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Biomedical subjects

O Larsson

Publications and source records attributed to O Larsson.

At least 181 records · Page 10Linked to original sources
PubMed1985

Commitment events in early G1 requirement for the synthesis of dolichol dependent glycoproteins.

Dolichol functions as a carrier of oligosaccharides to polypeptide chains in the biosynthesis of N-linked glycoproteins. It is here reported that a short (4 hours) transient exposure to tunicamycin, (a specific inhibitor of dolichol dependent glycosylation) causes a cell cycle delay in post-mitotic 3T3-cells. From kinetic point of view the delay following treatment by tunicamycin resembles the delay caused by short exposures to serum deprivation or treatment by cycloheximide, indicating that the expression of N-linked glycoproteins may be involved in the cell cycle regulation. Evidence is that the availability of dolichol may be a limiting factor in this process is also presented.

Animals↗
PubMed1985

Kinetic analysis of regulatory events in G1 leading to proliferation or quiescence of Swiss 3T3 cells.

Kinetic analysis of cellular response to serum deprivation or inhibition of protein synthesis was performed on Swiss 3T3 cells. Time-lapse cinematographic analysis of individual cells transiently exposed to serum-free medium (with or without the addition of purified growth factors) or cycloheximide enabled a detailed mapping of the magnitude and variability of cellular response in different parts of the cell cycle. In all cells, in all stages of the cell cycle, serum deprivation resulted in inhibition of protein synthesis, but only in postmitotic cells in the first 3-4 hr of G1 (here denoted the G1pm phase) did it produce cell-cycle arrest. During G1pm, the cells are highly dependent on the continuous presence of serum growth factors and a high level of protein synthesis in order to progress toward mitosis. A 1-hr exposure to serum-free medium or to cycloheximide was sufficient to force most G1pm cells into a state of quiescence (G0), from which the cells required 8 hr to return to G1pm. During G1pm the cells complete the growth factor-dependent processes leading to commitment for proliferation. Thereafter they enter the growth factor-independent pre-DNA-synthetic part of G1 (here denoted G1ps). The commitment process in G1pm could be successfully completed in the presence of platelet-derived growth factor as the only supplied growth factor. Epidermal growth factor and insulin were insufficient for the completion of the commitment processes in G1pm, although they were able to temporarily prevent the G1pm cells from entering G0 during serum starvation. Under conditions optimal for proliferation, the cells complete the commitment processes in G1pm within a remarkably constant time period. Almost all cells in the population left G1pm and entered G1ps between the third and fourth hour after mitosis. The duration of G1ps, on the other hand, showed a large intercellular variability consistent with a transition-probability event. In fact, G1ps accounts for most of the variability in G1 and cell cycle time.

Animals↗
PubMed1985

Cell-cycle-specific induction of quiescence achieved by limited inhibition of protein synthesis: counteractive effect of addition of purified growth factors.

We have previously shown that Swiss 3T3 cells located in the first part of G1 (post-mitotic G1 cells younger than 4.0 h or G1pm cells) were arrested after 9-10 h in the cell cycle by a short (1-8 h) exposure to serum-free medium or by a short (2-4 h) exposure to low doses of the protein synthesis inhibitor cycloheximide (CH). Kinetic data indicate that such G1pm cells rapidly return to G0 during this brief treatment and thereafter require a preparatory period of 8 h before continuing to G1. Cells older than 4 h, i.e. cells in mid or late G1 are already committed to DNA synthesis (presynthesis or G1ps cells). These cells as well as S and G2 cells were consequently unaffected by the brief serum starvation or the brief treatment with cycloheximide. In the present paper we show that the 10-h intermitotic delay that follows a 1-2 h exposure to serum-free medium can be completely counteracted by the presence of any one of the purified growth factors, epidermal growth factor (EGF), insulin or platelet-derived growth factor (PDGF). In contrast, the intermitotic delay following a longer exposure (8 h) to serum-free medium could no longer be counteracted by EGF or insulin. However, PDGF was still active in this respect. Most interestingly, the 12 h gross intermitotic delay induced by a 4h exposure to CH could be efficiently counteracted by EGF, PDGF or insulin. However, this effect on CH-treated cells could be counteracted by the growth factor only in the presence of 10% serum. This indicates the existence of a cooperative effect between PDGF, EGF or insulin and an unidentified serum factor. The effects on the cell cycle time of brief serum starvation and exposure to CH were compared with the effects on rate of protein synthesis and degradation. Although the effects of serum starvation on protein synthesis and degradation were found to be partially normalized by growth factors, we suggest that growth factors prevent cells from leaving the cell cycle by another mechanism and not merely by affecting the level of overall protein accumulation.

Animals↗
PubMed1985

Consequences of parental exposure to serum-free medium for progeny cell division.

Proliferating serum-dependent 3T3 cells prolong their intermitotic time by 9-10 h after exposure to serum-free medium for only 1 h. This delay was only observed in cells younger than 4 h, i.e. cells in the postmitotic G1 phase (G1pm), as defined by time elapsed since previous mitosis. These data confirm earlier findings that cells are very sensitive to growth factor or serum depletion during the first part of G1 and that only a short exposure to serum-free medium is sufficient for the cells to leave the cell cycle. However, such cells that have delayed their first cell cycle in response to a short exposure to serum-free medium in early G1 exhibit a reduced capacity to delay the subsequent cycle in response to a repeated exposure to serum-free medium. In contrast cells older than 4 h that are exposed for short periods to serum-free medium undergo cell division on schedule, but delay the subsequent cell cycle by several hours. This delay of the progeny cycle is mainly ascribable to the postmitotic part of G1 (G1pm). These data suggest that short exposures to serum-free medium exert an indirect effect on the progeny cell cycle and demonstrate that cycle times are not necessarily determined de novo in the lifetime of every cell, but may be influenced by events in the preceding cycle.

Animals↗
PubMed1985

Kidney transplantation in diabetic renal failure. A clinical and physiological study.

The results of kidney transplantation in 100 consecutive diabetic patients, transplanted between December 1972 and June 1982, are presented. Cardiac function was studied in parallel using non-invasive methods (phonocardiography, apexcardiography, carotid pulse tracing and M-mode echocardiography) in a subsample of the patients before transplant (n = 27) and repeatedly after successful transplant (n = 17). The study period was divided into two parts: 1972-1976 (era I, 21 patients) and 1977-1982 (era II, 79 patients). A high percentage of living related donors (LRD) characterised era II. A group of 168 non-diabetic patients, aged 20-54 years, served as controls to the 72 juvenile-onset diabetics during era II. During era II both patient (PS) and graft (GS) survival had improved considerably compared to era I. Actuarial PS was comparable to non-diabetic controls in the three years following transplant in both recipients of LRD (82% vs 97%) and cadaveric donor (CD) kidneys (70% vs 77%) and, in addition, in LRD recipients for five years (79% vs 88%). In diabetic LRD recipients, actuarial GS was similar to controls until five years after transplant (68% vs 72%) but was inferior in CD recipients at three years (37% vs 56%, p less than 0.05). The overall GS in CD transplantation was influenced positively by a high success rate in retransplantation. Cardiac mortality was low after successful transplant but increased substantially after graft failure. Peripheral vascular insufficiency was the dominating posttransplant complication and primary cytomegalo viral infections were common also. Hypertension was a constant finding pretransplant and posed a problem also at posttransplant, despite good graft function. Rejection accounted for the majority of primary graft failures. Stable glomerular filtration rate prevailed after successful transplant in LRD recipients. Hospital stay during the first three years following successful transplant in LRD recipients averaged one month per year, about twice as long as for controls. Rehabilitation was good, however, in these diabetics. The left ventricular (LV) function was severely compromised pretransplant, with impaired diastolic function and a pronounced LV hypertrophy as the most prominent features. The LV systolic function was well preserved in relation to end-systolic wall stress. The haemodynamic situation was that of a hyperdynamic circulation. Successful transplantation was associated with a gradual reversal of hypertrophy, normalisation of end-systolic wall stress and a raise in myocardial contractility.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Corelease of vasoactive intestinal polypeptide and peptide histidine isoleucine in relation to atropine-resistant vasodilation in cat submandibular salivary gland.

Parasympathetic nerve stimulation of the submandibular salivary gland in the cat caused salivary secretion, vasodilation and a corelease of vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) immunoreactivities (IR) into the venous effluent, as indicated by an increase in output. The ratio between the released VIP-IR and PHI-IR was close to 1:1. Gel-permeation chromatography of plasma from the submandibular venous effluent indicated that the released VIP-IR and PHI-IR were very similar to porcine VIP and PHI, respectively. Atropine pretreatment enhanced output of both VIP-IR and PHI-IR during the parasympathetic nerve stimulation to a similar extent (about 5-fold) compared to control stimulations. This increase could be due to an inhibitory presynaptic muscarinic receptor regulation of VIP and PHI release. Since VIP and PHI are present in the same postganglionic parasympathetic nerves in the gland and both peptides have vasodilator activity, the present data suggest that both VIP and PHI may contribute to the atropine-resistant vasodilation seen upon stimulation of the chorda-lingual nerve. The parasympathetic control of salivary gland function may thus involve, a multimessenger system with the classical transmitter acetylcholine and the peptides VIP and PHI.

Acetylcholine↗
PubMed1984

Captopril in hypertension after renal transplantation.

The experience with captopril is limited in patients who are hypertensive after renal transplantation. An increased risk of side effects has been expected because of immunosuppressive therapy and a reduced renal function. We have used captopril in 58 transplanted patients with hypertension. On previous antihypertensive treatment diastolic blood pressure could not be maintained below 100 mm Hg. All patients were on immunosuppressive therapy using prednisolone in combination with azathioprine or cyclosporin. Before captopril treatment the mean s-creatinine concentration was 225 +/- 143 mumol/l. Fifty-four patients were treated for more than four weeks and 28 of them for six months or more. The mean daily dose of captopril was 90 mg. All patients also used furosemide and 2/3 were on a beta-blocker. Captopril was discontinued in nine cases within the first two months, in three because of an unsatisfactory effect on BP, in four because of side effects and in two after successful treatment of a renal artery stenosis of the transplant. The patients who were treated with captopril within the first year after transplantation responded better than patients where treatment was started more than one year after transplantation (p less than 0.05). Half of the patients given captopril early even showed a decrease of s-creatinine during treatment. Captopril in combination with a diuretic and a beta-blocker reduces blood pressure in patients with treatment resistant hypertension following renal transplantation. The risk for serious side effects is small provided that the captopril dose is low and white cell counts and s-creatinine levels are closely monitored.

Adult↗
PubMed1984

Renin secretion in advanced diabetic nephropathy.

Low basal and stimulated plasma renin activity (PRA) levels have been reported in patients with diabetic nephropathy (DN). We have measured PRA before and after stimulation with captopril in 28 patients with DN and in 25 control patients. Renal function impairment was similar in both groups. Most patients were treated with furosemide. In 19 patients with DN the PRA-response to dihydralazine was also studied. PRA before and after captopril were higher in the DN than in the control group (p less than 0.001). PRA increased from 4.6 +/- 3.6 to 6.3 +/- 5.3 in the DN, and from 1.8 +/- 2.7 to 2.7 +/- 3.4 in the control patients. The increases in PRA, caused by decreased angiotensin II feed-back inhibition, were comparable. PRA did not increase after dihydralazine despite a pronounced blood-pressure reduction. The difference in response to these stimuli indicate selective lesions involving both the sympathetic innervation and the renal baroreceptor function in DN. Overhydration is a plausible explanation to the low PRA earlier reported in DN. The results thus indicate that a preserved renin secretion capacity is present in DN. Differences in PRA between the both groups can only partly be explained by other factors than DN. Our findings indicate a role for the reninangiotensin-system in hypertension in DN.

Adult↗
PubMed1984

Survival in end-stage diabetic renal disease. A prospective study of 100 kidney transplant patients.

The results of renal transplantation in patients with diabetes mellitus were studied in 100 consecutive patients transplanted between Dec. 1972 and June 1982. The study period was divided into two parts, 1972-76 (era I, 21 patients, 18 with juvenile onset diabetes) and 1977-82 (era II, 79 patients, 72 with juvenile onset diabetes). A group of 168 non-diabetic patients, aged 20-54 years, receiving primary grafts during the same period served as controls to the 72 juvenile onset diabetics from era II. The three-year actuarial patient survival of transplanted diabetics improved from 48% during era I to 76% during era II and was then not significantly inferior to that of the non-diabetic controls. The three-year actuarial graft survival rate was significantly higher for recipients of kidneys from living related donors than for those who had received kidneys from cadaveric donors (CD) among both diabetic and non-diabetic patients. However, the three-year graft survival rate was significantly higher (56%) for non-diabetic than diabetic CD recipients (37%). The overall survival in diabetes mellitus was strongly influenced by the outcome of retransplantation during era II (12 patients). Thus, 69 patients were alive, 64 with a functioning graft, at the end of the observation period.

Adult↗
PubMed1984

Data base management systems for evaluation of analytical procedures.

The present paper gives a short introduction to data base management systems, and their application in the clinical laboratory for evaluating the quality of analytical procedures. Two applications based on the MIMER relational data base management system are described in some detail: An internal quality control data base under development at the clinical chemistry laboratory of the University Hospital in Uppsala, and a data base system for external quality assessment developed in a previous NORDKEM project.

Chemistry, Clinical↗
PubMed1984

A platelet aggregation inhibitor--ticlopidine--in diabetic nephropathy: a randomized double blind study.

A randomized double blind trial was performed to investigate the effect of the platelet aggregation inhibitor ticlopidine on the rate of decline in renal function in diabetic nephropathy. Twenty-two patients with insulin dependent diabetes complicated by nephropathy completed the trial--11 on ticlopidine, and 11 on placebo for one year. Ticlopidine effectively reduced platelet aggregation in vitro. Renal clearance of 51Cr-EDTA declined from 39 +/- 10 to 30 +/- 13 ml/min per 1.73 m2 body surface in the ticlopidine group and from 42 +/- 9 to 39 +/- 13 in the placebo group. The difference in decline between the two groups was not significant. In the ticlopidine group renal function expressed as the slope coefficient for 1/S-creatinine per month remained the same as before the trial. It is concluded that although there is much evidence to suggest a role of platelets in the development or progression of diabetic nephropathy treatment with ticlopidine could not prevent this process.

Adult↗
PubMed1983

Protein-reduced diet in diabetic renal failure.

The effect of treatment with a protein-reduced diet (20-30 g/day) and essential amino acids was studied in 21 patients with diabetes mellitus and renal failure. The mean treatment time was 5.0 (0.5-14) months. Most patients experienced considerable amelioration of their uremic symptoms and the mean serum value was reduced by 50% of the initial value during treatment. Residual renal function continued to decrease during treatment. Vigorous treatment of fluid retention and hypertension was a prerequisite for a successful course and may also have decreased the rate of progression towards dialysis. Compliance with the diet was not different from that found in non-diabetic uremic patients. Satisfactory control of blood glucose levels was obtained with no or only minor adjustments of the insulin dosage. It is concluded that dietary therapy should be considered in diabetic patients with renal failure for treatment of uremic symptoms.

Adult↗
PubMed1982

Growth activation of resting cells: induction of balanced and imbalanced growth.

Little is known about how mitogenic factors generate growth regulatory signals and how these are mediated within the cell. We have developed three different types of mitogenic stimuli in order to identify the possible existence of common denominators in a complex and perhaps pleiotypic signal-response system. 3T3 cells, starved to quiescence by reducing the serum content of the culture medium 100-fold, can be irreversibly committed to undergo DNA replication and mitosis in a serum-free medium after an initial exposure of short duration to (a) serum factors and cholesterol, (b) a relative excess of glutamine, or (c) alkaline pH. Cells stimulated by any of these procedures, and subsequently incubated in serum-free Dulbecco's modified Eagle's medium (DMEM) undergo DNA replication and mitosis in the absence of concomitant cellular enlargement (imbalanced growth). However, cellular enlargement is induced after the initial mitogenic stimuli (a, b, and c, as described previously) if the cells are subsequently incubated in DMEM containing greater than or equal to 0.5% serum, supraphysiological concentrations of insulin, or normal concentrations of somatomedin C.

Animals↗
PubMed1981

Planned third-party transfusions prior to first transplantations from liver related donors.

Seventy-nine first living related donor transplants performed in Gothenburg, Sweden, from April 1977 to October 1980 were studied. The patient survival was 97% at 30 months. The graft survival in HLA-identical sibling combination was 100%. Thirty previously non-transfused recipients of one-haplotype mismatched grafts were given 2 units of third-party blood as preparation for transplantation. The graft survival was 92% at 30 months. No patients became sensitized against their donor. Thirty-one recipients of haplotype-mismatched grafts, previously transfused for medical reasons, had a graft survival of 82% at 30 months. The deliberate third-party blood transfusion protocol has been rewarding and resulted in a highly satisfactory graft survival.

Antilymphocyte Serum↗