Search PubMed⌕ Search

Biomedical subjects

K Carlson

Publications and source records attributed to K Carlson.

At least 91 records · Page 5Linked to original sources

In vivo restriction. Sequence and structure of endonuclease II-dependent cleavage sites in bacteriophage T4 DNA.

Endonuclease II of bacteriophage T4 is required for in vivo restriction of cytosine-containing DNA from its host, Escherichia coli, (as well as from phage mutants lacking cytosine modification), normally the first step in the reutilization of host DNA nucleotides for synthesis of phage DNA in infected cells. The phage cytosine-DNA is fragmented incompletely to yield genetically defined fragments. This restriction is different from that of type I, II, or III restriction enzymes. We have located seven major endonuclease II-dependent restriction sites in the T4 genome, of which three were analyzed in detail; in addition, abundant sites were cleaved in less than or equal to 5% of all molecules. Sites I, II, and III shared the sequence 5'-CCGNNTTGGC-3' and were cleaved in about 25% (I and III) and 65% (II) of all molecules, predominantly staggered around the first or second of the central unspecified base pairs to yield fragments with one 5' base. The less frequently cleaved sites I and III deviated from site II in predicted helical structure when viewed from the consensus strand, and in sequence when viewed from the opposite strand. Thus, interaction with a particular helical structure as well as recognition of the bases in DNA appears important for efficient cleavage.

Base Sequence↗

Acute hemodynamic effects of terazosin in hypertensive and normotensive patients.

Terazosin, a selective alpha 1-adrenergic antagonist, was administered intravenously to 10 patients undergoing cardiac catheterization to determine its short-term hemodynamic effects. Hemodynamic measurements were performed before and 30 minutes after three doses of the drug: 1, 1, and 3 mg. One milligram of terazosin reduced the blood pressure (systolic/diastolic, mean) from a mean of 152.0/86.3, 110.7 mm Hg by -24.3/-9.4, -15.3 mm Hg (p less than 0.05). In the five patients who received 5 mg of the drug, blood pressure declined in a dose-dependent manner by -21.8/-3.8, -11.6 mm Hg after 1 mg, and by -35.8/-14.8, -22.8 mm Hg (p less than 0.05) after all 5 mg of the drug. The changes in blood pressure paralleled the terazosin-induced decrease in systemic resistance. Similar changes were recorded for pulmonary artery and capillary wedge pressures and pulmonary vascular resistance. The greatest hemodynamic response was noted with the first drug dose; succeeding doses had a progressively diminished incremental effect. Cardiac output, heart rate, and maximum left ventricular dp/dt demonstrated little change, whereas left ventricular end-diastolic pressure decreased after all three doses, reaching significance after 2 mg (-3.4 +/- 0.9 mm Hg, p less than 0.05), and left ventricular ejection fraction tended to increase (+5.6% +/- 2.4%, p less than 0.05 after 1 mg) and showed a dose dependence analogous to that of systemic resistance. Although not generally reaching statistical significance, indexes of aortic stiffness and compliance displayed a favorable effect. These data are consistent with terazosin's specific alpha 1-antagonism. Left ventricular performance is improved by afterload reduction, since terazosin demonstrated no direct effect on cardiac contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Measurement of estrogen receptors in normal and neoplastic lymph node tissue from dogs.

Estrogen receptors were measured in normal canine lymph nodes and neoplastic tissue from dogs with lymphoma, using a commercially available [3H]estradiol dextran-coated charcoal assay. Using the same assay, estrogen receptors were detected in the positive-control tissues--dog uterus, rat uterus, and lyophilized bovine uterus. Specific binding of [3H]estradiol was not detected in rat skeletal muscle or in any of the canine lymphoid tissues, indicating that the specimens did not contain estrogen receptors.

Animals↗

Renal function after autologous bone marrow transplantation.

Seventy-two out of 102 consecutive patients autografted for various hematologic and lymphoid malignancies had a relapse-free survival of greater than 6 months after autologous bone marrow transplantation (ABMT) and were evaluated for long-term effect of the treatment on the renal function. The myeloablative therapy included total body irradiation (TBI) in a single fraction of 7.5 Gy in 41/72 patients. Mean glomerular filtration rate (GFR) showed a significant decrease (p less than 0.01) and serum creatinine and serum urea an increase (p less than 0.05) 6 months after ABMT. Twelve of 72 patients (17%) developed renal dysfunction defined as greater than 25% decrease in GFR, in most cases accompanied by hematuria and proteinuria. Onset was 3-6 months after ABMT. Some patients have later improved considerably, but others continue to deteriorate in renal function. The single most important risk factor for renal dysfunction after ABMT was irradiation. Renal damage was most frequent in lymphoma patients conditioned with BEAC (carmustine [BCNU], etoposide, cytarabine, cyclophosphamide) followed by irradiation, suggesting that this drug combination might have potentiated the toxicity of irradiation. Nephrotoxic antibiotics probably contributed to renal damage in individual cases. Young age did not appear to be a risk factor. Our data indicate that combined treatment with BEAC and TBI should be used with caution and that renal function should be monitored in all patients after bone marrow transplantation to detect any new toxicity patterns of the various conditioning regimens currently used.

Adolescent↗

Maternal hemodynamics and aortic diameter in normal and hypertensive pregnancies.

The aortic diameters of 89 normotensive pregnant women were compared with those of nine rigorously defined preeclamptic women and 59 women who required antihypertensive therapy. Over the course of normal pregnancy, the diameter increased significantly; it was larger in preeclamptic than in normotensive women throughout pregnancy. The aortic diameter in women with high-resistance hypertension was smaller than that in normotensive women and in those with high-output, low-resistance hypertension, but it was larger in women with low-resistance hypertension than in normotensive women. The aortic diameter increased after treatment of high-resistance hypertension with hydralazine, but decreased after treatment of high-output, low-resistance hypertension.

Aorta↗

Inhibition of streptozotocin-induced islet cell tumors and N-nitrosobis(2-oxopropyl)amine-induced pancreatic exocrine tumors in Syrian hamsters by exogenous insulin.

The effects of streptozotocin (SZ) and N-nitrosobis(2-oxopropyl)amine (BOP), separately or in combination, on the pancreas, common duct, and gallbladder, all target tissues of BOP, were studied in Syrian golden hamsters. Groups of hamsters were treated with either a single dose (20 mg/kg body weight) of BOP (BOP group), or a single i.p. dose (50 mg/kg body weight) of SZ and 14 days later with a single s.c. injection of the same dose of BOP (SZ + BOP group). Another group of animals was treated similarly with BOP and SZ except that they received twice daily injections of insulin, beginning 1 day after SZ administration and for the duration of the experiment (52 weeks) (SZ + insulin + BOP group). The control group consisted of hamsters treated with a single dose of BOP and daily doses of insulin (insulin + BOP group). Hamsters treated with SZ recovered spontaneously from their diabetes, although the mortality was high (86%). BOP treatment inhibited the diabetogenic effects of SZ in both SZ + BOP and SZ + insulin + BOP groups and reduced the mortality to 43 and 74%, respectively. SZ pretreatment inhibited the incidence of BOP-induced pancreatic ductal/ductular cell carcinomas in the SZ + BOP group (P less than 0.01); this protective effect of SZ on carcinoma development was potentiated by additional treatment with insulin (SZ + insulin + BOP group, P less than 0.001). Although the frequency of BOP-induced tumors in the gallbladder (all polyps) was not altered by either SZ or insulin, the frequency of the common duct polyps was significantly lower in the SZ + insulin + BOP group than in the BOP group (P less than 0.005). Hamsters in the SZ, SZ + BOP, and SZ + insulin + BOP groups developed islet cell adenomas (insulomas). However, the SZ + insulin + BOP group had significantly fewer insulomas than in the SZ + BOP group (P less than 0.0005). The overall data confirm the inhibitory effect of SZ on BOP-induced pancreatic cancer and suggest that this effect is related to the diabetic condition of hamsters rather than insulin deficiency and that intact islets appear to be prerequisite for exocrine pancreatic cancer induction by BOP. On the other hand, the inhibitory action of insulin on insuloma induction by SZ and on ductal/ductular cancer induction by BOP seems to be related to the suppressive effect of this hormone on beta-cell and ductal/ductular cell replication, respectively.

Adenoma, Islet Cell↗

Insulin therapy prevents spontaneous recovery from streptozotocin-induced diabetes in Syrian hamsters. An autoradiographic and immunohistochemical study.

Streptozotocin (Sz) given as a single dose of 50 mg/kg body wt. caused severe diabetes in Syrian hamsters. However, the level of blood glucose decreased gradually after 21 days post-Sz and reached the near normal level at 70 days in 90% of hamsters. The recovery from diabetes was associated with the regeneration of the beta-cells of islets and a reduction in the initially increased number of alpha- and delta-cells. Daily treatment of diabetic hamsters with insulin was associated with the persistence of severe diabetes, lack of or minimal tendency for beta-cell regeneration and sustained hyperplasia of alpha- and delta-cells in 90% of hamsters. Insulin also inhibited DNA synthesis (as measured by incorporation of tritiated thymidine), in ductal, ductular and acinar cells in Sz-pretreated hamsters but not in normoglycemic control hamsters treated with insulin alone. The results demonstrate a deleterious effect of exogenous insulin in the course of Sz-induced diabetes in hamsters.

Animals↗

Cost-effectiveness study of the extracorporeal shock-wave lithotriptor.

We performed a cost-effectiveness analysis to examine the relative efficacy and costs of percutaneous ultrasonic lithotripsy (PUL), extracorporeal shock-wave lithotripsy (ESWL), and surgery for the treatment of upper urinary tract stones. We developed a Markov model with 35 states, cycles of 3 months, and a time frame of 5 years. Probability estimates were derived from a meta-analysis of the published literature. For stones less than or equal to 2 cm, ESWL is preferred to PUL, since it prevents 2 additional days of morbidity and saves $440. For larger stones, PUL is preferable to ESWL, avoiding 4 days of morbidity, and saving $722. Both ESWL and PUL were superior to surgery. Sensitivity analysis showed that the results are sensitive to ESWL efficacy rates, the stone recurrence rate, and the hospital component of the ESWL cost. Our analysis suggests that although ESWL is preferable, relatively small changes in the efficacy and cost can shift the preferred strategy; in addition, these findings underscore the need for more reliable data.

Cost-Benefit Analysis↗