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Biomedical subjects

C Bender

Publications and source records attributed to C Bender.

At least 19 recordsLinked to original sources

Plant pathogen forensics: capabilities, needs, and recommendations.

A biological attack on U.S. crops, rangelands, or forests could reduce yield and quality, erode consumer confidence, affect economic health and the environment, and possibly impact human nutrition and international relations. Preparedness for a crop bioterror event requires a strong national security plan that includes steps for microbial forensics and criminal attribution. However, U.S. crop producers, consultants, and agricultural scientists have traditionally focused primarily on strategies for prevention and management of diseases introduced naturally or unintentionally rather than on responding appropriately to an intentional pathogen introduction. We assess currently available information, technologies, and resources that were developed originally to ensure plant health but also could be utilized for postintroduction plant pathogen forensics. Recommendations for prioritization of efforts and resource expenditures needed to enhance our plant pathogen forensics capabilities are presented.

Bioterrorism↗

Critical soft tissue parameters of the zygomatic implant.

AIM: Zygomatic implants have been introduced for the rehabilitation of patients with severe bone defects of the maxilla. The soft tissue aspects of the palatal emergence situation have not been described yet. The aim of this study was to evaluate the incidence and clinical impact of possible periimplant alterations of zygomatic implants. MATERIALS AND METHODS: From 1998 to 2001 all patients with zygomatic implants were included into this study (24 patients, 37 zygomatic implants). One implant was lost in the loading phase giving a survival rate of 97%. Fourteen patients with 20 zygomatic implants fulfilled the inclusion criteria and were all available for the recall examination. Thirteen zygomatic implants were inserted in cases of severe maxillary atrophy, seven in cases of tumour-resection of the maxilla. Clinical examination and microbial analysis using a DNA probe was performed. The implants had a mean time in situ of 598 days (min: 326, max: 914). RESULTS: Colonisation with periodontal pathogens was found at four of the 20 implants. A positive microbiologic result of the periimplant pocket and the maximum pocket probing depth were not statistically related. Nine of the 20 implants showed bleeding on probing, four of these had positive microbiologic results. At sites without bleeding on probing only negative microbiologic samples were found (p=0.026). The mean palatal and mesial probing depth was 1 mm deeper than at the vestibular and distal aspect. Thus at nine out of the 20 implants both, bleeding on probing and pocket probing depth >/=5 mm indicated soft tissue problems resulting in a success rate of only 55%. The patient's history (tumor versus atrophy) or smoking habits seemed not to have influence the situation. CONCLUSION: These soft tissue problems should be taken into account if zygomatic implants are considered as an alternative therapy option in the maxilla.

Alveolar Bone Loss↗

Hypercontractile heart failure caused by catecholamine therapy in premature neonates.

UNLABELLED: Catecholamine treatment for hypotension is common practice in neonatal intensive care units. In the presence of left ventricular hypertrophy, the positive inotropic action of catecholamines with mainly beta-receptor specificity can lead to excessive hypercontractility and paradoxical hypotension. This reports presents two cases of hypercontractile heart failure during beta-agonist treatment in very low birthweight (VLBW) infants. Both patients (27 wk, 5 d; and 26 wk, 6 d of gestation) underwent surgical arterial duct ligation and coarctation repair. After operation they developed arterial hypotension that failed to respond to epinephrine (adrenaline) or dobutamine treatment. Echocardiography demonstrated a complete systolic obliteration of the left ventricular cavity. Epinephrine and dobutamine were stopped, and norepinephrine (noradrenaline) was successfully used to control the hypotension. CONCLUSION: Treatment of hypotension with beta-agonists in VLBW infants with left ventricular hypertrophy can lead to hypercontractility and left ventricular obliteration with paradoxical hypotension. Careful echocardiographic monitoring is indicated in such cases.

Adrenergic Agonists↗

Ultradian oscillations in cranial thermoregulation and electroencephalographic slow-wave activity during sleep are abnormal in humans with annual winter depression.

The level of core body, and presumably brain temperature during sleep varies with clinical state in patients with seasonal affective disorder (SAD), becoming elevated during winter depression and lowered during clinical remission induced by either light treatment or summer. During sleep, brain temperatures are in part determined by the level of brain cooling activity, which may be reflected by facial skin temperatures. In many animals, the level of brain cooling activity oscillates across the NREM-REM sleep cycle. Facial skin temperatures during sleep in patients with winter depression are abnormally low and uncorrelated with rectal temperatures, although their relationship to EEG-defined sleep stages remains unknown. We therefore measured the sleep EEG, core body and facial skin temperatures in 23 patients with winter depression and 23 healthy controls, and tested the hypothesis that ultradian oscillations in facial skin temperatures exist in humans and are abnormal in patients with winter depression. We found that facial skin temperatures oscillated significantly across the NREM-REM sleep cycle, and were again significantly lower and uncorrelated with rectal temperatures in patients with winter depression. Mean slow-wave activity and NREM episode duration were significantly greater in patients with winter depression, whereas the intraepisodic dynamics of slow-wave activity were normal in patients with winter depression. These results suggest that brain cooling activity oscillates in an ultradian manner during sleep in humans and is reduced during winter depression, and provide additional support for the hypothesis that brain temperatures are elevated during winter depression.

Activity Cycles↗

Removal of oxygen free-radical-induced 5',8-purine cyclodeoxynucleosides from DNA by the nucleotide excision-repair pathway in human cells.

Exposure of cellular DNA to reactive oxygen species generates several classes of base lesions, many of which are removed by the base excision-repair pathway. However, the lesions include purine cyclodeoxynucleoside formation by intramolecular crosslinking between the C-8 position of adenine or guanine and the 5' position of 2-deoxyribose. This distorting form of DNA damage, in which the purine is attached by two covalent bonds to the sugar-phosphate backbone, occurs as distinct diastereoisomers. It was observed here that both diastereoisomers block primer extension by mammalian and microbial replicative DNA polymerases, using DNA with a site-specific purine cyclodeoxynucleoside residue as template, and consequently appear to be cytotoxic lesions. Plasmid DNA containing either the 5'R or 5'S form of 5',8-cyclo-2-deoxyadenosine was a substrate for the human nucleotide excision-repair enzyme complex. The R diastereoisomer was more efficiently repaired than the S isomer. No correction of the lesion by direct damage reversal or base excision repair was detected. Dual incision around the lesion depended on the core nucleotide excision-repair protein XPA. In contrast to several other types of oxidative DNA damage, purine cyclodeoxynucleosides are chemically stable and would be expected to accumulate at a slow rate over many years in the DNA of nonregenerating cells from xeroderma pigmentosum patients. High levels of this form of DNA damage might explain the progressive neurodegeneration seen in XPA individuals.

Base Sequence↗

Impact of recent welfare and immigration reforms on use of Medicaid for prenatal care by immigrants in California.

This study investigates the impact of the recent welfare and immigration changes on the use of Medicaid by low-income pregnant immigrant women in California. The study presents findings from interviews with government officials, safety-net prenatal care providers, and immigrant advocates who serve low-income pregnant Asian and Latina immigrants at the national, state, or local levels. These informants spoke of policy actions that affect immigrants' abilities to use Medicaid for coverage of prenatal care. These actions include (1) the sharing of information between the California Department of Health Services and the federal Immigration and Naturalization Service, (2) the slow and confusing implementation of the reforms, and (3) the intimidating Medicaid eligibility process. The findings demonstrate how the policies changed the immigrant women's relationship with safety-net prenatal care providers, and sparked intense actions on the part of their advocates to sustain the women's access to perinatal care.

Journal Article↗

Virulence of the phytopathogen Pseudomonas syringae pv. maculicola is rpoN dependent.

We cloned the rpoN (ntrA and glnF) gene encoding sigma(54) from the phytopathogen Pseudomonas syringae pv. maculicola strain ES4326. The P. syringae ES4326 rpoN gene complemented Pseudomonas aeruginosa, Escherichia coli, and Klebsiella aerogenes rpoN mutants for a variety of rpoN mutant phenotypes, including the inability to utilize nitrate as sole nitrogen source. DNA sequence analysis of the P. syringae ES4326 rpoN gene revealed that the deduced amino acid sequence was most similar (86% identity; 95% similarity) to the sigma(54) protein encoded by the Pseudomonas putida rpoN gene. A marker exchange protocol was used to construct an ES4326 rpoN insertional mutation, rpoN::Km(r). In contrast to wild-type ES4326, ES4326 rpoN::Km(r) was nonmotile and could not utilize nitrate, urea, C(4)-dicarboxylic acids, several amino acids, or concentrations of ammonia below 2 mM as nitrogen sources. rpoN was essential for production of the phytotoxin coronatine and for expression of the structural genes encoding coronamic acid. In addition, ES4326 rpoN::Km(r) did not multiply or elicit disease symptoms when infiltrated into Arabidopsis thaliana leaves, did not elicit the accumulation of several Arabidopsis defense-related mRNAs, and did not elicit a hypersensitive response (HR) when infiltrated into tobacco (Nicotiana tabacum) leaves. Furthermore, whereas P. syringae ES4326 carrying the avirulence gene avrRpt2 elicited an HR when infiltrated into Arabidopsis ecotype Columbia leaves, ES4326 rpoN::Km(r) carrying avrRpt2 elicited no response. Constitutive expression of ES4326 hrpL in ES4326 rpoN::Km(r) partially restored defense-related mRNA accumulation, showing a direct role for the hrp cluster in host defense gene induction in a compatible host-pathogen interaction. However, constitutive expression of hrpL in ES4326 rpoN::Km(r) did not restore coronatine production, showing that coronatine biosynthesis requires factors other than hrpL.

Amino Acid Sequence↗

Characterization of the surface proteins of influenza A (H5N1) viruses isolated from humans in 1997-1998.

Influenza A (H5N1) viruses infected humans in Hong Kong between May and December, 1997. Sixteen viruses, including 6 from fatal cases, were isolated during this outbreak. Molecular analysis of the surface proteins genes encoding the hemagglutinin (HA) and neuraminidase (NA) of these H5N1 isolates, of a subtype not previously known to infect humans, are presented. The 16 human H5 HA sequences contain multiple basic amino acids adjacent to the cleavage site, a motif associated with highly pathogenic avian influenza A viruses. The phylogenetic relationship among both avian and human H5 hemagglutinins indicates that the human isolates are related directly to isolates that circulated among chickens in the live poultry markets in Hong Kong prior to and during the outbreak in humans. HA sequences from the human isolates and a recent chicken isolate represent a separate clade, within which there are two subgroups that are distinguishable antigenically and by the presence of a potential glycosylation site. Likewise the N1 neuraminidases of the human H5 isolates represent a clade that is evolutionarily distinct from previously characterized N1 neuraminidases. The recent human H5N1 virus NA genes are avian-like, indicating direct introduction from an avian source rather than evolution of a human N1 NA. All of the 16 human NA genes encode a shortened stalk due to a 19-amino acid deletion, also found in the recent avian H5N1 isolates from Hong Kong. Two unique amino acids were identified in the N1 NAs of the recent human isolates; however, it is not known if these residues influence host range. Neither the HA nor the NA genes of the human H5N1 virus isolates show evidence of adaptive changes during the outbreak. Although analyses of the surface protein genes of the H5N1 viruses from this outbreak did not provide immediate answers regarding the molecular basis for virulence, the analyses provided clues to potentially important areas of the genes worth further investigation.

Adolescent↗

The socialization of newly hired medical staff into a large health system.

The acquisition of private medical practices by large health care systems often results in the transition of the physician from self-employment to salaried employee. In order to be successful, new physicians must be socialized into the new environment, requiring both concrete information and cultural orientation. This Mayo Clinic study of recently hired physicians yielded information about both content and delivery mechanisms that will help in planning an integrated system of orientation experiences.

Delivery of Health Care, Integrated↗

Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.

An avian H5N1 influenza A virus (A/Hong Kong/156/97) was isolated from a tracheal aspirate obtained from a 3-year-old child in Hong Kong with a fatal illness consistent with influenza. Serologic analysis indicated the presence of an H5 hemagglutinin. All eight RNA segments were derived from an avian influenza A virus. The hemagglutinin contained multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza A viruses. The virus caused 87.5 to 100 percent mortality in experimentally inoculated White Plymouth Rock and White Leghorn chickens. These results may have implications for global influenza surveillance and planning for pandemic influenza.

Amino Acid Sequence↗

Analysis of genes involved in biosynthesis of coronafacic acid, the polyketide component of the phytotoxin coronatine.

Coronafacic acid (CFA) is the polyketide component of coronatine (COR), a phytotoxin produced by the plant-pathogenic bacterium Pseudomonas syringae. The genes involved in CFA biosynthesis are encoded by a single transcript which encompasses 19 kb of the COR gene cluster. In the present study, the nucleotide sequence was determined for a 4-kb region located at the 3' end of the CFA biosynthetic gene cluster. Three open reading frames were identified and designated cfa8, cfa9, and tnp1; the predicted translation products of these genes showed relatedness to oxidoreductases, thioesterases, and transposases, respectively. The translational products of cfa8 and cfa9 were overproduced in Escherichia coli BL21; however, tnp1 was not translated in these experiments. Mutagenesis and complementation analysis indicated that cfa8 is required for the production of CFA and COR. Analysis of a cfa9 mutant indicated that this gene is dispensable for CFA and COR production but may increase the release of enzyme-bound products from the COR pathway; tnp1, however, had no obvious function in CFA or COR biosynthesis. A genetic strategy was used to produce CFA in a P. syringae strain which lacks the COR gene cluster; this approach will be useful in future studies designed to investigate biosynthetic products of the CFA gene cluster.

Amino Acid Sequence↗

Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong.

Genes of an influenza A (H5N1) virus from a human in Hong Kong isolated in May 1997 were sequenced and found to be all avian-like (K. Subbarao et al., Science 279:393-395, 1998). Gene sequences of this human isolate were compared to those of a highly pathogenic chicken H5N1 influenza virus isolated from Hong Kong in April 1997. Sequence comparisons of all eight RNA segments from the two viruses show greater than 99% sequence identity between them. However, neither isolate's gene sequence was closely (>95% sequence identity) related to any other gene sequences found in the GenBank database. Phylogenetic analysis demonstrated that the nucleotide sequences of at least four of the eight RNA segments clustered with Eurasian origin avian influenza viruses. The hemagglutinin gene phylogenetic analysis also included the sequences from an additional three human and two chicken H5N1 virus isolates from Hong Kong, and the isolates separated into two closely related groups. However, no single amino acid change separated the chicken origin and human origin isolates, but they all contained multiple basic amino acids at the hemagglutinin cleavage site, which is associated with a highly pathogenic phenotype in poultry. In experimental intravenous inoculation studies with chickens, all seven viruses were highly pathogenic, killing most birds within 24 h. All infected chickens had virtually identical pathologic lesions, including moderate to severe diffuse edema and interstitial pneumonitis. Viral nucleoprotein was most frequently demonstrated in vascular endothelium, macrophages, heterophils, and cardiac myocytes. Asphyxiation from pulmonary edema and generalized cardiovascular collapse were the most likely pathogenic mechanisms responsible for illness and death. In summary, a small number of changes in hemagglutinin gene sequences defined two closely related subgroups, with both subgroups having human and chicken members, among the seven viruses examined from Hong Kong, and all seven viruses were highly pathogenic in chickens and caused similar lesions in experimental inoculations.

Amino Acid Sequence↗

[TP53 gene aberrations in chondromatous neoplasms: correlation with immunohistochemical p53 accumulation and MDM2 expression].

Histological differentiation between chondroma and chondrosarcoma is a common problem in surgical pathology. In a former study (3) we were able to show, that immuno-histochemical p53-accumulation in chondromatous neoplasias might be an additional hint for malignancy. Now we tried to find out, whether p53-accumulation is caused by TP53-aberrations or functional inactivation of p53-wildtype protein by MDM2. For this purpose, paraffin-embedded material of 80 chondromatous neoplasms (18 chondromas, 18 chondromatous neoplasms of uncertain dignity (i.e. cytologically suspicious but without definite invasive growth), and 44 chondrosarcomas (24 GI, 13 GII, 7 GIII)) were screened for TP53 gene-aberrations by means of DGGE (denaturing gradient gel electrophoresis; exons 5-8). The results were correlated with immunohistochemical p53-accumulation (DO-7, DAKO) and MDM2-expression (AB-1, Oncogene). A total of 43% of all chondromatous neoplasms showed TP53-aberrations in DGGE-analysis, i.e. 27% of chondromas, 50% of chondromatous neoplasms of uncertain dignity, 46% of GI-, 46% of GII- and 71% of GIII-chondrosarcomas. Exon 6 (58% of all cases with aberrations) and exon 8 (47%) were affected most frequently. No significant correlation between TP53-aberration and either p53-accumulation or MDM2-expression was present. A statistically significant correlation could be found between p53-accumulation and MDM2-expression (p < 0.0001). Regarding histological tumor-classification, p53-accumulation and MDM2-expression discriminated between chondromas/chondromatous neoplasms of uncertain dignity and well differentiated chondrosarcomas in a statistically significant manner. In the subgroup of p53-positive and MDM2-negative cases significantly more TP53-aberrations were detected by DGGE-analysis than in the other groups. Interestingly, the subgroup of p53- and MDM2-negative cases showed the second highest rate of TP53-DGGE-aberrations. Nearly 50% of these aberrations, however, were localized in exon 8, a mutation that is known to cause no p53-protein-accumulation. In conclusion, TP53-aberrations occur frequently in chondromatous neoplasms and show no significant association to either immunohistochemical p53-accumulation or MDM2-expression. Functional inactivation of p53 wildtype protein by MDM2-expression seems to be the major cause of p53-accumulation in chondromatous neoplasms and emphasizes the role of these parameters as additional hint for malignancy.

Bone Neoplasms↗

Extended sleep in humans in 14 hour nights (LD 10:14): relationship between REM density and spontaneous awakening.

The sleep patterns of 8 normal subjects living in a winter-type photoperiod (10 h light and 14 h darkness; LD 10:14) for 4 weeks were characterized by the presence of periods of spontaneous wakefulness alternating with periods of spontaneous sleep. Transitions from sleep to wakefulness occurred much more frequently out of REM sleep than out of NREM sleep (P < 0.002). REM periods that terminated in wakefulness showed shorter REM durations (P < 0.0005) and higher REM densities (P < 0.0005) than REM periods that did not terminate in wakefulness. The authors discuss these results in terms of a possible relationship between REM density and arousal level. The higher REM density preceding wakefulness and the increased number of REM periods terminating in spontaneous awakenings could reflect an enhanced level of a brain arousing process, resulting from reduced sleep pressure in the extended nights.

Adult↗

Improving undergraduate biology education in a large research university.

The campus-wide Undergraduate Biology Research Program (UBRP) at the University of Arizona improves undergraduate science education by expanding student opportunities for independent research in faculty laboratories. Within the supportive community of a research laboratory, underclassmen, nonscience majors, and those aspiring to scientific careers all learn to appreciate the process of science. The Program impacts more than the students, promoting departmental cooperation, interdisciplinary collaborations, and improvements in undergraduate science education throughout a Research I University.

Adult↗