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Biomedical subjects

C Wolf

Publications and source records attributed to C Wolf.

At least 199 records · Page 11Linked to original sources

Breast cancer protein PS2 synthesis in mammary gland of transgenic mice and secretion into milk.

PS2, a small estrogen-inducible secretory polypeptide with structural analogies to a growth factor, is produced by approximately 50% of human breast tumors. The function of PS2 is, however, unknown. To determine whether PS2 may play an autocrine role in the development of mammary tumors we constructed transgenic mice bearing fusion constructs designed to direct the expression of human PS2 in the lactating mammary gland under the control of the whey acidic protein (WAP) promoter. Mouse lines bearing the genomic PS2 gene under the control of the WAP promoter region (WAP-PS2-2) failed to express the transgene. However, mice harboring the fusion construct WAP-PS2-1, in which the PS2 coding sequence is inserted into the 5' untranslated region of the complete WAP gene, were observed to express the transgene. Expression was restricted to the secretory epithelium of the mammary gland during lactation, and PS2 protein was secreted into the milk. Nevertheless, no mammary gland dysplasia was observed, and PS2 expression had no discernable effect upon the physiology and/or development of the suckling young or the transgenic mother.

Animals↗

Method for rapid separation of 3,5,3'-triiodothyroacetic acid in human serum by fast protein liquid chromatography.

The 3,5,3'-triiodothyroacetic acid (TRIAC) has been approved as a valuable agent in the management of hyperthyroidism secondary to inappropriate secretion of thyrotropin. We have developed a fast protein liquid chromatography (FPLC) method for separation and quantification of TRIAC. Serum samples charged with TRIAC were extracted with methanol/ammonium acetate, the supernatants were evaporated to dryness, reconstituted in NaOH and injected on a reversed phase column for chromatography. For separation an isocratic elution method (methanol water; 0.1% trifluoroacetic acid) was used. The area under the curve (ml%) was compared with those of the calibration curves. Recoveries were 70 +/- 10.8%. TRIAC was eluted in 2.33 ml. Conclusively, the present method shows that TRIAC can be measured by FPLC and may be applied to the measurement of TRIAC in pharmacological studies.

Chromatography, High Pressure Liquid↗

Binding of spin-labeled clofibrate to lipoproteins.

The binding of spin-labeled clofibrate to native and partially delipidated lipoproteins is a rapid, linear and non-saturable process observed up to the critical micellar concentration of the drug. Low-density lipoproteins (LDL) display a lower affinity for the drug than very-low-density lipoproteins (VLDL) and high-density lipoproteins (HDL) relative to their respective specific volume. Unlike various lipophilic drugs, uptake of spin-labeled clofibrate does not correlate with lipoprotein lipid volume. Spin-labeled clofibrate binding to LDL is enhanced when the temperature increases above 25 degrees C. The binding to HDL and VLDL is less temperature-sensitive. The simulation of the ESR spectra has shown that two types of motion should be superimposed for the spin-labeled clofibrate in HDL, in LDL or in partially delipidated LDL. From 40 down to 25 degrees C for HDL and LDL, a fast anisotropic motion is observed. From 25 degrees C down to 5 degrees C, a two-component motion takes place, including a slow isotropic motion of the probe tumbling in a highly hydrophobic environment. Interactions of spin-labeled clofibrate with the apolipoproteins in HDL and LDL are assumed from the emergence of this strongly immobilized component observed when the temperature decreases. In contrast, for spin-labeled clofibrate inserted in the apolar core of VLDL, ESR shows only one component in the whole temperature range (5-40 degrees C). The location of the spin-labeled drug inside the various lipoprotein particles is discussed as a function of temperature.

Clofibrate↗

The 'Kennard effect' before Kennard. The early history of age and brain lesions.

The role of age in recovery of function after brain damage has been of particular interest since the mid-1930s when Kennard described sparing of motor function following brain damage in infant monkeys. In the years since her initial papers, this phenomenon has become known as the "Kennard principle." This article describes a number of observations of the Kennard principle prior to Kennard's first publication. Included are descriptions of both early animal research and neurologic cases.

Aging↗

Do oral carotenoids protect human skin against ultraviolet erythema, psoralen phototoxicity, and ultraviolet-induced DNA damage?

This study was performed in order to (1) assess the magnitude of a possible protective effect of oral carotenoids on ultraviolet B (UVB)-, ultraviolet A (UVA)-, and psoralen ultraviolet A (PUVA)-induced erythema in human skin and (2) to evaluate whether the postulated prevention of skin cancer by prophylactic administration of carotenoids is based on a decrease in UVB-induced DNA damage. Twenty-three healthy volunteers received oral carotenoids (150 mg/day) for 4 weeks. Serum levels were quantitated, and ranged from 390 to 1710 micrograms/dl. Before and after carotenoid administration, the UVA- and UVB-MEDs and the PUVA-MPD were determined by standard phototesting. DNA damage was assessed by autoradiographical measurement of unscheduled DNA synthesis (UDS) following UVB exposure before and after treatment. No statistically significant carotenoid-dependent protection was found against UVA, UVB, and PUVA erythema by comparing the pre- and postcarotenoid erythema doses. Also at the DNA level there was no indication of a protective effect that could be detected with the methods employed: the amount of UVB-induced UDS was not decreased after carotenoid treatment. We conclude that (1) carotenoids do not reduce UVB-, UVA-, or PUVA-induced erythema in human skin; that (2) reactive oxygen species may not be involved in PUVA-erythema production or, alternatively, carotenoids may not quench these radicals sufficiently in vivo; and that (3) carotenoid protection against UVB-induced carcinogenesis does not operate by reducing the number of mutagenic lesions in DNA.

Administration, Oral↗

[The syndrome of chronic actinic dermatitis. Persistent light reaction--actinic reticuloid].

The clinical, histological and photobiological features of persistent light reaction and actinic reticuloid are discussed with reference to the literature. Both conditions are characterized by extreme light sensitivity, have been reported exclusively in elderly men, and are interpreted as a consequence of a photoallergic reaction. In our view, persistent light reaction and actinic reticuloid do not represent separate entities, but rather the two extremes of a single spectrum of disease; in common with other workers, we prefer to call it chronic actinic dermatitis. This opinion is supported by a detailed analysis of three of our patients, who illustrate all variations of this photodermatosis.

Chronic Disease↗

[Severe poisoning with a cholinesterase inhibitor].

We report on a case of severe intoxication in an 18-year-old female who had ingested an insecticide with suicidal intent. The insecticide (thionacine) is a cholinesterase inhibitor used in gardening and agriculture. The resources of modern intensive care permitted successful treatment with artificial respiration and atropine. Treatment with oximes is controversial and may be dangerous. We suggest hospitalization even in mild cases of intoxication, in view of danger of changes in the course of the illness.

Adult↗

The Limulus amebocyte lysate assay. A rapid and sensitive method for diagnosing early gram-negative peritonitis in patients undergoing continuous ambulatory peritoneal dialysis.

The Limulus amebocyte lysate (LAL) assay was used in a blinded, prospective fashion to analyze peritoneal fluids from 35 consecutive patients undergoing continuous ambulatory peritoneal dialysis (CAPD), who presented with clinical peritonitis. The results were correlated with standard microbiologic culture results. The LAL assay was positive in all three patients with gram-negative peritonitis, was appropriately negative in 24 of 28 gram-positive infections (sensitivity, 100%; specificity, 86%) and was positive in two of five cases in which there was no microbiologic growth. One of the two patients in this last group yielded a gram-negative organism two days later. It was then demonstrated that therapeutic concentrations of a variety of antibiotics (cefazolin sodium, gentamicin sulfate, tobramycin sulfate, ticarcillin disodium, penicillin G potassium, vancomycin hydrochloride, metronidazole hydrochloride, piperacillin sodium, and trimethoprim/sulfamethoxazole) did not interfere with the LAL assay. Together, these data indicate that the LAL assay is useful for identifying patients at high risk for gram-negative peritonitis and for excluding from possible aminoglycoside exposure the majority of patients with peritonitis undergoing CAPD, most of whom will have gram-positive infections. Furthermore, lack of antibiotic interference allows the possibility of monitoring treatment efficacy.

Anti-Bacterial Agents↗

Comparative diagnostic value of a new computerized vectorcardiographic method (cardiogoniometry) and other noninvasive tests in medically treated patients with chest pain.

The diagnostic value of cardiogoniometry (CGM), a new computerized vectorcardiographic method, for the identification of coronary artery disease was compared with other noninvasive tests in 48 medically treated patients with chest pain. Coronary angiography revealed one-vessel disease in 18, two- or three-vessel disease in 21, and normal coronary arteries in 9 patients. Cardiogoniometry was less sensitive (63%) than thallium-201 (201T1) scanning (82%), but slightly more sensitive than the exercise ECG (50%) or a recently proposed parameter of exercise performance (50%). On the other hand, specificity was comparable among these tests (exercise ECG 78%, thallium-201 scanning 72%, CGM 67%, new parameter of exercise performance 66%). Moreover, the false negative rate of noninvasive testing was reduced from 8 to 3% when CGM was added to thallium-201 scanning and exercise ECG. Our findings indicate that in view of the easier feasibility with computerized technology, the future role of vectorcardiographic methods such as CGM in the noninvasive diagnosis of coronary artery disease should be redefined.

Adult↗

Comparison of the effects of three different treatment regimens of recombinant interferons (r-IFN alpha, r-IFN gamma, and r-IFN alpha + cimetidine) in disseminated malignant melanoma.

A total of 30 patients with progressively growing visceral and/or cutaneous malignant melanoma metastases were entered in a prospective phase II trial comparing three different therapeutic regimens of recombinant interferons (r-IFN). The first group of 12 patients received r-IFN alpha A 9-36 IU/day i.m. on 5 consecutive days/week. A second group of 11 patients was treated with r-IFN alpha A and oral cimetidine, 1000 mg/day. The third group of 7 patients had i.v. infusions of r-IFN gamma 0.25-0.5 mg/m2 on 3 days/week. Of the 12 r-IFN alpha A-treated patients, 1 responded (complete response, CR), 5 patients exhibited no change (NC), 3 patients had progressive disease (PD), and 3 patients could not be evaluated after therapy. In the group treated with r-IFN alpha A plus cimetidine 3 patients responded (1 CR, 2 partial responses) and 3 exhibited NC. The remaining patients showed PD. Treatment responses were found exclusively in patients with cutaneous and/or lymph node metastases. In contrast, none of the r-IFN gamma-treated patients responded to therapy. Known IFN side effects of varying degrees, sometimes severe, were observed in all patients. Despite the small numbers of patients treated, our preliminary data indicate that r-IFN alpha A therapy seems (1) to be of some therapeutic value in the treatment of cutaneous melanoma metastases, (2) to be superior to r-IFN gamma therapy, and (3) that overall response rates improve with the addition of oral cimetidine to r-IFN alpha A treatment.

Cimetidine↗

Behavioral correlates of vitamin D deficiency.

Rats deprived of vitamin D at weaning were compared to control rats on open field, stabilimeter, radial arm maze and spatial reversal tasks in order to test the hypothesis that vitamin D deficiency alters behavior and learning. The deficient animals engaged in statistically less open field rearing activity and spent more time each day negotiating the radial maze than did the control rats. These findings are consistent with the known influence of vitamin D on the musculoskeletal system. The deprived rats did not differ from the control animals on the learning measures. This would indicate that vitamin D deficiency may not significantly impair cognitive functions in young adult rats.

Animals↗

Effects of medial frontal cortex lesions on DRL performance in rats.

Rats with medial frontal cortical lesions (MFC) and control animals with sham operations were tested on an ascending series of 8 DRL schedules of reinforcement ranging from 5 to 70 seconds. Rats with MFC lesions did not differ from the control group in performance when response rate, responses per reinforcement and efficiency were analyzed. These results indicate that deficits in "response inhibition" often displayed by rats with MFC lesions may be task-specific.

Animals↗

Large and small medial frontal cortex lesions and spatial performance of the rat.

Rats with sham operations, or small or large medial frontal cortex lesions were compared for the acquisition of a position habit and for learning a series of 4 position habit reversals. No differences were found during acquisition of the position habit. On the reversals, the rats with the larger lesions were markedly impaired, while less severe deficits or control-like performance characterized the rats with the smaller ablations. Analyses of the error scores showed that the rats with the larger lesions made more perseverative errors than the other groups and performed more sporadically even after breaking a previous position habit. These results confirm the hypothesis that a strong relationship exists between medial frontal cortex lesion features (depth and length) and performance. The differences found in acquisition vs. reversal learning, and the nature of the errors observed, also suggest that this part of the brain functions as more than simply a spatial analyzer.

Animals↗

Human glomeruli release fatty acids which stimulate thromboxane synthesis in platelets.

The cell-free medium of isolated human glomeruli exhibited a procoagulant activity and stimulated thromboxane (TXB2) synthesis in human platelets in a dose-dependent manner. The amount of TXB2 measured was 16-fold higher than what could have been predicted (TXB2 synthesized by the platelets under control conditions plus TXB2 present in the glomerular supernatant). The lipid extract of the glomerular supernatant and its purified fraction including the fatty acids was still able to stimulate--although at a lesser degree--TXB2 synthesis in platelets. Stimulation was abolished after treatment of this fraction by charcoal or albumin. Gas chromatography/mass spectrometry analysis demonstrated the presence in the purified glomerular fraction of several long-chain saturated or monoenoic fatty acids at a total concentration of 80 microM with the following order of abundance: stearic, palmitic, myristic and oleic acids. Addition to human platelets of these same exogenous synthetic acids resulted in a dose-dependent stimulation of TX synthesis. It was maximum with three or four fatty acids tested in combination, but still present with myristic acid used separately. Arachidonic acid was absent in the glomerular supernatant. Thus the stimulation observed could not be related to a greater availability of substrate. Fatty acids did not act on platelets through a non-specific detergent effect since addition of high doses of detergents inhibited TXB2 formation in platelets. The combination of fatty acids from glomerular origin identified in the present study represents a novel factor involved in the control of intracapillary hemostasis, but different from the procoagulant activity common to many tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗

Relapses of idiopathic diffuse crescentic glomerulonephritis without immune deposits: report of 6 cases.

Idiopathic diffuse crescentic glomerulonephritis without immune deposits is a variant of rapidly progressive glomerulonephritis which can account for up to 40% of crescentic nephritis. The prognosis may depend on both the severity of histological injury at presentation and the efficacy of treatment. Recent advances in therapy have improved the outlook further, and prolonged stable remissions with mild renal failure can occur which contrast with the previously common evolution towards end-stage renal failure within a few weeks. However, relapses in otherwise stable remission may be seen, and we describe a series of 6 acute relapses interrupting such prolonged remissions. The relapses were defined by clinical and histological means. This modification of the natural history of some crescentic glomerulonephritis may reflect new therapeutic strategies, and the relapses may reflect a cyclical nature to the disease evolution which was previously hidden by hemodialysis. The possibility of successive flares suggests that kidney biopsies should be repeated when a rapid deterioration of renal function occurs, since treatment such as high-dose steroids and/or plasma exchange can be again effective if started early.

Adult↗