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Biomedical subjects

J Holm

Publications and source records attributed to J Holm.

At least 127 records · Page 7Linked to original sources

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↗

A high-affinity folate binding protein in human semen.

The presence of a folate binding protein of high-affinity type (affinity constant 3.10(10) M-1, maximum folate binding 1.4 nM) in human semen was demonstrated in equilibrium dialysis experiments (37 degrees C, pH 7.4) with the radioligand 3H-folate. Radioligand dissociation from the binding protein was slow at pH 7.4, but rapid at pH 3.5. By use of rabbit antibodies against 25 kDa human milk folate binding protein we determined the concentration of folate binding protein in 16 specimens of human semen in an enzyme-linked immunosorbent assay. The concentration of immunoreactive folate binding protein was independent of the number of spermatozoa in individual specimens. Gel filtration showed that immunoreactive and radioligand bound folate binding protein coeluted in two peaks: a major one of 100 kDa and a minor one of 25 kDa.

Antibodies↗

High-affinity folate binding in human liver membranes.

High-affinity binding of 3H-folate in Triton X-100 solubilized membranes of human liver displayed characteristics, e.g. apparent positive cooperativity, which are typical of specific folate binding. Ultrogel AcA 44 chromatography of solubilized membranes saturated with 3H-folate revealed a major peak of 100 kDa and a minor peak of 25 kDa. The 100 kDa peak could represent a hydrophobic membrane associated molecular form of the protein. This notion was supported by the fact that the two peaks had identical molecular weights as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis with immunoblotting.

Binding Sites↗

Chronic lower limb ischaemia. A prospective randomised controlled study comparing the 1-year results of vascular surgery and percutaneous transluminal angioplasty (PTA).

In a prospective randomised study, performed over a 6-year period, 102 patients with severe lower limb ischaemia or claudication resistant to exercise training were randomised either to percutaneous transluminal angioplasty (PTA) or vascular surgery. Only patients who could be treated by both methods were included, constituting only 5% of the total number of patients treated during this period. The two groups were similar regarding age, severity of symptoms and diabetes. The immediate and 1-year results showed similar success and complication rates. There was, however, a significantly shorter hospital stay for patients treated with PTA. Due to early complications and initial failures PTA should, however, only be used in institutions where vascular surgical facilities are available since PTA demands access to such treatment.

Adult↗

Interferon-gamma inhibits arterial stenosis after injury.

BACKGROUND: Arterial injury initiates a proliferative response among the smooth muscle cells of the artery. This leads to the formation of a thickened intima that may reduce the diameter of the arterial lumen. Such intimal lesions often develop after vascular surgery and angioplastic procedures. Previous cell culture studies have shown that the lymphokine, interferon-gamma (gIFN), inhibits smooth muscle cell proliferation. METHODS AND RESULTS: We therefore tested whether administration of exogenous gIFN could inhibit the development of intimal lesions. Rat carotid arteries were denuded with a balloon catheter, resulting in the formation of a standardized intimal lesion. The animals were then treated with recombinant rat gIFN at 200,000 units (approximately 400,000 units or 100 micrograms/kg body wt) administered parenterally once daily for 7 days. Autoradiographic analysis of 3H-thymidine incorporation revealed that gIFN reduced the early smooth muscle replication by approximately 75%. gIFN treatment for 1 week resulted in a 50% reduction of intimal cross-section area at 2 weeks after injury when compared to control rats injected with buffer alone. The difference in lesion development persisted in rats analyzed 10 weeks after injury, suggesting that proliferative events during the first week determine the long-term development of the intima. Inhibition of lesion development was accompanied by expression of the class II histocompatibility (Ia) gene, RT1B, suggesting that both were directly related to the administration of gIFN. CONCLUSIONS: These results show that gIFN is a potent inhibitor of the formation of arterial proliferative lesions in vivo. It is possible that gIFN could be useful in preventing arterial stenosis after surgery and angioplasty in man.

Animals↗

Leukocyte interferon in the treatment of chronic myelogenous leukemia in second chronic phase.

Four patients with Philadelphia chromosome positive CML were treated with 18-42 x 10(6) IU of purified natural leukocyte IFN-alpha per week, after high-dose chemotherapy for blast phase and attainment of 2nd chronic phase. The second blast phase occurred within 3 months in 3 patients, but one patient is still in second chronic phase after 22 months of treatment. Treatment consisted of interferon only during the first year, and interferon in combination with hydroxyurea during the second year. During the second year suppression of the Philadelphia chromosome was seen in one patient, with 20% Philadelphia negative bone marrow metaphases. The toxicity of purified natural leukocyte IFN-alpha was similar to the toxicity of recombinant IFN-alpha. Antibodies to IFN-alpha were not detected in any patient.

Adult↗

Induction of tenascin in rat arterial injury. Relationship to altered smooth muscle cell phenotype.

Arterial smooth muscle cells produce large amounts of extracellular matrix molecules during repair processes and in primary culture. This occurs after a transition of the cells from a contractile to a synthetic phenotype and together with the acquisition of proliferative capacity. Here, the deposition of the glycoprotein tenascin in the extracellular matrix of rat arterial smooth muscle cells in vivo and in vitro was studied by immunofluorescence microscopy and immunoblotting. Tenascin was found in the intimal layer of the adult rat aorta and carotid artery, but not in the media. Tenascin also appeared in the neointima formed by proliferating smooth muscle cells 2 weeks after balloon catheter injury of the carotid artery. To determine if the deposition of tenascin in the neointima after arterial injury was related to changes in smooth muscle function, freshly isolated rat aortic smooth muscle cells were seeded on a substrate of plasma fibronectin and allowed to modulate from a contractile to a synthetic state in a serum-free medium. In these quiescent cultures, a tenascin-containing extracellular matrix was formed after 3 to 4 days. Taken together, the results show that tenascin production is induced concomitantly with changes in smooth muscle phenotype both in vivo and in vitro.

Animals↗

Conversion of an apparent 100 kDa folate binding protein from human milk to a 25 kDa molecular species by phospholipase D.

Gel filtration studies in the presence of Triton X-100 showed that treatment with phospholipase D reduced the apparent molecular size of the 100 kDa folate binding protein from human milk to 25 kDa, which is the molecular size of the low molecular weight folate binding protein. A phospholipase D induced cleavage of a hydrophobic phospholipid domain inserting the protein into Triton X-100 micelles could account for this phenomenon.

Carrier Proteins↗

Atrial natriuretic peptide and renal adaptation to contralateral nephrectomy in healthy man.

Atrial natriuretic peptide (ANP), angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) in plasma were determined in 12 healthy renal transplant donors before and 5, 12, 26, 54 days after uninephrectomy (Nx) in order to study the possible role of these hormones in functional adaptation to acute reduction in renal mass. Glomerular and tubular function was studied by measurements of the clearances of 51Cr-EDTA, lithium, sodium, potassium, and albumin. ANP was 7.4 +/- 3.1 pmol l-1 (mean +/- SD) before Nx and 8.7 +/- 6.1 pmol l-1 at 5 days after Nx and remained at this level through the observation period. Aldo showed a non-significant transient fall at 5 days after Nx. AII and AVP remained normal after Nx. At 5 days after Nx glomerular filtration rate (GFR) of the remaining kidney had risen from 45 +/- 7 ml min-1 before Nx to 57 +/- 8 ml min-1 (p less than 0.01), lithium clearance had risen from 13 +/- 2 ml min-1 before Nx to 20 +/- 7 ml min-1 (p less than 0.01), and sodium and water balance was normal. To conclude, plasma ANP, AII, Aldo and AVP do not appear to be responsible for the hyperfiltration and depression of fractional proximal sodium and water reabsorption observed in recently uninephrectomized man with normal sodium and water balance.

Absorption↗

Acute lower limb ischemia: failure of anticoagulant treatment to improve one-month results of arterial thromboembolectomy. A prospective randomized multi-center study.

The value of short-term anticoagulant treatment in improving the early outcome in patients operated on for acute lower-limb ischemia has been debated and so far unproven. In this prospective randomized multi-center study, 188 such patients were randomized on admission, either to preoperative and postoperative anticoagulant medication (AC group, n = 94) or no anticoagulant treatment during the first month after surgery (O group, n = 94). Background factors were evenly distributed in the two groups, and 89% of the cases were considered as embolic. Analysis on an intention-to-treat basis showed no differences in outcome after 30 days. Good results, survivors who had amputation, and patients who died in the two groups are given respectively: AC group, 61%, 9%, 30%; O group, 65%, 11%, 24%. The results were similar in the two treatment groups also if only patients with a cardiac source of embolism were analyzed. Local bleeding complications were more common in the AC group (17% vs 2%, p less than 0.01). It is concluded that preoperative and early postoperative anticoagulant medication should not be routinely administered since such treatment is unlikely to improve the short-term results of lower-limb arterial thromboembolectomy while bleeding complications increase. The possible value of late (beyond 1 month) long-term anticoagulant treatment remains to be studied.

Amputation, Surgical↗