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Biomedical subjects

T Koivula

Publications and source records attributed to T Koivula.

At least 19 recordsLinked to original sources
PubMed1992

Sequence encoding ribosomal protein L33 of Lactococcus lactis.

A cloned fragment from Lactococcus lactis chromosome encoding the L33 ribosomal protein was sequenced. Two incomplete open reading frames (ORFs) were also found: the upstream ORF shows similarity to the tetracycline-resistance protein (Tet) of Bacillus stearothermophilus, and the downstream ORF shows homology to a protein of Bacillus subtilis participating in sporulation (SpoVE), and to proteins of Escherichia coli involved in cell division (FtsW) and the maintenance of cell shape (RodA).

Amino Acid Sequence↗
PubMed1992

Small subgroup of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation.

BACKGROUND: Mutations in the p53 gene resulting in the accumulation of altered p53 proteins with prolonged half-life have been found in a large variety of human malignancies. PURPOSE: We studied the significance of p53 protein accumulation in prostatic carcinoma. METHODS: The material consisted of 137 paraffin-embedded, primary prostatic carcinomas. Accumulation of p53 protein was studied by immunohistochemical staining using a polyclonal p53-specific CM-1 antibody. Proliferation activity was determined by DNA flow cytometry and by immunohistochemical detection of proliferative cell nuclear antigen (PCNA) using a monoclonal PC10 antibody. RESULTS: Eight (6%) of the tumors showed intense p53 staining in more than 20% of the tumor cells, 15 (11%) had only lower level immunoreactivity, and 114 (83%) showed no staining. High-level p53 accumulation was associated with high histologic grade (P less than .001), DNA aneuploidy (P less than .05), and high cell proliferation rate as defined by flow cytometric S-phase analysis (P less than .01) or PCNA expression (P less than .01). High-level p53 accumulation predicted short, progression-free interval (P less than .01) and poor survival (P less than .001), with about a 12-fold relative risk of death as compared with p53-negative cases. Low-level p53 accumulation had no prognostic significance. CONCLUSIONS: Accumulation of p53 confers proliferative advantage for prostatic carcinoma cells and defines a small subgroup of highly malignant carcinomas.

Aged↗
PubMed1992

Moderate and heavy alcohol consumption have no favorable effect on lipid values.

Moderate alcohol consumption has been reported to provide protection against coronary heart disease. We studied serum lipid values in 380 men, including 184 controls (37 teetotalers and 147 moderate drinkers), 90 heavy drinkers, and 106 alcoholics. Total cholesterol values were significantly lower among alcoholics than controls (mean +/- SEM, 5.43 +/- 0.15 mmol/L [210 +/- 5.8 mg/dL] vs 6.01 +/- 0.08 mmol/L [232 +/- 3.1 mg/dL]), but their high-density lipoprotein (HDL) cholesterol values were higher (1.66 +/- 0.07 mmol/L [64 +/- 2.7 mg/dL] vs 1.14 +/- 0.02 mmol/L [44 +/- 0.8 mg/dL]). Accordingly, there was a highly significant difference in the HDL/total cholesterol ratio (0.32 +/- 0.13 vs 0.19 +/- 0.01). Heavy drinkers had significantly higher total cholesterol values than controls (6.30 +/- 0.13 mmol/L [244 +/- 5.0 mg/dL] vs 6.01 +/- 0.08 mmol/L [232 +/- 3.1 mg/dL]); the same was true of HDL cholesterol values (1.25 +/- 0.07 mmol/L [48 +/- 2.7 mg/dL] vs 1.14 +/- 0.02 mmol/L [44 +/- 0.8 mg/dL]). No significant difference was found in the HDL/total cholesterol ratio between controls and heavy drinkers or between teetotalers and moderate drinkers. Therefore, moderate alcohol intake apparently does not change HDL/total cholesterol ratio; if moderate drinking is protective against coronary heart disease, the mechanism is probably not via lipids.

Adult↗
PubMed1992

Galactitol is not a cause of senile cataract.

It has been postulated that the accumulation of sugar alcohol, galactitol, from milk induces cataract in the eye lens through an osmotic mechanism. In this study the concentrations of galactitol and other sugar alcohols (sorbitol, mannitol and inositol) were measured by sensitive gas chromatography in the lenses of 15 patients operated on for senile idiopathic cataracts and in 14 clear lenses removed at autopsy. Large amounts of inositol (mean +/- SD, 4.1 +/- 3.1 vs 4.7 +/- 3.0 mumol/g lens wet weight) and small amounts of mannitol and sorbitol were detected in both study groups. Galactitol levels remained clearly below the detection limit (2 nmol/g) in all lenses. It seems unlikely that senile cataract is a result of the accumulation of galactitol in the eye lens.

Adult↗
PubMed1992

Postoperative hyperglycaemia--are the patients diabetic?

The aim of this study was to investigate the occurrence and causes of postoperative hyperglycaemia. Blood sugar was measured after operation in 262 patients who had undergone minor emergency operations, when the patients were receiving 5% glucose infusion at the rate of 170 ml/h. In 32 patients (12%) blood glucose was over 8.0 mmol/l. Serum insulin concentration in these patients was significantly higher than in reference patients, who had blood glucose below 5.5 mmol/l. The number of insulin receptors in red cells and the affinity of insulin to receptors were similar in both groups. Serum cortisol was higher, but free fatty acid concentration lower, in the hyperglycaemic group than in the reference group. The tests done postoperatively were repeated two weeks later without surgical stress. The values recorded, indicating the patients' normal metabolism, did not differ between the two groups, except that serum cortisol was somewhat higher in the reference patients. The oral glucose tolerance test was normal in all patients except one. The results suggest that patients prone to postoperative hyperglycaemia are not diabetic, but that their production of glucose is increased during surgical stress.

Adult↗
PubMed1992

Drinking habits and detection of heavy drinking among middle-aged women.

Little is known about alcohol consumption and the efficiency of alcohol questionnaires among women. In the present study 40-year-old (n = 90) and 45-year-old (n = 75) women participating in a health screening gave a self-report about their alcohol consumption and filled out the Malmö modified Michigan Alcoholism Screening Test (Mm-MAST) and the CAGE questionnaires. Teetotallers comprised 11% of the 40-year-old group and 8% of the 45-year-old women. CAGE, but not Mm-MAST worked with the traditional cut-off point of two recommended for men. When the criterion for heavy drinking was a self-reported consumption > or = 140 g of absolute alcohol per week or a positive (> or = 2) finding in the CAGE or > or = 4 'yes' answers in the Mm-MAST, 20% of the 40-year-old and 17% of the 45-year-old group (together 19%) proved positive. Neither of the two questionnaires nor self-report alone worked perfectly for identifying the heavy drinker group (n = 31) screened. Using the three above criteria; of the heavy drinkers 52% were detected by self-report, 55% by CAGE, and 45% by Mm-MAST. CAGE in combination with self-report detected 90% and this combination, being short and simple, can be recommended for clinical practice.

Alcohol Drinking↗
PubMed1992

Abnormalities of hematologic parameters in heavy drinkers and alcoholics.

Hematologic parameters measured by a Technicon H-1 analyzer and reticulocyte values were studied in three middle-aged male groups; 184 social drinkers, 88 heavy drinkers, and 106 alcoholics. Erythrocyte mean cell volume (MCV) correlated positively (p less than 0.001) with red cell distribution width (r = 0.388) and negatively with red blood cells (r = -0.594, p less than 0.001), hemoglobin distribution width (r = -0.330, p less than 0.001), cell by cell counted hemoglobin concentration (CHCM) (r = -0.434, p less than 0.001), and the ratio between standard deviation of CHCM and CHCM (r = -0.375, p less than 0.001). In spite of these correlations high red cell distribution width values were also found in alcoholic patients with normocytosis (MCV less than or equal to 96 fl). Alcohol induced abnormalities primarily in erythrocytes. The only significant abnormality in the heavy drinker group was a high value of erythrocyte MCV, which was found in 22.7%. In the alcoholic group the MCV value was high in 39.6%, and low erythrocyte values were detected in 16%. A high erythrocyte mean cell distribution width value indicating anisocytosis was found in 40.6% of the alcoholic group. In this material the specificities of these values were also good. The scatter cytogram for red blood cells did not give any valuable visual information in the abuser groups. Thus, certain abnormalities in the Technicon H-1 system parameters, even other than MCV, can be explained by alcohol abuse.

Adult↗
PubMed1992

Human immunodeficiency virus type 1 enhances intracellular growth of Mycobacterium avium in human macrophages.

Disseminated Mycobacterium avium infections are common in patients with AIDS and result in a reduced life expectancy. Human monocytes/macrophages are important target cells for both human immunodeficiency virus (HIV) and M. avium. We have studied the interaction in vitro of M. avium and HIV type 1 (HIV-1) in human macrophages. Human monocytes isolated from the peripheral blood of healthy individuals were infected with HIV-1, M. avium, or both. The intracellular growth of M. avium and the replication of HIV-1 were monitored for up to 5 weeks. Intracellular mycobacterial growth was seen in all M. avium infected cell cultures and was paralleled by increased production of interleukin 1 alpha and beta. Preinfection of the macrophages with HIV-1 reduced the interleukin 1 production and accelerated the intracellular growth of M. avium. These findings may explain in part the impaired control of mycobacterial infections seen with patients with AIDS.

Cells, Cultured↗
PubMed1992

Expression of epidermal growth factor receptor and ERBB2 (HER-2/Neu) oncoprotein in prostatic carcinomas.

Expression of epidermal growth factor receptor (EGFR) and ERBB2 oncoprotein were studied in paraffin-embedded normal (n = 2), hyperplastic (n = 17), and malignant (n = 147) prostatic tissues by immunohistochemistry. Strong immunoreactivity was detected in the epithelial cells of all normal and hyperplastic prostates with a new EGFR antibody (Mab31G7). In prostatic carcinomas, the EGFR immunoreactivity was variable with 47% showing uniform, 39% partial, and 14% no staining. Tumors with partial or uniform EGFR immunoreactivity were locally more advanced and of higher histological grade than the EGFR-negative tumors. EGFR-positive tumors also had two to three times higher S-phase fraction, suggesting that EGFR expression conferred proliferative advantage. Patients who had either partially or uniformly EGFR-positive carcinomas had a worse 10-yr progression-free (p = 0.05), overall (p = 0.03), and prostatic carcinoma-specific (p = 0.007) survival than those with EGFR-negative carcinomas. However, according to a multivariate analysis, EGFR did not have independent prognostic value. None of the normal, hyperplastic, or malignant prostate tissues showed clearly positive ERBB2 immunoreactivity with MAb1 antibody.

Carcinoma↗
PubMed1992

Effect of a high dose of ethanol on serum pancreatic enzymes in young healthy adults.

Short-term effects of a high dose of ethanol on the serum activities of pancreatic enzymes were studied in young healthy adults. There were 10 males and 10 females in the study group, and two males and three females in the control group. In the study group, ethanol (2 g/kg of body weight) was given during 4 h, resulting in the blood ethanol level of 1.6 +/- 0.3 g/l at 6 h. No significant changes in serum pancreatic enzyme activities were observed in the control group during the 56-h experiment. In the study group, none of the individuals demonstrated a marked increase (double from the baseline) in serum pancreatic enzyme activities. In the male study group, the serum total amylase activity increased slightly at 6 h, but the serum pancreatic isoamylase activity remained unchanged. These data suggest that, in nonalcoholic individuals, short-term exposure to a high dose of ethanol does not induce such injury in the pancreas that would appear as a leak of enzymes from the acinar cells into the circulation.

Adult↗
PubMed1992

Acetaldehyde-modified hemoglobin as a marker of alcohol consumption: comparison of two new methods.

We examined the diagnostic value of acetaldehyde-hemoglobin adducts in the detection of heavy drinking and alcoholism. Acetaldehyde adducts from red cells were measured by new chromatographic and immunologic methods. The study population included 20 men with well-documented histories of chronic alcoholism, 18 men who were heavy drinkers, 22 male healthy control subjects, and 8 control subjects with liver disease that was not related to alcohol use. In addition, 20 healthy volunteers and 5 control subjects participated in the study to determine the effect of an acute dose of ethanol. The results that were obtained by the two new methods correlated significantly (r = 0.38, p = 0.002). With both methods, the concentrations of acetaldehyde-hemoglobin adducts were found to be significantly higher in red cells of heavy drinkers (p less than 0.001) and subjects with alcoholism (p less than 0.001) when compared with control subjects. Acetaldehyde-modified hemoglobins appear to have at least the same sensitivity (chromatographic determination = 50% and immunologic determination = 50%) to detect heavy drinking as the most widely accepted conventional biochemical markers of alcohol abuse, gamma-glutamyltransferase (39%) or mean corpuscular volume (17%). In a group of 20 healthy volunteers, acetaldehyde-hemoglobin adducts increased significantly even after a single high dose of ethanol (2 gm/kg), whereas there was no change in the conventional markers of alcohol consumption at the same time. Acetaldehyde-hemoglobin adducts assays should be useful for the detection of heavy drinking in clinical settings.

Acetaldehyde↗
PubMed1991

Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer.

c-erbB-2 protein over-expression was studied immunohistochemically in 319 paraffin-embedded breast carcinomas representing 89% of all breast-cancer cases operated in the Tampere University Hospital between 1977 and 1981. The immunohistochemical evaluation of c-erbB-2 was optimized using protease pre-treatment and verified using antibodies for both the external and the internal domains of the protein. c-erbB-2 over-expression was found in 72 (23%) of the 319 cases and was associated with high histological and nuclear grade (p less than 0.0001), DNA aneuploidy (p = 0.003), high tumor S-phase fraction (p less than 0.0001), and lack of estrogen (p less than 0.0001) and progesterone (p = 0.03) receptors. Overall, breast-cancer patients with c-erbB-2 over-expression had about 2.2-fold relative risk (RR) of death (p less than 0.001) as compared with those without over-expression. According to a multivariate analysis, c-erbB-2 over-expression was an independent prognostic factor in the whole material as well as in the node-negative sub-set. In node-negative breast-cancer tumor size, S-phase and c-erbB-2 status defined a large patient group with only 4% 5-year and 15% 10-year mortality rate without adjuvant therapy. In comparison with c-erbB-2-negative tumors, those with over-expression of this gene metastasized 3 times more often (p = 0.0002) to the lungs, liver and brain and 3 times less often to the bone. Our findings suggest that the prognostic value of c-erbB-2 over-expression may be related not only to increased cell proliferation rate but also to a distinctive pattern of metastasis.

Adult↗
PubMed1991

Elevated high-density-lipoprotein cholesterol and normal triglycerides as markers of longevity.

Serum cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides of 85 year old home-living persons were compared to those of controls and of patients who had severe coronary artery disease (CAD) at an early age. Eighty-five-year-olds had higher serum HDL cholesterol than controls and patients with CAD. Patients with severe CAD had higher serum total cholesterol and serum triglycerides and lower HDL-cholesterol than other groups. When 85-year-old persons were divided into quintiles according to serum HDL cholesterol, women with highest HDL cholesterol had lowest mortality, men with lowest HDL cholesterol had highest mortality. We conclude that elevated HDL cholesterol is correlating with longevity and low HDL cholesterol with CAD at an early age.

Aged↗
PubMed1991

Nucleotide sequence of the secY gene from Lactococcus lactis and identification of conserved regions by comparison of four SecY proteins.

Sec Y is an integral membrane protein which participates in the translocation of proteins through the bacterial cell membrane. We have cloned the sec Y gene of Lactococcus lactis, and found its deduced protein sequence, 439 amino acids long, to be similar in length to the previously determined Sec Y proteins of Escherichia coli, Bacillus subtilis and Mycoplasma capricolum. Comparison of the L. lactis Sec Y to the 3 other Sec Y proteins revealed 90 conserved amino acid residues (21%). Nearly half of the conserved residues are clustered in 2 of the 10 transmembrane segments, and in 2 of the 6 cytoplasmic regions. Some of the conserved regions are apparently responsible for the interactions of Sec Y with signal sequences, and the proteins SecE and SecA.

Amino Acid Sequence↗
PubMed1991

Improved prognostic impact of S-phase values from paraffin-embedded breast and prostate carcinomas after correcting for nuclear slicing.

Nuclear debris may significantly interfere with the analysis of S-phase fraction (SPF) from paraffin-embedded tumors. We used a background subtraction algorithm to compensate for the effects of slicing of tumor cell nuclei during preparation of paraffin-embedded specimens. DNA histograms were analyzed from 88 node-negative breast and from 78 prostatic carcinomas. Median SPFs corrected for nuclear slicing were lower than uncorrected ones in both breast cancer (7.6% vs. 5.7%) and prostate cancer (6.7% vs. 4.2%). The median SPF value in each group was used as a cut-off point in survival studies. As compared with the uncorrected SPFs, corrected SPF levels resulted in a more significant survival difference between breast cancer patients with above and below median SPF (p = 0.0014 vs. p = 0.014) and in a higher relative risk (RR) of death (4.5 vs. 3.1). The same was true for prostate cancer survival (p less than 0.0001 vs. p = 0.002) and RR (5.3 vs. 3.1). Compared with the exponential background subtraction method, the sliced nuclei correction was more reproducible and could be applied in all evaluable histograms without the risk of overcompensation. In conclusion, our results support the use of background correction with the sliced nuclei model in DNA flow cytometric studies of archival tissues.

Breast Neoplasms↗
PubMed1991

Association of a haemoglobin-acetaldehyde adduct with questionnaire results on heavy drinkers.

A new biological alcohol marker, the ratio between the acetaldehyde-induced haemoglobin fraction HbA1ach and the glycated haemoglobin fraction HbA1c (HbA1ach/HbA1c), was studied in association with data obtained in a questionnaire, the Malmö modified Michigan alcoholism screening test (Mm-MAST), completed by 270 consecutive middle-aged men participating in a voluntary health screening. None of them had earlier alcoholic health or alcohol-dependent social problems. The nine-question Mm-MAST correlated positively with the ratio of HbA1ach/HbA1c (r = 0.272, P less than 0.001). In the three drinker groups defined according to the questionnaire, HbA1ach/HbA1c values were significantly higher among heavy drinkers (mean = 40, S.E.M. = 1) than among teetotallers (mean = 32, S.E.M. = 2, P less than 0.01) or social drinkers (mean = 35, S.E.M. = 1, P less than 0.01). In the groups formed according to the respondents' own alcohol anamnesis there was no significant difference between the marker values, but the Mm-MAST score was significantly higher in both social (P less than 0.001) and heavy drinkers' (P less than 0.001) groups as compared with teetotallers. This shows that the questionnaire detected heavy drinkers better than the self-given anamnesis. The correlation of HbA1ach/HbA1c and the questionnaire means that the biological marker studied represents a new possibility to identify heavy drinkers before alcoholic health problems or social consequences have appeared.

Acetaldehyde↗