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Biomedical subjects

M Roos

Publications and source records attributed to M Roos.

At least 37 records · Page 2Linked to original sources
PubMed1999

Zebrafish semaphorin Z1b inhibits growing motor axons in vivo.

Zebrafish semaphorin 1b (sema Z1b) is a new member of the semaphorin family, related to mammalian sema D/III. It is expressed in rhombomeres three and five, and in the posterior half of newly formed somites which is avoided by ventrally extending motor axons. Embryos injected at the 1-2 cell stage with synthetic sema Z1b mRNA developed normally but many (63%) showed missing or severely stunted ventral motor nerves. Other axons, somites, and hindbrain rhombomeres were not affected. No abnormalities were seen in control embryos injected with lacZ mRNA. Sema Z1b might normally influence the midsegmental pathway choice of the ventrally extending motor axons by contributing to a repulsive domain in the posterior somite.

Amino Acid Sequence↗
PubMed1999

Expression of stromelysin 3 in keratoarcanthoma and squamous cell carcinoma.

Stromelysin 3 (ST3) is a member of the metalloproteinase family, which is expressed in the skin during wound healing and in the stroma of basal cell carcinoma. A high level of expression of ST3 has been observed in carcinomas of poor prognosis. In benign tumors, though, ST3 is not expressed or is at a low level. We have immunohistochemically studied the expression of ST3 in 89 randomly selected cases of squamous cell carcinomas (SCCs), 104 of keratoacanthomas (KA), and 23 cases of metastatic SCC. Stromelysin 3 was expressed only by fibroblasts surrounding the tumors and not by epithelial cells. The proportion of tumors positively stained was 22% of KA, 47% of randomly selected SCC, and 70% of metastatic SCC. In areas of poorly demarcated neoplastic cells, a reinforcement of the staining was observed in the stroma. The intensity and dispersion of staining were used to determine the level of expression. There were significantly more SCC in the groups of high expression levels, and both parameters were significantly higher in SCC than in KA. Expression of ST3 in benign tumors is unusual. Its expression in the the stroma of keratoacanthomas can be related to the high tissue remodeling activity observed in these tumors. It also could be interpreted as in favor of the neoplastic nature of KA. Nevertheless, the level of expression was higher in SCC than in KA and seemed to be related to the prognosis of these tumors. These results correlate well with those obtained in breast cancers and in noncutaneous SCC.

Carcinoma, Squamous Cell↗
PubMed1998

The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy.

OBJECTIVE: To investigate the relationship between exposure to antiretroviral drugs and the initial decline of plasma HIV-1 RNA. DESIGN: Open-label study in antiretroviral-naive HIV-1 infected patients using a quadruple drug regimen [nelfinavir (NFV), saquinavir (SQV), stavudine, and lamivudine]. METHODS: The elimination rate constant (k) for HIV-1 clearance was calculated during the first 2 weeks of treatment in 29 patients. Exposure to NFV and SQV was quantified on each study visit. Observed NFV and SQV concentrations were related to those expected in a reference population and a concentration ratio was calculated. The median concentration ratios for NFV and SQV, the baseline CD4+ lymphocyte count and baseline log10 HIV-1 RNA were correlated with k. RESULTS: A significant positive correlation was observed between k and the median NFV (P = 0.001) or SQV concentration ratio (P = 0.016) in univariate analysis. In multivariate analyses, the median NFV concentration ratio remained significantly correlated with k. CONCLUSIONS: The variation in the rate of decline of plasma HIV-1 RNA between patients after the initiation of a quadruple drug regimen could be explained by differences in exposure to NFV or SQV. Determination of k could be used to optimise further antiretroviral drug therapy and may be a first tool to assess antiretroviral activities of new or increasing doses of drugs administered in combination regimens. Furthermore, our data suggest that exposure to antiretroviral drugs should be incorporated in mathematical models to describe HIV-1 dynamics in more detail.

Anti-HIV Agents↗
PubMed1998

Alternative multidrug regimen provides improved suppression of HIV-1 replication over triple therapy.

OBJECTIVE: To compare the viral suppression of two antiretroviral regimens using three drugs or five drugs. DESIGN: Two open-label studies using a three-drug (zidovudine, lamivudine and ritonavir) and a five-drug regimen (zidovudine, lamivudine, abacavir, indinavir and nevirapine) in study-drug-naive patients, except for one in the five-drug study. METHODS: Participants with > or = 10 000 HIV-1 RNA copies/ml in plasma at baseline were compared by means of Kaplan-Meier curves for time to < 50 copies/ml, as well as linear regression analysis for the first phase of decline using log-transformed copy numbers. RESULTS: The elimination rate constants for HIV-1 RNA in 15 participants of the three-drug study were compared with nine participants of the five-drug study. The level of < 50 copies/ml was reached earlier when using the five-drug than when using the three-drug regimen (P log rank = 0.0005): median time to reach this level was 4 weeks and 12 weeks, respectively. No differences were found in HIV-1 RNA elimination rate constants in the first 2 weeks after the initiation of therapy. When the viral load declines were calculated from day 2 onwards, adjusting for differences in pharmacological delay of the drugs used, again no differences in early viral load decline were found between the two regimens. CONCLUSION: With the five drugs used in this study, the median time to reach < 50 HIV-1 RNA copies/ml was 8 weeks shorter than with the three-drug regimen. This finding shows that suppression of viral load in HIV-infection by standard triple-drug therapy can be improved upon.

Adult↗
PubMed1998

Evidence that both HIV and HIV-induced immunodeficiency enhance HCV replication among HCV seroconverters.

The objective of this retrospective cohort study is to assess the mechanism by which human immunodeficiency virus type 1 (HIV) influences hepatitis C virus (HCV) replication in injecting drug users. Virological (HCV and HIV RNA levels) and immunological (CD4+, CD8+ cell counts, and anti-CD3 reactivity) parameters were determined in 19 HCV seroconverters in sequential samples over a period of 1 to 9 years. Among these subjects, 10 were HIV-seronegative (HIVneg), 4 were HIV-seropositive (HIVpos), and 5 seroconverted for HIV (HIVsc) during the observation period. HCV RNA levels were higher in HIVpos subjects than in HIVneg subjects. In subjects seroconverting for HIV, HCV, RNA levels increased significantly immediately after HIV seroconversion (P < 0.0001), while they remained stable over time in HIVpos and HIVneg subjects. HCV RNA correlated inversely with CD4+ cell counts in both the HIVpos population (R = -0.22, P < 0.05) and the HIVneg population (R = -0.45, P < 0.0001). In addition, when subjects were stratified according to CD4+ cell counts a significant difference was found in HCV RNA levels between HIVpos and HIVneg subjects with CD4+ cell counts > 500 cells/microliter (P = 0.001), but not in the population with CD4+ cell counts < 500 cells/microliter. In no population was a correlation found between HCV RNA levels and CD8+ cell counts or anti-CD3 reactivity. Both HIV infection and CD4+ cell counts are apparently associated with HCV RNA levels. The direct association, independent of CD4+ cell counts, between HIV infection and HCV replication appears to be stronger than the association between HIV-induced CD4+ cell decline and HCV replication. We conclude that (i) HCV replication is in some way directly influenced by the presence of HIV; (ii) HCV-specific host immunity controls, in part, HCV replication; and (iii) HCV replication increases when the immune system is impaired by HIV.

CD4 Lymphocyte Count↗
PubMed1998

Improved high-performance liquid chromatographic separation of peptidoglycan isolated from various Staphylococcus aureus strains for mass spectrometric characterization.

Reversed-phase high-performance liquid chromatography (RP-HPLC) of muropeptides, obtained by muramidase digestion of peptidoglycan in combination with amino acid analysis and plasma desorption time-of-flight mass spectrometry is today by far the best tool to analyze the fine structure of the peptidoglycans. Here we report further improvements of the RP-HPLC separation of muropeptides for analyzing the peptidoglycans of various methicillin-resistant strains of Staphylococcus aureus, with emphasis on a more detailed characterization of the interpeptide bridge of the peptidoglycans of this species.

Chromatography, High Pressure Liquid↗
PubMed1998

Post-translational modifications of endothelin receptor B from bovine lungs analyzed by mass spectrometry.

A new mild experimental approach for isolation of peptide membrane receptors and subsequent analysis of post-translational modifications is described. Endothelin receptors A and B were isolated on oligo(dT)-cellulose using N-(epsilon-maleimidocaproyloxy)succinimide endothelin coupled to a protected (dA)-30-mer. This allowed a one-step isolation of the receptor from oligo(dT)-cellulose via variation solely of salt concentration. The identity of the receptor was confirmed by direct amino acid sequencing of electroblotted samples or by using antibodies against ETA and ETB receptors. The method used here is very fast, requires only very mild elution conditions and, for the first time, gave both ETA and ETB receptors concurrently in very good yield. Following enzymatic in-gel digestion, MALDI, and electrospray ion trap mass spectrometric analysis of the isolated endothelin B receptor showed phosphorylation at Ser-304, -418, -438, -439, -440, and -441. Further phosphorylation at either Ser-434 or -435 was observed. The endothelin B receptor is also palmitoylated at Cys residues 402 and 404. Phosphorylation of Ser304 may play a role in Hirschsprung's disease.

Amino Acid Sequence↗
PubMed1998

Anterior-posterior subdivision of the somite in embryonic zebrafish: implications for motor axon guidance.

The ventral branches of the segmental peripheral nerves in the zebrafish embryo are pioneered by the caudal primary (CaP) motor axons, which extend midsegmentally at the interface of the somite and the notochord. The signals that define the CaP pathway are not well understood. To gain insight into the nature of the guidance cues, we have examined the environment of the CaP motor axons by using electron microscopy and histochemistry. Specifically, we have mapped the distribution of the transcription factor engrailed, of a chondrotin sulfate epitope, and of the recognition molecules zebrafish semaphorin z1b and zebrafish tenascin C. Ultrastructural examination of dye-labeled CaP motor axons revealed a close association with the medial surface of the somite but not with the notochord. The CaP axons were always accompanied by cells that appeared to migrate at the interface of somite and notochord. These cells were confined to the posterior half of the somite. Some of the cells may be neural crest derived, many others are probably of sclerotomal origin. The putative migratory cells expressed a chondroitin sulfate epitope that is a marker of sclerotome in the chick. The pathway of the CaP axon and the distribution of the putative neural crest and sclerotome cells correlated with a subdivision of the myotome into an anterior and posterior components, which were evident at the histological level and by the expression of the markers engrailed, semaphorin z1b, chondroitin sulfate, and tenascin C. We suggest that both the pathway choice of the CaP axon and the route of migratory cells reflect this anterior-posterior bipartition of the myotome.

Animals↗
PubMed1997

Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European multicenter trial.

A randomized, double-blind multicenter trial was performed to compare the safety and efficacy of a new low-molecular-weight heparin (LMWH) (LU 47311, Clivarine) and standard unfractionated heparin for the prophylaxis of postoperative venous thromboembolism. Altogether 1351 patients scheduled to undergo abdominal surgery were included. Main outcome measures included the incidence of thromboembolic events (deep vein thrombosis, pulmonary embolism, or both) and bleeding complications, including wound hematoma. A total of 655 patients received 1750 anti-Xa IU of LMWH plus a placebo injection daily; 677 patients received 5000 IU of unfractionated heparin (UFH) twice a day. Both drugs were found to be equally effective, as 4.7% of patients in the LMWH group and 4.3% in the UFH group developed postoperative thromboembolic complications. However, the incidence of bleeding complications was significantly reduced in the LMWH group: 55 (8.3%) patients in the LMWH group and 80 (11.8%) in the UFH group developed bleeding complications, a relative risk (RR) of 0.70 (95% CI 0.51-0.97;p = 0.03); wound hematoma occurred in 29 (4.4%) of the LMWH group compared with 55 (7.7%) in those in the UFH group for an RR of 0.57 (95% CI 0.37-0.88;p = 0.01). This study confirmed that a very low dose of 1750 anti-Xa IU daily of this new LMWH is as effective as 10,000 IU of UFH for preventing postoperative deep vein thrombosis. At this dose its administration is associated with a significant reduction in the risk of bleeding including wound hematoma.

Adult↗
PubMed1997

AIDS prognosis based on HIV-1 RNA, CD4+ T-cell count and function: markers with reciprocal predictive value over time after seroconversion.

OBJECTIVE: HIV-1 RNA levels in peripheral blood are strongly associated with progression to AIDS, CD4+ T-cell decline, or death. Their predictive value is reportedly independent of the predictive value of CD4+ T-cell counts. Because the interrelations between these parameters of HIV-1 infection are poorly understood, we studied the kinetics and predictive value of serum HIV-1 RNA levels, CD4+ T-cell counts, and T-cell function. DESIGN AND METHODS: HIV RNA levels, CD4+ T-cell counts, and T-cell function were measured from seroconversion to AIDS in 123 homosexual men who seroconverted during a prospective study and were followed over 10 years. RESULTS: Two patterns of median HIV-1 RNA levels were found during infection: a steady-state and a 'U-shaped' curve. Steady-state high RNA levels were related to rapid disease progression. For the U-shaped curve, there were groups with high and low RNA levels related to disease progression. At 1 year after seroconversion, RNA level was the only marker that was strongly predictive. Furthermore, decreasing RNA levels in the first year following seroconversion were related to better prognosis than stable low levels. Low CD4+ T-cell count and T-cell function became predictive of progression to AIDS at 2 and 5 years after seroconversion, respectively. CONCLUSIONS: With ongoing infection, the predictive value of low CD4+ T-cell count and T-cell function increases, whereas the predictive value of high HIV-1 RNA level decreases. These findings reflect the observation that infection with HIV progressively leads towards immune deficiency, which in later stages is most predictive of disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1997

[Fifty years of dental nurse education in Finland].

The first training-course for dental nurses was arranged by the Finnish Dental Association in 1947-1948. Professional help was needed in dental offices in assisting the dentists, taking care of the patients, particularly children, and in cleaning the equipment. As early as 1922 the Scandinavian Dental Association had pointed out that "clinic sisters" would be needed in dental training centers, but the suggestion was not put into effect. The first nine-month curriculum for dental nurses already included all disciplines of dentistry. Lectures in pharmacology, bacteriology and first-aid were also given. Practical training was arranged at the Institute of Dentistry, University of Helsinki. The students further trained for three-week periods both at dental clinics and at privat dental offices. Nine students completed the course and received their diplomas at the end of May, 1948.

Dental Assistants↗