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Biomedical subjects

J Albers

Publications and source records attributed to J Albers.

At least 19 recordsLinked to original sources
PubMed1996

Tumor proliferative activity is predictive of pathological stage in clinical stage A nonseminomatous testicular germ cell tumors.

PURPOSE: Traditional histopathological features have failed to predict accurately the pathological stage of clinical stage A nonseminomatous germ cell tumors of the testis. Based on pilot studies in nonconsecutive patients at our university, we evaluated nontraditional risk factors (cell cycle analysis by flow cytometry, deoxyribonucleic acid analysis by single cell cytophotometry [image analysis] and assessment of proliferative activity by immunohistochemistry) combined with histopathological features in consecutive patients with clinical stage A nonseminomatous testis cancer. MATERIALS AND METHODS: Orchiectomy specimens from 105 consecutive patients with clinical stage A nonseminomatous germ cell tumors who underwent retroperitoneal lymph node dissection (76 with pathological stage A disease and 29 with proved metastasis) were recut, histopathologically reviewed, immunohistochemically stained with proliferation markers (for example Ki-67/MIB-1), and examined by flow cytometry and image analysis. RESULTS: After multiple logistic regression analysis, the G2M+S cell cycle fraction of the aneuploid tumor stemline was the most predictive parameter of pathological stage (p = 0.0004). Using a cutoff of 41%, patients with metastasis were predicted with a sensitivity of 71%. Of 61 patients with a G2M+S value of less than 41%, 53 had pathological stage A cancer (negative predictive value 87%). A low volume of embryonal carcinoma was predominant in patients at low risk for metastasis and MIB-1 immunohistochemical staining identified 23% of patients with pathological stage A tumor who were at extremely low risk for metastatic disease. CONCLUSIONS: Assessment of tumor cell proliferation cannot classify accurately high risk patients at a clinically applicable level. However, identification of patients at low risk for metastasis by flow cytometry, immunohistochemical proliferation markers and volume of embryonal carcinoma may be possible at the 90% level. MIB-1 staining is able to classify patients at extremely low risk for metastasis. These parameters deserve further study, since identification of patients at extremely low risk for metastasis could potentially decrease overall morbidity in the management of clinical stage A nonseminomatous testis cancer.

Cell Division↗
PubMed1995

Immunohistochemical assessment of tumor proliferation and volume of embryonal carcinoma identify patients with clinical stage A nonseminomatous testicular germ cell tumor at low risk for occult metastasis.

BACKGROUND: Thirty percent of patients with clinical Stage A nonseminomatous testicular germ cell tumor (NSGCT) are incorrectly clinically staged. In a previous retrospective study at Indiana University, the combination of tumor proliferation rates by flow cytometry and histopathologic evaluation defined risk groups for occult metastatic disease in these patients with clinical Stage A NSGCT: A new immunohistochemical proliferation marker (MIB-1) was therefore used to assess growth fraction in combination with histopathology in an effort to predict pathologic stage in patients with clinical Stage A NSGCT: METHODS: Primary orchiectomy specimens from 90 consecutive patients with clinical Stage A NSGCT (January 1992-November 1993) who underwent retroperitoneal lymph node dissection at Indiana University were histopathologically evaluated. Formalin fixed, paraffin embedded tissue sections were immunohistochemically stained using a monoclonal antibody against the nuclear proliferation-associated antigen Ki-67 (MIB-1). Satisfactory staining was obtained by using an antigen retrieval method based on microwave oven heating of paraffin sections. RESULTS: MIB-1 immunohistochemical staining showed significant differences in mean values between 65 patients (66.1%) with pathologic Stage A NSGCT and 25 (80.4%) patients with pathologic Stage B NSGCT (P = 0.0032). The negative predictive value for patients with pathologic Stage A disease was 87% using a cut-off of 80% or less MIB-1 positively stained cells. A combined approach, using the absolute volume of embryonal carcinoma per patient (< 2 ml) and MIB-1 immunostaining (< or = 80%) was able to define a group of 30% of all patients who were at extremely low risk for occult metastatic disease. CONCLUSIONS: MIB-1 immunostaining in combination with histopathology aided in defining a low risk group patients with clinical Stage A NSGCT but failed to identify patients at high risk for metastasis. The risk factors need to be tested in a prospective clinical trial to determine if they are potentially useful in assigning therapy to individual patients.

Antigens, Neoplasm↗
PubMed1995

[New parameters for prediction of pathological stage in clinical stage I non-seminomatous testicular tumors].

Traditional histopathological risk factors have failed to predict pathological stage accurately in clinical stage I nonseminomatous testicular germ cell tumours. Histopathology, flow cytometry, cytophotometry, and immunohistochemical staining techniques were used in an effort to define high- and low-risk groups for occult metastasis in a consecutive series of 105 patients who underwent retroperitoneal lymph node dissection. After multiple logistic regression analysis, the proliferative S + G2M cell cycle fraction of the aneuploid tumour stemline was the most highly predictive parameter of pathological stage (P = 0.0004). Using a cut-off of 41%, pathological stage II patients were predicted with a sensitivity of 71%. There were 61 patients with S + G2M values below 41%, and 43 of them had pathological stage I disease (negative predictive value 87%). A low volume of embryonal carcinoma was predominant in low-risk patients, and MIB-1 immunohistochemical staining identified a subgroup of 23% of patients with pathological stage I disease and at extremely low risk of metastatic disease. Assessment of tumour cell proliferation does not allow accurate classification of high-risk patients at a level that is adequate for clinical application. Patients who are at low risk of metastasis, however, can be identified by flow cytometry, immunohistochemical proliferation markers and volume of embryonal carcinoma with 90% certainty. These parameters deserve further study, since identification of a subgroup of patients at extremely low risk of metastasis could potentially reduce the overall morbidity in the management of clinical stage I nonseminomatous testis cancer.

Animals↗
PubMed1993

Differences of size and shape of active and inactive X-chromosome domains in human amniotic fluid cell nuclei.

It is a widely held belief that the inactive X-chromosome (Xi) in female cell nuclei is strongly condensed as compared to the largely decondensed active X-chromosome (Xa). We have reconsidered this problem and painted X-chromosome domains in nuclei of subconfluent, female and male human amniotic fluid cell cultures (46,XX and 46,XY) by chromosomal in situ suppression (CISS) hybridization with biotinylated human X-chromosome specific library DNA. FITC-conjugated avidin was used for probe detection and nuclei were counterstained with propidium iodide (PI). The shape of these nuclei resembling flat ellipsoids or elliptical cylinders makes them suitable for both two-dimensional (2D) and three-dimensional (3D) analyses. 2D analyses of Xi- and Xa-domains were performed in 34 female cell nuclei by outlining of the painted domains using a camera lucida. Identification of the sex chromatin body in DAPI-stained nuclei prior to CISS-hybridization was confirmed by its colocalization with one of the two painted X-domains. In 31 of the 34 nuclei the area AXi for the inactive X-domain was smaller than the area AXa for the active domain (mean ratio AXa/AXi = 1.9 +/- 0.8 SD, range 1.0-4.3). The signed rank test showed a highly significant (P < .0001) difference both between AXa and AXi and between the ratios r(Xa) and r(Xi), calculated by dividing the maximum length L of each X-domain by its maximum width W. In most nuclei (26/34) we found r(Xa) > r(Xi) demonstrating a generally more elongated structure of Xa. For 3D analysis a confocal scanning laser fluorescence microscope (CSLFM) was used. Ten to 20 light optical sections (PI-image, FITC-image) were registered with equal spacings (approx. 0.4 microns). A thresholding procedure was applied to determine the PI-labeled nuclear and FITC-labeled X-domain areas in each section. Estimated slice volumes were used to compute total nuclear and X-domain volumes. In a series of 35 female nuclei most domains extended from the top to the bottom nuclear sections. The larger of the two X-chromosome domains comprised (3.7 +/- 1.7 S.D.)% of the nuclear volume. A mean ratio of 1.2 +/- 0.2 SD (range 1.1-2.3) was found for the volumes of the larger and the smaller X-domains in these female nuclei. In a series of 27 male amniotic fluid cell nuclei the relative X-chromosome domain volume comprised (4.0 +/- 2.6 S.D.)%.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic Fluid↗
PubMed1990

Lecithin cholesterol acyl transferase deficiency: molecular analysis of a mutated allele.

The enzyme, lecithin cholesterol acyltransferase (LCAT), is responsible for the esterification of plasma cholesterol mediating the transfer of an acyl group from lecithin to the 3-hydroxy group of cholesterol. Deficiency of the enzyme is a well-known syndrome with a widespread geographic occurrence. We have cloned an allele from a patient homozygous for the LCAT deficiency. The only change that we could detect is a C to T transition in the fourth exon of the gene; this causes a substitution of Arg for Trp at position 147 of the mature protein. The functional significance of such a substitution with respect to the enzyme defect was demonstrated by transfecting the mutated LCAT gene in the cell line COS-1.

Alleles↗
PubMed1989

Serum zinc changes due to iron supplementation in teen-age pregnancy.

Serum zinc and iron concentrations in a group of pregnant teen-agers supplemented with a multivitamin were compared during pregnancy with a group supplemented with a multivitamin containing 18 mg Fe. Serum measurements were at 13 wk of gestational age (prestudy) and during supplementation at 20, 32, and 38 wk, delivery, and 4 and 12 wk postpartum. Hematocrit measurements were used to adjust the measured metal concentrations for the diluting effect of the normal blood-volume increase. The non-Fe-group mean, adjusted serum Zn concentrations showed no change, but the serum Fe decreased to 28% below prestudy concentrations at 38 wk. In contrast, the Fe-supplementation group showed a progressive increase in Fe concentrations to a maximum of 38% above prestudy concentrations at 4 wk postpartum and a 35% decrease from prestudy Zn concentrations during the third trimester. The results of this study suggest that 18 mg Fe/d is adequate supplementation for nonanemic teen-age pregnancy and depresses the serum Zn concentration.

Adolescent↗
PubMed1985

omega-123I-hexadecanoic acid metabolic probe of cardiomyopathy.

The utility of omega-123I-hexadecanoic acid myocardial scintigraphy as a metabolic probe of cardiomyopathies was investigated. Sixteen patients with a variety of cardiomyopathies and myopathies that involve cardiac muscle and ten volunteers were imaged in the postabsorptive state in a 40 degrees LAO projection after a standard dose of omega-123I-hexadecanoic acid. An elimination T1/2 was calculated from the left ventricular myocardial time-activity curve. An uptake index, corrected for chest wall attenuation, was also computed in 7 of 10 volunteers and 8 of 16 patients. Of the 16 patients, only 2 had distinctly abnormal omega-123I-hexadecanoic acid myocardial tracer kinetics. The first patient had a metabolic disorder of which carnitine deficiency was one component. The second patient had endocardial fibroelastosis, a process which has been linked to disorders which deprive the myocardium of oxygen and energy. Therefore, the cardiomyopathy may have been caused by some abnormality of cardiac metabolism other than carnitine deficiency. Although of limited utility in the overall cardiomyopathic population, omega-123I-hexadecanoic acid myocardial scintigraphy should be further investigated as a screening test for carnitine deficiency and related metabolic abnormalities in patients at risk.

Adolescent↗
PubMed1983

Strategic planning.

The use of long-range planning techniques is essential if health care organizations are to survive. The regulatory and competitive forces that exist right now are likely to become even stronger in the future. It is important to remember that these forces represent opportunities as well as risks. Health care organizations can best resolve the conflicts that exist by using the strategic planning process to identify alternate voluntary means to achieve the same goals.

Hospital Administration↗
PubMed1979

Automated determination of total plasma cholesterol: a serum calibration technique.

The automated (AutoAnalyzer II) determination of cholesterol in nine serum pools in the concentration range 3.465-8.871 mmol/l, gave results that were approximately 10% higher than reference values when the analyses were based on unesterified cholesterol standards containing the same amount of water as the sample extracts (1963 analyses in 12 laboratories during a 12 month period; automated value = 0.032 + 1.10 X (Reference value)). A serum calibration procedure was successful ilues, and was equally effective in correcting the values observed for aliquots of 368 fresh-frozen plasma samples analyzed in each of the 12 laboratories during a 38 month period.

Autoanalysis↗
PubMed1978

Analytical performance and comparability of the determination of triglycerides by 12 Lipid Research Clinic laboratories.

Twelve Lipid Research Clinic laboratories performed automated fluorometric triglyceride analyses on four control serum pools of known concentration by a modified Hantzsch reaction. The analyses were done during a two-year period, with use of common standards, methodology, and quality-control procedures. Estimates of analytical bias, variability, and short- and long-term trends for each instrument and for the entire group of LRC instruments are presented. High accuracy, precision, and interlaboratory comparability were achieved through rigorous standardization and control of the entire analytical procedure. Individual instrument biases varied from an average of 4.9% below to 1.0% above reference values. Between-run variability was often less than within-run variability and interlaboratory variation was substantially less than intralaboratory variation. The total standard deviation for all instruments ranged from 37 to 63 mg/liter. Only 5 to 14% of this variation was due to differences among instruments. The among-instruments standard deviation ranged from 12 to 17 mg/liter; the between-run, within-instrument standard deviation ranged from 29 to 46 mg/liter, and within-run standard deviation from 27 to 40 mg/liter. The significance of the results for long-term collaborative studies is discussed.

Analysis of Variance↗
PubMed1977

Regulation of low density lipoprotein receptor activity by cultured human arterial smooth muscle cells.

The ability of cultured human arterial smooth muscle cells to regulate low density lipoprotein (LDL) receptor activity was tested. In contrast to human skin fibroblasts incubated with lipoprotein deficient medium under identical conditions, smooth muscle cells showed significantly reduced enhancement of 125I-labeled LDL and 125I-labeled VLDL (very low density lipoprotein) binding. Smooth muscle cells also failed to suppress LDL receptor activity during incubation with either LDL or cholesterol added to the medium, while fibroblasts shoed an active regulatory response. Thus, in comparison with the brisk LDL receptor regulation characteristic of skin fibroblasts, arterial smooth muscle cells have and attenuated capacity to regulate their LDL receptor activity. These results may be relevant to the propensity of these cells to accumulate LDL and cholesterol and form "foam cells" in the arterial wall in vivo, a process associated with atherogenesis.

Aorta, Thoracic↗
PubMed1976

Glucocorticoids and triglyceride transport: effects on triglyceride secretion rates, lipoprotein lipase, and plasma lipoproteins in the rat.

In order to elucidate the mechanism(s) of hyperlipidemia following glucocorticoid administration, dexamethasone (0.125 mg/Kg) was administered daily intramuscularly for 2 wk to male Sprague-Dawley rats and the effects on plasma triglyceride (TG) and cholesterol (Chol), lipoprotein neutral lipids, hepatic triglyceride secretion rates (TGSR; Triton), and epididymal fat lipoprotein lipase (LPL) were determined. Special measures were taken to maintain positive caloric balance and keep the weights of control and dexamethasone-treated animals comparable. Significant increases (p less than 0.001) in TG and very-low density lipoprotein (VLDL) triglyceride associated with no change in Chol and actual reduction in both triglyceride and cholesterol in low density lipoprotein (ldl) were observed in the steroid-treated animals. Dexamethasone treatment was associated with increased basal insulin and glucose levels, an insignificant increment in TGSR, and a highly significant reduction (p less than 0.001) in LPL. These findings suggest that glucocorticoid treatment increases splanchnic triglyceride production rates, but the resulting hypertriglyceridemia is primarily a consequence of impaired VLDL removal due to low adipose tissue LPL activity.

Animals↗
PubMed1976

Effects of chronic uremia, hemodialysis, and renal transplantation on plasma lipids and lipoproteins in man.

Since quantitative and qualitative alterations in plasma lipoproteins may provide insights into mechanism(s) of altered lipid transport in renal failure, whole plasma triglyceride (TG) and cholesterol (Chol) concentrations and lipoprotein neutral lipids and composition were examined in patients with chronic renal failure (undialyzed and dialyzed) and following successful renal transplantation. Both uremic groups demonstrated increased TG (p less than 0.001) and normal Chol in whole plasma and increased total TG and Chol in the very low-density lipoprotein fraction (VLDL). All hyperlipidemic subjects showed a Type IV phenotype. The percentage triglyceride in VLDL was slightly higher than control in the dialysis patients, and significantly increased in LDL in both undialyzed (p less than 0.001) and dialyzed (p less than 0.005) uremic groups. Transplant patients had significant increases (p less than 0.001) in both TG and Chol in whole plasma, and increased total TG and Chol in both the low-density lipoproteins (LDL) and VLDL fractions. Transplant patients with hyperlipidemia showed a variety of phenotypes and an enrichment of triglyceride in VLDL and LDL. These findings indicate that abnormalities in lipoprotein metabolism in renal failure patients are not appreciably affected by chronic dialysis treatment and continue following successful transplantation. The tendency toward increased VLDL and LDL triglyceride content in these patients resembles the lipoprotein neutral lipid composition found in nonrenal patients with similarly elevated plasma lipids. These alterations could result from primary disturbances in VLDL production and/or removal.

Blood Glucose↗