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Biomedical subjects

H Morrison

Publications and source records attributed to H Morrison.

At least 73 records · Page 4Linked to original sources

Important risk factors for death in adults: a 10-year follow-up of the Nutrition Canada survey cohort.

Data on mortality among over 8000 Canadians aged 35 to 79 years who participated in the Nutrition Canada survey are presented. The effects of various risk factors on mortality were assessed with a multivariate Poisson regression analysis. Factors associated with a significantly increased risk of death over a 10-year follow-up period ending in 1981 included cigarette smoking, hypertension and diabetes mellitus. A shallow U-shaped mortality pattern was observed for body mass index and for serum cholesterol level. No statistically significant increases in risk were associated with alcohol consumption. The population attributable risks for smoking, hypertension and diabetes were 39%, 8% and 6% respectively for men and 21%, 12% and 7% respectively for women.

Adult↗

Adoptive immunotherapy for stage IV renal cell carcinoma: a novel protocol utilizing periodate and interleukin-2-activated autologous leukocytes and continuous infusions of low-dose interleukin-2.

In a pilot study involving 13 patients with advanced stage IV renal cell carcinoma, anti-tumor effects and toxicity of a novel form of adoptive immunotherapy were determined. The protocol utilizes infusions of autologous mononuclear leukocytes treated with the oxidizing mitogen sodium periodate (IO4-) and cultured in medium containing human recombinant interleukin-2 (IL-2), and continuous infusions of low-dose IL-2 (mean +/- SD dose = 39.5 +/- 8.6 X 10(3) U/kg/24 hours). Leukocytes (5 to 10 X 10(9] were removed by leukapheresis three times per week, mononuclear cells were separated, activated with IO4- and cultured in medium containing IL-2 (500 U/ml) for 48 to 72 hours. The cells were re-infused following the next leukapheresis procedure. IL-2 was administered five days per week. Treatment was continued for two three-week cycles. An increase in peripheral blood mononuclear cells bearing the natural killer cell (NK) surface marker, Leu 11, an increase in NK- and antibody-dependent cell-mediated cytotoxicity, and a slight increase in spontaneous cytotoxicity for non-NK targets were noted. Regressions (more than 50 percent decrease in tumor mass) of pulmonary, liver, bone, or soft tissue metastases were induced in six patients. Severe fluid retention did not develop in any patient and no patient required treatment in the intensive care unit. Five of the patients who showed a response have experienced a relapse at 5.2 +/- 1.0 (mean +/- SD) months. These observations indicate that IO4-/IL-2-activated killer cells plus continuous infusions of low-dose IL-2 can result in regression of metastatic renal cell carcinoma.

Adult↗

Perirenal spaces: CT evidence for communication across the midline.

The perirenal spaces may communicate across the midline, anterior to the lower aorta and vena cava. The connecting channel has a relatively narrow anteroposterior dimension on computed tomographic (CT) scans, both in vivo and in injected cadavers. It may therefore be difficult to visualize on abdominal radiographs and may be mistaken for unopacified bowel on CT scans. The midline extension of perirenal fluid is usually contiguous to the lower abdominal great vessels anteriorly but does not surround them completely, possibly because of fibrous septa within the perivascular fat. Hematomas from ruptured aortic aneurysms extend mainly into the perirenal spaces. Thus, the lower abdominal great vessels are located, in effect, within the midline extension of these spaces. Superiorly, the perirenal spaces extend to the diaphragm, abutting the lateral and anterior margins of the psoas and quadratus lumborum muscles and the bare area of the liver. Inferiorly, perirenal collections appear to diverge into the pelvis, along the psoas muscles, ureters, and iliac vessels.

Cadaver↗

Stereospecific inhibition of human epidermal cell interleukin-1 secretion and HLA-DR expression by cis-urocanic acid.

UV radiation is known to photoisomerize trans-urocanic acid (trans-UCA) into a stable isomer, cis-urocanic acid (cis-UCA). To study the possible immunomodulatory effects of cis-UCA, the two isomers were added separately to different in vitro assays employing human epidermal cell suspensions or purified human peripheral T lymphocytes, supplemented with epidermal cells. Cis-UCA but not trans-UCA suppressed interleukin-1 (IL-1) production by epidermal cell suspensions in a dose-dependent fashion and diminished the number of HLA-DR positive epidermal cells to 61% of control values. An inhibitory effect on epidermal cell accessory function could be demonstrated with both isomers of UCA, but only if UVB-irradiated epidermis was used as a source for the epidermal cells. Taken together, the findings of our study lend indirect support to the concept of cis-UCA as a possible mediator of UV-radiation-induced immunosuppression.

Adjuvants, Immunologic↗

Conjugation of organic compounds in isolated hepatocytes from a marine fish, the plaice, Pleuronectes platessa.

A method is described for the preparation of viable hepatocytes from a marine fish, the plaice. Their ability to detoxify organic compounds was measured by the formation of glucuronic acid and sulphate conjugates with the model substrates 1-naphthol and phenolphthalein. 1-Naphthol was conjugated three- to four-fold faster than phenolphthalein and glucuronidation predominated with both substrates. Strong substrate inhibition of glucuronidation was observed with 200 microM 1-naphthol or phenolphthalein. No measurable sulphate conjugation was detected with phenolphthalein. Treatment of fish with 3-methylcholanthrene induced formation of both glucuronide and sulphate conjugates by two- to three-fold. Compared with rat hepatocytes, the extent of sulphation was 100-fold lower in plaice hepatocytes whereas glucuronide formation was only 10-fold lower. The observations indicate that isolated plaice hepatocytes provide a suitable system for studies of the detoxication of xenobiotic pollutants in fish liver.

Animals↗

Induction of cell damage by menadione and benzo(a)pyrene-3,6-quinone in cultures of adult rat hepatocytes and human fibroblasts.

The cytotoxicity of menadione (2-methyl-1,4-naphthoquinone) and benzo(a)pyrene-3,6-quinone (BP-3,6-Q) was tested in cultures of adult rat hepatocytes and human fibroblasts. Menadione induced DNA strand breaks, cell membrane damage and depletion of reduced glutathione (GSH) in both hepatocytes and fibroblasts. In fibroblasts, effects on both DNA and membrane integrity were potentiated by the presence of dicoumarol, a specific inhibitor of the 2-electron reduction of quinones by DT-diaphorase, whereas in hepatocytes only the cell membrane damage was sensitive to dicoumarol. Results indicate that menadione toxicity is mediated via 1-electron reduction, although in hepatocytes different reactive species may be responsible for damage to DNA and to the membrane. BP-3,6-Q induced DNA strand breaks in fibroblasts at concentrations as low as 1 microM. The extent of DNA damage was insensitive to dicoumarol. Even after GSH depletion and inhibition of glucuronidation and sulphate conjugation, BP-3,6-Q caused no DNA damage in hepatocytes. In contrast to menadione, BP-3,6-Q did not induce cell membrane leakage or decrease in GSH levels in either hepatocytes or fibroblasts. These studies show the complexity of the metabolic pathways involved, in terms of activation and detoxification processes, in the toxicity of quinones.

Animals↗

Photochemistry and photobiology of urocanic acid.

E-Urocanic acid is a metabolite of histidine which accumulates in the skin and is excreted in sweat. It has been of interest to photobiologists and photodermatologists because of its intense absorption band at approximately 270 nm, a feature suggestive of a role as a natural photoprotecting agent for DNA. Early work concentrated on the E----Z isomerization resulting from UV excitation. Recent studies have revealed additional, potentially significant, photobiological properties, i.e. photochemical binding to DNA and an apparent involvement of the Z isomer in the phenomenon of photoimmunosuppression.

Animals↗

Induction of DNA damage by menadione (2-methyl-1,4-naphthoquinone) in primary cultures of rat hepatocytes.

The cytotoxicity of menadione (2-methyl-1,4-naphthoquinone) had been investigated using primary cultures of rat hepatocytes. Menadione was found to induce DNA strand breaks which were actively repaired by the cells. Dicoumarol, an inhibitor of DT diaphorase, did not potentiate menadione-induced DNA strand breaks. Neither had metyrapone, an inhibitor of cytochrome P-450 dependent monooxygenases, any effect on the extent of DNA damage. Covalent binding of menadione metabolite(s) to DNA was detected in the cultured hepatocytes and, in addition, hepatic microsomes were also found to metabolize menadione to DNA-binding products. The extent of binding of menadione to DNA in vitro, was markedly decreased by inclusion of the hepatic cytosol fraction, or reduced glutathione, in the incubations. In the presence of dicoumarol, menadione was also found to induce cell membrane damage. It also caused a rapid loss in cellular glutathione which was augmented by the presence of dicoumarol. The results suggest that both the cell membrane damage and DNA damage induced by menadione are mediated by one-electron reduction of the quinone to free radical intermediate(s). DT diaphorase appears to protect the cell from membrane damage, whereas reduced glutathione may have an important role in the prevention of DNA damage.

Animals↗

Wrist disarticulation of a deformed hand: appropriate prosthesis and the habilitation of a severely retarded young man.

A 24-year-old man, who was late attaining developmental milestones and tested in the severely mentally retarded range, had incurred third- and fourth-degree burns at 2.5 years that resulted in a deformed, anesthetic, and useless distal left upper limb. Following wrist disarticulation, he was fitted with a cosmetic prosthesis that he accepted enthusiastically. It permitted him to use his left upper limb as an effective assister. Attempts to wear and use a functional prosthesis were not successful because the bulbous stump was covered with abnormal skin that ulcerated whenever he wore the prosthesis. At present, he resides at home with his mother and has all self-care skills. He attends a day treatment program and helps his mother with household chores as well as neighborhood errands. The prognosis for continued functional improvement is good, even though he remains severely mentally retarded.

Adult↗

Status of reduced glutathione in primary cultures of rat hepatocytes and the effect on conjugation of benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide.

The intracellular level of reduced glutathione (GSH) and GSH conjugation have been investigated in primary cell cultures of hepatocytes isolated from control rats, phenobarbitone (PB) and 3-methylcholanthrene (MC) treated rats. The data demonstrate that in all cell cultures the GSH concentrations show a triphasic pattern: (i) within 1 h of culture an initial marked decrease to 50% of the levels found in fresh hepatocytes; (ii) recovery of GSH concentrations to above the levels observed in fresh cells. This occurs after 6 h in culture with control cells and after 10-24 h with cells from either PB or MC treated rats and was most prominent in cells from PB-treated rats. (iii) A slow decline to between 30 and 40 nmol GSH/mg protein from 24 to 96 h in culture. Synthesis of GSH was slower in cultured cells from PB treated rats and this was confirmed by the resynthesis rates when diethylmaleate (DEM) was used to deplete GSH. The formation of GSH conjugates with racemic 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) was measured in control cells in suspension and after 3 and 24 h in culture. Despite the decrease in GSH concentrations observed between 1 and 4 h after culture, the conjugation rates were not decreased.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗