric tetramesitylporphyrin derivatives in butyronitrile at - 78 degrees C. Evidence for the formation of six-coordinate oxoiron (IV) tetramesitylporphyrin pi-cation radical complexes FeIV = O(tmp*)X (X = Cl-, Br-), by Mössbauer and X-ray absorption spectroscopy.

The generation of six-coordinate oxoiron (IV) tetramesitylporphyrin pi-caption radical complexes by m-CPBA (meta-chloroperbenzoic acid) oxidation of ferric tetramesitylporphyrin derivatives in butyronitrile at - 78 degrees C was investigated. UV-Vis and EPR spectroscopies indicate that the axial ligand present in the ferric starting derivatives is retained in the high-valent iron complexes. Indirect evidence for the formation of six-coordinate oxoiron (IV) tetramesitylporphyrin complexes FeIV = O(tmp*)X (X=Cl-, Br-) by m-CPBA oxidation of FeX(tmp) (X=Cl-, Br-) in butyronitrile at - 78 degrees C was also obtained by Mössbauer spectroscopy. Direct confirmation of the presence of a halide ion as second axial ligand of iron in these high-valent iron species was obtained by X-ray absorption spectroscopy. The EXAFS spectra of the samples obtained by m-CPBA oxidation of FeX(tmp) (X=Cl-, Br-) were refined using two different coordination models including both four porphyrinato-nitrogens and the axial oxo group. The two models include (model I) or exclude (model II) the axial halogen. The statistical tests indicate the presence of a halide ion as second axial ligand of iron in both derivatives. The refinements led to the following bond distances: FeIV=O(tmp*)Cl(3):Fe-O=1.66(1),Fe-Cl=2.39(2) and Fe-Np=1.99(1) A;FeIV=O(tmp*)Br(4):Fe-O=1.65(1),Fe-Br=2.93(2), Fe-Np=2.02(1) A. The lengthening of the Fe-X(X=Cl-, Br-) distances relative to those occurring in the ferric precursor porphyrins is, most probably, related to the strong trans influence of the oxoiron(IV) fragment present in 3 or 4.

Chlorobenzoates↗
PubMed2000

Evolutionarily conserved and divergent expression of members of the FGF receptor family among vertebrate embryos, as revealed by FGFR expression patterns in Xenopus.

Fibroblast growth factors (FGFs) mediate many cell-cell signaling events during early development. While the actions of FGFs have been well-studied, the roles played by specific members of the FGF receptor (FGFR) family are poorly understood. To characterize the roles played by individual FGFRs we compared the regulation and expression of the three Xenopus FGFRs described to date (XFGFR-1, XFGFR-2, and XFGFR-4). First, we describe the expression of Xenopus FGFR-4; XFGFR-4 is present as a maternal mRNA and is found in the embryo through at least the tadpole stage. XFGFR-4 and XFGFR-1 mRNAs are present at comparable levels, arguing that both mediate FGF signaling during early development. Second, the expression of XFGFR-4 in animal caps differs from the expression of XFGFR-1 and XFGFR-2, suggesting that the FGFRs are independently regulated in ectoderm. Third, using whole-mount in situ hybridization, we show that XFGFR-1, XFGFR-2, and XFGFR-4 are expressed in dramatically different patterns, arguing that specific FGF signaling events are mediated by different members of the FGFR family. Among these, FGF signaling during the induction of neural crest cells is likely to be mediated by XFGFR-4. Comparison of our results with previously reported FGFR expression patterns reveals that FGFR-1 expression is highly conserved among vertebrate embryos, and FGFR-2 expression shows many features that are conserved and some that are divergent. In contrast, the expression pattern of FGFR-4 is highly divergent among vertebrate embryos.

Animals↗
PubMed2000

Dynamics of low-frequency R-R interval oscillations preceding spontaneous ventricular tachycardia.

BACKGROUND: Increased sympathetic activity is believed to be an important trigger of sustained ventricular tachyarrhythmias (VT) and is believed to be responsible for the increased heart rate that we and others have reported before the onset of spontaneous VT. However, in the patients reported herein, heart rate variability (HRV) indexes that reflect sympathetic activity unexpectedly declined, whereas heart rate increased. To explain this apparent paradoxic behavior, we tested the hypothesis that baseline levels of HRV determine its reaction to short-term autonomic perturbations before the onset of VT. METHODS AND RESULTS: Holter electrocardiograms from 47 patients (ejection fraction 36% +/- 15%) with recorded VT were analyzed. Frequency domain HRV indexes (low-frequency power [LFP] 0. 04 to 0.15 Hz, high-frequency power [HFP] 0.15 to 0.4 Hz, and total power [TP] 0.01 to 0.4 Hz) were studied in 5-minute intervals and over a period of 24 hours. Patients were divided into those with a decrease in LFP in the 2-hour period before VT (group A, n = 32) and those with an increase or no change (group B, n = 15). The data were logarithmically transformed. Heart rate increased 15 minutes before the onset of VT compared with the 24-hour mean in both groups (group A: 80.3 +/- 15.4 to 86.1 +/- 20.0 beats/min, P =.005; group B: 80.6 +/- 13.5 to 86.7 +/- 14.0 beats/min, P =.017). Group A had higher TP, LFP, and LFP/HFP 2 hours before VT, and these variables decreased 15 minutes before the onset of VT (TP from 7.31 +/- 1.28 to 6.88 +/- 1.35, LFP from 6.09 +/- 1.28 to 5.38 +/- 1.33, LFP/HFP from 1.33 +/- 0.89 to 0.96 +/- 0.80, P <.001 for all 3 variables). HFP also decreased 15 minutes before VT compared with 2 hours (from 4.78 +/- 1.05 to 4.49 +/- 1.24, P =.028). In group B, which had lower baseline TP, LFP, and LFP/HFP at 2 hours before VT, these variables increased 15 minutes before the event (TP from 6.41 +/- 1.41 to 6.86 +/- 1.42, P =.004; LFP from 4.59 +/- 1.51 to 4.95 +/- 0.62, P <.001; LFP/HFP from 0.22 +/- 1.22 to 0.52 +/- 1.38, P =.10), whereas HFP did not change significantly (4.40 +/- 0.94 and 4.53 +/- 1.01, P =. 50). CONCLUSIONS: An increase in heart rate and a drop in the low-frequency oscillations of R-R intervals before the onset of VT occurred in patients with higher baseline level of oscillatory activity. These changes suggest a dissociation between the average and rhythmic modulation of R-R intervals. A decline of the low-frequency oscillations in the setting of increasing heart rate could reflect an abnormal response to increased sympathetic activity in most of the patients from the studied group. The different behaviors of the HRV indexes before the onset of VT in the 2 groups suggest that change in the dynamics of R-R intervals, rather than the direction of change, facilitates arrhythmogenesis.

Aged↗
PubMed2000

Micromachined pipette arrays.

In this paper, the design and characterization of batch fabricated metallic micromachined pipette arrays is described. The process used to fabricate the micromachined pipette arrays (MPA) includes p+ etch-stop membrane technology, anisotropic etching of silicon in potassium hydroxide, sacrificial thick photoresist micromolding technology, and electrodeposition. Arrays of one to ten pipettes have been fabricated using nickel as the structural material and palladium as the biocompatible coating of inside walls. The inner dimensions of the individual pipettes fabricated to date range from 30 microns to 1.5 mm in width, 0.5 mm to several cm in length, and 5-50 microns in thickness. The center-to-center spacing of these pipettes varies from 100 microns to several centimeters. The MPA have a number of advantages when compared to the current micropipette technology, including the ability to transfer precise volumes of samples in the submicroliter range; the ability to manipulate samples, reagents, or buffers in a highly-parallel fashion by operating hundreds of individual pipettes simultaneously; and the compatibility with the submilimeter center-to-center dimensions of the microscale biochemical analysis systems. The application of the MPA to high lane density slab gel electrophoresis is explored. Sample wells are formed in agarose gels by using micromachined combs (solid MPA) at center-to-center spacing ranging from 250 microns to 1.9 mm. The samples are loaded using the MPA. The results of the micro-gel separations compare favorably with the standard mini-gel separations and show a twofold increase in the number of theoretical plates as well as a sixfold increase in lane density.

Biochemistry↗
PubMed2000

Genetic vaccination against malaria infection by intradermal and epidermal injections of a plasmid containing the gene encoding the Plasmodium berghei circumsporozoite protein.

The circumsporozoite protein (CSP) from the surface of sporozoite stage Plasmodium sp. malaria parasites is among the most important of the malaria vaccine candidates. Gene gun injection of genetic vaccines encoding Plasmodium berghei CSP induces a significant protective effect against sporozoite challenge; however, intramuscular injection does not. In the present study we compared the immune responses and protective effects induced by P. berghei CSP genetic vaccines delivered intradermally with a needle or epidermally with a gene gun. Mice were immunized three times at 4-week intervals and challenged by a single infectious mosquito bite. Although 50 times more DNA was administered by needle than by gene gun, the latter method induced significantly greater protection against infection. Intradermal injection of the CSP genetic vaccine induced a strong Th1-type immune response characterized by a dominant CSP-specific immunoglobulin G2a (IgG2a) humoral response and high levels of gamma interferon produced by splenic T cells. Gene gun injection induced a predominantly Th2-type immune response characterized by a high IgG1/IgG2a ratio and significant IgE production. Neither method generated measurable cytotoxic T lymphocyte activity. The results indicate that a gene gun-mediated CS-specific Th2-type response may be best for protecting against malarial sporozoite infection when the route of parasite entry is via mosquito bite.

Animals↗
PubMed2000

Characterization of hydrogenase II from the hyperthermophilic archaeon Pyrococcus furiosus and assessment of its role in sulfur reduction.

The fermentative hyperthermophile Pyrococcus furiosus contains an NADPH-utilizing, heterotetrameric (alphabetagammadelta), cytoplasmic hydrogenase (hydrogenase I) that catalyzes both H(2) production and the reduction of elemental sulfur to H(2)S. Herein is described the purification of a second enzyme of this type, hydrogenase II, from the same organism. Hydrogenase II has an M(r) of 320,000 +/- 20,000 and contains four different subunits with M(r)s of 52,000 (alpha), 39,000 (beta), 30,000 (gamma), and 24,000 (delta). The heterotetramer contained Ni (0.9 +/- 0.1 atom/mol), Fe (21 +/- 1.6 atoms/mol), and flavin adenine dinucleotide (FAD) (0.83 +/- 0.1 mol/mol). NADPH and NADH were equally efficient as electron donors for H(2) production with K(m) values near 70 microM and k(cat)/K(m) values near 350 min(-1) mM(-1). In contrast to hydrogenase I, hydrogenase II catalyzed the H(2)-dependent reduction of NAD (K(m), 128 microM; k(cat)/K(m), 770 min(-1) mM(-1)). Ferredoxin from P. furiosus was not an efficient electron carrier for either enzyme. Both H(2) and NADPH served as electron donors for the reduction of elemental sulfur (S(0)) and polysulfide by hydrogenase I and hydrogenase II, and both enzymes preferentially reduce polysulfide to sulfide rather than protons to H(2) using NADPH as the electron donor. At least two [4Fe-4S] and one [2Fe-2S] cluster were detected in hydrogenase II by electron paramagnetic resonance spectroscopy, but amino acid sequence analyses indicated a total of five [4Fe-4S] clusters (two in the beta subunit and three in the delta subunit) and one [2Fe-2S] cluster (in the gamma subunit), as well as two putative nucleotide-binding sites in the gamma subunit which are thought to bind FAD and NAD(P)(H). The amino acid sequences of the four subunits of hydrogenase II showed between 55 and 63% similarity to those of hydrogenase I. The two enzymes are present in the cytoplasm at approximately the same concentration. Hydrogenase II may become physiologically relevant at low S(0) concentrations since it has a higher affinity than hydrogenase I for both S(0) and polysulfide.

Amino Acid Sequence↗
PubMed2000

[Prevalence of Chlamydia infections in breeding sows and their importance in reproductive failure].

To investigate the prevalence of chlamydial infection and their significance for reproductive disorders in sow breeding herds in Germany, blood samples of 1493 pigs were taken for a serological survey by enzyme-linked-immunosorbent-assay (ELISA). Antibodies to Chlamydiae were found in 33% of the samples, in all herds investigated responders could be detected. The rate of seropositive animals in different farms varied from 4.3% to 72.7%. The percentage of positive responders in the farms correlated positively with the occurrence of MMA-syndrome (mastitis, metritis, agalactia), return to oestrus and diseases of the piglets. Also these herds showed less weaned piglets per sow and litter. Comparison of seronegative and seropositive sows within single farms revealed also worse reproductive data for seropositive sows. A significant relationship could be found between farms with a high quota of sero-positive sows and poor hygiene status as well as poultry keeping. As a second step 124 cervical swabs and 9 aborted piglets were investigated for chlamydial antigen by capture-ELISA and polymerase chain reaction (PCR). Using the capture-ELISA for investigation only 3 probes with chlamydial antigen could be detected, however, examination by the more sensible PCR gave positive results in 50% of the probes. 20% of the PCR-positive animals were clinically healthy sows, 80% of the PCR-positive probes originated from sows with reproductive disorders. A significant relationship could be shown between PCR-positive probes and the incidence of abortion and litters with stillborn piglets and piglets with low viability. Swabs from 93 of the 124 sows were investigated as well for other bacterial pathogens of reproductive disorders. A high degree of micro-organisms of different species could be detected in 70% of the samples of sows with reproductive disorders and in 35% of the samples of clinically healthy sows. Species differentiation of the chlamydial antigen positive samples was done by southern blot hybridisation. Herewith C. psittaci could be diagnosed in all positive samples. Additionally 8 probes revealed a mixed infection with C. psittaci and C. trachomatis. The results of the present study show, that the prevalence of chlamydial infections in breeding herds is high and underline the importance of chlamydial infections for reproductive disorders. Single chlamydial infections as well as mixed infections with other pathogens must be considered.

Animals↗