Search PubMed⌕ Search

Biomedical subjects

T Ruutu

Publications and source records attributed to T Ruutu.

At least 19 recordsLinked to original sources
PubMed1992

Chromosomal in situ suppression hybridization of immunologically classified mitotic cells in hematologic malignancies.

Chromosomal in situ suppression (CISS) hybridization was performed with library DNA from sorted human chromosomes 8, 9, 15, 17, 21, and 22 on immunologically stained bone marrow cells of four patients with a hematologic neoplasm, including two patients with myelodysplastic syndrome and trisomy 8, one patient with promyelocytic leukemia bearing the translocation t(15;17)(q22;q11-12), and one patient with chronic myeloid leukemia and the translocation t(9;22)(q34;q11). In all patients, the results of conventional karyotype analysis could be confirmed by one- or two-color CISS hybridization using the appropriate chromosome-specific libraries. Our results show that CISS hybridization can detect both numerical and structural chromosome changes in immunologically classified cells with high specificity and reliability. The fact that chromosome spreads of very poor quality can now be included in such analyses is a decisive advantage of this approach. In addition, the suitability of this approach for interphase cytogenetics is discussed.

Chromosome Aberrations↗
PubMed1992

Phenylarsine oxide augments tyrosine phosphorylation in hematopoietic cells.

Tyrosine phosphorylation and dephosphorylation are implicated in the regulation of cell growth and differentiation. A diverse identification of key regulatory proteins by their content of phosphotyrosine has been hampered by the very low level of tyrosine phosphorylation. This is presumably caused by the relative preponderance of phosphotyrosine phosphatase activity in many cells. We report that treatment of hematopoietic cells with phenylarsine oxide (PAO), a membrane-permeable phosphotyrosine phosphatase inhibitor, induced a dramatic accumulation of phosphotyrosine in a number of cellular proteins. No changes in serine or threonine phosphorylation were detected. The PAO-induced accumulation of phosphotyrosine occurred well before any signs of toxicity or irreversible damage to the cells were seen. Addition of dithiothreitol reversed the effect of PAO. Our data demonstrate that phosphotyrosine phosphatase activity has a major impact on the level of phosphotyrosine in cellular proteins, even in cells with high protein tyrosine kinase activity. Cells with constitutively elevated tyrosine kinase activity are easily detected following treatment with PAO and substrates with an otherwise too low phosphotyrosine content or too rapid phosphate turnover can be studied. This effect of PAO allows determinations of tyrosine phosphorylation-dependent complex formation between proteins.

Aged↗
PubMed1992

Immunohistology of skin and rectum biopsies in bone marrow transplant recipients.

We have studied histological and immunohistological specimens of 39 skin biopsies from 21, and 30 rectal biopsies from 17 bone marrow transplant recipients. The biopsies were taken before transplantation, during acute and chronic graft-versus-host disease (GVHD), and at times with no GVHD. In biopsies taken during cutaneous aGVHD grade I to III, epithelial changes were seen in 16/23 biopsies. The cutaneous infiltrates during aGVHD consisted of CD2-, CD4-, CD8- and FMC-33-positive cells both in the epithelium and in the dermis. CD57-positive NK cells were also detected in most biopsies. During chronic GVHD the cutaneous cellular infiltrates were similar to those seen in moderate aGVHD, i.e. both CD4- and CD8-positive lymphoid cells were present. When the biopsy was taken after the beginning of corticosteroid treatment for aGVHD, or at times when the patient did not have GVHD symptoms, the cellular infiltrates were considerably smaller in the dermis. During clinical intestinal aGVHD mucosal epithelial changes were relatively uncommon; instead, increased numbers of both CD4- and CD8-positive lymphocytes in the lamina propria (LP) were seen in 11/13 samples. During chronic GVHD the number of CD4-positive cells exceeded that of CD8-positive cells in the LP, and the large lymphoid infiltrates also reached the muscularis mucosae. In rectal biopsies the differences were not so prominent because most of the pretransplant biopsies showed CD2-, CD4-, CD8- and CD57-positive lymphocytes both in the lamina propria and epithelium.

Acute Disease↗
PubMed1991

Autosomal dominant erythrocytosis caused by increased sensitivity to erythropoietin.

We describe here a family with autosomal dominant erythrocytosis. In in vitro cultures, performed using the methyl cellulose assay, the number of erythroid colonies was normal or marginally increased when a standard concentration of erythropoietin (Epo) was used, but at lower Epo concentrations, the investigated persons formed more colonies than the controls. The difference was generally greater the lower the Epo concentration became. Some erythroid colony growth was seen even in the absence of any added Epo (apart from the minute concentration found in fetal calf serum), a phenomenon not seen in the controls. This finding indicates that the erythrocytosis in this family is caused by hypersensitivity of erythroid progenitors to Epo. The serum Epo concentration was low or low normal in all of the investigated family members, which is in good accordance with hypersensitivity to Epo. The erythrocytosis has not had any obvious effect on the health or life-span of the affected individuals. Many of them have reached an advanced age, and one of the affected family members has won several Olympic gold medals and world championships in endurance sports.

Erythropoiesis↗
PubMed1991

Acceleration of chronic myeloid leukemia correlates with calcitonin gene hypermethylation.

Calcitonin gene methylation at CCGG sites were determined in 39 chronic myeloid leukemia patients by isoschizomeric restriction endonuclease analysis. A total of 27 patients were analyzed while still in the chronic phase: 20 patients had a normal gene, and seven had a hypermethylated gene. There were 12 patients initially studied in accelerated or blastic phases. All but one patient showed gene hypermethylation, suggesting a good correlation between gene methylation and disease stage. All five patients who, while still in the chronic phase, had a major 3.1-kb hypermethylated calcitonin gene fragment, accelerated within 2 to 27 months. In consecutively analyzed patients, the initially normal calcitonin gene changed to a hypermethylated state as the disease escalated. The hypermethylation predicted disease acceleration with a median lead time of 6 months before any morphologic or clinical signs of disease progression were seen. The disease progressed in 8 of 27 patients initially studied in the chronic phase: in only two patients this occurred without predictive methylation changes. The results suggest that the assessment of calcitonin gene methylation status may be a promising tool for monitoring chronic myeloid leukemia disease escalation.

Biomarkers, Tumor↗
PubMed1991

Prevention of alloimmunization in patients with acute leukemia by use of white cell-reduced blood components--a randomized trial.

Platelet refractoriness arising from HLA alloimmunization is a serious complication of transfusion therapy. In a prospective randomized trial, white cell (WBC)-reduced blood components were compared to standard platelet and red cell concentrates with respect to alloimmunization, refractoriness, and platelet increments after transfusion. Sixteen of 31 adult acute leukemia patients received only WBC-reduced platelet concentrates (PCs) and red cells (RBCs), with fewer than 10(6) WBCs per unit. Fifteen control patients received standard blood components with a mean of 0.1 x 10(9) (PCs) and 1 x 10(9) (RBCs) WBCs per unit. Platelet loss during cotton-wool filtration averaged 14 percent (range, 3-32%) from fresh PCs and 24 percent (range, 9-62%) from stored PCs. Filtration did not change corrected increments (CI) measured after transfusion of fresh PCs. The Cl 1 hour after filtration of stored PCs diminished by 27 percent, but the difference was smaller after 18 hours, which suggests better survival of WBC-reduced platelets. The number of platelet units transfused did not differ in the two groups. No patient in the WBC-reduced group developed permanent platelet refractoriness; transient HLA antibodies of low titer developed in two patients. In the control group, one patient became refractory because of immunization and two developed transient HLA antibodies. It can be concluded that the reduction of WBCs in blood components can effectively prevent alloimmunization.

Adolescent↗
PubMed1991

Serum amyloid A levels in acute graft-versus-host disease in bone marrow transplant recipients.

We studied serum amyloid A levels of 31 bone marrow transplant recipients with and without acute graft-versus-host disease. Before transplantation the mean SAA concentration was 5.1 +/- 0.8 mg/l (mean +/- SEM). It remained low in patients with no signs of aGVHD but increased significantly during aGVHD to 54.0 +/- 8.2 mg/l (p less than 0.001 compared to pre-BMT value). Severe infections also induced high SAA levels.

Adrenal Cortex Hormones↗
PubMed1990

Cytomegalovirus is frequently isolated in bronchoalveolar lavage fluid of bone marrow transplant recipients without pneumonia.

We prospectively studied the presence of cytomegalovirus in bronchoalveolar lavage through virus isolation in 21 bone marrow transplant recipients before and after transplantation. All 14 lavage specimens collected before bone marrow transplantation were negative for cytomegalovirus. During the period from 20 to 90 days after transplantation, 12 of 24 lavage specimens (50%) from 14 patients without lung problems were positive for cytomegalovirus. Cytomegalovirus was isolated from 4 of 10 lavage specimens (40%) in 7 patients with pneumonia during the same interval. We conclude that culture for cytomegalovirus in bronchoalveolar lavage fluid is not a reliable method for establishing the virus's causative role in pneumonia soon after bone marrow transplantation. Among 14 patients in whom bronchoalveolar lavage was done at an asymptomatic stage, 6 of 9 patients with cytomegalovirus and none of 5 without cytomegalovirus in the lavage fluid later developed pneumonia. All of the patients subsequently developing pneumonia also had acute graft-versus-host disease, suggesting an immunopathologic mechanism, possibly triggered by cytomegalovirus, for cytomegalovirus-associated pneumonia.

Adult↗
PubMed1990

Cardiac involvement in bone marrow transplantation: serial changes in left ventricular size, mass and performance.

Forty-five consecutive adult patients with haematological malignancies were studied prospectively to evaluate cardiac involvement in bone marrow transplantation (BMT). Echocardiography and measurement of systolic time intervals were performed before conditioning with cyclophosphamide (CY) (120 mg kg-1) and total body irradiation (10-12 Gy), and repeated 1 month and 1 year after BMT. The left ventricular (LV) changes at the 1-month study included increases in mass index (85.1 +/- 4.0 g m-2 vs: 76.1 +/- 3.3 g m-2, mean +/- SE; P less than 0.001) and in the pre-ejection period/ejection time ratio (0.46 +/- 0.01 vs. 0.36 +/- 0.01, P less than 0.001), and decreases in fractional shortening (24.9 +/- 1.0% vs. 27.9 +/- 0.8%, P less than 0.01) and in the peak normalized diameter lengthening rate (2.2 +/- 0.1 s-1 vs. 2.6 +/- 0.1 s-1, P less than 0.01). Four patients developed congestive heart failure. Twenty-four patients were alive and relapse-free 1 year after BMT. The LV measurements were then no longer different from the pre-transplant readings. Thus BMT that is preceded by conditioning with CY and total body irradiation results in increased LV mass and impaired systolic and diastolic LV function. These changes are mostly subclinical, and are also reversible if the recipient survives the initial months after transplantation.

Adult↗
PubMed1990

Pure red-cell aplasia of long duration after major ABO-incompatible bone marrow transplantation.

We describe a patient with an exceptionally long-lasting red-cell aplasia of 330 days following ABO-incompatible bone marrow transplantation (BMT). Before BMT, the anti-B titre was high, 1:1,024, and it was only temporarily reduced by extensive plasma exchange. The anti-B titre remained above the level of 1:64 for 270 days, and host-derived isoagglutinin could still be detected 3 years after BMT. In vitro bone marrow cultures during the red-cell aplasia showed greatly reduced numbers or total absence of CFU-E, while the number of BFU-E colonies was only moderately subnormal. Six years after BMT, bone marrow and peripheral-blood cell counts are normal.

ABO Blood-Group System↗
PubMed1990

Acute phase response in Pneumocystis carinii pneumonia.

The acute phase response induced by 19 episodes of Pneumocystis carinii pneumonia (PCP) was analysed in a retrospective study. There were 9 men and 1 woman with HIV, aged 25-45 years (mean 37.2) and 4 men and 4 women with other immunodeficiencies, aged 18-35 years (mean 26.2). The outcome of these two groups with PCP did not differ: in the HIV group 4 died and in the non-HIV group 2 died. In the HIV group, peak serum C-reactive protein (S-CRP) ranged 41-228 mg/l, mean 126 (77.3), and in the non-HIV group 19-290 mg/l, mean 105 (89.1) (NS). The patients with a fatal outcome had higher mean peak S-CRP: 186 (73.8) mg/l versus 85.3 (63.5) mg/l in the survivors (p = 0.007). The HIV infection itself did not increase the S-CRP concentration, which was normal before or after PCP in all 7 survivors of the 11 episodes. Thus, PCP induces a clear-cut S-CRP response, which may be used for monitoring the treatment and evaluating the prognosis of the patient.

Acute-Phase Reaction↗
PubMed1990

Cardiac involvement in bone marrow transplantation: electrocardiographic changes, arrhythmias, heart failure and autopsy findings.

In order to evaluate cardiac involvement in bone marrow transplantation (BMT) we reviewed serial electrocardiograms, chest X-rays and cardiac pathology at autopsy in 45 consecutive adult patients undergoing BMT for hematologic malignancies at our institution. All patients were pretreated with cyclophosphamide (CY, 120 mg/kg) and total body irradiation (TBI, 10-12 Gy). A total of 15 patients developed electrocardiographic ST-segment or T-wave changes and/or arrhythmias post-BMT; four of them also suffered from congestive heart failure. The arrhythmias included frequent ventricular extrasystoles (two patients), paroxysmal atrial fibrillation (one patient), repeated supraventricular tachycardia (one patient) and QT-prolongation with ventricular tachyarrhythmias (one patient). Twelve patients showed an early drop of the total QRS voltage sum exceeding 15% of the pretransplant reading. In a subgroup of five patients the voltage drop was associated with ST-segment or T-wave changes; three of them developed congestive heart failure. At autopsy in 15 patients, the heart weight was on the average 113% of predicted. Myocardial edema, fibrosis and cellular hypertrophy were the most common microscopic findings. Two patients had marantic endocarditis of the aortic valve. Thus, in our experience clinically significant heart involvement affects 5-10% of patients undergoing BMT after pretreatment with CY and TBI. While cardiac complications are generally not a major problem of BMT, they may have serious consequences for individual patients and should therefore be carefully watched for in the treatment of BMT recipients.

Adolescent↗
PubMed1990

Use of bronchoalveolar lavage cytology and determination of protein contents in pulmonary complications of bone marrow transplant recipients.

Bronchoalveolar lavage (BAL) cytology and immunoglobulin components of lavage fluid were studied during non-bacterial/non-fungal interstitial pneumonitis, bacterial/fungal pneumonia, and Pneumocystis carinii infection. Lavages done before bone marrow transplantation and in asymptomatic phases were used as controls. The total cell recovery was increased during lung processes of any aetiology. Non-bacterial/non-fungal pneumonitis caused a significant increase in the number of lymphocytes; the number of neutrophils increased particularly during bacterial pneumonia. In Pneumocystis carinii pneumonia the typical cell picture was an increased percentage of lymphocytes together with blasts. During acute graft-versus-host disease without respiratory symptoms the cytology in lavage fluids did not differ from the controls. Cytomegalovirus (CMV) isolation was frequently positive in lavage fluids regardless of the presence or absence of pulmonary symptoms, but most of the symptom-free CMV-positive patients did not have any marked changes in BAL cytology. The albumin content of BAL fluid increased during infectious and immunological processes in lungs.

Bone Marrow Transplantation↗
PubMed1990

A Nordic registry for volunteer marrow donors?

A meeting took place in Helsinki in November 1989 to consider the scientific, clinical and financial implications of establishing a registry of volunteer bone marrow transplant donors in the Nordic countries. The possible contributions of new techniques for defining HLA genes and gene products, notably the study of restriction fragment length polymorphisms and allele specific oligonucleotides, and for selecting optimal donors, notably the assay of cytotoxic T lymphocyte precursors in the graft-versus-host direction, were discussed. The differing approaches actually used to establish new donor registries in the United Kingdom, United States and France were contrasted. The clinical results of using unrelated donors for transplanting patients with chronic myeloid leukaemia, severe aplastic anaemia and other haematological diseases were presented. Finally, participants heard details of the International Marrow Unrelated Search and Transplant Study which collects and analyses data internationally on patients for whom searches are initiated and on patients who actually receive transplants from volunteer donors.

Bone Marrow Transplantation↗
PubMed1990

Effect of culture conditions on in vitro erythroid colony formation in myelodysplastic syndromes.

In vitro colony formation by erythroid progenitors from the bone marrow was studied in 42 patients with a myelodysplastic syndrome using both a standard assay for growing erythroid colonies and an assay designed for growing megakaryocyte colonies. In the standard assay 5 patients had normal numbers of erythroid burst-forming unit (BFU-E) colonies, 8 showed reduced numbers of colonies, and 29 patients had no colony formation. Six patients with markedly reduced numbers of erythroid colonies or no colonies at all in the standard assay showed normal or increased numbers of erythroid colonies in the megakaryocyte assay. In three of these patients the erythroid colony morphology was normal, whereas the other three showed abundant diffuse growth of erythroid subclusters with no normal colonies. In the other patients, the erythroid culture results were similar in both assays. These results indicate that the impairment of erythroid colony growth seen in most patients with a myelodysplastic syndrome is, at least in a number of patients, not due to reduced numbers of erythroid progenitors but to unusual milieu requirements of abnormal progenitors.

Bone Marrow↗
PubMed1990

DNA-fingerprint changes compared to karyotypes in acute leukemia.

Chromosomal analysis is routinely used in follow-up studies of acute leukemia, but it cannot be used in patients who do not have karyotypic abnormalities in blastic phase (10-46% of all cases). Recently we have demonstrated that unspecific DNA-fingerprint (DNA-F) changes can be detected in blastic phase of leukemia by DNA-F analysis. These changes can be used as molecular markers of the disease and in the follow-up studies of acute leukemia karyotyping and DNA-F analysis are complementary. The comparative analyses of leukemia samples with both these methods could help to localize minisatellite loci in chromosomes and reveal new DNA areas related to leukemia. New, more specific probes targeted to specific chromosomes could consequently be developed. We compared the DNA-F to the karyotypes of 50 acute leukemia patients. In blastic phase, 19 patients had DNA-F alterations and 31 patients abnormal karyotypes, 12 patients had both DNA-F alterations and karyotypic abnormalities. DNA-F changes were detected in six of the 16 patients with normal karyotypes and 19 patients with normal DNA-F had abnormal karyotypes at the time of diagnosis. Eleven patients showed neither DNA-F changes nor abnormal karyotypes in blastic phase. Three acute myeloid leukemia (AML) patients with DNA-F changes in blastic phase had trisomy eight as a sole abnormality or combined with balanced translocation, which suggests that there might be AML associated minisatellite locus in chromosome 8. In other cases the karyotypes were complicated and no clear evidence of the relationship of DNA-F changes with other chromosomes could be found.

Acute Disease↗