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Biomedical subjects

M Lehtinen

Publications and source records attributed to M Lehtinen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Outcome for patients with leukemia, multiple myeloma and lymphoma who relapse after high dose therapy and autologous stem cell support.

Relapses after autologous transplantation are a serious clinical problem in patients with haematological diseases. The decision making for handling of such patients is difficult and the aim of this retrospective analysis of posttransplant relapses was 1) to obtain information of practical importance for the management of future relapses and 2) to evaluate the basis for clinical phase I-II trials of salvage therapy combined with biological modifiers. Included in the study were 283 patients with acute leukemia, multiple myeloma and malignant lymphoma who relapsed after autologous transplantations during a five year period from 1989 to 1994. Chemo- and radiotherapy was given to 229 patients after relapse or due to progressive disease and the response evaluated after 90 days. Fifty four patients (24%) obtained a complete remission and 44 patients (19%) partial responses. The overall median survival from relapse was 5 months. In the group given salvage treatment the median survival was 7 months and in the 54 patients who obtained remission the median survival was 15 months. So far 6 of 14 patients in continuous complete remission have a remission time after relapse longer than the time in remission after transplantation. Survival after relapse depended upon the time from transplantation to relapse, primary disease and if salvage therapy was given. In conclusion posttransplant relapses can be treated but the strategy has to be evaluated in future clinical trials.

Adolescent↗
PubMed1995

Human T helper cell epitopes overlap B cell and putative cytotoxic T cell epitopes in the E2 protein of human papillomavirus type 16.

Activation of T helper cells is a prerequisite for the function of cytotoxic T lymphocytes (CTL) and the maturation of the B cell response. Because epitopes recognized by each of these cells may overlap, we scanned the E2 protein of human papillomavirus (HPV) type 16 to identify the T helper cell epitopes. Four major T helper cell epitopes (mapping between aa:s 11-25, 141-155, 191-205 & 231-245) and adjacent human B cell epitopes were found. The first peptide-defined epitope (RLNV) 11CQDKILTHYENDSTD25 overlapped five putative HLA-I (A1, A2, A0205, A3 & A11) binding motifs (CQDKILTHY, RLNVCQDKI, NVCQDKIL, RLNVCQDK & RLNVCQDK). This epitope is also part of an N-terminal alpha-helix which may form four HLA-II (DR2, DR4, DR7 & DR8) specific agretopes for structures recognizable by the T cell receptor (e.g. KILT). The second epitope 141EEASVTVVEGOVDYY155 (GLYY) overlapped the putative HLA-A1 & HLA-Bw37 binding motifs (VVEGQVDYY/QVDYYGLYY and EEASVTVV), and two HLA-II (DR1 & DR3) specific agretopes. The third and fourth epitopes were not associated with more than one putative CTL epitope each. Only the first epitope shared considerable aa-homology with corresponding regions of other genital HPV types.

Amino Acid Sequence↗
PubMed1995

Human papillomavirus type 16 capsids expose multiple type-restricted and type-common antigenic epitopes.

The study of viral infectivity and detection of viral capsid antigens of the major cervical cancer-associated human papillomavirus (HPV) type, HPV-16, requires knowledge of which epitopes are exposed in clinical specimens of infected tissue or on intact capsids. To define the antigenic epitopes of HPV-16, antisera to 66 overlapping synthetic peptides corresponding to the HPV-16 capsid proteins L1 and L2 and to seven peptide analogues were tested in immunoperoxidase stainings of consecutive sections from formalin-fixed, paraffin-embedded HPV infected tissue. Antisera against eleven different peptides from L1 and against seven different peptides from L2 recognized the HPV capsid antigen. Most epitopes were only found on the capsid antigen of certain genital HPV types, but four antigenic epitopes in L1 were detectable also in cutaneous wart specimens. All antigenic epitopes in L2 were restricted to genital HPV types and four L2 epitopes were only detectable in HPV-16 or HPV-33 positive specimens. The surface exposure of the antigenic epitopes was investigated by comparing the reactivity of the antipeptide antisera with intact or disrupted virions or capsids of HPV-11, HPV-16 and bovine papillomavirus (BPV). Twenty antipeptide sera from L1 and seven antipeptide sera from L2 were reactive with intact HPV-16 capsids at titres up to 1:146,000. Sixteen of these antisera were also reactive with disrupted HPV-16 capsids. Cross-reactivity with disrupted HPV-11 and BPV was detected for eleven and six antisera, respectively, whereas intact HPV-11 or BPV virions showed only weak cross-reactivity. In conclusion, the HPV-16 L1 and L2 capsid proteins contained multiple antigenic epitopes, most of which were shared with one or several additional HPV types.

Amino Acid Sequence↗
PubMed1995

Increased chemiluminescence of whole blood and normal T-lymphocyte subsets in severe nodular acne and acne fulminans.

To investigate the inflammatory and immunological aspects of severe acne, we examined the luminol-enhanced chemiluminescence of whole blood, T-cell subsets and natural killer cell functions in 11 patients with severe nodular acne and 4 patients with acne fulminans. In patients with severe nodular acne, the active phase of the disease, compared to the values in remission (means 47 mV, SD 24.8 and 32 mV, SD 8.3, p < 0.05). The patients with acne fulminans also showed high values in the active phase of the disease (mean mV 68.3, SD3.5) compared to remission (mean 30.5 mV, SD 15.3). No marked alterations were seen in the percentages of T-helper cells, T-suppressor cells or DR-positive lymphocytes or in the levels of soluble interleukin 2 receptor. The percentages and activities of natural killer cells did not show any significant changes either. Five patients (4 with severe nodular acne and one with acne fulminans, accounting for 33% of all patients) carried HLA Cw6 antigen, which is a significantly increased frequency compared to health controls (pc = 0.015). The present chemiluminescence results suggest that peripheral blood neutrophils are activated in patients with severe acne.

Acne Vulgaris↗
PubMed1995

Detection of herpes simplex virus DNA by polymerase chain reaction in the cerebrospinal fluid of patients with viral meningoencephalitis using primers for the glycoprotein D gene.

A novel set of primers for polymerase chain reaction (PCR) which amplified the portion of US6 sequence coding for the main type-common neutralizing epitope of glycoprotein D (gD) was used for detection of herpes simplex virus (HSV) DNA in 44 cerebrospinal fluid (CSF) samples from 29 patients with clinical symptoms of viral meningitis or meningoencephalitis. The primers in question amplified the DNA of 9 out of 10 low-passage HSV-1 isolates and of 5 out of 10 HSV-2 low-passage isolates as well as the DNA of all laboratory strains examined when tested in the supernatant fluid of infected cells cultures. The PCR was positive in 5 CSF samples (taken on days 2, 4, 8, 10 and 56 after the onset of symptoms, but not later than day 8 after starting acyclovir (ACV) therapy) obtained from 4 patients with intrathecal antibody response. The PCR was repeatedly negative in CSF of 15 patients who had antibodies to HSV in serum and CSF, but did not show intrathecal antibody production. It was also negative in 10 patients who had no HSV antibodies in CSF. Our results confirmed that positive PCR for HSV DNA in the CSF is an indication for starting and/or continuing ACV therapy even in the absence of classical symptoms of HSV encephalitis.

Acyclovir↗
PubMed1994

A population-based seroepidemiological study of cervical cancer.

The epidemiology of cervical cancer indicates the presence of a sexually transmitted risk factor, attributable at least in part to infection with human papillomavirus (HPV) type 16 or 18. We performed a seroepidemiological study of HPV and cervical cancer in the counties of Västerbotten and Norrbotten in Northern Sweden, a low-risk area for cervical cancer. Sera from 94 cases of incident cervical cancer were matched against 188 age- and sex-matched controls derived from a population-based blood bank. IgG and IgA antibodies were measured against a panel of 12 antigens derived from HPV types 6, 11, 16, or 18, as well as against Herpes simplex virus type 1 and 2, Chlamydia trachomatis, cytomegalovirus, Epstein-Barr virus, and bovine papillomavirus. Significantly increased relative risks (RRs) were found for IgG to HPV 16- or 18-derived antigens from the L1 (RR = 3.1), E2 (RRs = 2.8 and 9.2), and E7 (RRs = 3.8 and 2.7) open reading frames and for IgA to HPV 16-derived antigens from the E2 (RR = 3.3) and E6 (RR = 2.7) open reading frames. The highest RR (9.2, confidence intervals 4.4-19.4) was associated with IgG to an HPV 18 E2 antigen. Antibodies against cytomegalovirus, Herpes simplex virus type 2, Epstein-Barr virus, or bovine papillomavirus were, on their own, not significantly associated with cervical cancer, but seropositivity against multiple infections was associated with a successively increased relative risk. An increased risk was also found for IgG to Chlamydia trachomatis (RR = 1.7, confidence interval = 1.0-2.7). The results indicate that several HPV antibodies are strongly associated with cervical cancer, providing further seroepidemiological support for an etiological role of HPV in cervical cancer.

Adult↗
PubMed1994

Antibody response to adenovirus E1b-derived synthetic peptides and serum levels of p53 in patients with gastrointestinal and other malignant lymphomas.

Serum levels of p53 and antipeptide antibody levels to adenovirus type 12 (Ad12) E1b protein were measured in a case-control study of 62 newly diagnosed patients with malignant lymphoma. While patients with gastrointestinal lymphoma did not differ from their matched controls, p53 positive lymphoma patients had significantly (P < 0.04) increased antipeptide IgG antibody levels to the Ad12 E1b. Concomitant detection of serum p53 and antipeptide antibodies to Ad12 E1b was associated with an increased risk (OR = 17.0, 95% confidence limits 1.5, 58.5) of malignant lymphoma suggesting synergism between expression of Ad12 E1b and accumulation of p53 in patients with malignant lymphoma.

Adenovirus E1B Proteins↗
PubMed1994

Antibody response to B cell epitopes of Chlamydia trachomatis 60-kDa heat-shock protein and corresponding mycobacterial and human peptides in infants with chlamydial pneumonitis.

To study antibody response to the hypersensitivity protein B of Chlamydia trachomatis, also known as the 60-kDa heat-shock protein (hsp60), epitope scanning was done over the entire protein. Human sera with antibodies to C. trachomatis identified 5 major antigenic regions (peptides 2, 5, 9, 17, and 21) and several minor regions (peptides 34-37, 39, 50, and 59-62). Clear-cut IgG antibody responses to chlamydial peptide 2 (YNEEARKKIQKGVKT) and a corresponding mycobacterial peptide (YDEEARRGLERGLNA) were found in 8 of 16 infants with chlamydial pneumonitis and in 1 of 18 controls. Peptide 50 (RLAKLSGGVAVIRVG) showed an 80% identity with its human counterpart (RLAKLSDGVAVLKVG), which was derived from human mitochondrial protein P1, but specific antipeptide antibody responses were found in 3 of 16 cases only. In summary, both IgG antibody response to C. trachomatis hsp60 and occasional autoantibody formation in infants with chlamydial pneumonitis were found.

Amino Acid Sequence↗
PubMed1994

Oral induction and consolidation of acute myeloid leukemia with etoposide, 6-thioguanine, and idarubicin (ETI) in elderly patients: a randomized comparison with 5-day TAD. Finnish Leukemia Group.

In order to study the efficacy of an oral induction and consolidation regimen in the treatment of acute myeloid leukemia (AML) in elderly patients assessed not to tolerate full-scale intensive chemotherapy, 51 patients over 65 years of age with newly diagnosed AML were randomized to receive two cycles of either totally oral ETI (25 patients) or conventional 5-day TAD (26 patients). The median age of the patients was 73 years, range 65-87 years. Thirty-eight patients had de novo AML and the remaining patients AML subsequent to myelodysplastic syndrome ((n = 11) or treatment related AML (n = 2)). ETI consisted of etoposide 80 mg/m2 and thioguanine 100 mg/m2 twice a day on days 1-5, and idarubicin 15 mg/m2 on days 1-3, all given orally. TAD consisted of oral thioguanine and i.v. cytarabine, both in the dose of 100 mg/m2 twice a day on days 1-5, and daunorubicin 60 mg/m2 on day 5. The maintenance treatment was daily oral mercaptopurine 70 mg/m2 and weekly oral methotrexate 12 mg/m2. In the ETI group complete remission (CR) was achieved in six patients after the first cycle and in nine more patients after the second cycle. The CR rate was 15/25 = 60%. The corresponding figures for the TAD group were four and two remissions, CR rate 6/26 = 23% (p = 0.007). The survival was significantly longer in the ETI arm (p = 0.042). The median survival was 9.9 months in the ETI group and 3.7 months in the TAD group. There were no significant differences in the side effects between the two arms. In conclusion, the totally oral ETI regimen resulted in a significantly higher remission rate and longer survival than the 5-day TAD regimen in elderly patients with AML, with no more toxicity.

Acute Disease↗
PubMed1993

Serum antibodies and subsequent cervical neoplasms: a prospective study with 12 years of follow-up.

Approximately 40,000 blood samples drawn in 1968-1972 by the Social Insurance Institution's mobile clinic in Finland have been stored. Linking cancer incidence data obtained from the Finnish Cancer Registry with this material yielded 32 cases of cervical cancer diagnosed after drawing of the blood sample. These 32 individuals and 64 matched controls were analyzed for serum antibodies indicative of past infection with Chlamydia trachomatis, Neisseria gonorrhoeae, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus type 2. After adjustment for smoking and other sexually transmitted diseases, antibodies to C. trachomatis showed the strongest association with cervical cancer (odds ratio = 5.0 (95% confidence interval 1.6-15.7)), but the numbers were too small for drawing conclusions as to the sexually transmitted diseases with which cervical cancer is most specifically associated.

Adolescent↗
PubMed1993

Antibodies to E1b protein-derived peptides of enteric adenovirus type 40 are associated with celiac disease and dermatitis herpetiformis.

Sera from 41 children with untreated celiac disease (CD), and 16 children with dermatitis herpetiformis (DH), and 57 matched controls were studied for serum antibodies to synthetic peptides derived from an early E1b protein of adenovirus type 12 and type 40 (Ad12, Ad40) and A-gliadin. In addition to peptides which share homology with A-gliadin, "nonhomologous" peptides derived from Ad12 and Ad40 E1b proteins were used as antigens in ELISA. Patients with CD and DH had significantly higher IgG antibody levels than those of controls to the nonhomologous Ad40 E1b peptide. Concomitant presence of antipeptide IgA antibodies to A-gliadin and Ad12 E1b or Ad40 E1b peptides (which share no homology with A-gliadin) increased the risk of CD/DH suggesting that both adenovirus infections and gluten exposure contribute to the development of CD/DH.

Adenovirus E1B Proteins↗
PubMed1993

Increased risk of malignant lymphoma indicated by elevated Epstein-Barr virus antibodies--a prospective study.

We estimated Epstein-Barr virus (EBV) antibody-associated relative risks (RR) of malignant lymphoma/leukemia within a cohort of 39,000 healthy Finnish adults followed up for 12 years. Antibody analyses to EBV capsid antigen (VCA), early antigen (EA), and nuclear antigens (EBNA, EBNA1, and EBNA2) were based on concomitantly evaluated ELISA techniques. No increased risk was associated with mere EBV seropositivity. However, elevated EBV EA and EBNA antibody levels were associated with a statistically significant excess risk of malignant lymphoma/leukemia (RREA = 3.4, 95 percent confidence interval [CI] = 1.0-11.0; RREBNA = 4.5, CI = 1.2-16.9). These elevated antibody responses may be due either to destruction of neoplastic EBV positive B-cells and/or to activation of latent EBV infection early in the lymphomagenesis.

Adult↗
PubMed1993

Evaluation of serum antibody response to a newly identified B-cell epitope in the minor nucleocapsid protein L2 of human papillomavirus type 16.

The aim of this work was to identify B-cell epitopes in the minor nucleocapsid (L2) protein of human papillomavirus (HPV) type 16 and characterization of allied antibody response. Serum samples of 513 individuals (323 women with various degrees of cervical atypia, 150 men and 40 small children) were available for the study. Synthetic peptides overlapping the L2 protein of HPV 16 twice were applied in ELISA for epitope scanning and antibody determination. An HPV 16 L2 derived dodecamer SGYIPANTTIPF (amino acids 391-402) proved to be the major B-cell epitope. Both IgA antipeptide antibody positivity (range 7-28%) and mean IgA antibody levels (range 13.2 EIU to 42.4 EIU, P < 0.05) increased with the degree of cervical atypia, whereas antipeptide IgG antibodies showed an opposite trend. During a 2-years follow-up significantly (P < 0.0005) decreasing IgA antibody levels to the SGYIPANTTIPF peptide were associated with regression of koilocytotic atypia. Analysis of anti-peptide IgA antibodies of 118 women with known HPV type revealed that a majority of positives had HPV 16/18 DNA. It was concluded that antibody response to the newly discovered peptide was partially type- and disease-specific. Our results also suggest an impairment of the IgG but not IgA class antibody response to HPV 16 in patients with persistent cervical HPV infection.

Journal Article↗
PubMed1993

Depletion of Langerhans cells in cervical HPV infection is associated with replication of the virus.

We studied the quantity of Langerhans cells in 36 patients with cervical human papillomavirus (HPV) infection. Significantly fewer Langerhans cells (p < 0.05) were found in patients with compared to those without DNA tetraploidy. Similarly, patients positive for HPV 16/18 DNA by in situ hybridization or antipeptide IgA antibodies to HPV 18 tended to have fewer Langerhans cells than those negative for HPV 16/18 DNA or IgA antibodies. Our results suggest that depletion of Langerhans cells is associated with productive HPV 16/18 infection in the cervical epithelium.

Antibodies, Viral↗
PubMed1993

Antipeptide antibodies to adenovirus E1b protein indicate enhanced risk of celiac disease and dermatitis herpetiformis.

The relationship between adenovirus type 12 (Ad12), celiac disease (CD) and dermatitis herpetiformis (DH) was evaluated by enzyme-linked immunosorbent assay (ELISA). Diagnostic phase serum samples from 44 children with CD, 16 children with DH and 60 matched controls were studied for serum antibodies to synthetic peptides derived from an early E1b protein of Ad12 and A gliadin. Both the patient groups had significantly (p < 0.001) higher IgG antibody levels to the Ad12 E1b peptide than the controls. The difference was especially pronounced for girls (p < 0.005). Antipeptide IgG antibodies to Ad12 E1b and A gliadin posed a synergistic increase in the CD and DH risk suggesting that infection with Ad12 is associated with CD and DH.

Adenovirus E1B Proteins↗
PubMed1993

Evaluation of plasma levels of thymidine kinase and mutated p53 in 81 patients with newly diagnosed malignant lymphoma.

We analysed diagnostic phase plasma levels of thymidine kinase (TK) and mutated p53 in 81 patients with malignant lymphoma. Forty-three (53%) patients had increased (> 10 U/l) TK activity whereas 30 (37%) were positive for the mutated p53 gene product. In general, patients with p53 mutation positive tumors tended to have higher TK activity than those without. Furthermore, patients with high-grade non-Hodgkin's lymphoma (NHL) showed almost a linear correlation (rs = 0.79) between plasma levels of mutated p53 and TK. We conclude that the monoclonal antibody assisted detection of mutated p53 gene product may prove a useful adjunct to the diagnostic procedures of malignant lymphomas.

Adult↗