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Biomedical subjects

B Holm

Publications and source records attributed to B Holm.

At least 19 recordsLinked to original sources
PubMed1992

Different subsets of T cells in the adult mouse bone marrow and spleen induce or suppress acute graft-versus-host disease.

Fractionation of normal adult mouse spleen and bone marrow cells (C57BL/Ka) was performed by discontinuous Percoll density gradients. The fractionated low density (1.050-1.060 g/ml) C57BL/Ka spleen cells completely suppressed acute lethal graft vs host disease (GVHD) when coinjected with unfractionated C57BL/Ka spleen cells into sublethally irradiated (400 rad) BALB/c mice. In dose response experiments, as few as 0.5 x 10(6) low density cells from the spleen fractions suppressed acute GVHD induced by 2.5 x 10(6) unfractionated allogeneic spleen cells. Although the low density spleen fractions inhibited acute GVHD, the high density (1.075-1.090 g/ml) spleen fractions induced acute GVHD in sublethally irradiated BALB/c recipients. Fractionation of C57BL/Ka bone marrow cells showed that none of the high or low density fractions or unfractionated cells induced lethal GVHD. When these fractions were tested for their capacity to suppress GVHD by coinjection with C57BL/Ka unfractionated spleen cells, all fractions protected the BALB/c recipients. Unfractionated bone marrow cells showed modest protection. Evaluation of the dose response characteristics of the suppressive activity of the low and middle density (1.060-1.068 g/ml) bone marrow cell fraction showed that reproducible protection could be achieved at a 5:1 ratio of inducing to suppressing cells. The low density fractions of both bone marrow and spleen cells had a marked depletion of typical TCR(+)-alpha beta CD4+ or CD8+ T cells, and a predominant population of TCR(+)-alpha beta CD4- CD8- T cells. Purified populations of the latter cells suppressed GVHD. Recipients given unfractionated C57BL/Ka spleen cells and protected with low-density bone marrow or spleen cells were chimeras.

Animals↗
PubMed1992

Treatment of BCL1 leukemia by transplantation of low density fractions of allogeneic bone marrow and spleen cells.

C57BL/Ka bone marrow and spleen cells fractionated by density gradients were transplanted to lethally irradiated (800 rad) BALB/c recipients. Unfractionated bone marrow and spleen cell mixtures (1:1), or high density fractions of these cells induced acute lethal graft-vs-host disease (GVHD). In contrast, low and middle density fractions of bone marrow and spleen cell mixtures reconstituted the irradiated hosts, and the majority survived for at least 100 days. The latter cells contained sufficient hemopoietic cells for reconstitution, but were deficient in inducing GVHD. Examination of the T cell subsets in the low density fractions showed a reduction of typical alpha beta TCR+ CD4+ or CD8+ cells and little change in the proportion of alpha beta TCR+ CD4- CD8- cells. BALB/c mice injected with the BCL1 B cell leukemia/lymphoma were lethally irradiated and transplanted with unfractionated BALB/c or C57BL/Ka bone marrow and spleen mixtures or low density fractions of C57BL/Ka mixtures. All control unirradiated BALB/c mice given the BCL1 tumor cells died by day 55. Almost all BALB/c mice given the BCL1 tumor cells, irradiation, and injected with a syngeneic marrow and spleen mixture died by day 95. All of the latter recipients tested showed evidence of tumor relapse. Almost all BALB/c mice given BCL1 cells, irradiation, and a C57BL/Ka unfractionated marrow and spleen mixture died by day 40. The survival of BALB/c mice given BCL1 cells, irradiation, and a low density fraction of the C57BL/Ka mixture was markedly prolonged as compared to those recipients given unfractionated allogeneic or syngeneic mixtures. None of the low density fraction recipients tested showed evidence of tumor relapse. Similar results were obtained with leukemic C57BL/Ka x BALB/c F1 hybrid mice. Thus, the low density fraction fails to induce acute lethal GVHD, but retains graft-vs-leukemia activity.

Animals↗
PubMed1992

Studies of CD4- CD8- alpha beta bone marrow T cells with suppressor activity.

The predominant T cell subset in the bone marrow of specific pathogen-free C57BL/Ka and BALB/c mice expressed the alpha beta+ TCR CD4- CD8- surface phenotype. Purified C57BL/Ka alpha beta+ TCR CD4- CD8- marrow cells obtained by cell sorting suppressed the MLR of C57BL/Ka responder and BALB/c stimulator spleen cells. Although the percentage of typical T cells in the spleen was markedly reduced in adult nude mice or normal neonatal mice as compared to the normal adult, the percentage of alpha beta+ TCR CD4- CD8- cells in the spleen and marrow was not. The percentage of "self-reactive" V beta 5+ T cells in the BALB/c spleen was markedly reduced as compared to that in the C57BL/Ka spleen. However, the percentages in the bone marrow were similar. The results indicate that the predominant subset of marrow T cells in these pathogen-free mice differ with regard to surface marker phenotype, function, dependence on the adult thymus, and deletion of certain self-reactive V beta receptors as compared to typical spleen T cells. The marrow T cells appear to develop directly from marrow precursors without rearranged beta chain genes during a 48 hour in vitro culture.

Animals↗
PubMed1992

Pathophysiology of congenital diaphragmatic hernia II: the fetal lamb CDH model is surfactant deficient.

The high mortality for congenital diaphragmatic hernia (CDH) has been attributed to a combination of pulmonary hypoplasia and pulmonary hypertension. We hypothesize that a surfactant deficiency may in part be contributing to the pathophysiology of CDH. This study documents the functional, quantitative, and qualitative aspects of the surfactant status of the alveolar air-liquid interface and the type II pneumocyte in the fetal lamb CDH model. Ten lamb fetuses (gestational age, 80 days) had a CDH created via a left thoracotomy and then were allowed to continue in utero development until term. Three litter mates and three nonoperated time-dated fetuses served as controls. At term, pressure-volume curves were performed to measure pulmonary compliance and total lung capacity. Alveolar lavage was then performed to measure the quantitative and the qualitative aspects of pulmonary surfactant. Finally, isolation of type II pneumocytes allowed quantification of phospholipid synthesis. When compared with controls (N = 6), the CDH lambs (N = 5) had significantly smaller lungs (P = .009), decreased total lung capacity (P less than .001) and compliance (P less than .001), reduced total lavaged phospholipids (P = .006), and decreased percent phosphatidylcholine (P = .02). CDH lambs also had increased total lavaged proteins (P = .05) and higher minimum dynamic surface tension (P less than .001). A surfactant deficiency may be contributing to the pathophysiology of CDH. Surfactant replacement therapy in premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Exogenous surfactant may also benefit infants with CDH.

Animals↗
PubMed1991

Incidence and follow-up of asymptomatic multiple myeloma. The myeloma project of health region I in Norway. II.

During a general population follow-up study in Health Region I in Norway, 162 patients with multiple myeloma (MM) were diagnosed. 71 of these (44%) were asymptomatic, and were observed without chemotherapy. The great majority (90%) were in stage I, and there were only 2 with light chain disease. 45 of the 71 asymptomatic patients developed progressive disease during the 4-5 year follow-up period. Estimated median time to disease progression was 26 months. The presence at diagnosis of osteolytic lesions and/or at least 20% plasma cells in the bone marrow defined a group with significantly shorter time to progression (median 10 vs 39 months). Median survival from diagnosis for the asymptomatic patients was 45 months, which is significantly longer than the 26 months of the symptomatic group. However, when estimated from the start of treatment, the survival was similar for the two groups.

Adult↗
PubMed1990

[Factors determining the development of wound infection after appendectomy].

In order to illustrate which factors are of significance for the development of wound infection after appendectomy, an extensive prospective material of 2,097 patients submitted to appendectomy was analysed. Regression analyses demonstrated that age alone, employment of preoperative antibiotics (cefoxitin) and patient delay (time from onset of symptoms till admission) were of significance. The present authors conclude, on the basis of this material, that all patients over 25 years of age should be given preoperative antibiotic prophylaxis which covers aerobic and also anaerobic microorganisms. If a gangrenous or perforated appendix is found, antibiotics should be administered intraoperatively if prophylactic treatment has not been administered. In cases of perforation, antibiotics should be administered postoperatively for 72 hours.

Adolescent↗
PubMed1990

Cellular and molecular characteristics of transformed T cells from an antigen-specific T-cell line.

An antigen-specific T-cell line which transforms into T-lymphoma cells in vitro but apparently not in vivo is described. Membrane markers, tumorigenicity and T-cell receptor (TcR) V alpha and V beta-gene usage of the in vitro transformed T-cell line were analysed to investigate whether the transformation event was poly-, oligo-, or monoclonal. The results indicate that the T lymphoma has no chromosome abnormalities, contains no tumour-inducing virus, can induce clone-specific immunity, and is oligoclonal with respect to TcR V alpha and V beta expression. The nature of the transformation event and clinical application of vaccination against T lymphomas is discussed. In addition, the expressed TcR V alpha and V beta repertoire of Con A T blasts was apparently not affected by the Igh-l or the MHC haplotype, as investigated in Igh-l and MHC congeneic C57Bl mice.

Animals↗
PubMed1990

Unilateral, isometric bite force in 8-68-year-old women and men related to occlusal factors.

Unilateral bite force was studied in 63 women and 59 men, 8-68 yr of age. The subjects had a minimum of 24 teeth and no symptoms or signs of disorders of the craniomandibular system. Bite force was stronger in men (522 N) than in women (441 N). It increased with age until 25 yr (P less than 0.0001). The level decreased significantly after this age in women, whereas it only tended to decrease in men and not until after 45 yr of age. Body height was positively associated with force. However, the strongest correlation (r: 0.43-0.49, P less than 0.01) with adult bite force was occlusal contact. The normal bite-force values with important determining factors provide reference data for screening of elevator muscle strength in routine examination of craniomandibular function.

Adolescent↗
PubMed1989

Antibiotic prophylaxis in acute nonperforated appendicitis. The Danish Multicenter Study Group III.

In a prospective, block-randomized, multicenter study, the safety and efficacy of cefoxitin in preoperative prophylaxis were studied. 1735 patients undergoing appendectomy were evaluable, and half of these patients received 2 g of cefoxitin before undergoing operation. The patients were divided into three groups: patients with a normal appendix, patients with an acutely inflamed appendix, and patients with a gangrenous appendix. The study showed for each group a significant reduction of the incidence of wound infection in patients receiving prophylaxis. However, intra-abdominal abscess formation was not influenced by preoperative antibiotic prophylaxis. Consequently, routine preoperative prophylaxis is recommended before appendectomy.

Abdomen↗
PubMed1988

The effect of hydralazine on steady-state plasma concentrations of metoprolol in pregnant hypertensive women.

We have studied the plasma concentrations levels of metoprolol after its twice daily administration in a dose of 50 mg for 4 days in ten, hypertensive pregnant women to the during monotherapy and in combination with 25 mg of hydralazine given twice daily. Hydralazine increased the median AUC and Cmax of metoprolol by 38% and 88% respectively, and decreased the tmax from 1.5 h to 1.0 h. Hydralazine had no effect on the plasma concentrations of alpha-OH-metoprolol. These results suggest that the effect of hydralazine on metoprolol plasma concentrations is primarily due to a reduction in first-pass elimination.

Adult↗
PubMed1987

Interactions of human blood platelets with three circulating plasma fibrinogens of different molecular weights.

The ability of three naturally occurring human fibrinogen species, HMW, LMW and LMW', to support ADP-induced platelet aggregation was investigated and compared to their ability to bind to gel-filtered platelets. Whereas HMW had intact subunit chains, LMW and LMW' had defined lesions in the C-terminal part of one (LMW) or both (LMW') of the A alpha-chains. The ADP-induced aggregation of gel-filtered platelets in the presence of LMW was about 75 per cent of that obtained with HMW (0.2 mumol/l of fibrinogen and 10 mumol/l of ADP). A mixture of equal amounts of LMW and LMW' showed around 50% decrease in aggregation. Compared to these difference in aggregation co-factor function, direct binding to gel-filtered platelets was less affected by the A alpha-chain degradation. However, a difference between LMW, LMW' and HMW binding was significant when the fibrinogens labelled with two different isotopes of iodine were present simultaneously. These results demonstrate that naturally occurring plasma fibrinogens differ in their interactions with platelets. As the HMW/LMW ratio changes during the acute phase, this may be of physiological significance.

Adenosine Diphosphate↗
PubMed1987

The predictive value of the third day temperature in the decision whether to continue or terminate antibiotic treatment in perforated appendicitis.

The third day temperature is frequently used in the decision whether to continue or terminate antibiotic treatment following appendicectomy in perforated appendicitis. To assess the value of the third day temperature in predicting intraperitoneal infectious complications we studied 235 consecutive patients treated with a 3-day course of cefoxitin after surgery for perforated appendicitis. The results demonstrated that regardless of the level of elevated temperature chosen, the predictive value ranged between 16 and 33%. In consequence, elevated third day temperature per se does not provide any rational basis for continuing antibiotic treatment in order to prevent intraperitoneal infectious complications following appendectomy in perforated appendicitis.

Abdomen↗
PubMed1986

Binding properties on Sepharose insolubilized fibrinogen and fibrin, of various species of fibrinogen and fibrin solubilized in plasma.

Radiolabelled tracers of fibrinogen, fibrin des-AA and fibrin des-AABB were solubilized in recalcified, prothrombin depleted plasma, adding either 125I-fibrin des-AA or 125I-fibrin des-AABB together with 131I-fibrinogen, and subsequently subjected to affinity chromatography, utilizing short columns of Sepharose insolubilized preparations of fibrinogen, fibrin des-AA and fibrin des-AABB, respectively. Two naturally occurring fibrinogen species, of high molecular weight (HMW; m.w. 340.000) and of low molecular weight (LMW; m.w. 305.000) exhibited similar binding characteristics, as judged by adsorption and desorption experiments. In subsequent studies all tracer preparations were derived from HMW-fibrinogen. Sepharose insolubilized fibrinogen favoured the adsorption of soluble fibrins as compared to fibrinogen in solution; the adsorption of soluble des-AA fibrin was similar to that of soluble des-AABB fibrin. To insolubilized fibrin, adsorption of soluble tracers of fibrinogen and fibrins increased considerably, and soluble fibrins were no longer preferentially adsorbed. The latter observation was supported by similar desorption characteristics of these tracers. These findings may indicate that the E-domains of soluble fibrin become largely inaccessible to the D-domains of Sepharose insolubilized fibrinogen, probably due to complexing fibrinogen in plasma. Furthermore, adsorption was largely related to the a-epitope of insolubilized fibrin.

Animals↗
PubMed1986

The release of small amounts of fibrinopeptide-B (FPB) is of critical importance for the thrombin clotting time.

When fibrinogen is clotted with thrombin, mainly fibrinopeptide-A (FPA) is released at gel point, the FPB-release being delayed. The present study present evidence that the small amounts of des-AABB fibrin found at visible gelation improves polymerization, thereby determining the thrombin clotting time. 1. Purified fibrinogen was clotted with thrombin or Reptilase, peptide release monitored radioimmunologically. With thrombin, significantly less fibrin (released FPA) was necessary for gel formation than when Reptilase was used. Furthermore, approximately 10% of the available FPB had been released by thrombin at gel point. 2. Polymerization of monomers prepared by incubation of fibrinogen with Reptilase (des-AA) and thrombin (des-AABB) in urea, were examined by light scattering. Des-AA fibrin monomers polymerised after a lag-phase of 4 minutes. When 20% of these monomers were substituted with des-AABB monomers, the lag was reduced to 1 1/2 minutes. 3. Finally, polymerization of preformed des-AA monomers was studied with and without the addition of small amounts of thrombin, and the FPB-release monitored. The presence of 0.04 NIH U/ml of thrombin reduced the lag from 10 minutes to 3 minutes. At this time approximately 10% of FPB had been released. It is concluded that even small amounts of des-AABB fibrin substantially improves polymerization of des-AA fibrin.

Blood Coagulation Tests↗