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Biomedical subjects

J Holm

Publications and source records attributed to J Holm.

At least 19 recordsLinked to original sources

Hawkinsinuria in two families.

Hawkinsinuria, a disorder of tyrosine metabolism has been documented in two families in the United States, in one of which there was clear evidence of autosomal dominant inheritance. Metabolic acidosis and failure to thrive appear to be confined to infancy. Tyrosyl metabolites and 5-oxoproline are also found only in infancy, while 4-hydroxycyclohexylacetic acid was present only with time. The disease may be detected by organic acid analysis or by staining an electropherogram for sulfur containing compounds.

Acidosis

Conversion of an apparent 100 kDa folate binding protein from human milk, choroid plexus and semen to a 25 kDa molecular species by phosphatidylinositol-specific phospholipase C.

Gel filtration studies in the presence of Triton X-100 showed that treatment with phosphatidylinositol-specific phospholipase C reduced the apparent molecular size of the 100 kDa folate binding protein from human milk, choroid plexus and semen to 25 kDa. Cleavage of a hydrophobic glycosyl phosphatidylinositol domain (a membrane anchor) inserting the protein into Triton X-100 micelles could account for this phenomenon.

Carrier Proteins

Preoperative assessment of the risk for cardiac death following thrombo-embolectomy for acute lower limb ischaemia.

Cardiac monitoring and the selective use of initial non-operative management is reported to reduce the high mortality rate in patients with acute lower limb ischaemia. Early estimation, prior to selection of initial therapy, of the risk for intraoperative or postoperative cardiac death following thrombo-embolectomy is therefore important. The aim of this prospective multi-centre study was to develop a simple and clinically useful index for assessment of the risk of post-operative cardiac death. Patients judged to need thrombo-embolectomy for acute lower limb ischaemia were evaluated on admission for routine clinical, cardiac and limb ischaemia parameters that could be related to cardiac function and these parameters compared to postoperative cardiac outcome. Sixteen per cent of the 117 patients died from intraoperative or postoperative cardiac complications. Analysis revealed five admission parameters that significantly and independently predicted a high risk for cardiac death: mean arterial blood pressure below 90 mmHg, clinical sign(s) of cardiac decompensation, ischaemia affecting the thigh, haemoglobin concentration exceeding 140 gl-1, and a history of a myocardial infarction in the previous 4 weeks. Definition of risk points for each risk factor allowed a simple classification of each patient into one of three significantly different cardiac risk classes with cardiac death rates of 6 +/- 3%, 27 +/- 8% and 75 +/- 16%, respectively. More than two thirds of the patients belonged to the low risk group. The described risk index provides a tool for preoperative assessment of the cardiac death risk associated with early thrombo-embolectomy in patients with acute lower limb ischaemia.

Aged

A high-affinity folate binding protein in proximal tubule cells of human kidney.

High-affinity 3H-folate binding in solubilized brush border membranes of human kidney cortex display characteristics such as apparent positive cooperativity typical of specific folate binding. The folate binding activity and the activity of the brush border membrane-marker enzyme, gamma-glutamyltransferase, were eightfold higher in brush border membranes compared to crude kidney homogenate. Ultrogel AcA 44 chromatography revealed a major (Mr approximately 100 kDa) and a minor (Mr approximately 25 kDa) folate binding protein in brush border membranes. The large molecular size form may represent a membrane-derived hydrophobic folate binding protein inserted in Triton X-100 micelles. This notion was supported by the identical molecular weights of the 100 kDa and 25 kDa folate binding peaks determined by sodium dodecylsulfate polyacrylamide gel electrophoresis and immunoblotting. The folate binding protein in renal brush border membranes cross reacted with rabbit antibodies against 25 kDa human milk folate binding protein, and showed immunoprecipitation in the presence of these antibodies. Paraffin embedded sections of kidney cortex showed immunostaining of cells in the convoluted proximal tubules after exposure to rabbit antiserum (1:8000 dilution). Glomeruli and distal tubules showed no immunostaining.

Carrier Proteins

Bioavailability of starch in various wheat-based bread products: evaluation of metabolic responses in healthy subjects and rate and extent of in vitro starch digestion.

Glucose and insulin responses to bread products were evaluated in healthy subjects. Also studied were the rate of in vitro starch digestion and the content of in vitro resistant starch (RS). Three white-wheat-bread (WWB) products varying in crust-crumb ratio and monoglyceride addition, three bread products with a high soluble fiber content (HSFB), and two coarse-wheat breads (CB) were included. The metabolic responses to WWBs were in general higher than those to CB and HSFB products. The most prominent reduction in metabolic responses was noted with the CBs with intact kernels and the HSFBs with oat bran. The starch in these products was also more slowly released from a dialysis tubing after enzyme incubation of chewed samples. The RS content ranged from 0 to 1.7 g/100 g starch. HSFBs and the CB with intact kernels showed a higher satiety score than did the WWBs immediately after the test meal.

Adult

A look at ear canal changes with jaw motion.

Two procedures were used with one subject to examine changes in the ear canal with jaw motion. Silicone ear impressions were examined to measure the effect of jaw position. Magnetic resonance imaging was used to define the three-dimensional structure of the canal and visualize key underlying tissue. Results showed that inexpensive impressions can detail changes in the cartilaginous region of the canal. Approximately a 25% change in this subject's ear canal with different jaw positions was observed in the anterior/posterior plane with essentially no change in the superior/inferior plane. This is likely related to asymmetric stress from action of the mandibular condyle on neighboring cartilaginous tissue. Solutions to jaw motion-induced feedback problems are suggested.

Ear Canal

EDTA treatment of intermittent claudication--a double-blind, placebo-controlled study.

A double-blind, randomized multicentre study was undertaken to evaluate the possible effect of chelation treatment with ethylenediamine-tetraacetic acid (EDTA) in patients with severe intermittent claudication. A total of 153 patients received 20 intravenous infusions of either 3 g Na2EDTA or placebo during a period of 5-9 weeks. Vitamin, mineral and trace element supplements were administered orally. The changes observed in the pain-free and maximal walking distances, measured on a treadmill, were similar in the two groups. During the 3-month (n = 149) and 6-month (n = 123) follow-up period, no long-term therapeutic effect of EDTA could be demonstrated. The ankle-brachial blood pressure index remained unchanged throughout the study period. This study failed to demonstrate any effect of EDTA chelation treatment in intermittent claudication.

Aged

Urinary excretion of albumin and retinol-binding protein in lithium-treated patients: a longitudinal study.

The urinary excretion of albumin and retinol-binding protein was determined by means of sensitive immunochemical methods in a 2-year longitudinal study of 22 lithium-treated patients. During lithium treatment, there were no significant changes in the median albumin:creatinine ratios or retinol-binding protein:creatinine ratios. However, the median albumin:creatinine ratios were significantly higher in lithium-treated patients than in 22 normal subjects, which indicates that glomerular permeability is increased; no correlation with serum lithium level or duration of lithium treatment could be shown. In patients treated with slow-release tablets, the urinary excretion of albumin was significantly higher after 2 years than in patients given lithium carbonate. The median retinol-binding protein:creatinine ratios did not differ significantly between lithium-treated patients and normal subjects, suggesting that lithium does not affect the catabolism of low-molecular-weight proteins in the proximal tubules. In conclusion, the study supports the hypothesis that lithium treatment produces a small but significant and nonprogressive elevation of the urinary excretion of albumin.

Adult

T lymphocytes in human atherosclerotic plaques are memory cells expressing CD45RO and the integrin VLA-1.

The cellular composition of human atherosclerotic plaques has been analyzed in several immunohistochemical studies in recent years. These studies have shown that the main cell types of the plaque are macrophages, smooth muscle cells, and T lymphocytes. To further characterize the T-lymphocyte population in atherosclerotic plaques, human plaque tissue was digested enzymatically and the released cells were labeled with fluorescent antibodies and analyzed by flow cytometry. Fifteen patients undergoing carotid endarterectomy were studied. Sixty-four percent of plaque T cells expressed the low-molecular-weight form (CD45RO) of the leukocyte common antigen (CD45). Many of these cells expressed the integrin very late activation antigen-1 (VLA-1), which suggests that they are in a state of late activation. In contrast, only 1% of peripheral blood T cells from the same patients expressed VLA-1. Other markers of T cell activation, such as Ta1 (CD26) and HLA-DR, were also increased on plaque T cells. The interleukin-2 receptor (CD25), which is transiently expressed after activation, was present on only a small proportion of the cells. Taken together, this analysis of plaque lymphocytes shows that the majority of plaque T cells are memory cells, many of which are in a state of late or chronic activation. This T-cell phenotype may be the result of a preferential recruitment and/or retention of activated peripheral blood T cells or local antigenic stimulation of resting T cells.

Aged

Can immunocompetent cells and their cytokines play a role in atherogenesis?

The human atherosclerotic plaque represents a mixture of inflammation, lipid accumulation and fibrosis. Cholesterol deposits are predominantly found in the core of the plaque, which is surrounded by a fibrotic cap. Much of the cholesterol is intracellular in macrophage-derived foam cells, and other macrophages together with T lymphocytes are intermixed with smooth muscle cells in the fibrous cap. Recent studies have shown that cytokines released by inflammatory cells can regulate cell proliferation, cholesterol metabolism, and differentiation of vascular cells. Interferon-gamma, one of the major secretory products of activated T lymphocytes, inhibits smooth muscle proliferation and reduces expression of alpha-actin. This suggests that T cells, by releasing gamma-interferon, may inhibit the formation of arterial stenosis and spasm. Recent animal experiments support this hypothesis by demonstrating that injections of recombinant gamma-interferon reduce arterial intimal lesions after balloon catheter injury. In similar experiments, it was shown that larger intimal lesions develop in T cell-depleted rats and in athymic nude rats. This shows that T cells inhibit the vascular response to injury and supports the notion that gamma-interferon released by these T cells is an important paracrine regulator of arterial cell proliferation. The cytokines, gamma-interferon and TNF, also downregulate scavenger receptor expression in monocyte-derived macrophages, leading to an inhibition of the transformation of these cells into foam cells. Taken together, these data show that cytokines of the immune system are important regulators of cholesterol deposition and cell proliferation in atherogenesis.

Arteriosclerosis

Influence of sterilization, drying and oat bran enrichment of pasta on glucose and insulin responses in healthy subjects and on the rate and extent of in vitro starch digestion.

The effects of sterilization and oat bran enrichment of pasta on the glucose and insulin responses in healthy subjects were evaluated. Cooked and canned spaghetti and cooked fettucini without and with enrichment with oat bran (28%) were compared. Further, the effects of various low- and high-temperature drying conditions for spaghetti, cooking time and sterilization on the starch digestion rate and content of enzyme-resistant starch (RS) in vitro were also studied. Various cooking quality data were also determined to allow interpretation of results. The incremental glucose area (0-120 min) produced by canned spaghetti was twice the area of that produced by cooked spaghetti (69.03 vs 35.45 mmol/l x min, P less than 0.01). The incremental insulin area (0-120 min) was also significantly higher with canned spaghetti (17,500 vs 12,600 pmol/l x min, P less than 0.05). The rapid digestion was caused by excessive swelling of starch during sterilization that promoted a very soft texture of the spaghetti. Enrichment of fettucini with oat bran reduced slightly the incremental insulin area (15,600 vs 20,100 pmol/l x min, P less than 0.05, for 0-120 min), but did not significantly reduce the glucose area. Drying conditions and cooking times could be varied within broad limits without affecting the rate of starch digestion in vitro of cooked spaghetti. In sterilized spaghetti the content of resistant starch was higher than that found in cooked 'al dente' spaghetti (2.2-3.4 vs 0.5 mg/100 mg total starch). In conclusion, sterilization influences the nutritional properties of starch in pasta by substantially increasing the glucose and insulin responses and by formation of resistant starch. The effect of oatbran environment is restricted mainly to a slight decrease in the insulin response.

Adult

T lymphocytes inhibit the vascular response to injury.

The proliferation of vascular smooth muscle cells is controlled by specific growth factors and cytokines acting in paracrine networks. Macrophage products such as the platelet-derived growth factor and interleukin 1 promote smooth muscle proliferation and are released in the arterial wall during atherosclerosis and repair processes. T lymphocytes are also present in vascular tissue, but their role in vascular growth control in vivo has been unclear. We now demonstrate that rats in which T lymphocytes have been eliminated by a monoclonal antibody develop larger proliferative arterial lesions after balloon-catheter injury. Larger lesions also develop in athymic rnu/rnu rats that lack T lymphocytes, when compared with rnu/+ littermates with normal T-cell levels. Finally, injection of the lymphokine interferon gamma inhibits smooth muscle proliferation and results in smaller lesions compared with controls injected with buffer alone. These results indicate that T lymphocytes modulate smooth muscle proliferation during vascular repair. We propose that T lymphocytes may play an important, immunologically nonspecific role in tissue repair processes.

Animals

High-affinity folate binding in human choroid plexus. Characterization of radioligand binding, immunoreactivity, molecular heterogeneity and hydrophobic domain of the binding protein.

High-affinity [3H]folate binding in solubilized human choroid plexus homogenate displayed characteristics, e.g. apparent positive co-operativity, which are typical of specific folate binding. The highest folate-binding activity per g of protein was associated with the 27000 g membrane pellet where the membrane-marker enzyme gamma-glutamyltransferase had its main localization. Ultrogel AcA 44 chromatography revealed two major folate-binding proteins (molecular masses greater than 110 kDa and approx. 100 kDa) and one minor one (molecular mass approx. 25 kDa) and approx. 100 kDa) and one minor one (molecular mass approx. 25 kDa) in the Triton X-100-solubilized membrane pellet. After exposure of the membrane pellet to phosphatidylinositol-specific phospholipase C there was only one large 25 kDa peak of folate binding. This could suggest that the folate-binding protein is anchored to the membrane by a glycosylphosphatidylinositol moiety, which can be inserted into Triton X-100 micelles and thus can give rise to forms of large molecular size on gel filtration. This notion was supported by the identical molecular masses of the greater than 110 kDa and 25 kDa folate-binding peaks determined by SDS/PAGE and immunoblotting. The folate-binding protein in choroid plexus cross-reacted with rabbit antibodies against the 25 kDa human milk folate-binding protein, and paraffin-embedded sections of choroid plexus showed immunostaining after exposure to rabbit anti-(human milk folate-binding protein) serum (1:8000 dilution).

Binding Sites