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G G Klee

Publications and source records attributed to G G Klee.

At least 55 records · Page 3Linked to original sources
PubMed1996

Clinical usage recommendations and analytic performance goals for total and free triiodothyronine measurements.

The major clinical role for total triiodothyronine (TT3) and (or) free T3 (FT3) is the assessment of hyperthyroidism in patients with suppressed sensitive thyrotropin (sTSH) concentrations. The assays are particularly important in hyperthyroid patients with normal free thyroxine (FT4) concentrations to assess potential T3 thyrotoxicosis. Other specialized uses for T3 and FT3 measurements are monitoring thyroid hormone replacement therapy, the evaluation of amiodarone-induced thyrotoxicosis, and predicting outcome of antithyroid drug therapy in patients with Graves hyperthyroidism. The roles of these tests in assessing heart function in cardiopulmonary bypass surgery, evaluation of patients with neuropsychiatric disorders, and monitoring of patients on anticonvulsant therapy are not well defined. These assays are not recommended for diagnosis of hypothyroidism. Analytic recommendations include CV < 5.2% for T3 and < 3.8% for FT3; < 0.2% cross-reactivity with L-T4; and < 1.0% cross-reactivity with D-T4, D-T3, and reverse T3.

Graves Disease↗
PubMed1996

Pancreastatin secretion by pituitary adenomas and regulation of chromogranin B mRNA expression.

Pancreastatin, a carboxyl-terminal amidated peptide derived from chromogranin (Cg)A, inhibits secretion of insulin and parathyroid hormone. Our recent studies found significant amounts of immunoreactive pancreastatin in all pituitary adenomas except prolactin adenomas. To analyze the effects of pancreastatin on pituitary cell function, 17 cultured pituitary adenomas were examined for immunoreactive pancreastatin and pancreastatin secretion by the tumors. The effects of pancreastatin on pituitary hormone secretion and on pituitary hormone (follicle-stimulating hormone and prolactin), CgA, and CgB mRNA levels were also examined. Immunoreactive pancreastatin and CgA were present diffusely in gonadotroph and null cell adenomas, but only a few prolactin adenoma cells expressed pancreastatin or CgA. When cells were treated with hypothalamic peptides, gonadotroph adenomas were the only group that released increased amounts of pancreastatin in response to gonadotropin-releasing hormone (10(-7) mol/L). Pancreastatin (10(-7) mol/L) treatment did not stimulate pituitary hormone secretion significantly. In situ hybridization analyses showed that gonadotropin-releasing hormone and pancreastatin treatment led to significant increases in CgB and follicle-stimulating hormone mRNAs in gonadotroph adenomas, whereas CgA mRNA levels did not change significantly. These results show that there is a differential distribution of pancreastatin secretion in pituitary adenomas and that the hypothalamic hormone gonadotropin-releasing hormone and the CgA-derived peptide pancreastatin can regulate CgB mRNA in gonadotroph adenomas, suggesting an autocrine effect of pancreastatin on pituitary tumor function.

Adenoma↗
PubMed1996

Prostate-specific human kallikrein (hK2) as a novel marker for prostate cancer.

BACKGROUND: Although prostate-specific antigen (PSA) has aided significantly in the diagnosis of prostate cancer, more sensitive and accurate assays are needed. Presently, we are developing a sensitive immunoassay for hK2 protein for the detection of prostate cancer. METHODS: Polyclonal and monoclonal antibodies specific for hK2 were produced and used for Western blot analysis and immunohistochemistry for detection of hK2 protein in serum and human tissues. The reverse-transcriptase polymerase chain reaction (RT-PCR) was utilized to detect hK2 mRNA from patient blood samples. RESULTS: Western blot analysis demonstrated that the antibodies used are monospecific for hK2. Immunohistochemistry showed that hK2 is expressed only in prostatic epithelia. An RT-PCR study showed that hK2 mRNA would be a useful candidate for early detection of prostatic micrometastasis. CONCLUSIONS: Monospecific antibodies for hK2 have been developed for detecting hK2 protein. Our studies indicate that hK2 may be a useful marker for prostate cancer.

Antibodies, Monoclonal↗
PubMed1995

Incidence of prostate cancer diagnosis in the eras before and after serum prostate-specific antigen testing.

OBJECTIVE: To estimate the incidence of prostate cancer in Olmsted County, Minnesota, from 1983 through 1992 to describe the secular changes that have occurred since the introduction of serum prostate-specific antigen (PSA) testing to the community medical practice in 1987. DESIGN: Population-based, descriptive epidemiological study with ecological and individual level comparisons over time. STUDY SETTING: Olmsted County, Minnesota, where the Rochester Epidemiology Project provides passive surveillance of the population for health outcomes. SUBJECTS: All 511 biopsy-proven incident cases of adenocarcinoma of the prostate diagnosed from 1983 through 1992. The community inpatient and outpatient medical records of all incident cases were reviewed to evaluate the presenting characteristics of men at the time of diagnosis. RESULTS: The age-adjusted incidence of biopsy-proven prostate cancer increased from 64 per 100,000 person-years in 1983 to 216 per 100,000 person-years in 1992. The increase occurred primarily between 1987 and 1988 and was predominately for organ-confined tumors. The age-specific incidence increased dramatically in this same period among men aged 50 years and older. Among men aged 70 years and older, however, prostate carcinoma incidence rates declined after 1990 following the initial increase. This decline among older men contrasted with community-based estimates of PSA utilization rates, which demonstrated consistent increases since 1987 to nearly 50% of the older population in 1992. CONCLUSION: These results support the premise that the recent increase in prostate cancer is due in part to the increased utilization of serum PSA testing. Further, the increased incidence appears to be a transient phenomenon due to the depletion of previously undiagnosed cases from the previous pool. Finally, these data suggest that, in terms of stage at diagnosis, early detection efforts may be effective in identifying more early stage (smaller) cancers.

Adenocarcinoma↗
PubMed1995

Overexpression of a human prostate-specific glandular kallikrein, hK2, in E. coli and generation of antibodies.

The genomic and the cDNA clones of human glandular kallikrein (hK2), a member of the kallikrein family, have been isolated; however, the hK2 protein has not yet been identified and characterized. The deduced sequence of hK2 is highly homologous to prostate specific antigen (PSA), a widely accepted prognostic indicator of prostate carcinoma. Also, hK2 mRNA, like PSA mRNA, is exclusively expressed in prostatic epithelia. These two properties make hK2 a potentially useful marker for studying prostate cancer. In this paper, we describe for the first time the overexpression of the entire hK2 protein (pre-pro hK2:pphK2) in the E. coli system. Our system yields high levels of authentic pphK2 (as determined by partial amino acid sequence analysis) comprising about 40% of total cellular protein. pphK2 was purified to near homogeneity by preparative SDS/PAGE and used to generate anti-pphK2 antibodies in rabbits. The antibodies recognize the recombinant hK2 protein and a major band of approximately 34 kDa in seminal fluid.

Amino Acid Sequence↗
PubMed1995

Free, complexed and total serum prostate specific antigen: the establishment of appropriate reference ranges for their concentrations and ratios.

PURPOSE: Prostate specific antigen (PSA) exists in the serum in several molecular forms that can be measured by immunodetectable assays: free PSA, PSA complexed to alpha 1-antichymotrypsin (complexed PSA) and total PSA, which represents the sum of the free and complexed forms. We determined the normal distribution of values and established the appropriate reference ranges for these 3 molecular forms of PSA and their ratios (free-to-total, complexed-to-total and free-to-complexed PSA). Knowing the amount and ratio of these molecular forms appears to be useful in enhancing the ability of PSA to distinguish potentially curable prostate cancer from benign prostatic hyperplasia and in decreasing the number of unnecessary prostate biopsies. MATERIALS AND METHODS: A total of 422 healthy men 40 to 79 years old was randomly chosen from the male population of Olmsted County, Minnesota and underwent a detailed clinical examination that included digital rectal examination, serum PSA determination and transrectal ultrasound to exclude the presence of prostate cancer. Using newly developed, monoclonal-monoclonal immunofluorometric assays for each molecular form, the free, complexed and total PSA, and the ratios of these 3 forms were determined for each study participant. RESULTS: All 3 molecular forms correlated directly with patient age (r = 0.45, r = 0.43 and r = 0.45, respectively). Using the 95th percentile, the recommended age-specific reference ranges for the free, complexed and total PSA forms, respectively, are 0.5, 1.0 and 2.0 ng./ml. for men 40 to 49 years old; 0.7, 1.5 and 3.0 ng./ml. for men 50 to 59 years old; 1.0, 2.0 and 4.0 ng./ml. for men 60 to 69 years old, and 1.2, 3.0 and 5.5 ng./ml. for men 70 to 79 years old. With regard to each of the ratios (free-to-total, complexed-to-total and free-to-complexed PSA) none correlated with patient age. As a result, the appropriate upper limit of normal (95th percentile) for all 3 ratios is constant for men of all ages. These reference ranges are greater than 0.15 for free-to-total PSA ratio, less than 0.70 for complexed-to-total PSA ratio and greater than 0.25 for free-to-complexed PSA ratio. The free-to-total PSA ratio will have its greatest value for men with a serum PSA value between 2 and 10 ng./ml. CONCLUSIONS: The establishment of appropriate reference ranges for free, complexed and total PSA as well as the ratios will allow the practicing urologist to incorporate these new parameters into the diagnostic evaluation of men at risk for early, potentially curable prostate cancer.

Adult↗
PubMed1995

Stability of serum prostate-specific antigen determination across laboratory, assay, and storage time.

OBJECTIVES: To understand the comparability of serum prostate-specific antigen (PSA) determinations across assays and storage time. METHODS: Serum PSA levels were determined for men aged 40 to 79 years from the clinical subset of the Olmsted County Study of Urinary Symptoms and Health Status Among Men on fresh samples and after a median of 32 months on banked samples, frozen at -70 degrees C. Baseline serum PSA levels were determined by Tandem-R PSA assay. Follow-up levels on the banked samples were determined by the IMx PSA assay and a repeat Tandem-R PSA assay in a different laboratory and by an immunofluorometric PSA assay at another site. RESULTS: The median serum PSA level determined by Tandem-R assay at baseline was 1.0 ng/mL (25th percentile, 0.6; 75th percentile, 1.7). The distributions of determination made by follow-up Tandem-R, IMx, and immunofluorometric analyses were essentially identical. Overall, the assays were highly correlated. The correlations between the baseline serum PSA determination and repeated Tandem-R, IMx, and immunofluorometric determinations were 0.96, 0.96, and 0.97, respectively (all P < 0.001). The median duration of frozen storage was 32 months (range, 26 to 39 months), and the correlations between baseline and follow-up determinations did not change when stratified by duration of storage. CONCLUSIONS: These data provide important reassurance about the use of serum PSA determinations obtained by different assays, in different laboratories, and in properly stored samples across time.

Adult↗
PubMed1995

Nifedipine, but not verapamil, acutely elevates parathyroid hormone levels in premenopausal women.

BACKGROUND: Calcium channel antagonist therapy in humans has been associated with changes in anterior pituitary, thyroid and adrenal hormone secretion. Human studies assessing effects of calcium channel antagonists on calciotropic hormones have been few and typically involved small numbers of subjects studied for short periods of time. Few of these previously published studies have included women. The endocrine effects of calcium channel antagonists in women have become increasingly important as more women are taking these agents for diseases such as hypertension, angina, Raynaud's phenomenon and migraine. OBJECTIVE: To assess both acute and chronic effects of calcium channel antagonists on calciotropic hormones in women. DESIGN: A four-week prospective, randomized trial. SUBJECTS: Twenty-nine premenopausal women, randomly assigned to receive either 240 mg of sustained release verapamil or 30 mg of sustained release nifedipine daily. LABORATORY END-POINTS: Total and ionized serum calcium, phosphate, creatinine, parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP) and calcitonin, measured at baseline, after 24 hours, and 28 days of treatment. RESULTS: Total and ionized calcium, phosphate, creatinine, PTHrP and calcitonin levels were not altered significantly after 24 hours or 28 days in any of the subjects, when compared to baseline. There were no significant differences in PTH levels after 24 hours or 28 days of verapamil treatment. There was a significant increase in serum PTH levels after 24 hours of nifedipine therapy; however, these differences were not evident after 28 days of therapy. CONCLUSIONS: The short-term administration of nifedipine results in increased release of parathyroid hormone; however, long-term administration has no significant effect on the concentrations of calciotropic hormones.

Adult↗
PubMed1995

Differential regional effects of octreotide on human gastrointestinal motor function.

The effects of octreotide on regional motor function in the human gut are unclear. In a randomised, blinded study the effects of octreotide (50 micrograms, subcutaneously, three times daily) and placebo on gastric, small bowel, and colonic transit, and colonic motility and tone were assessed in 12 healthy volunteers whose colon had been cleansed. Octreotide accelerated initial gastric emptying (p = 0.05), inhibited small bowel transit (p < 0.01), and reduced ileocolonic bolus transfers (p < 0.05). Colonic transit was unaltered by octreotide; the postprandial colonic tonic response was inhibited (p < 0.05 v placebo), whereas colonic phasic pressure activity was increased by octreotide (p < 0.05 v placebo). These data support the use of octreotide in diarrhoeal states but not in diseases that cause small bowel stasis and bacterial overgrowth. Simultaneous measurements of colonic transit, tone, and phasic contractility are valid in studying the effects of pharmacological changes and may be applicable to the study of the human colon in health and disease.

Adult↗
PubMed1994

Four-marker serum screening for Down's syndrome.

The value of measuring the separate sub-units of human chorionic gonadotrophin (free alpha-hCG and free beta-hCG) instead of total hCG together with alpha-fetoprotein (AFP) and unconjugated oestriol (uE3) was examined to determine the effect on the performance of serum screening for Down's syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples relating to 75 singleton pregnancies with fetal Down's syndrome and 367 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the serum sample, supplemented by data from 970 white women with unaffected pregnancies. Using the four serum markers AFP, uE3, free beta-hCG, and free alpha-hCG, in addition to maternal age, 65 per cent of Down's syndrome pregnancies were detected for a 5 per cent false-positive rate compared with 59 per cent with the conventional triple test (AFP, uE3, total hCG with maternal age). If gestation was based on an ultrasound scan examination, the detection rate was 72 per cent using the four serum markers compared with 67 per cent with the triple test. As an alternative illustration, if the detection rate was kept at 60 per cent and gestation was estimated by an ultrasound scan examination the four-marker test reduced the false-positive rate by one-third from 3 per cent using the triple test to 2 per cent with the four-marker test. Screening performance was hardly affected by adjusting marker levels for maternal weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1994

Measurement of serum prostate specific antigen using IMx prostate specific antigen assay.

The analytical characteristics of singlet determinations of the IMx prostate specific antigen (PSA) assay are similar to the mean of duplicates using the Tandem-R not equal to PSA assay. The 2 assays are standardized equally and provide test results that correlate well (r = 0.9997). The IMx PSA assay is more automated, requires less technologist time and provides faster test results. This assay has a minimal detection limit of 0.02 to 0.04 ng./ml. and functional sensitivity at a 20% coefficient of variation of 0.06 to 0.13 ng./ml. With a sensitive lot of IMx PSA reagents, only 38% of post-radical prostatectomy patients had nondetectable values compared to 60% with the Tandem-R PSA assay. The within-person, biological standard deviation of PSA concentrations in post-radical prostatectomy patients was 0.01 ng./ml. Therefore, with a sensitive assay these low concentration measurements should be reliable for monitoring. However, the clinical use of these low concentrations for early detection of tumor recurrence must await further studies.

Analysis of Variance↗
PubMed1994

Prostate-specific antigen: critical issues for the practicing physician.

BACKGROUND: Serum prostate-specific antigen (PSA), when used in combination with existing detection methods, improves the clinician's ability to detect early and potentially curable prostate cancer. FINDINGS: This report describes clinically important issues about use of the serum PSA concentration for detecting early prostate cancer. Other PSA-related factors--PSA density, PSA velocity, and age-specific reference ranges--seem to enhance the ability of clinicians to distinguish benign prostatic conditions from early prostate cancer. Because digital rectal examination only minimally affects the serum PSA concentration, delaying a determination after this examination is unnecessary. Finasteride therapy for benign prostatic hyperplasia should be initiated only after the prostate has been evaluated for cancer because this 5 alpha-reductase inhibitor lowers the serum PSA value by approximately 50%; however, reassessment of the prostate for cancer is necessary if the PSA level fails to decrease as expected or increases to more than 2 ng/mL during finasteride treatment. CONCLUSION: Currently, PSA is the most important, accurate, and clinically useful tumor marker for prostate cancer.

Adult↗
PubMed1994

Prostate-specific antigen: concepts for staging prostate cancer and monitoring response to therapy.

FINDINGS: The prostate-specific antigen (PSA) level alone does not facilitate precise pathologic staging on an individual basis, although advanced stage tends to correlate with an increased PSA level. The staging accuracy of PSA, however, can be enhanced by considering the variables of tumor grade and clinical stage. Staging radionuclide bone scans in asymptomatic, untreated patients with clinically localized prostate cancer and a PSA value of less than 10.0 ng/mL are unnecessary. After radical prostatectomy, the serum PSA level is exquisitely sensitive to recurrent or residual disease. Ultrasensitive PSA assays can increase the sensitivity of PSA as a tumor marker after surgical removal of the prostate. Currently, however, the clinical usefulness of PSA concentrations detected in the ultrasensitive range after radical prostatectomy is unknown. Serum PSA values aid in monitoring patients who have received definitive radiation therapy for prostate cancer. Patients in whom the serum PSA level decreases to the reference range have a favorable prognosis. An increasing serum PSA concentration after radiation therapy heralds progressive prostate cancer. The serum PSA level after androgen deprivation therapy (ADT) also has prognostic importance in that a decrease to the normal range predicts a prolonged remission in most patients. Because expression of PSA is under direct hormonal influence, however, ADT can decrease the serum PSA value independent of antitumorigenic activity. Patients who have received ADT must be closely monitored for signs of clinical progression because, in some patients, a serum PSA concentration within the reference range may underestimate actual tumor burden and activity. CONCLUSION: PSA is the most useful and accurate tumor marker for staging and monitoring prostate cancer after therapy.

Biomarkers, Tumor↗
PubMed1994

Development of a highly sensitive immunochemiluminometric assay for prostate-specific antigen.

OBJECTIVES: An assay is described for measuring very low concentrations of prostate-specific antigen (PSA) which could be used to reliably monitor patients with radical prostatectomies potentially to detect early recurrence of prostate cancer. METHODS: A combination of immobilized and acridinium ester-labeled monoclonal antibodies was used to develop a two-step, 90-minute chemiluminometric assay. The reference standards for the serum assays were prepared by adding patient sera with a high concentration of PSA to base pools of female sera, which were selected because of low background counts and good recovery of added PSA. The assay was standardized to match the Abbott IMx PSA Assay. RESULTS: The serum-based analytic detection limit (calculated as response 2.5 standard deviations [SD] above the zero standard) is 0.004 ng/mL, whereas the "biologic detection limit" (calculated as 2.0 SD above the analytic detection limit) is 0.008 ng/mL. The assay is highly reproducible with interassay coefficients of variation (CV) under 12% down to 0.02 ng/mL, qualifying this as a "second generation" assay (eg, CV < 20% at 0.05 ng/mL). CONCLUSION: This assay can measure very low concentrations of PSA in plasma and a wide range of PSA concentrations in urine. This assay will provide a valuable analytic tool for the future evaluation of the clinical utility of "ultrasensitive" PSA measurements for the management of prostate cancer.

Analysis of Variance↗
PubMed1994

Comparability of the Tandem-R and IMx assays for the measurement of serum prostate-specific antigen.

OBJECTIVES: To assess the comparability of the Tandem-R and IMx serum prostate-specific antigen (PSA) assays across levels of the ratio of free-to-total serum PSA found in a community-based population of healthy men. METHODS: Banked serum samples from the baseline component of the Olmsted County Study of Urinary Symptoms and Health Status Among Men were thawed and analyzed using the Tandem-R and IMx PSA assays. Serum levels also were determined for the free, noncomplexed form of PSA, PSA complexed to alpha-1 antichymotrypsin, and total PSA with a research-based immunofluorometric assay. RESULTS: The results of the Tandem-R and IMx assays were strongly correlated at all levels of the ratio of free-to-total serum PSA. The Spearman correlation coefficients ranged from 0.87 to 0.98 (all p < 0.001). The relationship between the Tandem-R and IMx assays, however, differed at low levels of free-to-total serum PSA compared with high levels. In the lowest 10th percentile of the ratio of free-to-total serum PSA (0.04 to 0.18), the IMx assay read lower than the Tandem-R (slope +/- standard error = 0.92 +/- 0.04, intercept +/- standard error = 0.21 +/- 0.14); whereas in the upper 10th percentile of free-to-total ratio (0.46 to 0.65) the IMx assay yielded values higher than the Tandem-R assay (slope = 1.21 +/- 0.07, intercept = 0.14 +/- 0.05). In the middle 90%, the slope did not statistically differ from 1.0. CONCLUSIONS: For the majority of men, results of the Tandem-R and IMx PSA assays were virtually identical. The small differences found would not be of clinical significance for most men but should be considered when comparing results of different assays in sequential determinations for a specific man.

Adult↗