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Biomedical subjects

D Lee

Publications and source records attributed to D Lee.

At least 541 records · Page 30Linked to original sources
PubMed1986

Chronic gentamicin nephrotoxicity. Continued tubular injury with preserved glomerular filtration function.

After an initial episode of acute tubular necrosis, apparent resistance to gentamicin nephrotoxicity develops in rats during prolonged drug administration. The authors studied this phenomenon by examining the autoradiographic distribution of 3H-gentamicin and 3H-thymidine during 5 weeks of gentamicin treatment and by analyzing renal structure and function after a 12-week course of treatment. These studies show that regenerating cells exclude gentamicin, but concentrate it again after maturation, and that the rate of thymidine incorporation is still high well after recovery from acute toxic injury. After 12 weeks of gentamicin, the glomerular filtration rate was only modestly diminished, whereas in vitro cortical organic ion transport was substantially impaired. Light and electron microscopy demonstrated all phases of injury and recovery among cells of most proximal tubules and evidence of chronic tubulointerstitial disease. It is concluded that "resistance" to gentamicin is a state of persistent tubular cell injury obscured functionally by preservation of the glomerular filtration rate and histologically by asynchrony of cell necrosis and regeneration.

Acute Kidney Injury↗
PubMed1985

The influence of hapten density on the assay of penicilloylated proteins in fluids.

The use of inhibition radioimmunoassays for the measurement of penicilloylated proteins in biological fluids is compromised by the dominant influence of hapten density. Precise quantitation, and therefore assessment of antigenicity and immunogenicity, cannot be achieved in the absence of knowledge of the number and distribution of haptenic groups on the protein carrier. These assays may not, therefore, be appropriate for the measurement of potential allergenic residues in food products.

Allergens↗
PubMed1985

Etodolac: effect on prostaglandin concentrations in gastric mucosa of rats.

Etodolac is a structurally novel compound exhibiting potent analgesic and anti-inflammatory activity in laboratory animals and man, with excellent G. I. tolerance. Like other nonsteroidal anti-inflammatory drugs (NSAIDs) etodolac inhibits prostaglandin (PG) biosynthesis. In view of the cytoprotective role of PGE2, we have investigated in normal rats the effect of etodolac on the gastric mucosal concentration of PGE2 as well as of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin; naproxen and piroxicam served as reference NSAIDs. The orally effective anti-inflammatory doses in the chronic arthritic rat model (3 mg/kg for etodolac and naproxen; 0.5 mg/kg for piroxicam), and their arbitrarily selected multiples of 10 were used. Rats were killed at 1, 2, 6 and 24 hr after single doses and the PG concentrations were measured by RIA. With the low dose, 2 and 6 hr after dosing, etodolac diminished the PGE2 concentration by 20-25% (vs control) while naproxen and piroxicam caused a fall of 53-65%; the difference between etodolac and the untreated control group is not statistically significant but the difference between etodolac and both piroxicam and naproxen is significant (p less than 0.001). At the high doses, the lowering in PGE2 was similar after all three drugs, i.e. about 70% at 1 and 2 hr; 50% at 6 hr, and 20-50% at 24 hr after dosing. Except for the consistently smaller reduction of concentrations after etodolac, the effects on 6-keto-PGF1 alpha concentration followed a similar pattern but the differences are not significant. The lack of the G.I. irritation of etodolac in rats and man at therapeutically effective doses may be attributed to the benefits of the relatively short-lived and slight decrease in gastric mucosal PGE2 concentrations found in this study.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Long-term survivors after breast cancer.

A retrospective analysis of two groups of patients, one surviving 16-20 years and the other dying within 10 years after diagnosis and treatment of primary breast cancer has been undertaken to determine whether there were particular clinical or histological features associated with long-term survival. The striking histological difference between the tumours of the two groups of patients was the prevalence of tumours of 'special' invasive types (cribriform, tubular, lobular and medullary) in the long-term survivors. Micro-invasive and non-invasive carcinomas were also more common in the survivors. The tumours of the surviving group which were not of a 'special' type more commonly had a better histological grade than those tumours of patients dying early from breast cancer. In the overall group elastosis was present in significantly more tumours of the survivors whereas tumour necrosis, vascular and lymphatic invasion were all significantly more common in the short-term survival group. Although there was a significantly increased incidence of earlier stage tumours in the long-term survivors, the histological distinctions between the two groups were independent of the differences in clinical features.

Adult↗
PubMed1985

Carcinoma of the breast in women 80 years of age and older: still a lethal disease.

Cancer of the breast is a frequent and potentially lethal problem in women 80 years of age and older. In our experience, many present with advanced disease which indicates the continuing need for patient and doctor education concerning the significance of a breast lump in the elderly. Although many of these patients have other diseases, only a small number, if thoughtfully managed, will not be fit for appropriate standard methods of treatment. In the majority of patients who died, death was due to the breast cancer and many who did die from other causes had the added misery of persisting or metastatic breast cancer. In those patients with potentially curable cancer, we recommend either wide local excision, axillary node dissection and irradiation, or modified radical mastectomy. When simple mastectomy alone is used, there is a very high local recurrence rate. Although the patients studied were treated before the era of tamoxifen therapy, it is noteworthy that hormone manipulation would be of value in many of these patients and in selected cases, chemotherapy should also be considered.

Age Factors↗
PubMed1985

In vitro recombination of bacteriophage T7 DNA: further characterization of the reaction using plasmid DNA.

We have used a plasmid which contains a cloned fragment of T7 DNA to study the properties of general recombination of phage T7 in vitro. It was shown that T7-infected cell extracts promote recombination by the exchange of double strands of DNA. While both products of these double-strand exchanges were detected, we were unable to show that they were formed during a single recombination event.

Cloning, Molecular↗
PubMed1985

Effects of chronic dietary lithium on behavioral indices of dopamine denervation supersensitivity in the rat.

The present study was designed to test the hypothesis that chronic lithium (Li) treatment could alter the behavioral manifestations of dopamine (DA) denervation supersensitivity. Rats were maintained on a Li diet continuously for 4 weeks before and 4 weeks after bilateral chemical denervation of DA terminal fields in the nucleus accumbens (N.Acc.) and the caudate nucleus (CN). We examined the behavioral responses of these animals to apomorphine (0.1 mg/kg s.c.) treatment 2 and 4 weeks postdenervation. Animals exposed to similar chemical denervation but maintained on a control diet exhibited well-documented "supersensitive" behavioral responses to apomorphine: N.Acc. denervated animals demonstrated increases in ambulatory sniffing, rearing and locomotor activity; CN-denervated animals demonstrated increases in rearing and focused sniffing in one location but no increases in locomotor activity. Compared to these control-fed animals, Li-diet animals receiving either CN- or N.Acc-denervation demonstrated a significantly decreased "supersensitive" behavioral response to apomorphine. N.Acc.-denervated animals receiving Li showed less apomorphine-induced locomotor activity. CN-denervated animals receiving Li showed less focused behavior which became evident as actual increases in locomotor activity after apomorphine. These results suggest that chronic dietary Li modifies postsynaptic mechanisms to suppress elements of the behavioral manifestations of supersensitive mesolimbic and nigrostriatal DA activity.

Animals↗
PubMed1984

Late response in exercise-induced asthma.

Eight subjects induced bronchospasm by free-range running. Four of these demonstrated a late response at 5-6 hr after exercise. When compared to the other group of four subjects, who also developed an early response but no late response, the difference in FEV1 at 5-6 hr was highly statistically significant. Although the phenomenon is not universally manifest it should no longer be held that there is no late response in exercise-induced asthma.

Adolescent↗
PubMed1984

BK virus-plasmid expression vector that persists episomally in human cells and shuttles into Escherichia coli.

We describe a novel expression vector, pBK TK-1, that persists episomally in human cells that can be shuttled into bacteria. This vector includes sequences from BK virus (BKV), the thymidine kinase (TK) gene of herpes simplex virus type 1, and plasmid pML-1. TK+-transformed HeLa and 143 B cells contained predominantly full-length episomes. There were typically 20 to 40 (HeLa) and 75 to 120 143 B vector copies per cell, although some 143 B transformants contained hundreds. Low-molecular-weight DNA from TK+-transformed cells introduced into Escherichia coli were recovered as plasmids that were indistinguishable from the input vector. Removal of selective pressure had no apparent effect upon the episomal status of pBK TK-1 molecules in TK+-transformed cells. BKV T antigen may play a role in episomal replication of pBK TK-1 since this viral protein was expressed in TK+ transformants and since a plasmid that contained only the BKV origin of replication was highly amplified in BKV-transformed human cells that synthesize BKV T antigen.

BK Virus↗