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Biomedical subjects

M Lehtinen

Publications and source records attributed to M Lehtinen.

At least 109 records · Page 6Linked to original sources

Quantity of nuclear DNA in malignancies and benign lymphadenopathies associated with Epstein-Barr virus.

The quantity of nuclear DNA in 90 tumours with a strong probability of being associated with Epstein-Barr virus (EBV) (11 cases with nasopharyngeal carcinomas, seven cases of endemic and 26 of non-endemic Burkitt's lymphoma, and 46 cases of Hodgkin's disease) were analysed by flow cytometry. Twenty three cases with benign lymphadenopathies were analysed in a similar way. Except for endemic Burkitt's lymphoma most of the tumours were diploid. Near-diploid aneuploidy (with a DNA index ranging from 1.06 to 1.26) was also found in endemic Burkitt's lymphoma as well as in six non-endemic Burkitt's lymphomas and in eight cases of Hodgkin's disease but was absent in nasopharyngeal carcinomas. Tetraploid aneuploidy was seen in three cases of nasopharyngeal carcinoma. Five of the 23 cases of lymphadenopathy also showed near-diploid DNA, one of which subsequently developed into a non-Hodgkin's lymphoma. It is concluded that near-diploid DNA content seems to be associated with the lymphatic origins of the tumours rather than with EBV.

Adolescent↗

Concentrations of tumor-associated trypsin inhibitor and C-reactive protein in serum in acute pelvic inflammatory disease.

We measured tumor-associated trypsin inhibitor (TATI) and C-reactive protein (CRP) in serum of 29 patients with proven pelvic inflammatory disease (PID). TATI values were increased in seven (24%), paralleling increases in CRP. TATI was increased by about 3.5-fold in seven of eight patients with CRP concentrations greater than 90 mg/L, but in none of 21 patients with CRP concentrations less than 90 mg/L. TATI concentration and severity of PID as determined by laparoscopy or endometrial biopsy were not correlated. These results suggest that, in severe infections, regulation of TATI synthesis resembles that of acute-phase proteins.

Acute-Phase Proteins↗

Immunoblotting analysis of class-specific antibody response in patients with primary HSV infection.

Class-specific immune response in acute herpes simplex virus (HSV) infections to individual virus specified polypeptide antigens was analysed by immunoblotting. The HSV specified glycoproteins B (gB), C (gC), and D (gD) were detected. IgG-antibody response was shown to develop to various other virus specific polypeptides as well. The IgM- and IgA-antibody responses remained restricted to only a few HSV specific proteins, namely VP 13 (80 kD), VP 20 (52 kD), and VP 23 (40 kD) and to the low molecular weight polypeptides.

Adult↗

Improving the prognostic value of DNA flow cytometry in breast cancer by combining DNA index and S-phase fraction. A proposed classification of DNA histograms in breast cancer.

To optimize the prognostic value of DNA flow cytometry in breast cancer the authors calculated several parameters from the DNA histogram, including the DNA index, the size and number of aneuploid peaks as well as S-phase and G2/M-phase cell cycle fractions. Of these, DNA index and S-phase fraction (SPF) proved to be the most valuable prognostic indices. DNA aneuploidy was associated with a three-fold risk of death as compared to DNA diploidy (P less than 0.0001). The highest risk of death was associated with hypertetraploid (greater than 2.20) DNA index, whereas a tetraploid DNA index (1.80-2.20) was associated with a relatively low risk. The SPF had significant additional prognostic value in both DNA diploid (P = 0.0002) and DNA aneuploid (P = 0.02) tumors. By combining DNA index and SPF the authors defined three types of DNA histograms, which were associated with favorable, intermediate, and poor prognosis of the patients. DNA diploidy together with low (less than 7%) SPF (type I DNA histogram) was associated with very favorable prognosis, whereas DNA aneuploidy with high DNA index (greater than 2.20) or high (greater than 12%) SPF (type III DNA histogram) was related to the worst prognosis with approximately eight-fold relative risk of death. In a Cox multivariate regression analysis the type of DNA histogram was an independent and most powerful prognostic indicator in breast cancer. The other independent factors in the Cox analysis were primary tumor size, nodal status, and progesterone receptor status.

Aged↗

Prognostic significance of DNA index, multiploidy, and S-phase fraction in ovarian cancer.

Paraffin-embedded tumor samples from 157 ovarian cancer patients were analyzed by DNA flow cytometry. Tumor ploidy had prognostic significance in both early and advanced ovarian cancer. After adjusting for stage, residual tumor mass, histopathologic type, treatment, and age of patient in a Cox regression analysis, the relative risk of death was two-fold higher in single DNA-aneuploid and sixfold higher in DNA-multiploid tumors as compared to DNA-diploid tumors (P less than 0.0001). A tetraploid DNA index was associated with a relatively low risk ratio, whereas hypertetraploid tumors were highly malignant. S-phase fraction (SPF) had prognostic value especially in DNA-diploid tumors. The simultaneous evaluation of DNA index, the number of aneuploid cell clones, and SPF gave more prognostic information than the determination of tumor ploidy alone. On the basis of these parameters we have developed a classification of tumor DNA histograms for better prognostic assessment of ovarian cancer.

Aged↗

Effect of gamma-vinyl GABA treatment on cholinergic and aminergic neurotransmission and on cyclic nucleotides in human complex partial epilepsy--a CSF study.

1. Gamma-vinyl GABA (GVG) is a new anticonvulsant drug that enhances levels of GABA in the brain by irreversibly inhibiting GABA transaminase. 2. To further evaluate the effects and mechanism of action of GVG in the human brain, we measured acetylcholinesterase (AChE) activity and levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), cyclic nucleotides (cAMP, cGMP), total GABA (TGABA), and GVG in CSF of 78 patients with complex partial epilepsy. The CSF samples were taken at baseline and after 3 months of GVG administration (3 g GVG per day). Thereafter, the responders (= 50% decrease in number of seizures) were divided (double-blind) into two groups that received either 1.5 g or 3 g of GVG per day for the next 3 months. The third CSF sample was taken after this double-blind period. 3. TGABA levels were increased during the GVG treatment (p less than 0.001). In the whole group of patients AChE, HVA, 5-HIAA, and cAMP did not differ from baseline values, cGMP levels were slightly elevated after 3 months of GVG administration (p = 0.019), but were no longer elevated after 6 months. Responders had slightly lower AChE activity than nonresponders (p = 0.041). After 6 months of drug treatment the cGMP levels of patients receiving 1.5 g of GVG did not differ from those receiving 3 g. 4. In conclusion, GVG administration elevates levels of TGABA in the CSF without any clear of constant change to cholinergic and aminergic transmission or effect on cyclic nucleotides. Our study further emphasizes the specific mechanism of action of GVG via GABAergic transmission.

Acetylcholinesterase↗

Serum CA 15-3 assay in the diagnosis and follow-up of breast cancer.

Serum CA 15-3 values were determined in 177 patients with primary breast cancer and in 41 with non-malignant breast disease. Increased preoperative serum CA 15-3 values (greater than 38 U ml-1) were observed in 7%, 17%, 64% and 67% of patients with stage I, II, III and IV disease, respectively and in none of the patients with benign breast disease. Patients with elevated serum CA 15-3 values had poor 3-year cumulative survival (27%). In the postoperative follow-up 9% of patients with no clinical evidence of disease, 33% with a single metastasis and 67% with two or more metastases had elevated values. Increasing or decreasing serum CA 15-3 values correlated with the clinical outcome in 26 out of 27 cases (96%), whereas serum values remaining in the reference range had no predictive value. At the time of recurrence elevated serum CA 15-3 values were also observed in patients with normal preoperative values. Increased serum CA 15-3 values preceded the clinical detection of tumour recurrence by up to 13 months. In conclusion, serum CA 15-3 levels had prognostic value in breast cancer, reflected the extent of clinically detectable disease and the presence of occult metastatic disease. Further research is warranted on the benefits of CA 15-3 assays in relation to adjuvant chemotherapy as well as the earlier detection and treatment of metastatic disease.

Antigens, Tumor-Associated, Carbohydrate↗

Effect of vigabatrin (gamma-vinyl GABA) on amino acid levels in CSF of epileptic patients.

Vigabatrin (gamma-vinyl GABA) is a new anticonvulsive drug that irreversibly inhibits the activity of GABA transaminase. The effect of vigabatrin on neurotransmission-related amino acids in CSF of 28 epileptic patients was studied and the relationship between the amino acid pattern and clinical response during 7 months of administration of vigabatrin. Of this study population, 46% had more than 50% decrease in seizure frequency (responders). In 54% the seizures decreased less than 50% (nonresponders). In the whole study group, the levels of total GABA during vigabatrin treatment were 283%, free GABA 197%, homocarnosine 310% and glycine 128% that of the levels at baseline in the same patients. Glutamate, glutamine, aspartate, asparagine, and taurine concentrations did not change. The amino acid pattern in CSF during administration of vigabatrin did not differ significantly in responders and nonresponders. The study suggests that both GABAergic and glycinergic neurotransmission are affected by vigabatrin. The changes in CSF levels of neurotransmitter amino acids are, however, not necessarily related to the clinical response.

Adolescent↗

Phospholipase A2 activity is copurified together with herpes simplex virus-specified Fc receptor proteins.

We purified Fc-binding proteins from herpes simplex virus (HSV)-infected Vero cells by using an inverse immunoaffinity column chromatography. Polyacrylamide gel electrophoresis analysis revealed a single, virus-specific 65-kd polypeptide both in HSV type 1- and HSV type 2-infected cell-derived preparations. A Ca2+-dependent phospholipase A2 activity was demonstrated to be associated with the viral Fc-binding proteins.

Animals↗

Correlation between serum tumor marker levels and tumor proliferation in small cell lung cancer.

We analyzed serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and thymidine kinase (TK) levels in 22 patients with small cell lung cancer. Tumor proliferation was expressed as the proportion of S-phase cells (SPF), determined by DNA flow cytometry, from concomitantly taken biopsy samples. A positive correlation between serum NSE (r = 0.41) or LDH (r = 0.65, p = 0.05) levels and tumor SPF was noted, but was not found between serum TK levels and the SPF. The correlation between NSE and SPF was even more pronounced if only patients with extensive disease were considered (r = 0.77). The serum NSE and LDH, but not TK levels, were significantly greater in the patients with extensive disease (NSE 50.4 ng/ml, LDH 621 U/ml) compared to the patients with limited disease (NSE 21.0 ng/ml, LDH 272 U/ml, p = 0.05). Our results suggest that the combined determination of serum LDH and NSE levels gives valuable data on the primary tumor mass and its proliferative activity in small cell lung cancer.

Adult↗

Immunoglobulin allotypes and virus antibodies in Finnish type 1 diabetic patients.

We have found elevated IgA class mumps and Coxsackie B4 virus antibodies and IgA/IgG antibody ratios in type 1 diabetic patients. However, IgA class herpes simplex (HSV1) virus antibodies showed no difference between patients and controls. To study the possible contribution of genetically polymorphic immunoglobulin markers to the pronounced IgA class reactivity Ig allotypes (Gm, A2m and Km determinants) were compared to virus antibodies in diabetic patients and healthy controls. Ig allotypes were equally distributed in both groups suggesting that the genes coding for these structures are not in close linkage disequilibrium with susceptibility gene(s) for type 1 diabetes. Accordingly, pronounced IgA class immune response in diabetic patients is hardly due to Ig allotype related factors. Patients had elevated IgA class mumps and Coxsackie B4 antibodies and IgA/IgG antibody ratios independently of the Gm phenotype group. In healthy subjects but not in diabetic patients IgA class mumps antibody levels and IgA/IgG mumps antibody ratios significantly correlated with the Gm phenotypes. Such Gm association was not observed in Coxsackie B4 or HSV1 antibodies. These results suggest that though Gm phenotypes have a general effect on mumps specific antibody response, some other factors than Ig allotypes are responsible for the elevated IgA class mumps and Coxsackie B antibody levels and IgA/IgG antibody ratios in type 1 diabetes.

Adolescent↗

Carcinoembryonic antigen levels in sera drawn 1 to 12 years before diagnosis of cervical malignancy.

We determined serum CEA and beta-HCG levels in women who developed cervical carcinoma 1 to 12 years after the serum samples were drawn. Only 32 diagnostic sera CEA and beta-HCG levels were found. However, the serum CEA levels of the carcinoma patients differed significantly from those of their matched controls, who remained cancer free during the following 8 to 12 years after serum withdrawal. The difference in CEA levels between cases and controls did not depend on the lag period between serum withdrawal and cancer diagnosis, the severity of underlying cervical disease, or smoking habits.

Adult↗

Enhanced monoaminergic neurotransmission by desglycinamide-arginine-vasopressin in human subjects.

The effect of desglycinamide-arginine-vasopressin (DGAVP) on monoaminergic neurotransmission was studied in human subjects. Samples of cerebrospinal fluid (CSF) were collected during 240 min after DGAVP (2 mg) had been administered intranasally, and monoamine metabolites in CSF were measured with HPLC using electrochemical detection. Levels of homovanillic acid and 5-hydroxyindoleacetic acid increased (P less than 0.05) 150 min after DGAVP administration, whereas levels of 3-methoxy-4-hydroxyphenylglycol were stable during the time monitored. These results suggest that in human subjects the mechanism of action of DGAVP may involve dopaminergic and serotonergic systems.

Adult↗

Amino acid levels in human CSF after generalized seizure.

We studied the possible role of excitatory and inhibitory amino acids and their balance during generalized convulsions. The levels of amino acids in postictal cerebrospinal fluid (CSF) were compared with amino acid concentrations in interictal CSF of ten patients with generalized tonic-clonic convulsions. Glu, Gln, Asp, Asn, Tau, Gly, total GABA (t-GABA), free GABA (f-GABA), and homocarnosine levels and Glu/Gln, Asp/Asn, t-GABA/Glu, f-GABA/Glu, f-GABA/Asp, and Glu/Asp ratios were similar in both samples (Student's paired t-test). Our results suggest that in humans possible changes in amino acids in brain tissue during the ictal stage are not reflected in the lumbar CSF.

Adult↗

Expression of the HSV specified major DNA-binding protein in virus infected RAJI and VERO cells.

We studied the expression of the Herpes Simplex virus type-2 (HSV-2) specified major DNA-binding protein (ICSP 11/12) in virus infected RAJI and VERO cells. Immunofluorescence staining by a specific ICSP 11/12 antiserum distinguished between different cell-virus interactions. ICSP 11/12 synthesized in the HSV-2 infected VERO cells showed dense homogenous nuclear staining early in the infection. During virus replication the pattern changed into a less dense, somewhat marginating staining. The corresponding protein synthesized during persistent HSV-2 infection in the RAJI cells showed granular cytoplasmic staining. Late in the infection a whole cell fluorescence was noted. In the absence of virus DNA-synthesis (PFA treated VERO cells) ICSP 11/12 showed dense homogenous or speckled nuclear pattern. The ICSP 11/12 protein extracted from the different virus-cell interactions also showed different elution from double stranded DNA.

Animals↗