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Biomedical subjects

K E Blick

Publications and source records attributed to K E Blick.

31 records · Page 2Linked to original sources

Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon.

Gram-negative septicemia elicits multiple abnormalities of the coagulation system. Although products of coagulation can lead to clot formation, thereby potentiating organ damage, recent work has shown that low concentrations of thrombin can protect animals from the shock state. Because these amounts of thrombin also lead to formation in vivo of the anticoagulant enzyme, activated protein C, we examined the role of protein C in modulation of Escherichia coli shock in baboons. First, we infused activated protein C and lethal concentrations of E. coli organisms, which prevented the coagulopathic, hepatotoxic, and lethal effects of E. coli. Second, using an antibody to protein C we blocked protein C activation in vivo to determine if this influenced the response to lethal and sublethal concentrations of E. coli organisms. Under these conditions the response to lethal concentrations of E. coli organisms was made more severe and the response to sublethal concentrations of E. coli was made lethal. The coagulopathic, hepatotoxic, and lethal responses in this latter case were prevented by infusion of exogenous protein C.

Alanine Transaminase↗

Four immunoassay methods and standards compared for measuring fibronectin.

Several companies have developed commercial kits to measure plasma fibronectin rapidly and inexpensively with readily available laboratory equipment. In two of these kits (Cooper Biomedical and Boehringer-Mannheim) an immunoturbidimetric method is used. In a third kit (Biomedical Technologies, Inc.) an enzyme immunoassay method is used. To evaluate these commercial kits for fibronectin assay, we selected nephelometry as a comparison method for ranking the kits with regard to precision and accuracy. We also compared antibody and fibronectin cross reactivity. The antibodies from various manufacturers appear similar, but the fibronectin standards from different sources showed significant variation. Rate nephelometry and the Boehringer-Mannheim kit had the best within-run precision (CVs of 0.38% and 5.5% respectively). Between-run precision for nephelometry was excellent (CV = 1.9%) and somewhat high for the Boehringer-Mannheim kit (CV = 15.4%). This study demonstrates a need for further standardization of antigen (fibronectin) and antibody in commercial kits and the development of suitable stable quality-control material.

Antibodies↗

Decline in serum calcium, magnesium, and phosphorus values with oral glucose in normal neonates: studies of serum parathyroid hormone and calcitonin.

In 10 normal term infants aged 52 +/- 2.5 hours, serum calcium, magnesium, phosphorus, ionized calcium, parathyroid hormone, and calcitonin were studied at 0, 1/2, 1, and 2 hours after administration of 1.77 +/- 0.08 gm/kg glucose orally over 20 minutes. In response to glucose administration, serum glucose concentration rose and serum P, Ca, and Mg concentrations fell. Serum PTH concentration rose significantly, and blood ionized Ca and pH were unaltered. Serum calcitonin was elevated, as compared with adult values, and did not change. We suggest that in neonates, as in adults, oral ingestion of glucose lowers serum Ca, Mg, and P, and a compensatory rise in serum PTH concentration maintains blood ionized Ca concentration.

Administration, Oral↗

Postnatal changes in calcium-regulating hormones in very-low-birth-weight infants. Effect of early neonatal hypocalcemia and intravenous calcium infusion on serum parathyroid hormone and calcitonin homeostasis.

In very-low-birth-weight (VLBW) infants, we studied the hypotheses that in early neonatal hypocalcemia the serum parathyroid hormone (PTH) concentration would rise; the serum calcitonin (CT) concentration would decline; and, in response to intravenous (IV) calcium (Ca) infusion, the serum PTH concentration would be lowered; and the serum CT concentration would rise. Fifteen infants appropriate for gestational age (age, less than 32 weeks; birth weight, less than 1,500 g) were enrolled in the study. In eight infants in whom the serum Ca level declined to less than 6.0 mg/dL, changes in serum magnesium, phosphorus, PTH, CT, and whole blood ionized calcium (iCa) were evaluated on entry into the study, when serum Ca declined to less than 6.0 mg/dL, immediately after infusion of 18 mg/kg of elemental calcium as calcium gluconate, and at eight hours post-Ca infusion (+ 8 hr). The serum Ca concentration declined from 7.9 +/- 0.6 baseline (mean +/- SE) to 5.2 +/- 0.2 mg/dL pre-Ca infusion and rose to 9.17 +/- 0.74 mg/dL post-Ca infusion and 7.1 +/- 0.5 mg/dL at +8 hr post-Ca infusion. Whole blood iCa declined from 4.82 +/- 0.24 to 3.72 +/- 0.19 mg/dL pre-Ca infusion, rose to 6.68 +/- 0.32 mg/dL post-Ca infusion, and was 4.12 +/- 0.21 mg/dL at + 8 hr post-Ca infusion. The serum P concentration did not change significantly. The serum PTH concentration rose from 116 +/- 17 to 204 +/- 34 pmole/L pre-Ca infusion, declined to 149 +/- 22 pmole/L post-Ca infusion, and was 187 +/- 28 pmole/L at + 8 hr post-Ca infusion. The serum CT concentration was elevated and did not change significantly. Thus, in infants less than 32 weeks' gestation, the serum PTH level rises in early neonatal hypocalcemia and is suppressed by IV Ca infusion; the serum CT level is markedly elevated and is not altered in early neonatal hypocalcemia and does not rise further in response to IV Ca infusion in VLBW infants. We suggest that hypercalcitoninemia occurs in VLBW infants and that serum CT concentrations are unresponsive to changes in serum Ca.

Calcitonin↗

Quality control of acid phosphatase assay improved by direct reconstitution of lyophilized control materials with citric acid.

Current quality control of assays of acid phosphatase (EC 3.1.3.2) with thymolphthalein substrate is inadequate when certain control-suppliers' instructions are followed for reconstituting and stabilizing human lyophilized control material. If such materials are reconstituted with a citric acid solution, then stored frozen, control vial-to-vial variability is minimized, as are losses of activity in freshly reconstituted controls and losses during room-temperature storage of the control material. Effects of pH of the reconstituting solution on the acid phosphatase activity of human lyophilized controls are also discussed.

Acid Phosphatase↗

Radioimmunoassay for prostatic acid phosphatase helps discriminate patients with prostatic cancer.

We measured serum prostatic acid phosphatase in ostensibly normal controls and a selected patient population, using both a modified radioimmunoassay and an enzymic method with thymolphthalein monophosphate as substrate. The upper limit of normal for the radioimmunoassay was 2.2 micrograms/L; its sensitivity and specificity for prostatic cancer were 71 and 95%, respectively, vs 51 and 99% for the enzymic method. For both methods the correlation between clinical staging and values for acid phosphatase was poor. Our data suggest that adjunctive use of the radioimmunoassay may help further discriminate those patients requiring needle biopsy.

Acid Phosphatase↗

Cell proliferation in the developing human kidney.

In a previous study, utilizing antibodies to proliferating cell nuclear antigen (PCNA), we determined the proliferation index (PI) (percentage of PCNA-positive cells) of intrinsic renal cell populations in the normal adult and pediatric kidney. We have found that the PI in both adult and pediatric kidneys was very low (below 0.5 in all examined cell populations). In our present study, we investigated cell proliferation in the developing human kidney with an antibody to PCNA. Histologically normal kidneys were collected from 25 fetuses (spontaneous abortions and stillborns) ranging from 10 wk of gestation to term. Immature mesenchyme (blastema), immature early tubules, ampulla of ureteric bud, proximal tubules, Tamm-Horsfall protein (THP)-positive tubules, distal tubules, collecting ducts, and glomeruli were evaluated separately. The PI for each cell population was calculated. The PI of immature early tubules remains high (33-43) throughout embryonic life. The PI of blastemal cells is initially similarly high, but gradually decreases starting from the second trimester. The PI of THP-positive tubules, distal tubules, collecting ducts, and glomeruli starts out relatively high (5.9, 8.6, 6.0, and 12.4, respectively) and decreases gradually as term approaches (1.8, 1.3, 1.2, and 1.4, respectively). Interestingly, as soon as proximal tubules become differentiated (appearance of light microscopic features of proximal tubular epithelium with TP lectin positive brush border), their PI becomes very low (below 1) irrespective of the age of the kidney. This is the first quantitative study to show changes of the PI in various renal cell populations during human nephrogenesis. These changes in the PI relate to the stage of differentiation of the developing nephron segments.

Cell Division↗

Lowered serum Ca, blood ionized Ca, and unresponsive serum parathyroid hormone with oral glucose ingestion in infants of diabetic mothers.

Oral glucose ingestion may lower serum Ca in infants of diabetic mothers (IDMs). Six metabolically stable IDMs were studied following ingestion of 1.7 +/- 0.1 g/kg (mean +/- SE) of glucose over 20 min and serum Ca, Mg, P, blood iCa, serum PTH, and CT were measured at 0, 1/2, 1, and 2 h. Data obtained in IDMs were compared with previously reported findings in 10 normal neonates. In IDMs as in normal neonates, serum Ca, Mg, P declined significantly after oral glucose ingestion. Blood Ca2+ was significantly lower at +1/2 h in IDMs versus normal neonates, and by analysis of covariance, trends in blood Ca2+ were significantly different in IDMs versus normal neonates, (p less than 0.05). Serum PTH concentrations were unaltered in IDMs versus a significant rise in serum PTH noted in normal neonates. The difference between the two groups was significant statistically (p less than 0.05). Baseline serum CT was elevated in both groups and did not change. Thus, in IDMs responses to oral glucose ingestion differs from that seen in normal neonates as follows: blood Ca2+ is lowered in IDMs versus normal neonates, and serum parathyroid hormone (PTH) does not respond to a decline in blood Ca2+ in IDMs, whereas in normal neonates serum PTH rises and blood Ca2+ is maintained. We speculate that relative parathyroid gland unresponsiveness occurs in IDMs, which may result in lowered blood Ca2+ after oral glucose ingestion in these infants.

Administration, Oral↗