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Biomedical subjects

W Arnold

Publications and source records attributed to W Arnold.

At least 109 records · Page 6Linked to original sources
PubMed1997

Cost, work, reimbursement, and the pediatric nephrologist in the United States Medicare/End-Stage Renal Disease Program.

The American Academy of Pediatrics, the American Society of Pediatric Nephrology, and the Renal Physicians Association combined their efforts to perform a survey of the work involved in providing care to children with end-stage renal disease (ESRD). These data document that the work of delivering care to infants and children on dialysis takes longer and is more intense than the care provided to adult patients. These data were presented to the American Medical Association Specialty Society Relative Value Scale Update Committee (RUC) to justify higher payment for pediatric ESRD care using previously developed monthly capitation payment Current Procedural Terminology codes based on patient age. Relative Work Units of 13.25 for infants (0-2 years), 9.13 for children (2-12 years), 6.47 for adolescents (12-19 years), and 5.24 for adults (> 19 years) were recommended by the RUC to Medicare. A suggested description of services for pediatric dialysis patients covered by the monthly capitated payment was developed.

Adolescent↗
PubMed1997

Generation of lymphoma-type variant hamster polyomavirus genomes in hamsters susceptible to lymphoma induction.

The hamster polyomavirus (HaPV) induces either hair follicle epitheliomas or lymphomas in either Z3 or HaP respectively. Syrian hamsters. In the lymphomas specifically deleted "lymphoma-type" (lt) HaPV genomes are accumulated. In the present study the temporal pattern of generation of HaPV (lt) DNA was investigated in context of the development of lymphomas in neonatally infected HaP hamsters. The generation of HaPV (lt) DNA was first detectable during the postnatal phase of high level replication of viral DNA in hemopoietic organs (at 7 days post infection), thus clearly preceding the development of overt lymphoma. A variety of HaPV (lt) DNA species is generated in lymphoid cells, but usually only one of them is accumulated to high amounts in lymphoma cells. Furthermore, the pattern of HaPV (lt) and wild-type (wt) DNA was studied in normal and tumor tissues of tumor-bearing hamsters as well as in tumor-free hamsters. In tumor-bearing hamsters predominantly HaPV (lt) DNA species were found in the infected tissues, while HaPV (wt) DNA was detected rarely and only in tumor-free tissues. In contrast, in tissues of tumor-free hamsters HaPV (wt) DNA prevailed over HaPV (lt) DNA species.

Animals↗
PubMed1997

Dopamine regulates the glutamatergic inner hair cell activity in guinea pigs.

Recent immunocytochemical and biochemical studies support a possible neurotransmitter function of dopamine (DA) in the efferent olivocochlear innervation of the guinea pig cochlea. However, the physiological role of DA in cochlear neurotransmission remains unknown. In the present study microiontophoretic techniques were used for testing the action of DA as well as D1- and D2-agonists and -antagonists on spontaneous and N-methyl-D-aspartic acid (NMDA)-, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-, kainic acid- or glutamate-induced firing of afferent fibres in the dendritic region of inner hair cells. Subsynaptic spike activities of anaesthetised guinea pigs were recorded after exposing the third or fourth turn of the cochlea for electrode penetration. Application of DA alone had very little effect on the spontaneous afferent firing rate. In contrast, firing induced by NMDA or AMPA could be depressed by additional administration of DA in a dose-dependent manner. A similar reduction of the induced spike activity was seen after co-administration of D1- or D2-agonists. The action of DA on glutamate agonist-induced firing could be blocked by D1- as well as D2-antagonists. These results show that DA can depress the activated firing rate of the afferent fibres and that this action is mediated by both D1- and D2-receptor subtypes.

Afferent Pathways↗
PubMed1997

RIFLE: rapid identification of microorganisms by fragment length evaluation.

Biological macromolecules represent a valuable source of information for the identification and phylogenetic classification of microorganisms. One of the most commonly used macromolecules for this task is the 16S rDNA. The WWW-based RIFLE system presented here supports large-scale identification tasks by comparing 16S rDNA restriction patterns to a database of restriction patterns derived from sequence databases. Computing efficiency and robustness against experimental errors are gained by employing a new distance measure for restriction patterns, the fragment length distance. Results from the application of the system to the identification of uncultured microorganisms associated with the seagrass halophila stipulacea show the reliability of the method.

Algorithms↗
PubMed1997

Medical, surgical, and technical complications with the COMBI-40.

We present the first report on complications of cochlear implantation with the COMBI-40 (Med-el, Innsbruck, Austria). Between January 1995 and May 1996 325 devices had been implanted by 58 different surgeons. Complications were reported with the help of standardized complication report form. The overall rate of complications was 4.6%. Most common problems were flap necrosis and incorrect positioning of the electrode. No technical failures occurred. The incidence of complications was lower than those reported by other authors.

Child↗
PubMed1997

[Endoscopic fusion of the lumbar vertebrae].

For certain indications, anterior fusion of the lumbar spine is a standard operation. The surgeon specializing in operations on the vertebral column needs to learn to utilize the advantages of laparoscopic surgery. However, an absolute must before employing the technique in patients is adequate training in its use in living animals. For this purpose, the pig is a highly suitable model. The surgical team comprises a surgeon experienced in spinal procedures, an abdominal surgeon with skills in laparoscopic surgery and an experienced camera assistant. In the animal model and in clinical trials, a change in position-organ preparation from the cranial direction, a suprasym-physial approach to the vertebrae-has proved expedient. The use of a special instrumentarium for maintaining the pneumo-peritoneum, for protecting the spinal cord and for exact centering, including the application of a special dowel (ESKA-spacer and instruments) is essential. The greater technical effort may be expected to result in shorter hospitalization (2-3 days) in the future.

Animals↗
PubMed1996

A defined chromosome 6q fragment (at D6S310) harbors a putative tumor suppressor gene for breast cancer.

Recent evidence obtained by cytogenetic and molecular studies indicates that in breast cancer chromosome 6q is often affected by genetic changes suggesting the existence of putative tumor suppressor genes (TSGs). However the function of gene(s) on this chromosome in breast cancer suppression is not understood. To substantiate further the presence of breast cancer related TSGs at 6q and to define their location, we first performed microcell-mediated transfer of chromosome 6 to CAL51 breast cancer cells for studying possible suppression of malignant phenotype and secondly, we analysed DNAs from 46 primary breast cancers for loss of constitutive heterozygosity (LOH) using 24 poly-morphic microsatellite markers. The chromosome transfer resulted in loss of tumorigenicity and reversion of other neoplastic properties of the microcell hybrids. Polymorphism analysis of single hybrids revealed that they harbored only a small donor chromosome fragment defined by the marker D6S310 (6q23.3-q25) and flanked by D6S292 and D6S311. The LOH data suggest that four tumor suppressor gene loci mapped to the central and distal portion of 6q may be independently deleted in breast cancer. One of these regions corresponds to the region identified by chromosome transfer.

Breast Neoplasms↗
PubMed1996

Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice.

We have studied the expression of members of the bcl-2 family in human breast cancer. The expression pattern of these genes in breast cancer tissue samples was compared with the expression pattern in normal breast epithelium. No marked difference with regard to bcl-2 and bcl-xL expression was observed between normal breast epithelium and cancer tissue. In contrast, bax-alpha, a splice variant of bax, which promotes apoptosis, is expressed in high amounts in normal breast epithelium, whereas only weak or no expression could be detected in 39 out of 40 cancer tissue samples examined so far. Of interest, downregulation of bax-alpha was found in different histological subtypes. Furthermore, we transfected bax-alpha into breast cancer cell lines under the control of a tetracycline-dependent expression system. We were able to demonstrate for the first time that induction of bax expression in breast cancer cell lines restores sensitivity towards both serum starvation and APO-I/Fas-triggered apoptosis and significantly reduces tumor growth in SCID mice. Therefore, we propose that dysregulation of apoptosis might contribute to the pathogenesis of breast cancer at least in part due to an imbalance between members of the bcl-2 gene family.

Animals↗
PubMed1996

Blocking the transcription factor E2F/DP by dominant-negative mutants in a normal breast epithelial cell line efficiently inhibits apoptosis and induces tumor growth in SCID mice.

The transcription factor E2F is regulated during the cell cycle through interactions with the product of the retinoblastoma susceptibility gene and related proteins. It is thought that E2F-mediated gene regulation at the G1/S boundary and during S phase may be one of the rate-limiting steps in cell proliferation. It was reported that in vivo overexpression of E2F-1 in fibroblasts induces S phase entry and leads to apoptosis. This observation suggests that E2F plays a role in both cell cycle regulation and apoptosis. To further understand the role of E2F in cell cycle progression, cell death, and tumor development, we have blocked endogenous E2F activity in HBL-100 cells, derived from nonmalignant human breast epithelium, using dominant-negative mutants under the control of a tetracycline-dependent expression system. We have shown here that induction of dominant-negative mutants led to strong downregulation of transiently transfected E2F-dependent chloramphenicol acetyl transferase reporter constructs and of endogenous c-myc, which has been described as a target gene of the transcription factor E2F/DP. In addition, we have shown that blocking of E2F could efficiently protect from apoptosis induced by serum starvation within a period of 10 d, whereas control cells started to die after 24 h. Surprisingly, blocking of E2F did not alter the rate of proliferation or of DNA synthesis of these cells; this finding indicates that cell-cycle progression could be driven in an E2F-independent manner. In addition, we have been able to show that blocking of endogenous E2F in HBL-100 cells led to rapid induction of tumor growth in severe combined immunodeficiency mice. No tumor growth could be observed in mice that received mock-transfected clones or tetracycline to block expression of the E2F mutant constructs in vivo. Thus, it appears that E2F has a potential tumor-suppressive function under certain circumstances. Furthermore, we provide evidence that dysregulation of apoptosis may be an important step in tumorigenesis.

Animals↗
PubMed1996

Hamster polyomavirus-encoded proteins: gene cloning, heterologous expression and immunoreactivity.

The hamster polyomavirus (HaPV) is associated with spontaneously appearing skin epithelioma of the Syrian hamster Z3 strain. Virus particles prepared from the skin epithelioma cause lymphoma and leukemia when injected into newborn hamsters from a distinct Syrian hamster colony (HaP); in contrast to the skin epithelioma the hemopoietic tumors are virus free but accumulate viral DNA. To study the humoral immune response of HaPV-infected Z3 hamsters we produced recombinant HaPV proteins in Escherichia coli as beta-galactosidase-, TrpE- and dihydrofolate reductase-fusion proteins or as non-fused proteins. Recombinant plasmids carried segments of all putative early and late HaPV proteins. The recombinant proteins were detected in stained SDS polyacrylamide gels and in Western blots using monoclonal anti-TrpE and anti-beta-galactosidase antibodies and sera of HaPV-infected hamsters. Sera from HaPV-infected Z3 hamsters and crude lysates of all clones were applied to Western blots to characterize the humoral immune response in the animals. HaPV-specific antibodies were found to be directed against early protein segments translated from the first common exon and from the second unique exon of LT and MT, resp., as well as against the late proteins VP1 and VP2/3. The almost complete VP2 was recognized by all sera whereas VP1 was detected only by a half of the sera. Our data suggest the presence of at least 2 immunodominant regions in VP2, one in the C-terminal VP1 and at least 4 in early proteins.

Animals↗
PubMed1996

[Carcinoma-in-carcinoma metastasis. In situ DNA quantification and immunohistochemical diagnosis].

In the rare event of cancer-to-cancer metastasis, one malignant neoplasm spreads to a second carcinoma. To date, 42 such cases have been published in the English- and German-language literature. We report two additional patients, each with metastatic bronchial cancer present in a renal carcinoma. In addition to immunohistochemical examinations, we performed in situ DNA image cytometry of histologic preparations as a novel analytical technique to differentiate metastatic tissue from the host tumor. In both cases DNA histograms of metastatic tumor resembled those of the primary malignancy but were clearly dissimilar to the host tumor. In 70% of previously reported cases renal carcinoma was the host tumor while in 50%, cancer of the lung was the most frequent donor tumor.

Adenocarcinoma↗
PubMed1996

In vivo replication of hamster polyomavirus DNA displays lymphotropism in hamsters susceptible to lymphoma induction.

Using the whole body section hybridization technique, we monitored the organ- and age-specific pattern of replication of hamster polyomavirus (HaPV) DNA in a colony of Syrian hamsters, which are susceptible to lymphoma induction. Three phases of viral infection and replication could be distinguished: first, a phase of acute infection characterized by high levels of replication of HaPV DNA in the haemopoietic organs and the liver. This culminated 5 to 7 days post-infection (p.i.); second, at 10 days p.i., a phase of viral clearance became evident; and finally, a third phase reflected both the restriction of HaPV replication in adult hamsters and the accumulation of HaPV DNA at sites of tumour development. A remarkable conformity was observed between the tissue specificity of viral replication and the induced tumour profile: high levels of replication of HaPV DNA were restricted to cells of the haemopoietic system and lymphoid tumours were induced. As shown by in situ hybridization, the viral infection in non-haemopoietic organs was due to the dissemination of HaPV-infected blood cells.

Animals↗