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Biomedical subjects

A Salmi

Publications and source records attributed to A Salmi.

At least 37 records · Page 2Linked to original sources

Therapy with antibody against leukocyte integrin VLA-4 (CD49d) is effective and safe in virus-facilitated experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is facilitated in resistant BALB/c mice by intraperitoneal infection with an avirulent Semliki Forest virus (SFV-A7). Viral infection increases the incidence of EAE from 15-30% to 60-90% and speeds up appearance of paralysis from 24 to 14 days. In this paper, we describe treatment of virus-facilitated EAE with monoclonal antibodies (mAbs) against leukocyte and/or endothelial cell adhesion molecules. Therapy with mAb against ICAM-1 (intercellular adhesion molecule-1) had a modest effect, but caused hemorrhagic brain and spinal cord lesions. Therapy with mAb against Mac-1 (alpha M beta 2-integrin) was well tolerated but had no effect. Therapy with mAb against VLA-4 (alpha 4 beta 1-integrin) was safe, diminished both clinical and histopathological signs of EAE, decreased induction of VCAM-1 (vascular cell adhesion molecule-1) on brain vessels and diminished infiltration of VLA-4+ cells into the brain. The amount of viral antigen in the brain was not altered. We conclude that facilitation of leukocyte entry into the brain is a major mechanism for viral facilitation of EAE in the BALB/c mouse, and that facilitation can be inhibited by anti-adhesion therapy. This may have implications for treatment of relapses triggered by viral infections in multiple sclerosis.

Animals↗

mRNA expression of insulin-like growth factor-I (IGF-I) is suppressed and those of IGF-II and IGF-binding protein-1 are constantly expressed in the endometrium during use of an intrauterine levonorgestrel system.

Insulin-like growth factors (IGF-I and IGF-II) are believed to mediate and modulate steroid hormone actions in the endometrium. In this study we determined the effects of an intrauterine system (IUS), releasing 20 microg levonorgestrel (LNG) daily, on endometrial expression of mRNAs encoding IGFs and insulin-like growth factor binding protein (IGFBP)-1. In Northern blotting, IGF-I mRNA was undetectable in all endometrial specimens from women with an LNG-IUS (n = 11) and in pregnancy decidua, whereas several transcripts of 0.6-7.6 kb were detected in proliferative and secretory phase endometria. In contrast, mRNAs encoding IGF-II and IGFBP-1 were strongly expressed in pregnancy and in all endometrial samples from women with an LNG-IUS, but were undetectable in proliferative or early to mid-secretory phase endometria. Using the more sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) method, IGF-I and IGF-II mRNAs were detectable in all cycling endometria, in early pregnancy decidua and in LNG-exposed endometrium. IGFBP-1 mRNA was constantly expressed in LNG-exposed endometrium, in early pregnancy decidua and in premenstrual endometrium, but was undetectable in all specimens from proliferative or early to mid-secretory endometrium. Our data demonstrate that progestin treatment can affect the gene expression of endometrial growth factors in vivo. The consistent expression of mRNAs encoding IGF-II and IGFBP-1, with suppression of IGF-I mRNA in endometria exposed to LNG, suggests that this mode of hormone treatment can inhibit IGF-I action in the endometrium. If IGF-I mediates and modulates oestrogen action, suppression of IGF-I mRNA may be one of the molecular mechanisms which accounts for the antiproliferative effects of progestogens on oestrogen-primed endometrium and the atrophy of endometrial epithelium resulting from use of an LNG-IUS.

Adult↗

Percutaneous ethanol injection in the treatment of hepatocellular carcinoma. A multicenter survey of evaluation practices and complication rates.

BACKGROUND: Percutaneous ethanol injection (PEI) has become a widely used procedure in the treatment of hepatocellular carcinoma (HCC). However, the criteria for selecting patients are not standardized, and little information is available about the complications of the procedure. METHODS: A questionnaire was sent to 11 experienced Italian centers. It investigated: the size and the number of HCC nodules suitable for treatment and the Child-Pugh risk class of the associated cirrhosis; the performance of the procedure; the number and characteristics of the patients treated; and, finally, any complications. RESULTS: Most of the centers performed PEI in single HCC nodules less than 5 cm in diameter or in multiple nodules if fewer than three, the larger being less than 3 cm. Patients in Child-Pugh's classes A, B, and C with single nodules were generally considered for PEI. A prothrombin time of less than 40% and a platelet count of less than 40,000/mm3 contraindicated PEI in most of the centers. PEI was generally performed on outpatients, using Chiba or spinal needles. One thousand and sixty-six patients (8118 sessions) were enrolled; 74% had a single HCC nodule and 26% multiple nodules. All except four had cirrhosis; 53% were in Child class A, 38% in class B, and 9% in class C. The mean number of sessions needed to destroy an HCC nodule was 6.7 (range, 2-14), with a mean alcohol injection volume of 5.0 ml per session (range, 2-20 ml). One death (0.09%) and 34 complications (3.2%) were reported. Among the complications we call attention to the hemorrhagic ones (eight cases) and tumoral seeding (seven cases). Severe pain experienced during the maneuver led to discontinuation of the procedure in 3.7% of the patients; 13.5% of the patients required analgesics and 24% had fever after PEI. CONCLUSIONS: Some procedural aspects of PEI treatment differ among the various centers a standardization is advisable. In the present survey PEI is a low-risk technique.

Aged↗

C-fos and c-jun expression in human endometrium and myometrium.

Estrogen is a mitogen in human endometrium and is considered to be responsible also for myometrial cell proliferation. Signalling pathways of estrogen action in these tissues are not known. In various other estrogen responsive cells, estrogen induces transient expressions of c-fos and c-jun mRNAs. We examined c-fos and c-jun mRNA expressions by Northern blotting in paired samples of endometrium, myometrium and leiomyoma tissues obtained from women under various hormonal environments as well as of endometrium and myometrium at term pregnancy. In nonpregnant endometria, strong expressions of c-fos (2.2 kb) and of c-jun (2.7 kb and 3.2 kb) were detected both in the follicular and luteal phase of the menstrual cycle, and the c-fos expression was significantly stronger in proliferative phase endometrium than in the adjacent myometrium. In most of the myometrial and leiomyoma tissue samples the signals for both protooncogenes were weak, and there were no systematic differences in the expressions between normal myometrium and myomatous tissue. In pregnant endometrium and myometrium, both the c-fos and c-jun mRNA expressions were nearly undetectable, and in pregnant endometrium expressions were significantly lower than those in nonpregnant endometrium. Also in late pregnancy myometria, the expression of c-jun was significantly lower than in nonpregnant tissues. These data suggest that c-fos and c-jun activation may be a part of estrogen-induced signal transduction in the endometrium, and that in term pregnancy endometrium this signalling pathway is inhibited. Due to the strong expression of c-jun and c-fos both in the proliferative and secretory phase endometrium, it is likely that these protooncogenes are related to functions other than epithelial cell proliferation in human endometrium. The weak expressions of c-fos and c-jun in the myometrium and in leiomyomata suggest that signalling pathways mediating steroid hormone action in endometrium and myometrium are different.

Adult↗

Natural history of focal nodular hyperplasia of the liver: an ultrasound study.

Sixteen cases of focal nodular hyperplasia (FNH) of the liver were followed by ultrasound (US) for a mean of 33 months (range 6-81). In 69% of the cases, the diagnosis was incidental. On US the lesions were single in 75% of the cases, localized in the right lobe in 75%, and subcapsular in 50%. No specific US-pattern could be identified. A central scar was found in 19% of the patients. At the end of the follow-up, the size was reduced in 7/16 cases, and in 1/16 the lesion disappeared. The spontaneous reduction of nodules in FNH must be considered in the management of this pseudotumor.

Adult↗

Measles virus hemagglutinin mediates monocyte aggregation and increased adherence to measles-infected endothelial cells.

The effect of measles virus (MV) infection on monocyte adhesion was studied using human peripheral blood monocytes and monocytic and endothelial cell lines. The infection of monocytic U-937 cells led to the formation of large cellular aggregates. Aggregation was independent of intercellular adhesion molecule-1 (ICAM-1)/lymphocyte function-associated antigen-1 (LFA-1), but could be inhibited by monoclonal antibodies (mAb) against the MV hemagglutinin glycoprotein (MV-H). mAb against the MV receptor, CD46, also blocked aggregation. No significant changes in the cell surface expression of adhesion molecules CD11a, CD11b, CD11c, CD18, CD54, CD44, CD49d (alpha 4-integrin) and CD62L (L-selectin) were observed on MV-infected monocytes. Infection of a human endothelial cell line, EAhy 926 (HEC), with MV led to a two-fold increase in 1CAM-1 expression and a two-fold increase in monocyte adherence to the HEC (from 22 +/- 1.6% to 42 +/- 4.8%). However, ICAM-1 mAb reduced monocyte adhesion to the control and MV-infected HEC to a similar degree, whereas anti-MV-H antibodies abolished the difference between binding to infected and control HEC. We conclude that MV hemagglutinin mediated both the homo typic aggregation in infected monocyte cultures and increased monocyte adherence to the infected endothelial cells.

Antibodies↗

Definition of three minimal T helper cell epitopes of rubella virus E1 glycoprotein.

To characterize T cell-recognized epitopes on rubella virus (RV) E1 glycoprotein, IL-2-dependent RV-specific T cell lines were established from 14 rubella-seropositive healthy donors. The responses of these lines were studied by using a panel of 94 partially overlapping synthetic peptides of 15 amino acids (aa) length covering the known nucleotide sequence of RVE1 glycoprotein. Two to seven peptide-defined epitopes were recognized by the T cell lines, but a large interindividual variation was found. T cell reactivity was most often localized to the regions between aa 276 and 290, aa 381 and 395 and aa 410 and 420. Analysis of overlapping, truncated peptides revealed three minimal T helper cell epitopes VIGSQARK, KFVTAALLN and RVIDPAAQ in aa positions 280-287, 385-393 and 412-419, respectively.

Animals↗

Proto-oncogenes c-jun and c-fos are down-regulated in human endometrium during pregnancy: relationship to oestrogen receptor status.

Oestrogen is the major stimulatory factor in endometrial cell proliferation. Animal and in-vitro studies have shown that proto-oncogenes c-fos and c-jun are regulated by oestrogen receptor (ER) complex. We have previously shown by Northern blot analysis that proto-oncogenes c-fos and c-jun are strongly expressed in human proliferative and early to mid-secretory endometrium. In this study, we examined the expression of the messenger RNA (mRNA) of the nuclear proto-oncogenes c-fos and c-jun in 10 early (6-10 weeks) and 20 term (30-40 weeks) pregnancy decidua by Northern blotting. In order to investigate the relationship between ER and these proto-oncogenes, the ER and progesterone receptors (PR) were identified in the same tissue samples by immunohistochemistry. When using 30-mer oligonucleotide probes, hardly any signals for c-fos and c-jun could be identified either in early or in late pregnancy decidua. Nuclear ER staining was intense in the epithelium and stroma of proliferative and early to mid-secretory endometrium but was sparsely scattered in stroma and lacking in epithelium during early pregnancy. In late pregnancy decidua, no positive ER staining was detectable. PR were present in abundance both in endometrial epithelium and stroma in proliferative and early secretory phase, and clear positive staining remained in stromal cells in late secretory phase and throughout pregnancy. The temporal association between immunoreactive ERs and the expression of c-fos and c-jun mRNA suggests that the activation of both proto-oncogenes is ER-mediated in human endometrium. The down-regulation of ER is one possible explanation for the repression of these immediate early genes during pregnancy.

Animals↗

A prospective study of changes in muscle dimensions following free-muscle transfer measured by ultrasound and CT scanning.

A retrospective study demonstrated that noninnervated free-muscle flaps do not lose bulk when evaluated at a mean of 41 months. The purpose of the present study was to evaluate changes in muscle bulk in noninnervated free-muscle transfers prospectively. This study included 22 flaps (17 latissimus dorsi, 4 rectus abdominis, and 1 gracilis). The thickness of the muscle was measured by ultrasonography preoperatively and 2 and 6 weeks and 3, 6, 9, 12, 15, 18, and 23 months postoperatively. The volume of the muscle was measured by computed tomographic (CT) scan preoperatively and 2 and 6 weeks and 3, 6, and 9 months postoperatively. Postoperative data were normalized to the preoperation measurements. The results demonstrated that the thickness of the muscle increased by a mean of 2.4 times (range 0.9 to 3.9) compared with the initial thickness in a 2-week period (p < 0.05), 2.0 times (range 0.9 to 4.2) in 6 weeks (p < 0.05), 1.7 times (range 0.8 to 4.2) in 3 months (p < 0.05), 1.5 times (range 0.6 to 3) in 6 months (p < 0.05), and 1.2 times (range 0.4 to 2.8) in 9 months (not significant). Thereafter, the mean thickness was the same as the initial thickness. CT scan measurements of the muscles confirmed the ultrasound findings. Our prospective study of free-muscle flaps found significant swelling that peaks at 2 weeks and extends until 6 months after the operation. This study also demonstrated that ultrasound evaluation of thickness gives the same conclusion as volumetric measurement by CT scanning.

Adolescent↗

Detection of rubella virus-specific immunoglobulin M antibodies with a baculovirus-expressed E1 protein.

The structural proteins of rubella virus (RV) were expressed in insect cells by using the baculovirus expression vector system. The recombinant E1 envelope glycoprotein was purified by immunoaffinity chromatography and used to detect RV-specific immunoglobulin M antibodies in a time-resolved fluoroimmunoassay. Correlation analysis between the reactivities of antibodies against this recombinant E1 and the reactivities against authentic RV antigen shows that purified E1 can detect RV antibodies of the immunoglobulin M type.

Antibodies, Viral↗

Use of ultrasonography to evaluate muscle thickness and blood flow in free flaps.

The purpose of this study was to investigate the common belief that a microvascular transfer of a non-innervated free muscle flap loses muscle bulk over time. Sixteen patients (latissimus dorsi = 8, rectus abdominis = 7, and gracilis muscle = 1) were evaluated an average of 41 months after free flap transfer. Latissimus dorsi and lower extremity flaps displayed significantly more swelling than the other flaps. Flap bulk was measured by ultrasound. The mean thickness of upper extremity flaps was 10.3 +/- 1.8 mm (control muscles 11.8 +/- 2.8), lower-extremity 14.5 +/- 3.7 mm (control muscles 10.9 +/- 0.7), latissimus dorsi 14.3 +/- 2.2 mm (control muscles 10.3 +/- 0.8, P = 0.018), and rectus abdominis 11.2 +/- 1.2 mm (control muscles 12.4 +/- 1.9). Color Doppler ultrasonography was used to detect the pedicles of the free flaps and also to measure the peak velocity of blood flow intramuscularly and in the pedicles. In the upper extremities (n = 5) the pedicles could be found in only 20% of cases whereas in the lower extremities (n = 11) 91% of pedicles were located. (P = 0.013). Peak flow within the free flaps was significantly higher in the lower extremity (50% of the peak flow of the common femoral artery) than in the upper extremity (5% of the peak flow of the common femoral artery, P = 0.013). This study demonstrated that non-innervated free muscle flaps in the extremities maintain the original muscle thickness, although lower extremity and latissimus dorsi flaps have a trend to be thicker. Most pedicles of free muscle flaps in the upper extremities could not be located by ultrasound. However, flaps in the lower extremities most often have patent pedicles and also more vigorous intramuscular blood flow.

Adolescent↗

Interferon-beta downregulates expression of VLA-4 antigen and antagonizes interferon-gamma-induced expression of HLA-DQ on human peripheral blood monocytes.

We have studied the effect of recombinant human IFN-beta on the basal and IFN-gamma-induced expression of adhesion molecules and class II MHC antigens on human peripheral blood monocytes and on ICAM-1 (intercellular adhesion molecule-1) expression of a human umbilical vein endothelial cell line (EAhy 926). We show that IFN-beta downregulates both basal and IFN-gamma-induced expression of VLA-4 (very late activation antigen-4) antigen on monocytes, but has no effect on the expression of CD11a, CD11b, CD11c, L-selectin, CD18, ICAM-1, beta 1-integrin or CD44 on monocytes or ICAM-1 on EAhy 926 cells. We also show that IFN-beta antagonizes the IFN-gamma-induced expression of HLA-DQ-antigen, but not HLA-DR or HLA-DP antigens on monocyte surface. These findings may partially explain the beneficial effect of IFN-beta in multiple sclerosis, since VLA-4-antigen is critical for leukocyte recruitment into inflamed brain and downregulation of HLA-class II expression diminishes antigen presenting capacity of monocytes.

Cells, Cultured↗

Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection.

PURPOSE: To define indications for percutaneous ethanol injection (PEI) in patients with hepatocellular carcinoma (HCC) and cirrhosis. MATERIALS AND METHODS: Survival rates were determined in 746 patients who had undergone PEI (567 men, 179 women; mean age, 64.3 years; mean follow-up, 36 months). RESULTS: In patients with Child A (n = 293), B (n = 149), or C (n = 20) cirrhosis and single HCCs 5 cm or smaller, the 3-5 year survival rate was 47%-79%, 29%-63%, and 0%-12%, respectively. In patients with Child A cirrhosis, it was 36%-68% for multiple HCCs (n = 121), 30%-53% for single HCCs larger than 5 cm (n = 28), and 0%-16% for advanced HCC (n = 16). Treatment was associated with a 1.7% rate of severe complications and a 0.1% mortality rate. CONCLUSION: PEI proved safe, effective, and repeatable and had a low cost. Survival after PEI was comparable to that after surgery, probably because of a balancing between greater radicality of surgery and absence of early mortality and liver damage of PEI.

Administration, Cutaneous↗

ACTH-induced c-myc proto-oncogene expression precedes antimitogenic effect during differentiation of fetal rat adrenocortical cells.

The regulation of proto-oncogenes has been connected with proliferation and differentiation in various cell types. In the present study, the ACTH-induced expression of c-myc mRNA and proliferation of fetal rat adrenocortical cells have been studied. Low levels of c-myc mRNA were detected in undifferentiated zona glomerulosa-like cells. Stimulation with ACTH for 2 to 6 h transiently increased the c-myc mRNA levels. Both basal and ACTH-induced expression levels were increased by the protein synthesis inhibitor cycloheximide. Treatment with a protein kinase C (PKC) activator 12-0-tetradecanoyl phorbol-13-acetate mimicked the effect of ACTH, whereas c-myc mRNA levels decreased by inhibiting the PKC with H-7. ACTH inhibited proliferation of fetal rat adrenocortical cells during the first 24 h of stimulation. The inhibitory effect began from 6 h, reached its maximum at 12 h and slowly vanished at 24 h. Our data demonstrated that ACTH transiently increased c-myc mRNA expression. Adrenocortical c-myc expression was mediated via PKC. In contrast to previous reports, where c-myc expression precedes proliferation of various cells, ACTH-induced c-myc mRNA expression of cultured fetal rat adrenocortical cells was followed by inhibition of proliferation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Morbidity of donor and recipient sites after free flap surgery. A prospective study.

Although free flap transfer is a routine procedure, we know of few studies about post-operative morbidity at recipient and donor sites. The strength of the shoulder extension after harvesting of a latissimus dorsi free flap (n = 12) and the patients' subjective opinions of morbidity at recipient and donor sites (n = 23) were assessed two and six weeks, and three,six, and nine months after transfer of free muscle flaps. The patients' subjective opinions were measured on a scale from 1 (normal) to 5 (very troublesome) and the strength of the shoulder was measured in N. The flaps used were latissimus dorsi (n = 18), rectus abdominis (n = 4), and gracilis (n = 1). All but one were transplanted to a lower extremity. The extension strength of the shoulder decreased from 105 N to 70 N immediately after the operation (p < 0.05), and strength did not improve during follow up. Subjectively assessed morbidity at the recipient site and cosmetic disability decreased from troublesome or very troublesome to moderate (p < 0.05). Swelling decreased from moderate at two weeks to normal or slight at nine months (p < 0.05). The subjective morbidity at the donor site decreased from slight at two weeks to normal at nine months for functional disability (p < 0.05). Cosmetic disability at the donor site was minimal during follow up. This study shows that shoulder extension strength deteriorated permanently after part of the latissimus dorsi muscle had been removed even though subjective morbidity was minimal. Morbidity at the recipient site decreased significantly with time. Subjective opinion of morbidity after latissimus dorsi transplantation did not differ from that after rectus abdominis transplantation.

Adolescent↗

HCV-RNA detection in ultrasound-guided fine needle biopsies of liver nodules and surrounding tissue.

HCV-RNA was examined in serum and liver tissue obtained from 8 hepatitis B surface antigen (HBsAg) negative patients with liver nodules ranging in size from 2 to 11 cm. Histological examination of ultrasound-guided fine needle biopsies revealed the presence of hepatocellular carcinoma (HCC) in six patients (5 of whom were anti-HCV positive), cholangiocarcinoma in 1 patient (anti-HCV positive) and dysplastic regenerative nodule in 1 patient (anti-HCV negative). The HCCs were surrounded by cirrhosis (3 cases), chronic active hepatitis (CAH) (n = 2) and post hepatitic fibrosis (n = 1), the cholangiocarcinoma by CAH and the regenerative nodule by cirrhotic liver. Total and replicative intermediate HCV-RNA was analyzed by reverse-transcription-nested PCR of the 5'-untranslated region. The five patients with HCC had HCV-RNA in serum, in tumorous and surrounding liver tissues. The viral nucleic acid was also detected in the cirrhotic tissue surrounding the cholangiocarcinoma but not in the tumor. Two out of 5 HCC patients had replicative intermediate RNA (negative strand) in tumorous tissue, 4 in nontumorous tissue and 3 in serum. These results demonstrate that fine needle biopsy can provide sufficient material for both histological examination and HCV-RNA determination and suggest the existence of continuous viral replication during the carcinogenic process.

Aged↗