PubMed Health⌕ Search

Biomedical subjects

K Klein

Publications and source records attributed to K Klein.

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

Differential impact of Raf-1 kinase activity on tumor cell resistance to paclitaxel and docetaxel.

Docetaxel (Taxotere) is becoming increasingly important in the treatment of many tumor sites and is unusually active in tumors that are resistant to the structurally similar taxane, paclitaxel. These data suggest that the processes that confer cellular paclitaxel resistance may have a substantially lower impact upon the cytotoxicity induced by docetaxel. We have recently reported that there is a marked Raf-1 kinase dependency of paclitaxel resistance in human cervical and ovarian tumor cell lines. We therefore characterized the impact that inherent and genetically induced variations in Raf-1 kinase activity have on the docetaxel cytotoxicity in human ovarian and cervical cancer cell lines. Our data suggest that docetaxel cytotoxicity is independent of Raf-1 kinase activity in the cell lines studied and that the lack of cross-resistance between these two taxane compounds may be due to the differential impact that Raf-1 kinase activity has on their cytotoxicity. Should these relationships pertain to the clinical situation, these findings could form the basis for a molecular-based triage of patients to receive docetaxel when response to paclitaxel may be unlikely due to high Raf-1 kinase activity.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Age at menarche and cortical bone geometry in premenopausal women.

Previous studies have suggested that the timing of puberty might have an impact on the adult skeleton. What composite of bone structure could be affected by the timing of puberty is unknown at present. In this study, we evaluated the relationship between age at menarche and bone cortex geometry at the distal radius. Using peripheral quantitative computed tomography, we determined total area of the radial cross section, cortical bone area, periosteal cortical perimeter, endosteal cortical perimeter, and cortical width in 169 healthy premenopausal women aged 40-45 years. When stratified according to age at menarche (early, <12 years In = 22]; intermediate, 12-14 years [n = 118]; late, >14 years [n = 29]), only endosteal cortical perimeter varied significantly between the groups (p = 0.02, by analysis of variance), the mean value being 10% higher in the late compared to the early menarche group. However, weight and body mass index also exhibited significant variations between groups. After adjustment for weight the differences in endosteal cortical perimeter remained significant (p = 0.03). In multiple regression analysis, endosteal cortical perimeter was the only parameter of cortex geometry, which was independently associated with age at menarche. In a model including height and weight, age at menarche explained about 2% of the variability in endosteal cortical perimeter (p = 0.04). These data suggest that the bone marrow cavity of the distal radius may be slightly larger when puberty occurs later. Whether this marginal effect influences fracture risk in later life appears questionable.

Adolescent↗
PubMed1999

Depression and anxiety symptoms in women at high risk for breast cancer: pilot study of a group intervention.

OBJECTIVE: The psycho-oncology literature to date contains only one outcome study based on a group model for high-risk relatives of breast cancer patients. The authors set out to study the effects of group intervention in high-risk relatives of breast cancer patients. METHOD: Thirty-three high-risk relatives of breast cancer patients participated in a six-session, 12-hour group intervention model that consisted of educational and psychosocial components. RESULTS: There was a significant reduction of depression symptoms as reported on the Center for Epidemiologic Studies Depression Scale. Similarly, there was a significant reduction of anxiety symptoms as reported on the State-Trait Anxiety Inventory state scale. CONCLUSIONS: In this pilot study, the investigators found the group intervention model effective at reducing symptoms of depression and reactive (not chronic) anxiety.

Adaptation, Psychological↗
PubMed1999

The reliability and stability of the Turner and Engle working memory task.

The present study explored the psychometric properties of Turner and Engle's (1989) operation span task, a widely used measure of working memory capacity. We administered the task three times to 33 college students, using equivalent test materials. The interval between the first and second administrations was 3 weeks, with 6-7 weeks between the second and third administrations. Alpha coefficients were all .75 or more. Recall accuracy decreased as operation set size increased. Raw test-retest correlations ranged from .67 to .81, the corrected reliability was .88, and stability scores ranged from .76 to .92. Performance improved from the first to the second test. Relative to reported reliabilities of other tasks used to assess individual differences in working memory capacity, the operation span task appears to have several statistical advantages.

Analysis of Variance↗
PubMed1999

Autism spectrum disorders at 20 and 42 months of age: stability of clinical and ADI-R diagnosis.

The association between, and stability of, clinical diagnosis and diagnosis derived from the Autism Diagnostic Interview-Revised (ADI-R; Lord, Rutter, & Le Couteur, 1994) was examined in a sample of prospectively identified children with childhood autism and other pervasive developmental disorders assessed at the age of 20 months and 42 months. Clinical diagnosis of autism was stable, with all children diagnosed with childhood autism at age 20 months receiving a diagnosis of childhood autism or a related pervasive developmental disorder (PDD) at age 42 months. Clinical diagnosis of childhood autism was also reasonably sensitive, with all children who went on to receive a clinical diagnosis of childhood autism at 42 months being identified as having autism or PDD at 20 months. However, clinical diagnosis for PDD and Asperger's syndrome lacked sensitivity at 20 months, with several children who subsequently received these diagnoses at 42 months receiving diagnoses of language disorder or general developmental delay, as well as in two cases being considered clinically normal, at the earlier timepoint. The ADI-R was found to have good specificity but poor sensitivity at detecting childhood autism at 20 months; however, the stability of diagnosis from 20 to 42 months was good. In addition, the ADI-R at age 20 months was not sensitive to the detection of related PDDs or Asperger's syndrome. The continuity and discontinuity between behavioural abnormalities identified at both timepoints in the three domains of impairment in autism was examined, both in children who met final clinical criteria for an autistic spectrum disorder, and for children with language disorder who did not, as well as for a small sample of typically developing children.

Autistic Disorder↗
PubMed1998

Does leptin have an effect on bone in adult women?

Recent studies have implicated leptin in the modulation of bone mass during skeletal development. Whether leptin also exerts an influence on bone after growth has stopped is unknown at present. In this cross-sectional study on 94 women (60 premenopausal, 34 postmenopausal) aged 40-60 years, we analyzed the relationship between serum leptin and bone density and bone cortex geometry and bone metabolism. Total and trabecular bone density as well as total and cortical bone area were determined by quantitative computed tomography (QCT) at the distal radius. Bone metabolism was assessed by measuring bone-specific alkaline phosphatase, osteocalcin, procollagen type I C-terminal propeptide (PICP) and collagen type I C-terminal telopeptide in serum, and deoxypyridinoline in urine samples. None of the indices of bone density or geometry was significantly related to leptin serum concentrations (P > 0.05) before or after adjustment for body mass index (BMI). PICP was associated with serum leptin in the postmenopausal group only (r = -0.40 after adjustment for BMI; P = 0.009). Yet, as none of the other markers of bone metabolism exhibited a significant correlation with serum leptin in any of the menopausal groups, this association is likely to be due to the influence of extraskeletal factors on PICP serum levels. Thus, it appears that leptin has less influence on the mature than on the growing skeleton.

Adult↗
PubMed1998

In vivo evaluation of a closed loop monitoring strategy for induced paralysis.

OBJECTIVE: Reliable closed loop infusion systems for regulating paralysis level can be a great convenience to the anesthesiologists in automating their task. This paper describes the in vivo performance evaluation of a self-tuning controller that is designed to accommodate large variations in patient drug sensitivity, drug action delays and environmental interfering noise. METHODS: The infusion system was evaluated in six adult mongrel dogs. Following the manual induction of paralysis by an anesthesiologist, the controller regulated the infusion of vecuronium to maintain a desired level of paralysis. The integrated EMG response of the hypothenar muscle to a train-of-four stimulation of the ulnar nerve quantified the depth of paralysis. The controller's robustness was tested by contaminating the sensed twitch signal with electrocautery noise and electrode disconnection. RESULTS: The controller reached the initial level of paralysis of 100% in about 4.0 minutes and arrived at the desired level of 90% with an overshoot of 6.38% (+/-6.82). It maintained the desired level of paralysis with a 2.04% (+/-1.20) mean offset at 90% and 0.4% (+/-0.5) mean offset at 80% steady state level, respectively. The mean infusion rate to sustain 90% and 80% paralysis were 2.70 (+/-2.05) and 2.15 (+/-2.57) ((mg/kg)/min), respectively. CONCLUSIONS: The system adapted to a large variation in the sample subject drug sensitivity. It remained stable despite large amplitude disturbances and maintained the paralysis at the desired level following the removal of the disturbances.

Animals↗
PubMed1998

The effect of a specific strength-development exercise on bone mineral density in perimenopausal and postmenopausal women.

The objective of this study was to assess the effect of physical activity on bone density at the distal radius in healthy perimenopausal (23) and postmenopausal (60) women. The 83 women, aged 40-62 years, were randomized into two groups. The women participated in an exercise program of 40 minutes of jogging and 20 minutes of gymnastics three times a week for 1 year (group 1, n = 46) or 6 months (group 2, n = 37), respectively. Subjects in group 2 served as controls during the first 6 months. They were introduced to exercise classes after the first 6 months of the study and wore wrist weights (0.8 kg on each arm) during the gymnastics session. None of the women were on hormone replacement therapy (HRT). Results show a decrease in bone mineral density (BMD) during the first 6 months of the study in group 1 (2%, p < 0.01) and group 2, although this was not significant for the latter group (1.2%, n.s., p = 0.045). There was no significant change in osteocalcin serum concentration, fasting urinary calcium excretion, and calcium serum concentration during the first half of the study. After an additional 6 months, it was possible to stop BMD loss in both groups. Osteocalcin serum concentration significantly increased, and calcium serum concentration significantly decreased in groups 1 and 2. Fasting urinary calcium excretion decreased in both groups, although this was significant only in group 2 during the 1-year study. In conclusion, it proved possible to prevent BMD loss at the distal radius by our exercise program in perimenopausal and postmenopausal women. The effects of exercise may be general as well as localized. According to our results, additional localized benefits from a specific strength-development exercise may be seen.

Adult↗
PubMed1997

Radiographic manifestations of multiple myeloma in the mandible: a retrospective study of 77 patients.

PURPOSE: This retrospective study was done to determine the frequency and radiographic pattern multiple myeloma in the mandible. PATIENTS AND METHODS: Seventy-seven patients with multiple myeloma were studied using skull and panoramic radiographs of the jaws made at the time of initial diagnosis. RESULTS: Skull manifestations were present in 46.7% and jaw manifestations in 15.6% of the cases studied. The pattern of jaw involvement was characterized by osteolytic lesions without other radiographic manifestations of bone involvement. There was no relationship between the pattern of jaw and extragnathic involvement and increased M-component of secreted immune globulin. Jaw involvement was largely unaccompained by oral symptoms. CONCLUSION: The results suggest that mandibular lesions are a common finding in multiple myeloma.

Adult↗
PubMed1997

Restricting smoking at the University of Köln, Germany: a case study.

The effects of a new policy limiting smoking to separate, designated areas in School of Education buildings at the University of Köln, Germany, were analyzed. Although the majority (77%) of the 1,223 students surveyed did not expect the changed policy to affect their smoking habits, approximately 28% of the men and 30% of the women said they were smoking less at the university after the change went into effect. Ninety-one percent of the nonsmoking students and 68% of the smokers supported the new policy. Smoking rates among Köln students are not significantly different from those of the adult German population, where 34% of the women and 41% of the men are smokers. The findings in this study indicate that such a policy change may result in a net decrease in amount smoked and could be a successful intervention in countries where smoking rates are traditionally higher than they are in the United States.

Attitude↗
PubMed1997

Determinants of radial bone density as measured by PQCT in pre- and postmenopausal women: the role of bone size.

The aim of the present study was to examine the influence of anthropometric, hormonal, and geometric factors on the variability of radial bone mineral density (BMD) in women. In 583 healthy pre- and postmenopausal females (aged 40-60 years) radial total (BD) and trabecular BMD (TBD) was measured by peripheral quantitative computerized tomography at the nondominant distal forearm. In addition, 29 women who had suffered a Colles' fracture after minor trauma were also evaluated. There was no age-dependent change in radial BD and TBD before menopause. We found a negative correlation between BMD and age and years since menopause (YSM) in postmenopausal women (BD = 422.73 - 2.342 age - 6.308YSM; r = 0.36, p = 0.0001, n = 128). The variation of YSM, body mass index (BMI), and age accounted for 20% of the variability of BD in postmenopausal women. In contrast, in premenopausal women, only 3% of the variability could be explained by anthropometric variables. Bone mineral content (BMC) and bone area, but not BMD at the distal radius, were significantly correlated to grip strength (r = 0.25, p = 0.006 for BMC, r = 0.26, p = 0.003 for area). The cross-sectional bone area of the CT slice showed a significant increase with aging (y = 263.02 + 1.25x; r = 0.14, p = 0.0009). There was a strong negative correlation between bone area and BD and TBD (y = 516.04 - 0.668x; r = -0.57, p < 0.0001 for BD). If BMD is normalized for BA, variation is reduced by 32% (for BD) and 10% (for TBD), respectively. Women with Colles' fracture had a significantly lower TBD normalized for BA (fracture group [-0.71 +/- 0.88] vs. normals (0.03 +/- 0.99]; p = 0.00009). Our results show that YSM and BMI are predictors of postmenopausal BMD. However, radial BMD is influenced strongly by geometric variables such as cross-sectional bone area.

Absorptiometry, Photon↗
PubMed1997

Delinquency during the transition to early adulthood: family and parenting predictors from early adolescence.

This longitudinal study examines the prediction of delinquency in early adulthood by family variables and one type of maternal parenting skill during early adolescence. In 132 Caucasian families, family variables (marital status, interparental conflict, mother-adolescent relationship, and maternal depressive mood) and maternal communication/problem-solving skills were assessed through self-report measures and behavioral observations during subjects' early adolescence. Outcome measures (minor and severe delinquency, arrests/convictions) were assessed six years later during early adulthood. Regression analyses revealed relationships between the predictors and severe delinquency and arrests/convictions, but not minor delinquency. The interaction of low levels of maternal communication/problem-solving skills and negative family variables (i.e., high maternal depressive mood) was associated with higher rates of delinquency, whereas the interaction of higher levels of such maternal skills and positive family variables was associated with lower rates of delinquency.

Adolescent↗
PubMed1996

Specific interaction of (R)-3-hydroxybutyrate dehydrogenase with membrane phosphatidylcholine as studied by ESR spectroscopy in oriented phospholipid multibilayers: coenzyme binding enhances the interaction with phosphatidylcholine.

The interaction of phospholipid with (R)-3-hydroxybutyrate dehydrogenase, a phosphatidylcholine-requiring membrane enzyme, has been studied using ESR spectroscopy of spin-labeled lipids, both as ordered multibilayers and in lipid vesicle suspensions (liposomes). Partially oriented phospholipid multibilayers were prepared from lipid vesicles composed of a 1:1 mixture of phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Vesicles containing (R)-3-hydroxybutyrate dehydrogenase yielded active preparations of the enzyme in such multibilayers. With increasing protein/lipid ratio, the order of the multibilayers was disrupted as monitored by ESR spectroscopy with a spin-labeled analogue of PC, 5-doxyl-PC (5 mol %, 10% of total PC) as a probe. The outer peak separation of 5-doxyl-PC varied with the lipid/protein ratio. The lower the ratio, the larger was the separation, with higher activity enzyme being more effective in exerting this effect. When 5-doxylstearic acid was substituted for 5-doxyl-PC or when the enzyme was inactive, the 2A(zz) value stayed practically constant at its lower limit (about 54 G). Multilayers composed of 81% PE, 11% diphosphatidylglycerol (DPG), and 8% 5-doxyl-PC (no unlabeled PC present) gave similar results. With this lipid mixture, the maximal 2A(zz) value (about 61 G) was reached at lower protein/lipid ratios, although the enzymic activity of (R)-3-hydroxybutyrate dehydrogenase is reduced to 40% in this system. The outer peak separation also depended on the presence of the coenzyme, NAD+, and 2-methylmalonate. The latter enhances binding of NAD+ about 100-fold by forming a ternary complex. With this ternary complex, the 2A(zz) values were increased unless the maximal values had been reached already in the absence of coenzyme. In all these experiments only a single ESR spectral component was observed. Similar results were obtained for the enzyme in liposomes, although the effect was less pronounced apparently due to the higher mobility of the probe. It is concluded that PC is motionally restricted by (R)-3-hydroxybutyrate dehydrogenase and yet is in rapid exchange with the bulk lipid on the ESR time scale. PC is required for formation of tight and functional complexes with NAD [Rudy et al. (1989) Biochemistry 28, 5354-5366], and such complexes strengthen the interaction of the enzyme with PC.

Animals↗
PubMed1996

[Current state of alimentary iodine deficiency in Germany].

Germany finds itself among the most iodine deficient countries of Europe. Voluntary use of iodized salt constitutes the only goiter prophylaxis. In the last few years, measures such as the opening up of European internal markets, abolition of lac pertaining to the alimentary iodine consumption. Random samples of urine collected from 5932 persons without thyroid ailment, distributed over 32 regions of Germany, were measured for iodine excretion. The median value of iodine excretion was 72.4 micrograms I/g creatinine. Children under 10 years (76.9) and persons over 70 years (80.7) showed a slightly higher iodine elimination than those between 11-70 years (71.9). No differences between the former East Germany and West Germany as well as North, South and middle regions of unified Germany were observed. 55% of the study population presented with iodine values between 50 and 100 micrograms, 19% with lower than 50 micrograms. Only 9% showed sufficient iodine state. The results expose the inadequacy of the voluntary measures to tackle the problem of alimentary iodine deficiency.

Adolescent↗
PubMed1996

Receptor-mediated phosphoinositide metabolism in peripheral nerve and cultured Schwann cells.

Peripheral nerve possesses muscarinic cholinergic receptors, predominantly of the M3 subtype, that stimulate phosphoinositide metabolism. Evidence suggests that one site of this response is the myelin sheath. Purified peripheral nerve myelin contains several heterotrimeric GTP-binding proteins. Furthermore, carbachol and guanosine-5'-(3-O-thio)triphosphate-stimulated hydrolysis of exogenous phosphatidylinositol-4,5-bis-phosphate that is blocked by atropine can be reconstituted in a purified peripheral myelin-rich fraction. Nerve phosphoinositide turnover is also stimulated by adenosine analogs and blocked by adenosine receptor antagonists in a pattern consistent with the presence of adenosine A2 receptors in the tissue. Receptor-mediated phosphoinositide metabolism has also been studied in a human tumor-derived Schwann cell line (NF1T) derived from a neurofibromatosis-1 patient. By the same experimental criteria, NF1T cells also appear to contain adenosine A2 receptors which upon activation stimulate phosphoinositide turnover. However, phosphoinositide metabolism in these cells is not increased by either carbachol or ATP. Our findings taken together with other reports suggest that Schwann cells may possess a variety of receptors which regulate phosphoinositide metabolism.

Cells, Cultured↗
PubMed1996

Cross cultural child injury prevention awareness.

PURPOSE: The purpose of this study was to determine how injury prevention awareness of children ages 3, 4, and 5, based on recognition of hazards in pictures differs in the United States, Belgium, East Germany and West Germany. METHODS: Children from these four countries were presented with 10 different pictures. Each picture represented a common injury producing situation to which children are exposed in traffic, home, and recreation. RESULTS: Results indicate that for pictures relating to home hazards, less than 22% of children from Belgium (21.5%), West Germany (4.7%), and the United States (20.3%) clearly recognized the essential hazards in the pictures, whereas over 40% of the East German children clearly recognized these dangers. A higher proportion of the children from all countries recognized the traffic hazards. Only 23.9% of all children had a clear recognition of the playground situations. The child's age had a bearing on ability to recognize hazards overall. CONCLUSIONS: Children need to be provided with better injury prevention education at an early age, especially those from West Germany.

Accident Prevention↗