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Biomedical subjects

C Kaufmann

Publications and source records attributed to C Kaufmann.

At least 37 records · Page 2Linked to original sources
PubMed2000

Windows 99: a source of suburban pediatric trauma.

BACKGROUND: Falls from windows in urban areas cause a significant number of pediatric injuries. Window falls have not been well described in the nonurban setting. We describe the epidemiology of window falls from residential homes among pediatric patients at a suburban Level I trauma center. METHODS: A review of patients admitted from January 1991 through November 1999 to a center serving a rapidly growing suburban area was performed. RESULTS: A total of 2,322 children, ages 0-14 years, were admitted during the study period. Falls comprised 41% of these admissions, and 11% of falls were from windows, greater than twice the national average. More than 39% of children who fell from windows were admitted directly to the intensive care unit. Overall mortality rate was 4%. Ages 0 to 4 years comprised the largest percentage (83%), and all children who died were in this age group. Children < or = 4 years were more likely to have an Abbreviated Injury Score > or = 2 (head injury) than those ages 10 to 14 years (p = 0.032). More than 31% of all children injured in window falls seen at the study institution between 1991 and 1999 were admitted in the last 2 years. CONCLUSION: Pediatric falls from windows in this suburban area appear to be increasing, with an incidence greater than the national average. Children at greatest risk are less than 4 years old. Further research in injury prevention at the national level aimed at suburban areas may be warranted.

Accidental Falls↗
PubMed2000

Genetic influence on laterality in schizophrenia? A twin study of neurological soft signs.

OBJECTIVE: This study explored the genetic basis of neurological soft signs in schizophrenia and addressed disturbed hemispheric lateralization. METHOD: The authors investigated neurological soft signs in 30 monozygotic twin pairs, 13 pairs discordant for schizophrenia or schizoaffective disorder and 17 healthy comparison twin pairs. RESULTS: The twins with schizophrenia showed higher total scores for neurological soft signs than did the comparison subjects. The total scores for neurological soft signs of the nonaffected discordant twins were significantly higher than those of the comparison twins. There was a significant difference between the nonaffected and affected discordant twins in total scores for neurological soft signs. In contrast to the comparison subjects, the nonaffected and affected twins of the discordant pairs showed a trend toward higher scores for neurological soft signs on the left body half. CONCLUSIONS: These results suggest that the occurrence of neurological soft signs and, more specifically, their lateralization to the left body half are genetically transmitted.

Adult↗
PubMed1999

Suggestive linkage of chromosome 10p to schizophrenia is not due to transmission ratio distortion.

The genome scan of the European-American schizophrenia families from the Human Genetics Initiative of the National Institute of Mental Health (NIMH) reported a suggestive linkage to chromosome 10p. Subsequently, Paterson and Petronis [1999] reported evidence for transmission ratio distortion on 10p to females. They suggested that transmission ratio distortion to females might have created spurious evidence for linkage to 10p. To address this issue, we reanalyzed our 10p data using only male-male affected sibling pairs. The two chromosome 10p markers that gave the most evidence for linkage in our prior report continued to show evidence for linkage: D10S1423 (NPL Z = 3.0, P = 0.001) and its neighbor D10S582 (NPL Z = 2.9, P = 0.002). These data suggest that our prior report of suggestive linkage of schizophrenia to markers on 10p cannot be attributed to the transmission ratio distortion to females reported by Paterson and Petronis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:607-608, 1999.

Chromosomes, Human, Pair 10↗
PubMed1999

Acid-base disorders in milk-fed calves with chronic indigestion.

Acid-base disorders were investigated in 50 calves with chronic indigestion and metabolic acidosis. In the calves that were unable to stand up, the acidosis was significantly more severe than in the calves that could stand up. The anion gap and four different components of the base excess were calculated by the method described by Fencl. The anion gap was high in more than half of the calves, and it was significantly associated with the base excess due to unidentified anions. However, in seven of the calves, the excess of unidentified anions would not have been detected without the calculations, which made it possible to measure the effect of sodium, chloride, plasma protein and unidentified anions on the acid-base balance. Twenty-four of the calves had a combination of hyperchloraemic and high anion gap metabolic acidosis. Changes in sodium and plasma protein concentrations had a minor impact on the calves' acid-base status.

Acid-Base Equilibrium↗
PubMed1999

Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization.

Axin was identified as a regulator of embryonic axis induction in vertebrates that inhibits the Wnt signal transduction pathway. Epistasis experiments in frog embryos indicated that Axin functioned downstream of glycogen synthase kinase 3beta (GSK3beta) and upstream of beta-catenin, and subsequent studies showed that Axin is part of a complex including these two proteins and adenomatous polyposis coli (APC). Here, we examine the role of different Axin domains in the effects on axis formation and beta-catenin levels. We find that the regulators of G-protein signaling domain (major APC-binding site) and GSK3beta-binding site are required, whereas the COOH-terminal sequences, including a protein phosphatase 2A binding site and the DIX domain, are not essential. Some forms of Axin lacking the beta-catenin binding site can still interact indirectly with beta-catenin and regulate beta-catenin levels and axis formation. Thus in normal embryonic cells, interaction with APC and GSK3beta is critical for the ability of Axin to regulate signaling via beta-catenin. Myc-tagged Axin is localized in a characteristic pattern of intracellular spots as well as at the plasma membrane. NH2-terminal sequences were required for targeting to either of these sites, whereas COOH-terminal sequences increased localization at the spots. Coexpression of hemagglutinin-tagged Dishevelled (Dsh) revealed strong colocalization with Axin, suggesting that Dsh can interact with the Axin/APC/GSK3/beta-catenin complex, and may thus modulate its activity.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Nuclear accumulation of S-adenosylhomocysteine hydrolase in transcriptionally active cells during development of Xenopus laevis.

The oocyte nuclear antigen of the monoclonal antibody 32-5B6 of Xenopus laevis is subject to regulated nuclear translocation during embryogenesis. It is distributed in the cytoplasm during oocyte maturation, where it remains during cleavage and blastula stages, before it gradually reaccumulates in the nuclei during gastrulation. We have now identified this antigen to be the enzyme S-adenosylhomocysteine hydrolase (SAHH). SAHH is the only enzyme that cleaves S-adenosylhomocysteine, a reaction product and an inhibitor of all S-adenosylmethionine-dependent methylation reactions. We have compared the spatial and temporal patterns of nuclear localization of SAHH and of nuclear methyltransferase activities during embryogenesis and in tissue culture cells. Nuclear localization of Xenopus SAHH did not temporally correlate with DNA methylation. However, we found that SAHH nuclear localization coincides with high rates of mRNA synthesis, a subpopulation colocalizes with RNA polymerase II, and inhibitors of SAHH reduce both methylation and synthesis of poly(A)(+) RNA. We therefore propose that accumulation of SAHH in the nucleus may be required for efficient cap methylation in transcriptionally active cells. Mutation analysis revealed that the C terminus and the N terminus are both required for efficient nuclear translocation in tissue culture cells, indicating that more than one interacting domain contributes to nuclear accumulation of Xenopus SAHH.

Adenosylhomocysteinase↗
PubMed1999

Leader behavior impact on staff nurse empowerment, job tension, and work effectiveness.

OBJECTIVE: The authors tested a model linking specific leader-empowering behaviors to staff nurse perceptions of workplace empowerment, occupational stress, and work effectiveness in a recently-merged Canadian acute care hospital. SUMMARY BACKGROUND DATA: An integration of Kanter's organizational empowerment theory and Conger and Kunungo's model of the leader empowerment process constituted the theoretical framework for the study. Few published studies were found in which specific leader behaviors were linked empirically to staff nurses' workplace empowerment. METHODS: Staff nurses (n = 537) were surveyed shortly after a merger of two large tertiary hospitals. Structural equation modeling techniques were used to test the proposed model. RESULTS: Leader-empowering behaviors significantly influenced employees perceptions of formal and informal power and access to empowerment structures (information support, resources, and opportunity). Higher perceived access to empowerment structures predicted lower levels of job tension and increased work effectiveness. The amount of explained variance in the final model was 42%. CONCLUSIONS: Support for the model tested in this study highlights the importance of nurse managers' leadership behaviors within current turbulent healthcare organizations.

Adult↗
PubMed1999

Controlled resuscitation for uncontrolled hemorrhagic shock.

OBJECTIVE: To test the hypothesis that controlled resuscitation can lead to improved survival in otherwise fatal uncontrolled hemorrhage. METHODS: Uncontrolled hemorrhage was induced in 86 rats with a 25-gauge needle puncture to the infrarenal aorta. Resuscitation 5 minutes after injury was continued for 2 hours with lactated Ringer's solution (LR), 7.3% hypertonic saline in 6% hetastarch (HH), or no fluid (NF). Fluids infused at 2 mL x kg(-1) x min(-1) were turned on or off to maintain a mean arterial pressure (MAP) of 40, 80, or 100 mm Hg in six groups: NF, LR 40, LR 80, LR 100, HH 40, and HH 80. Blood loss was measured before and after 1 hour of resuscitation. RESULTS: Survival was improved with fluids. Preresuscitation blood loss was similar in all groups. NF rats did not survive 4 hours. After 72 hours, LR 80 rats (80%) and HH 40 rats (67%) showed improved survival over NF rats (0%) (p < 0.05). Rebleeding increased with MAP. Attempts to restore normal MAP (LR 100) led to increased blood loss and mortality. CONCLUSION: Controlled resuscitation leads to increased survival compared with no fluids or standard resuscitation. Fluid type affects results. Controlled fluid use should be considered when surgical care is not readily available.

Animals↗
PubMed1999

Telepresence surgery system enhances medical student surgery training.

The telepresence surgery system (TeSS) permits the surgeon to operate on a patient across distances. This is achieved through real-time 3D video vision, stereo audio, and remote instrument control with haptic feedback. Telepresence surgery has been proposed to be useful in providing specialist operative consultation to remote areas. Remotely mentoring medical students with no surgical experience through complex procedures provides an even greater challenge. Third-year medical students with no prior operative experience were mentored exclusively through use of TeSS during a standard surgical skills lab. This two-day laboratory includes abdominal procedures and thoracic procedures. The medical students were alone in the operating room and the teaching surgeon was in an entirely separate room. Anatomy, surgical principles, and adjunct techniques were taught to the students. The students felt the experience was better than standard because of the enhanced learning secondary to the required verbal accuracy in describing the procedures. In addition, they felt they had better visibility since the instructor was not standing in the way. The telepresence surgery system can be successfully used to remotely mentor and enhance introductory surgical training for inexperienced medical students.

Animals↗
PubMed1999

[Obstructive urolithiasis in a female lamb].

In this report, the case of a 2-month-aged female lamb with obstructive urolithiasis, caused by calculi consisting of calcium-phosphate (apatite), is described. Urolithiasis as an often occurring problem in male sheep rarely emerges in female individuals. This lies mainly on the differences in anatomy between male and female urogenital apparatus. The account of diagnosis, therapy and clinical course in that special case are discussed, along with possible causes of the disease, the etiopathogenesis and recommended prophylactic steps.

Animals↗
PubMed1998

Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium.

The Genetics Initiative of the National Institute of Mental Health (NIMH) was a multisite study that created a national repository of DNA from families informative for genetic linkage studies of schizophrenia, bipolar disorder, and Alzheimer's disease. The schizophrenia families were collected by three sites: Washington University, Harvard University, and Columbia University. This article, one in a series that describes the data collected for linkage analysis by the schizophrenia consortium, presents the results for the European-American sample. The European-American sample comprised 43 nuclear families and 146 subjects. Ninety-six of the family members were considered affected by virtue of having received a DSM-III-R diagnosis of schizophrenia (N = 82) or schizoaffective disorder, depressed (N = 14). The families contained a total of 50 independent sib-pairs. Using the significance threshold criteria suggested by Lander and Kruglyak [(1995): Nat Genet 241-247], no region showed statistically significant evidence for linkage; two markers on chromosome 10p showed statistical evidence suggestive of linkage using the criteria of Lander and Kruglyak [(1995): Nat Genet 241-247]: D10S1423 (nonparametric linkage (NPL) Z = 3.4, P = .0004) and its neighbor, D10S582 (NPL Z = 3.2, P = .0006).

Adolescent↗
PubMed1998

Psychobiological heterogeneity of familial and sporadic schizophrenia.

BACKGROUND: Although schizophrenia is presumed to be heterogeneous, there has been limited success distinguishing familial from sporadic cases. We used psychobiological measures to examine heterogeneity, as they may be closer to neurobiology than symptoms. Smooth pursuit eye movement quality (SPEM) and dichotic listening (DL) tests to tones and words were used to assess hemispheric laterality asymmetry. METHODS: Forty-six research unit patients participated in assessments of family history (FH) and physiological measures. FH was categorized by three exclusive groups: FH-1 patients had a chronic schizophrenia-related psychosis in a first-degree relative, FH-2 had it in second-degree relative, and FH-3 had no family member with a reoccurrence. RESULTS: Analysis of variance showed a significant group difference for SPEM and DL tones. SPEM was significantly worse in all three schizophrenia groups than for the normal comparison subjects. Among the schizophrenia groups, the nonfamilial group (FH-3) had the worst SPEM quality, FH-2 had intermediate quality, and FH-1 had the best quality. Conversely, only the nonfamilials (FH-3) had normal right hemispheric lateralization for tones, whereas familials did not, and FH-2 again had intermediate values. The lateralization quotient for DL words did not significantly differ among the groups. CONCLUSIONS: SPEM was affected most in sporadic, not familial schizophrenia, whereas dichotic listening was most affected in familial schizophrenia. This double dissociation supports the utility of the familial/sporadic distinction and suggests that etiological factors in different forms of schizophrenia may impact principally on distinct neurobiological substrates, despite similar patient phenomenology.

Adult↗
PubMed1998

De novo expression of the alpha5beta1-fibronectin receptor in HT29 colon-cancer cells reduces activity of C-SRC. Increase of C-SRC activity by attachment on fibronectin.

Changes in integrin expression during malignant transformation have been observed in many tumors. Colon-carcinoma cells show reduced expression or even loss of the alpha5beta1 integrin compared to normal or adenoma cells. To determine the significance of absent alpha5beta1 integrin signaling, we transfected the cDNA coding for the alpha5 integrin sub-unit into the human colon-carcinoma cell line HT29, which constitutively lacks this subunit but does express the beta1 subunit. We show here that the newly expressed fibronectin receptor alpha5beta1 generates multiple signals, causing marked changes in cytoskeletal arrangements within a few minutes of adhesion to fibronectin. Cells expressing the alpha5beta1 integrin exhibit the formation of actin stress fibers and focal adhesions, as well as the induction of tyrosine phosphorylation of several proteins, within 10 min. We identified the focal adhesion kinase pp125FAK and the cytoskeletal protein paxillin as major phosphorylation substrates in these cells. These proteins remained hypophosphorylated when alpha5-negative control cells were plated on fibronectin. The tyrosine kinase pp60c-src, regarded as central in the regulation of cellular proliferation and constitutively over-expressed in HT29 and in colon-carcinoma cells, showed reduced intrinsic kinase activity in unstimulated HT29alpha5 cells. In contrast, fibronectin-induced signaling through alpha5beta1 increased pp60c-src activity. Moreover, immunoprecipitation of pp60c-src from extracts of HT29alpha5 cells cultivated on fibronectin for 20 min revealed complex formation of pp60c-src and tyrosine-phosphorylated pp125FAK. Our data suggest that de novo expression of the alpha5beta1 integrin in HT29 colon-cancer cells restores signaling via pp125FAK and pp60c-src. Thus, loss of this receptor during malignant transformation may contribute to tumor-cell autonomy, while reduced activity of pp60c-src in HT29alpha5-cells may participate directly in growth control.

Cell Adhesion↗
PubMed1998

Integrin alpha5beta1: a potent inhibitor of experimental lung metastasis.

The integrin alpha5beta1 seems to be the most relevant receptor of tumor cells for binding to fibronectin. Although numerous studies suggest a role of tumor cell fibronectin interaction in tumor metastasis, differential integrin expression on tumor cells has, however, not been correlated with metastatic capabilities. We addressed this question by transfection of the integrin alpha5beta1 cDNA into HT-29 human colon carcinoma cells which led to de novo expression of functional integrin alpha5beta1. Similar to other reports, expression of the integrin alpha5beta1 in HT-29 tumor cells exerted an inhibitory action on cell proliferation as indicated in our study by formation of fewer colonies in soft agar. The tumor growth inhibitory property of the integrin alpha5beta1 was also shown by reduction of subcutaneous xenograft growth in nude mice to approximately 50% of that of control transfectants. For the first time, we found that several clones of integrin alpha5 subunit transfectants displayed dramatically reduced formation of lung colonies and cutaneous metastasis after intravenous injection into nude mice. While most animals inoculated with control transfectant cells formed macroscopically visible lung colonies ranging from 12.6 +/- 2.6 to 22.0 +/- 6.6 (mean colony number +/- SEM), mice inoculated with HT-29 cell clones expressing the integrin alpha5beta1 were almost completely free of lung colonies (ranging from 0.0 +/- 0 to 0.2 +/- 0.1). Our results imply that integrin alpha5beta1 expression inhibits circulating tumor cells in pursuing late steps of the metastatic process as represented by the artificial metastasis (lung colonisation) model.

Animals↗
PubMed1998

Oral cytarabine ocfosfate in acute myeloid leukemia and non-Hodgkin's lymphoma--phase I/II studies and pharmacokinetics.

Cytosine arabinoside (AraC) is rapidly inactivated via systemic deamination with half-lives ranging from 1 h (i.v.) to 4 h (s.c.) -- and cannot be applied orally due to its hydrophilic properties. These limitations might be overcome by YNK01 -- a lipophilic prodrug of AraC -- that is resistant to deoxycytidine deaminase and can be applied orally. In the present study the therapeutic activity, side-effects and pharmacokinetics of YNK01 were evaluated in a phase I/II study including patients with relapsed or refractory acute myeloid leukemia (AML) (n=23) or low-grade non-Hodgkin's lymphoma (NHL) (n=20). YNK01 was given by 14 day cycles with escalating doses starting with a daily dose of 50 mg/m2 (equivalent to 20 mg/m2 AraC on a molar basis). The maximum tolerated dose was reached at the 600 mg/m2 dose level with WHO grade 3-4 diarrhoea as the main toxicity. In the 23 patients with AML two complete remissions, four partial remissions and three patients with stable disease were observed. In the 23 patients with AML two complete remissions, four partial remissions and three patients with NHL two cases reached partial remission and six other patients mainained stable disease. Pharmacokinetic evaluations were performed during 34 treatment cycles in 28 patients. The data suggest that YNK01 was absorbed in the distal part of the small intestine and taken up into hepatocytes. After hepatic psi and subsequent beta-oxydation of YNK01 the released AraC (and its deamination product AraU) appeared in the systemic circulation. Time of maximum concentration (h), half-life (h) and area under the curve (ng x h/ml, at the 1200 mg dose level) were as follows (VC variation coefficient) YNK01: 1.0 (0.58), 10.1 (0.43), 12622 (0.65); AraC: 23.2 (0.57), 22.6 (0.36), 3496 (0.76); AraU: 19.2 (0.58) 22.3 (0.33) 15441 (0.66). Of the total dose of YNK01 15.8% was absorbed and metabolized to AraC and AraU, defining the metabolic bioavailability of this prodrug. A linear relationship was observed between YNK01 dose and YNK01 AUC and AraC AUC over the whole dose range tested. AraC was released from hepatocytes over a prolonged period of time resulting in long lasting plasma levels similar to a continuous i.v. infusion. After administration of YNK01 at a dosage of 100-150 mg/m2 plasma levels of AraC were comparable to those achieved after low-dose AraC treatment (20 mg/m2) while at doses of YNK01 of 450-600 mg/m2 concentrations of standard-dose AraC (100 mg/m2) were obtained. We conclude that YNK01 shows considerable activity against relapsed and refractory AML and NHL and that its pharmacokinetic properties offers advantages in comparison to (standard) i.v. or s.c. AraC in clinical practice.

Acute Disease↗
PubMed1998

Three dimensional CT evaluation of occipito-atlanto-axial dislocation in rheumatoid arthritis.

Involvement of the upper cervical spine, with possible instability and dislocation of the atlanto-axial-cervico-occipital joints in patients with rheumatoid arthritis (RA), is routinely monitored with conventional radiographs. As disease progresses severe interpretation problems occur, especially when looking for cranial migration of the odontoid process. The aim of the present study was to evaluate whether three dimensional CT examination should be considered for such monitoring. After clinical and biochemical examination of 20 consecutive patients, diagnostic information about cranial migration of the odontoid process was obtained by conventional radiograms and by three dimensional CT examination. When using conventional radiographs the odontoid process and the its relation to the skull base could be outlined in 8 of the 20 patients. whereas all bony structures could be well demonstrated on the CT examination and the degree of cranial migration into the foramen magnum could be quantified. Three dimensional CT should be considered as a reliable examination for monitoring RA patients with involvement of the upper cervical spine and a possible cranial migration of the odontoid process.

Adult↗
PubMed1998

Lactated Ringer's solution resuscitation causes neutrophil activation after hemorrhagic shock.

PURPOSE: To determine the degree of neutrophil activation caused by hemorrhagic shock and resuscitation. METHODS: Awake swine underwent 15-minute 40% blood volume hemorrhage, and a 1-hour shock period, followed by resuscitation with: group I, lactated Ringer's solution (LR); group II, shed blood; and group III, 7.5% hypertonic saline (HTS). Group IV underwent sham hemorrhage and LR infusion. Neutrophil activation was measured in whole blood using flow cytometry to detect intracellular superoxide burst activity. RESULTS: Neutrophil activation increased significantly immediately after hemorrhage, but it was greatest after resuscitation with LR (group I, 273 vs. 102%; p < 0.05). Animals that received shed blood (group II) and HTS (group III) had neutrophil activity return to baseline state after resuscitation. Group IV animals had an increase in neutrophil activation (259 vs. 129%; p < 0.05). CONCLUSION: Neutrophil activation occurring after LR resuscitation and LR infusion without hemorrhage, but not after resuscitation with shed blood or HTS, suggests that the neutrophil activation may be caused by LR and not by reperfusion.

Animals↗