Search PubMed⌕ Search

Biomedical subjects

D Young

Publications and source records attributed to D Young.

At least 469 records · Page 26Linked to original sources
PubMed1986

Phase I/II trial of human recombinant beta-interferon serine in patients with renal cell carcinoma.

Beta-interferon serine (IFN-beta ser) is a genetically altered recombinant IFN with a specific activity of 2 X 10(8) IU/mg protein. We undertook a Phase I trial of this agent in 18 patients with metastatic renal cell carcinoma. IFN-beta ser was given by a 4-h intravenous infusion twice weekly (Monday and Thursday). Three patients were placed on escalating dose levels. Doses were also escalated in each patient if no unacceptable toxicity was detected on the previous treatment. The maximum initial tolerated dose was less than or equal to 150 million units/m2. However, development of patient tolerance allowed escalation beyond this dose and chronic therapy at this or higher doses in most patients. Toxicity was largely limited to the symptom complex of fever, malaise, mild hypotension, and anorexia. One patient developed reversible proteinuria (10 g/24 h) with no change in serum creatinine. Limited or no renal, hepatic, or hematological toxicity was observed. Six of 16 patients developed anti-IFN antibody levels. Fifteen patients received twice weekly treatments at near their maximum tolerated dose for greater than or equal to 4 weeks and were evaluable for response. Two patients developed a partial and one patient a minor response. We conclude that IFN-beta ser is a well tolerated IFN with minimal renal, hepatic, and bone marrow toxicity. It has apparent activity in metastatic renal cell carcinoma.

Aged↗
PubMed1985

Isolation and identification of 24-dehydroprovitamin D3 and its photolysis to 24-dehydroprevitamin D3 in mammalian skin.

Until now it had been assumed that mammalian skin contains only one provitamin D, 7-dehydrocholesterol, that is eventually converted to vitamin D3 after the skin is exposed to sunlight. Examination by reverse phase high performance liquid chromatography of lipid extracts from young rat skin, however, led to the observation that 7-dehydrocholesterol is not the only provitamin D in rat skin. Another provitamin D, accounting for 22 +/- 3% of the total provitamin content of the skin, was resolved from 7-dehydrocholesterol, and, on the basis of ultraviolet spectrophotometry, mass spectrometry, and nuclear magnetic resonance spectrometry, was identified as 24-dehydroprovitamin D3 (cholesta-5,7,24-trien-3 beta-ol). This new cutaneous provitamin D is not unique to the rat because it was also detected in the skin of reptiles, amphibians, birds, aquatic mammals, and humans. To be certain that the cutaneous 24-dehydroprovitamin D3 was as susceptible as 7-dehydrocholesterol to ultraviolet photolysis, rat skin was exposed to ultraviolet radiation. A reverse phase high performance liquid chromatographic analysis of a lipid extract of rat skin previously exposed to ultraviolet radiation demonstrated the presence of both previtamin D3 and 24-dehydroprevitamin D3. Therefore, these observations demonstrate for the first time that mammalian skin has the capacity to produce not one but at least two different vitamin Ds.

Animals↗
PubMed1985

Prediction of heparin requirements in acute thromboplastic venous disease.

It has been suggested that early heparin requirements are greater in patients with acute deep venous thrombosis (DVT) and pulmonary embolism (PE). Heparin requirements were recorded for 73 patients with suspected DVT and PE. The maintenance dosage (days 1 through 4) of heparin sodium required to achieve therapeutic partial thromboplastin times (PTTs) was significantly higher in patients with DVT (n = 54; mean +/- SD dosage, 1,151 +/- 246 units/hr) compared with patients with no DVT (n = 19; mean +/- SD dosage, 952 +/- 190 units/hr). The first posttreatment PTT was significantly lower in patients with DVT (mean +/- SD PTT, 68.74 +/- 27.96 s) compared with control patients (mean +/- SD PTT, 89.41 +/- 23.25 s). This study supports the clinical impression that initial heparin requirements are greater and heparin clearance is more rapid in patients with acute DVT and PE.

Acute Disease↗
PubMed1985

Growth of pulmonary metastases of B16 melanoma in mast cell-free mice.

The relationship of mast cells to tumor growth has been debated but not elucidated. The existence of a mast cell-free animal, the W/Wv mouse, provides a model in which tumor metastasis can be studied with special reference to host tissues and their mast cell content rather than to the adhesiveness of the tumor cell itself. Both hind footpads of 30 W/Wv mice and 30 control mice (+/+) were injected with 2 X 10(5) cells of B16-F10 melanoma cells. The left paw received 1000 rads orthovoltage radiation 12 hr before tumor inoculation. Growth of tumors in both paws was recorded. Ten animals from each group were killed on Day 31 after tumor inoculation, and the remaining animals were kept until they died. Autopsy was performed in all animals, and patterns of metastasis were recorded. Results showed that (1) preinoculation radiation significantly slowed tumor growth in the left paw (P = 0.0009), and (2) lung metastases were present in 4 of 10 W/Wv mice, but in none of 10 +/+ mice killed after 31 days (P = 0.05). Overall, 17 of 25 W/Wv mice and 8 of 26 +/+ mice had lung metastases (P = 0.008).

Animals↗
PubMed1985

Comparative radiopharmacokinetics of 18F-5-fluorouracil administered i.v. to rats bearing a mammary tumor.

In an attempt to compare the efficacy of various 5-fluorouracil (5-FU) regimens, we studied the kinetics of 18F-labeled and unlabeled 5-FU in rats. 18F-5-FU was synthesized in our laboratory and was administered in tracer doses to Fischer rats bearing either the 13762 or the R3230 mammary adenocarcinoma, and to Sprague-Dawley rats bearing the Walker-256 carcinosarcoma, with or without pre-treatment with a therapeutic dose of unlabeled 5-FU. In addition, the non-radioactive 5-FU was administered to control rats of both strains. All animals were followed for 70 min either by measuring their 18F blood levels continuously using an extracorporeal blood-loop, or by determining their 5-FU blood levels at discrete time intervals. The biphasic kinetic profile was characterized by determining alpha and beta rate constants and their corresponding half-lives. Differences in 18F elimination, as measured by the area under the curve during the elimination phase, were observed between the pre-treated 13762-bearing rats and the untreated group bearing the same tumor, as well as the pre-treated non-tumored controls and both W-256-bearing groups. Such differences could reveal changes in the ability of those rats to metabolize 5-FU, and hence correlate to the level of active metabolite(s) available to their tumor sites.

Adenocarcinoma↗
PubMed1985

Collagen expression in embryonic chicken chondrocytes treated with phorbol myristate acetate.

Growth of embryonic chicken sternal chondrocytes in the presence of phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, resulted in a dramatic morphological change from spherical floating cells to adherent fibroblastic cells. This morphological change was accompanied by a quantitative switch from synthesis of cartilage-specific type II procollagen to type I procollagen. Type II procollagen mRNA levels decreased 10-fold in PMA-treated cells. Activation of type I collagen genes led to the accumulation of type I procollagen mRNA levels comparable to those of type II mRNA in these cells. However, only type I procollagen mRNA was translated. In addition to gene activation, unprocessed pro alpha 1(I) transcripts present at low levels in control chondrocytes were processed to mature mRNA species. Redifferentiation of PMA-treated chondrocytes was possible if cells were removed from PMA after the morphological change and cessation of type II procollagen synthesis but before detectable amounts of type I procollagen were synthesized. Production of type I collagen thus marks a late phase of chondrocyte "dedifferentiation" from which reversion is no longer possible. Redifferentiated cell populations contained 24-fold more pro alpha 1(II) collagen mRNA than pro alpha 1(I) collagen mRNA, but the rates of procollagen synthesis were comparable. This suggests that the PMA-mediated dedifferentiation of chondrocytes as well as their redifferentiation is under both transcriptional and posttranscriptional regulation.

Animals↗
PubMed1985

The difference between date of suicidal act and recorded death certificate date in 204 consecutive suicides.

The date of death recorded on death certificates (DCD) was compared to the date of the suicidal act (DA) in a consecutive series of 204 suicides. The DA was known to be the same as the DCD in only 46 per cent of the cases. The DA was different from the DCD in 22 per cent of the cases. The difference between the DA and DCD should be taken into consideration in the analysis of temporal trends.

Death Certificates↗
PubMed1985

Tonic pupils following oculomotor nerve palsies.

Four patients developed a unilateral tonic pupil following ipsilateral oculomotor nerve palsy. The probable basis for this phenomenon is misdirection of injured oculoparasympathetic fibers in the oculomotor nerve proximal to the ciliary ganglion.

Accommodation, Ocular↗
PubMed1984

Brain norepinephrine depleting lesions selectively enhance behavioral responsiveness to novelty.

The noradrenergic innervation of the forebrain by cells from the locus coeruleus (LC) was interrupted by either electrolytic lesions of the LC or 6-hydroxydopamine (6-OHDA) lesions of the dorsal noradrenergic bundle (DB). Animals so treated were then tested in a modified open field test designed to measure responsiveness to environmental novelty and also tested for food consumption in their home cages. In addition, DB lesioned animals were tested in photocell activity cages for both their initial locomotor response to the novel cages as well as their activity level after habituation. The DB lesioned animals were also tested for rates of acquisition and extinction of an operant response. The DB lesion produced no deficits in either the acquisition or the extinction of a food rewarded operant response. The DB lesion did reduce the initial amount of locomotor activity in response to introduction to the activity cages but did not alter the rate of habituation of the locomotor response nor the "basal" level of activity at the end of two hr of exposure. Neither lesion affected the amount of food eaten by 24 hr-fasted animals in their home cages during the first 15 min. When fasted prior to being given access to food in a novel open field, however, both lesions resulted in decreased food consumption and decreased amounts eaten per approach to the food pedestal. The DB lesion, but not the LC lesion, resulted in decreased rearing and grooming in this setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Radioiodinated prolactin as a potential mammary tumor localizing agent.

The feasibility of using radioiodinated prolactin for early detection of solid mammary tumors was studied in the rat. Radioiodinated prolactin was first injected into tumored and control rats in order to define the localization of the labeled hormone in their target organs, then it was injected into extracorporeal blood-loop of tumored and healthy rats, in order to study its clearance in those animals. At 15 min post injection, 75-82% of the labeled hormone was recovered, of which 4-5% were counted in the tumor. Deiodination was apparent only 30 min after injection. As much as high deposition of the labeled hormone was not achieved in the hormone-dependent tumor lines investigated, some of the pitfalls that may be encountered are documented. The clearance of the labeled prolactin as determined by the blood-loop technique is 3.3 min in the R3230 tumor, and 6.4 min in the 13762 mammary tumor. The healthy rats had a blood clearance of 4.6 min.

Animals↗
PubMed1984

Prospective randomized trial of single dose cefuroxime against mezlocillin in elective gastric surgery.

A prospective randomized control trial was made in 78 patients undergoing elective operations on the stomach where the viscus was opened at operation, and the efficacy of single dose intravenous prophylaxis with cefuroxime 1.5 g or mezlocillin 2 g was compared. The overall rate of sepsis was 10.2 per cent. Infection in the cefuroxime group was significantly lower (2.5 per cent) than in the mezlocillin group (18 per cent) (P less than 0.05). Four of the seven patients with infections in the mezlocillin group were due to antibiotic resistant staphylococci. The only infections in the cefuroxime group were due to an antibiotic resistant strain of Pseudomonas aeruginosa. One case of pseudomembranous colitis occurred in the cefuroxime group. In view of the high rate of resistant organisms in patients receiving mezlocillin we believe that cefuroxime remains the antibiotic of choice for patients undergoing elective gastric operations.

Abscess↗
PubMed1984

Effects of age, brain damage and stress on antibody binding to the brain.

The direct immunoperoxidase technique was used to assess IgG and IgM nuclear and cytoplasmic binding to the mouse brain as a function of age, brain damage, and stress. Nuclear IgM binding was found to increase in older animals (over 30 months of age). There was also heightened nuclear and cytoplasmic binding 1 week after a frontal cortex lesion in mice approximately 2 months of age. Mice with brain lesions, however, did not show greater binding some months later and, if allowed to die from natural causes, actually showed less IgM nuclear binding than control animals. No association was found between lifespan and binding or between stress per se and binding. The capacity of the blood-brain barrier to repair itself after injury is discussed, and these findings are compared to earlier data based on indirect measurement procedures.

Age Factors↗