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Nephropathy is a major cause of premature morbidity and mortality in patients with non-insulin-dependent diabetes mellitus (NIDDM). The insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) is a genetic determinant of plasma ACE levels. Recent studies have found I/D polymorphism of the ACE gene to be associated with nephropathy in NIDDM. This association has not been evaluated in prospective studies. We, therefore, studied the relationship between ACE gene I/D polymorphism and diabetic albuminuria and glomerular filtration rate (GFR) in 83 NIDDM patients followed up for 9 years. At baseline, 29% (24 of 83) of the diabetic patients had an increased (>30 mg/24 h) urinary albumin excretion rate (UAER) and the prevalence of albuminuria at the 9-year examination was 35% (29 of 83). During the follow-up period, systolic blood pressure (p = 0.044), prevalence of hypertension (p < 0.01), and fasting blood glucose levels (p < 0.01) increased, while high-density lipoprotein cholesterol (p < 0.01) decreased. The declines of GFR during the follow-up period were 8.5, 14.1, and 16.3% within genotype groups of II, ID, and DD, respectively (p values for decreases: NS for II, <0.001 for ID, and <0.001 for DD). Patients with the DD genotype tended to have a steeper decrease of GFR, but the change was not statistically significant between the genotype groups. The increases of UAER during the follow-up period were 35.1, 8.3, and 122.4% within genotype groups of II, ID, and DD, respectively, but p values for all increases were not significant. Parallel to GFR, patients with the DD genotype tended to have a steeper increase of UAER, but the change was not statistically significant between the genotype groups. There were no differences in the ACE genotype distribution and allele frequencies between the patients with or without albuminuria either at follow-up or in cross-sectional settings. In conclusion, this 9-year follow-up study does not support the hypothesis that the ACE I/D polymorphism is a major genetic marker of diabetic nephropathy in NIDDM patients.

Oxidation of low-density lipoprotein (LDL) may be an important factor in the development of diabetic macrovascular and renal complications. The level of autoantibodies against oxidized LDL (oxLDL-Ab) can be used as an index of LDL oxidation in vivo. The purpose of this study was to investigate the association between the level of oxLDL-Ab and the presence of coronary heart disease and renal dysfunction in patients with non-insulin-dependent diabetes mellitus (NIDDM). We determined the plasma levels of oxLDL-Ab in 46 NIDDM patients and 48 well matched nondiabetic control subjects. NIDDM patients had a moderately higher level of oxLDL-Ab than control subjects (0.083 +/- 0.051 vs. 0.062 +/- 0.045, p = 0.04). However, there was no difference in the level of oxLDL-Ab between subjects with and without coronary heart disease, and the level of oxLDL-Ab was not associated with indices of glomerular filtration rate or urinary albumin excretion.

The missense mutation in the 677th nucleotide (C677T) of methylenetetrahydrofolate reductase gene causes substitution of valine (V) for alanine (A) resulting in three genotypes VV, VA and AA. The VV genotype causes hyperhomocysteinemia and may be a risk factor for coronary artery disease. We determined genotypes by polymerase chain reaction and subsequent restriction fragment length analysis and compared them in 84 patients with type 2 diabetes and in 115 non-diabetic subjects with and without coronary disease. Fractional urinary excretion rate of albumin was assessed by nephelometry. The VV, VA, and AA frequencies in the diabetic and in the control groups were 0.095, 0.357, 0.548 and 0.061, 0.417, 0.522, respectively (p = NS, diabetic vs. controls, chi2 test). Genotype frequencies did not differ in either diabetic or control subjects between those with or those without coronary disease (chi2 test). The fractional urinary excretion rate of albumin (mean +/-SD) in diabetic patients with the VV genotype i.e. 1.59 +/-0.71 was lower (Kruskall-Wallis test p = 0.002) than in the other genotypes i.e. VA 5.98 +/-9.75 and AA 3.75 +/-4.77, respectively (post-hoc Mann-Whitney test VV vs. VA p = 0.005 and VV vs. AA p = 0.054, respectively). We found that in patients with type 2 diabetes the methylenetetrahydrofolate reductase VV genotype was associated with a low urinary albumin excretion but not with coronary artery disease or diabetes per se.

Coronary heart disease (CHD) is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM) and the oxidation of low-density lipoprotein (LDL) may be an essential factor in the development of atherosclerotic lesions. Therefore, we studied the in vitro susceptibility of LDL to copper-induced oxidation in 72 NIDDM patients and 94 well-matched non-diabetic control subjects. There was no significant difference in the lagtime of LDL oxidation between NIDDM patients and control subjects (68.1+/-8.8 vs. 66.7+/-9.2 min, respectively, P=0.29). The plasma alpha-tocopherol/LDL-ratio was the most significant determinant of the lagtime in multiple regression analysis. High level of serum triglycerides was associated with decreased lagtime in control subjects, but not in NIDDM patients. Blood glucose balance was not associated with LDL susceptibility to oxidation in NIDDM patients. Subjects with CHD did not have LDL susceptibility to oxidation different from that of subjects without CHD in either of the study groups. Urinary albumin excretion or glomerular filtration rate was not associated with the lagtime of LDL oxidation in NIDDM patients. In conclusion, these data suggest that diabetes and hyperglycemia per se do not affect the susceptibility of LDL to oxidation. The presence of CHD or renal dysfunction were not associated with LDL susceptibility to oxidation.

Apolipoprotein A-IV (apoA-IV) is a glycoprotein constituent of triglyceride-rich and high-density lipoproteins (HDL) and may thus play an important role in lipid metabolism. In Finland two common isoforms (A-IV-1 and A-IV-2) of apoA-IV have been found. The isoforms are the result of the G to T substitution in the third base of the codon 360 in the apoA-IV-2 allele of the apoA-IV gene. The purpose of the study was to determine the apoA-IV allele frequencies in the Saami and the Finns, and to relate the apoA-IV phenotypes to serum lipids. The sample was drawn in connection with a Reindeer Herders' Health Survey performed in northern Finland in 1989. The study group included 248 men with known ethnic origin, Saami and Finns, who lived in the area of the nine northernmost municipalities of Finland. ApoA-IV phenotypes from 71 Saami (both parents Saami) and 177 Finns (both parents Finns) were determined by isoelectric focusing and Western blotting. Serum lipids were determined enzymatically. ApoA-IV allele frequencies in the Saami and the Finns were for A-IV-1 0.894 vs 0.944 and for A-IV-2 0.106 vs 0.056, respectively (chi2-test, P < 0.05). The effect of the apoA-IV phenotype on serum HDL-cholesterol levels differed significantly between the Saami and the Finns (two-way ANCOVA, interaction between ethnicity and apoA-IV phenotype, P < 0.02). In the Saami, HDL-cholesterol levels were significantly higher in the apoA-IV-2/1 than in the apoA-IV-1/1 phenotypes (ANCOVA, P < 0.05). Mean total cholesterol, low-density lipoprotein (LDL)-cholesterol, apolipoprotein B, HDL-cholesterol and triglyceride levels did not differ statistically significantly between the Saami and the Finns. Yet, there was a trend in the Saami of having higher mean total cholesterol, LDL-cholesterol and apolipoprotein B levels than the Finns among the apoA-IV-2/1 phenotypes, while there was only a small difference in these parameters between the Saami and the Finns among the apoA-IV-1/1 phenotypes. In conclusion, the Saami have a higher frequency of the apoA-IV-2 allele than the Finns and most of the other studied populations.

The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been shown to be associated with cardiovascular and renal diseases in diabetes mellitus, but the mechanism underlying this association is not known. In addition, recent studies of the effect of the ACE gene on blood pressure have yielded conflicting results. Therefore, we studied the association of the ACE gene I/D polymorphism with glucose intolerance and insulin resistance, and the contribution of this locus to genetic susceptibility to hypertension in non-insulin-dependent diabetic mellitus (NIDDM). We analysed the ACE genotype in 84 unrelated NIDDM patients with a known disease duration of less than 1 year and in 115 age- and sex-matched controls. The I/D polymorphism was determined by the polymerase chain reaction. There were no differences in ACE genotype distribution and allele frequencies between patients with NIDDM and nondiabetic controls. The frequencies of the D and I alleles in both groups were identical, viz., 0.65 and 0.35, respectively. The NIDDM patients with the DD genotype had significantly higher blood glucose levels in the oral glucose tolerance test than those with the other genotypes; the incremental glucose area under the curve in the order of II, ID, and DD was 7.2+/-2.4, 9.2+/-4.0, and 10.7+/-2.7 mmol/l x h (II vs ID vs DD, P=0.0066 by ANOVA). No significant difference was found between the ACE genotype and serum insulin values. Similarly, there were no differences in body mass index, blood pressure, or serum lipids between the three genotypes. Among the non-diabetic controls, there was no statistically significant association of the I/D polymorphism with serum lipids, blood glucose levels, serum insulin concentrations, or blood pressure values. In conclusion, NIDDM patients with the DD genotype have higher blood glucose levels and are more glucose intolerant; this may help to explain the reported association between the D allele and vascular complications in NIDDM.

Genetic polymorphism of apolipoprotein E (apoE) is linked with the risk of cardiovascular and Alzheimer's disease (AD). We determined apoE genotypes from mailed buccal cell swabs in 36 healthy individuals and 18 demented patients suffering from AD. DNA was released from the swabs by a rapid lysis technique. Polymerase chain reaction using 'hot start' and restriction enzyme digestion by HhaI was used for genotyping of apoE alleles, which were detected by polyacrylamide or MetaPhor agarose gel. ApoE genotypes determined from buccal cells or from stored leucocytes were identical to previously done phenotyping. An advantage of the present simplified buccal cell collection procedure is the possibility to collect DNA samples for apoE genotyping rapidly by mail from patients visiting their physician geographically distant from research laboratory. Moreover, venepuncture and storing of the samples in refrigerators are avoided and costs are reduced. This non-invasive and painless method is also applicable to other genetic screening tests in risk populations.

The effect of 1 wk of supervised fasting on plasma lipid concentrations in subjects with different apolipoprotein E (apo E) phenotypes was studied in 58 healthy free-living volunteers. The participants consumed an 870-kJ(208 kcal)/d liquid diet containing fruit and berry juices, tea, and water. The decline in plasma total cholesterol during 1 wk of fasting was 0.46 mmol/L in women and 0.35 mmol/L in men. The decreases were significant in both women and men. The response patterns of plasma total cholesterol were not significantly different between the sexes. In men, the changes in plasma low-density-lipoprotein cholesterol during the fast differed significantly (P = 0.0181) between the apo E phenotypes, whereas in women there were no differences due to phenotype (P = 0.695). The magnitude of the change in plasma triacylglycerol during the fast was different between the sexes (P = 0.0099). The changes in plasma triacylglycerols differed significantly between apo E phenotype groups in men (P = 0.0295) but not in women (P = 0.0661). Statistical comparison between different apo E phenotypes was performed with and without the small apo E3,2+E2,2 group, with essentially similar results. During fasting, plasma high-density-lipoprotein cholesterol concentrations decreased slightly but not significantly. The study shows significant differences in the associations of apo E alleles and sex on plasma lipid responses during fasting and illustrates the importance of gene-diet interactions in the regulation of lipid metabolism in humans.

The cultivated and uncultivated bacterial communities of an activated sludge plant were studied. Two samples were taken and a total of 516 bacterial isolates were classified into groups using their whole-cell protein patterns. The distribution of bacteria into protein-pattern groups differed significantly between the two samples, suggesting variation in culturable bacterial flora. Partial 16S rRNA gene sequences were determined for representatives of the commonest protein-pattern groups. Most of the sequences obtained were previously unknown, but relatively closely related to known sequences of organisms belonging to the alpha, beta or gamma subclasses of the proteobacteria, the first two subclasses being predominant. This classification of bacteria isolated on a diluted nutrient-rich medium differed from recent culture-dependent studies using nutrient-rich media. The uncultivated bacterial community was studied by analyzing ten partial 16S rRNA gene sequences cloned directly from activated sludge. None of the cloned sequences was identical to those determined for culturable organisms; or to those in the GenBank database. They were, however, related to the alpha or beta subclasses of the proteobacteria, or to the gram-positive bacteria with a high G + C DNA content.

Diversity within bacteria isolated from activated sludge and the Baltic sea and recognized by the rRNA targeted oligonucleotide probe ppT (designed by BRAUN-HOWLAND et al., 1993 to recognize C. testosteroni) was studied. The partial nucleotide sequences of 16S genes of the isolates revealed that the activated sludge and Baltic sea isolates each formed a separate group distinct from C. testosteroni. The analysis of phage and bacteriocin sensitivity as well as whole cell protein patterns revealed the same grouping, but in these characters also intragroup variation was observed. As a conclusion, neither of the studied groups were C. testosteroni, but they probably belong to two previously unknown species common in activated sludge or the Baltic sea.

Objective: To study tuberculosis patients in Guinea-Bissau with regard to clinical findings, bacteriologically verified diagnosis, human immunodeficiency virus (HIV) status and short term survival., Design: 763 consecutive patients referred to the tuberculosis clinic with pulmonary symptoms underwent clinical examination and Ziehl-Neelsen sputum microscopy. Sputum for culture of mycobacteria on Löwenstein-Jensen medium was collected from all hospitalized patients, who were also screened by enzyme linked immunosorbent assay for the presence of HIV-1 and HIV-2 antibodies. HIV-positivity was confirmed by Western blot., Results: 350 patients were diagnosed with tuberculosis and hospitalized. Adequate sputum samples were obtained from 301 patients, of whom 184 (61%) were positive on direct microscopy and the remaining 116 patients were diagnosed from clinical findings. Mycobacterium tuberculosis was cultured from 184 patients and M. avium in 16 patients, whereas in 101 patients the culture was negative. HIV-1 antibodies were found in 3.0%, HIV-2 antibodies in 16.4%, and dual infections in 2.0%. These figures, however, did not differ significantly from those of randomly selected age and sex matched controls. The prevalence of HIV-antibodies was statistically as common in patients with culture verified tuberculosis as in patients with clinically defined tuberculosis. Clinical acquired immunodeficiency syndrome was commonly diagnosed (80/301 patients) but significantly more often in HIV-positive, culture-positive tuberculosis patients, as were weight loss and lymphadenopathy. There was no statistical difference in short-time survival rate between the various patient groups., Conclusion: The diagnostic criteria applied, which are generally used in developing countries, identified most patients with pulmonary tuberculosis; however, a substantial number of patients are treated for tuberculosis without definite diagnostic criteria. The prevalence of HIV-infection was high but statistically no significant difference was demonstrated between the patient groups, controls and patients hospitalized for diseases other than tuberculosis.

Background: The present study was undertaken to clarify the progression of urinary albumin excretion rate (UAER) in non-insulin-dependent diabetic (NIDD) patients 6 years after diagnosis, and to elucidate the risk factors of nephropathy., Methods: This is a population-based controlled (baseline) cohort study. The prospective evaluation utilized the diabetic patients as internal controls. The setting was an urban primary health care centre. Main outcome measures were the UAER-24 h and fractional urinary albumin excretion rate (FAC) and their relation to mean blood pressure, haemoglobin Alc, fasting serum insulin and cholesterol and renal size., Results: UAER (mg/24 h) was increased (geometric mean, quartile 1 and 3) in the diabetic patients at baseline, compared to the non-diabetic control subjects; 21 (10 and 33) versus 12 (8 and 15), P = 0.0001 (Wilcoxon's rank test). The UAER-24 h was not increased in diabetic subjects at follow-up; 24 (7 and 49) P = 0.3791 versus diabetic subjects at baseline. Eighteen per cent of normoalbuminuric (UAER < 30mg/24 h) patients developed microalbuminuria (UAER = 30-300 mg/24 h) and 3% clinical nephropathy (UAER > 300 mg/24 h). Of the microalbuminuric subjects 19% progressed to clinical nephropathy, 46% remained microalbuminuric and 35% remitted to normoalbuminuria. Serum insulin concentration, after assessment of confounding factors, measured at the baseline predicted the UAER for all diabetic subjects at follow-up in multiple linear regression analysis in an independent and significant way (P = 0.01). Serum insulin concentration (P = 0.034) and diuretic therapy (P = 0.050) at baseline independently predicted the outcome of the categorical variable progressor/nonprogressor (n = 22/86) based on the UAER-24 h at baseline and at follow-up., Conclusions: Progression of the UAER during the first 6 years is found among approximately every fifth NIDD subject who develops either microalbuminuria (from normoalbuminuria) or clinical nephropathy (from microalbuminuria). The role of serum insulin (insulin resistance) or some factor associated with it, is suggestive in the genesis of kidney disease.

Setting: There is a need for more sensitive and rapid methods for laboratory confirmation in the diagnosis of tuberculosis., Objective: To investigate the applicability of a target rRNA amplified test system (AMTDT, Gen-Probe, CA) for rapid detection of Mycobacterium tuberculosis., Design: The rRNA amplified test system was compared to standard methods for acid fast microscopy and mycobacterial culture for the demonstration of M. tuberculosis in sputum samples from 247 patients in Guinea Bissau with suspected tuberculosis., Results: The highest incidence of positive samples was obtained with the AMTDT test. Out of 274 sputum samples 96 (35%) were positive by the AMTDT test, 82 (30%) were positive by culture and 38 (14%) by direct microscopy. Using culture as reference method the sensitivity of the test was 85% (after discrepancy analysis 87%), and the specificity was 86% (after discrepancy analysis 93%)., Conclusion: The sensitivity and specificity of the AMTDT test used in this setting indicates that it may be a valuable complement for improving the laboratory diagnosis of tuberculosis.

Some epidemiological studies have shown that serum total cholesterol increases with age. especially in women. On the other hand, the risk of coronary artery disease is smaller in women than in men. Earlier studies have shown that a small dense low density lipoprotein (LDL) is more atherogenic than a large LDL. We studied LDL size and apolipoprotein E (apo E) phenotypes in premenopausal and postmenopausal women and in men at the same age. In this study 342 subjects participating in a health screening study were examined. There were four subgroups: 40-year-old men (n = 85), 40-year-old women (n = 80), 70-year old men (n = 88) and 70-year-old women (n = 89). In the present study LDL size was larger (P < 0.01) in women (26.39 +/- 0.07 nm) than in men (25.95 +/- 0.07 nm). We found that LDL size correlated highly positively (r = 0.606; P < 0.001) with serum high density lipoprotein (HDL) concentration and inversely with serum triglyceride concentration (r = -0.627; P < 0.001). Measuring serum HDL cholesterol and triglycerides in health screening studies gives information indirectly about LDL size and its atherogenicity. Apo E phenotype was not significantly associated with serum triglycerides, but was associated with LDL size, LDL cholesterol, total cholesterol and HDL cholesterol. In our sample LDL size decreased and LDL cholesterol and total cholesterol increased according to the most prevalent apo E phenotypes in the order E2/3, E3/3, E3/4 and E4/4. Subjects with phenotype apo E4/4 had the smallest LDL size (25.70 +/- 0.19 nm), the highest total cholesterol (6.53 +/- 0.35 mmol/l) and the lowest HDL cholesterol values (1.28 +/- 0.04 mmol/l). We conclude that there was a significant interaction between sex and age in serum total cholesterol which was highest in older women. However, their LDL size was larger and their LDL is less atherogenic. Apo E phenotype had a significant influence on LDL size.

Diversity of culturable bacteria inhabiting the Baltic sea surface waters was studied in three separate locations. Based on electrophoretically separated whole cell proteins the number of operational taxonomic units (OTU) within each sampling location was high. Most of the OTUs were unique to single locations. Within each sampling location 8-22% of isolates belonged to a single OTU. Rarefaction analysis revealed that the bacterial community was more divergent at a polluted location than at clean areas. Also the most common OTUs were different in clean locations compared to the polluted site suggesting that both diversity and species composition of the bacterial community is greatly affected by pollution. The partial 16S rRNA gene sequences of the isolates of the most common OTUs are unique. Intragroup variation and an OTU-specific bacteriocin system was observed among the isolates of the second common OTU. The bacteriocin activity was linked to restriction fragment length polymorphism grouping, although additional variation correlating to geographic origin of isolates was observed.

The objective of the present study was to determine the occurrence of late specific complications, i.e., nephropathy, retinopathy, and autonomic neuropathy, in type II (non-insulin-dependent) diabetic subjects with a recent onset and with a disease duration of at least 5 years. The study design comprised of a population-based controlled cross-sectional survey of middle-aged type II diabetic subjects in the City of Tampere, Southwest Finland. The mean (SD) albumin excretion rate per 24 h was found to have increased in recently diagnosed diabetic subjects, i.e., 54 (111) mg (p < 0.0001), and in long-term diabetic subjects, 134 (479) mg (p < 0.0001), compared to nondiabetic controls, 16 (19) mg. Microalbuminuria (30 mg/24 h < or = albumin excretion rate < or = 300 mg/24 h) was detected in 8% of nondiabetic subjects and in 29% of recently diagnosed subjects and 27% of long-term diabetic subjects. The prevalence of clinical nephropathy (albumin excretion rate > 300 mg/24 h) was 7% in long-term and 4% in recently diagnosed diabetic subjects and zero in nondiabetic subjects. The differences between diabetic and nondiabetic subjects tested for microalbuminuria and clinical nephropathy were significant (p = 0.02-0.0001) exempting the difference between recently diagnosed female diabetic subjects and nondiabetic female subjects tested for clinical nephropathy. Seventy-five percent of biopsied diabetic subjects with an albumin excretion rate exceeding 100 mg/24 h were found to have diabetic glomerulosclerosis, while the rest had a normal finding. In long-term diabetic subjects the prevalence of nonspecific, background and proliferative retinopathies were present in 40%, 31%, and 8%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

In several populations, the apolipoprotein E (apo E) allele epsilon 4 is associated with high concentration of plasma total and low density lipoprotein (LDL)-cholesterol and coronary artery disease (CAD). We determined the apo E phenotypes of 309 patients with angiographically verified CAD and 38 patients without CAD by isoelectric focusing and Western blotting. In men with CAD, the plasma total and LDL-cholesterol increased according to apo E phenotype in the following order: E3/2 < E3/3 < E4/3 < E4/4 (P = 0.03 for total cholesterol, P = 0.007 for LDL-cholesterol). In women, there was a similar trend (P = 0.22 for total cholesterol, P = 0.15 for LDL-cholesterol). The relative frequency of men with three vessel CAD increased (P = 0.43) together with LDL-cholesterol levels (P = 0.05) according to apo E phenotype E3/2, E3/3, E4/3, E4/4. Total and LDL-cholesterol levels were higher in patients with three vessel CAD than in patients with less serious types of CAD (P = 0.02 for total cholesterol, P = 0.007 for LDL-cholesterol). The relative frequency of patients with myocardial infarction increased according to apo E phenotype (P = 0.51). Both in men and women, there were no differences between apo E phenotypes in age at occurrence of the first myocardial infarction. The apo E allele frequencies of patients with CAD vs. without CAD were 2.3% vs. 1.3% for epsilon 2, 79.0% vs. 76.3% for epsilon 3 and 18.7% vs. 22.4% for epsilon 4. There were no statistically significant differences in apo E allele or phenotype frequencies between patients with CAD and without CAD or between patients with CAD and the general Finnish population. Our results support previous studies in suggesting that the apo E allele epsilon 4 is a risk factor for atherosclerosis, which affects plasma total and LDL-cholesterol. In addition, our results suggest that the apo E allele determines the severity of CAD.

Objective: To estimate the occurrence of increased albumin excretion rate (AER) and its significance as a marker of diabetic kidney disease in non-insulin-dependent diabetic subjects., Design: Population-based, controlled cross-sectional study., Setting: A primary health care centre in the city of Tampere, south-west Finland., Subjects: Consecutive, recently diagnosed (n = 150) and long-term (n = 146) middle-aged non-insulin-dependent diabetic subjects. Matched non-diabetic control subjects (n = 150)., Main Outcome Measures: Albumin excretion rate, fractional AER, microalbuminuria (AER 30-300 mg 24 h-1), clinical nephropathy (AER exceeding 300 mg 24 h-1) and kidney biopsy in diabetic subjects with an AER exceeding 100 mg 24 h-1., Results: Mean (+/- standard deviation [SD]) 24-h AER was increased in recently diagnosed diabetic subjects, 54 (111) mg, and long-term diabetic subjects, 134 (479) mg, compared to non-diabetic control subjects, 16 (19) mg. The fractional AER was 7.5 (18.3) x 10(-6) in recent diabetic subjects, 53.1 (306.9) x 10(-6) in long-term diabetic subjects and 2.8 (3.7) x 10(-6) in non-diabetic control subjects. Microalbuminuria was found in 8% of non-diabetic subjects, in 29% of recent and in 27% of long-term diabetic subjects. The prevalence of clinical nephropathy was 7% in long-term and 4% in recent diabetic subjects, whilst no non-diabetic subject had nephropathy. In 12 of 16 eligible kidney biopsies, diabetic glomerulosclerosis was found, in four subjects the finding was normal., Conclusions: The AER is clearly increased in recent non-insulin-dependent diabetic subjects and further increased in diabetic subjects with a mean disease duration of 10 years. An increased AER in non-insulin-dependent diabetic subjects suggests diabetic kidney disease.

Most clinical laboratories participate in surveys of external quality assurance (EQA). The results are not, however, very commonly or effectively applied to controlling the accuracy, i.e., differences in the analytical level. Therefore, it is important that each laboratory has its own, valid reference values. Nevertheless, many laboratories do not follow the internationally accepted recommendations for determining reference intervals or use reference values from other laboratories or from literature. Techniques of the external quality assurance can be extended to the checking of the validity of reference limits.

Discharge diagnoses provide a possibility to select patients individually and then to establish reference values for both "pathological" and control groups. Currently, the available diagnostic information is still at its infancy and should be carefully evaluated before the reference values based on those groups are utilized. It is anticipated that electronic storage of diagnostic and therapeutic information will be applied more commonly in the future as the development of computers makes it easier. The advanced utilization of laboratory data challenges physicians both in the clinical and laboratory side to participate in this development in order to make the information systems serve their actual needs more closely.

Two approaches for deriving reference change limits from patient data are described. In the direct method, hospital database information is used for the selection of appropriate reference groups. If database information is not sufficient or reliable enough, but still most of the source data can be considered as health-related, an indirect method can be applied in the calculation of rough estimates for reference change limits. A computer program developed by us, GraphROC for Windows, includes both methods for the estimation of change limits from patient data. Time between specimen collections should be included as one classifying factor in the selection of source data. When only one previous result is available for comparison, change limits based on the reference sample group form the only available guide for clinical interpretation. However, when several previous results are available and the within-subject variances for the considered analyte are known to be heterogeneous between individuals, the clinical interpretation should rather be based on application of time series analysis.

We utilized the databases of a hospital information system to select for determination of reference values various individual hospitalized patients on the basis of their diagnoses at discharge. The nonparametric 2.5-97.5% "health-related" reference intervals were calculated for hemoglobin concentration, mean corpuscular volume (MCV), and erythrocyte count for both sexes. After excluding patients with diseases possibly affecting erythrocyte variables, we obtained a final group of 1786 women and 1450 men, ages 20-65 years, who were studied in age groups of 20-30, 30-45, 45-55, and 55-65 years. The upper reference limits of the MCV results obtained from hospitalized patients were higher than those produced conventionally from healthy individuals, as would be intuitively suggested by clinical experience. This method, based on selection by diagnosis, could be applicable to various analytes measured in hospital laboratories, provided sufficient data are available as databases.

Recently, high-dose short-term alcohol exposure has been observed not to induce acute pancreatic damage, as evaluated by serum pancreatic enzyme activities. In this study the effect of high-dose, long-term alcohol exposure on the pancreas was investigated in 32 consecutive alcoholics admitted to a unit to treat the problems of withdrawal after a long period of heavy drinking. None of the alcoholics complained of abdominal symptoms. The signs of clinical acute pancreatitis (pain, increased serum C-reactive protein concentration or blood white cell count) were not observed in any of the alcoholics. A significant increase in serum total amylase, pancreatic isoamylase and lipase activities developed by the second day after termination of alcohol intake. These enzyme activities remained significantly increased for one week after cessation of drinking. Seven alcoholics had signs of chronic pancreatitis at ultrasonography (pancreatic calcification, pseudocyst). These results suggest that heavy alcohol intake over the long term may frequently induce subclinical pancreatic injury.

Survival analysis of 144 histologically confirmed cases of colon carcinoma diagnosed in a 12 year period (1971-82) at the Tampere University Hospital was performed to test the hypothesis that p53 overexpression is associated with a poor clinical outcome. Immunohistochemical staining of paraffin-embedded sections using a polyclonal antibody CM-1 against p53 protein was performed to identify aberrant expression of the p53 tumour-suppressor gene. Sixty-nine per cent of the tumours (100/144) showed overexpression of the p53 protein. The prevalence of p53 overexpression was independent of age and sex of the patient and subsite of the tumour, but was slightly, although not statistically significantly, higher in advanced than in localised tumours. Overexpression was associated with a higher S-phase fraction. Some indication of a larger proportion of aneuploid tumours among those with overexpression was also observed, although this finding did not reach statistical significance. Significantly reduced patient survival for tumours with p53 overexpression was found. Patients with p53-overexpressing tumours had a corrected 5 year survival rate of 37% compared with 58% among patients whose tumours had normal expression of p53. The corresponding 10 year rates were 34% and 54%. In the multivariate analysis using a Cox model, the survival difference was independent of age and sex of the patient, as well as of subsite and stage of the tumour. Furthermore, the effect of p53 overexpression remained after controlling for flow cytometric parameters in an analysis of a subset of tumours. Thus, p53 overexpression appears to be a useful prognostic indicator in colon carcinoma.

Carbohydrate-deficient transferrin (CDT) has previously been reported to be an excellent marker of male alcoholics. Less is known of its efficiency among women and especially of early-phase alcohol abuse in nonselected populations. The present population-based study examined the diagnostic value of CDT among consecutive women, including 13 teetotallers, 135 social drinkers (mean alcohol consumption 45 +/- 34 g/week), and 57 nonalcoholic heavy drinkers (197 +/- 97 g/week). Sixty-two women with a well-documented history of chronic alcoholism (942 +/- 191 g/week) were also studied, as well as 36 pregnant women used as a reference group. Two weeks of abstinence among 11 alcoholics was followed. The CDT (containing part of isotransferrin with pI = 5.7, 5.8, and 5.9) was separated by anion exchange chromatography and assayed by radioimmunoassay. In the whole material, CDT correlated significantly with alcohol consumption (r = 0.43, p < 0.001) but not with conventional markers (gamma-glutamyltransferase, AST, ALT, and mean corpuscular volume). The CDT values of alcoholics (34 +/- 20 units/liter) were significantly (p < 0.001) higher than those of teetotallers (19 +/- 6 units/liter), social drinkers (20 +/- 6 units/liter), or pregnant women (16 +/- 3 units/liter). Heavy drinkers also had higher values (25 +/- 13 units/liter), but the difference did not reach statistic significance. The specificity of CDT was on the level of conventional markers when the cut-off value was increased from 26 to 29 units/liter. At a specificity of 95%, CDT found 19% of the heavy drinkers and 52% of the alcoholics; the best traditional marker, AST, with a specificity of 97%, found 7% and 56%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To determine the occurrence of elevated fetal hemoglobin (HbF) among the diabetic population and determine the clinical situation of importance., Research Design and Methods: A cross-sectional study was conducted. HbA1c and HbF were measured with high-performance liquid chromatography in 1,104 consecutive diabetic patients attending our clinic for HbA1c determination. The expression of clinical correlations between the high and low HbF group was performed for adults (> or = 15 years). A nondiabetic control group (n = 258) with the same age and sex distribution was included., Results: HbF was elevated (> 1.0% of total hemoglobin) in 7.5% of the total diabetic group. In the adult diabetic group, HbF was elevated in 6.5% of the patients, and in the control group, HbF was elevated in 1.9% (P < 0.01). In the insulin-treated adult group, HbF was elevated in 10.2% of the patients, and in the non-insulin-treated group, HbF was elevated in 3.8%. The mean HbA1c was 8.90 +/- 2.00% among the patients and 5.52 +/- 0.53% in the control subjects (P < 0.001). Patients with elevated HbF were younger (P < 0.02) and more often on insulin therapy (P < 0.001) or type I diabetic patients (P < 0.001). Sex, glycemic control, or duration of diabetes were not significantly different in the patients with high or low HbF. Correlation was not detected between the amount of HbF and HbA1c or age in the group of patients with elevated HbF. Hemoglobinopathies, anemias, or malignancies were not diagnosed from the patients with high HbF., Conclusions: Level of HbF is increased (> 1.0%) among 7.5% of unselected diabetic patients. In adult (> or = 15 years) diabetic patients, it is increased among 6.5%, which is 3.4 times more often than in the control population. Acute hematological conditions or malignancies do not explain the difference. Elevated HbF seems to be associated with type I diabetes and insulin treatment.

We investigated the ability of various blood markers to detect an alcoholic cause of acute pancreatitis. Serum carbohydrate-deficient transferrin (CDT) was significantly correlated with reported 2 month and 7 day ethanol consumptions and was significantly higher in 42 patients with alcoholic acute pancreatitis and in 24 patients with possibly alcoholic acute pancreatitis than in 20 patients with non-alcoholic disease. At a cutoff over 17 U/L, the specificity of CDT was 100% and the sensitivity was 75% to detect an alcoholic cause of acute pancreatitis. The lipase/amylase ratio index, erythrocyte mean corpuscular volume, and gamma glutamyl transferase could not distinguish alcoholic from non-alcoholic acute pancreatitis.

During the period 1965-1984 a total of 279 patients underwent carotid endarterectomy at the Tampere University Hospital; 160 of them were reexamined twenty-eight to two hundred nine months later to investigate whether there are any long-term differences in platelet properties according to the endpoint that led to operation. Platelet count, mean platelet volume (MPV), and plateletcrit were estimated and compared with the respective values for controls. Classified according to the indication for operation, patients with stroke had a significantly higher platelet count, 292 x 10(9)/L (SE 11), than patients with transient ischemic attack (TIA), 255 x 10(9)/L (SE 5, p < 0.01), or controls, 267 x 10(9)/L (SE 6, p < 0.05). Patients with stroke or TIA had a higher MPV than the controls. When the patients were grouped according to their physical condition at the time of the control examination, the largest platelets, 10.84 x 10(-15) L (SE 0.40), were found in the group of patients who felt well but who had a symptom or finding assumed to be due to a carotid disease.

Postprandial lipoprotein metabolism may play a role in the etiology of premature coronary artery disease (CAD). To determine whether apolipoprotein E (apo E) polymorphism and the size of low density lipoprotein (LDL) influence postprandial lipemia we studied 39 healthy men and 35 men with CAD. Venous blood samples were obtained before an oral fat load and 3, 5 and 7 h thereafter. Total cholesterol and high density lipoprotein (HDL) cholesterol concentrations did not change in either group during the fat load, but triglycerides increased more markedly in CAD patients compared with controls independently of apo E phenotypes. There was a positive correlation between the size of LDL and the concentration of HDL cholesterol (r = 0.541, P < 0.001); conversely, an inverse correlation was observed between LDL size and the level of fasting triglycerides (r = -0.582; P < 0.001). The patients with CAD had significantly smaller LDL particles (25.89 +/- 0.56 nm) than in controls (26.21 +/- 0.63 nm) (P < 0.05). The increase in triglyceride levels during the fat load was highest in CAD patients with a small size of LDL particles (< 25.5 nm) and lowest in controls with large LDL (> 25.5 nm). Our results suggest that the magnitude of the triglyceride response is a better indicator of CAD risk than the fasting triglyceride concentration. The best model in our logistic regression analysis selected as significant risk factors the change of triglyceride concentration from the baseline at 5 h after a fat meal and HDL cholesterol. This model classified 83% of the subjects correctly.

We have sequenced a gene from Bacillus acidocaldarius which encodes an open reading frame (ORF3) of 310 amino acids. The ORF3 was found to be related to the mammalian hormone-sensitive lipase (HSL). Searching the protein data base revealed five other bacterial proteins related to the HSL. Upon further sequence comparisons this HSL-group was found to be related to the family of carboxylesterases, and to a family of lipases (lipoprotein, hepatic and pancreatic lipases). The evolutionary relationship of these serine-dependent hydrolytic enzymes has not been studied previously, and it has not been known that these proteins belong to the same superfamily. Finally, the alignment of the HSL with the bacterial proteins allowed us to infer the location of the hormone-sensitive regulatory domain of the HSL-protein.

Background: Does the amount of recently consumed alcohol correlate with the severity of acute alcoholic pancreatitis?, Methods: One hundred one consecutive episodes of acute pancreatitis (AP) were prospectively studied. Seventy-three were alcoholic AP episodes; 40 patients had their first alcoholic AP episode. A standard personal interview was used to determine the alcohol consumption during 2 months and during 1 week before AP. The severity of AP was evaluated according to the Ranson criteria, the serum C-reactive protein (CRP) concentration measured 24 to 48 hours after admission, the length of the hospital stay, the development of complications, and the mortality rate., Results: In the 40 patients having their first alcoholic AP episode, the reported 2-month alcohol consumption correlated significantly with the number of positive Ranson criteria (correlation coefficient r = 0.44, p < 0.01), serum CRP concentration (r = 0.51, p < 0.001), and the length of the hospital stay (r = 0.45, p < 0.01). Complications occurred in eight of 14 patients with 2-month alcohol consumption of more than 5000 gm as compared with one of 14 patients with consumption of less than 2000 gm (p < 0.05). In the same 40 patients the 1-week alcohol consumption correlated with the number of positive Ranson criteria (r = 0.40, p < 0.05) and serum CRP concentration (r = 0.37, p < 0.05). Of the 12 patients who had consumed more than 1000 gm alcohol during the last week before admission, two died and complications developed in six (50%), as compared with none (p < 0.05) and six (21%), respectively, of those who had consumed less than 1000 gm. No significant correlations were observed between the reported alcohol consumption and any of the severity parameters in the 33 patients with recurrent episodes of alcoholic AP., Conclusions: The amount of alcohol consumed may be an important determinant of the severity of the first alcoholic AP episode but not of recurrent alcoholic AP.

Two starch-degrading enzymes produced by Bacillus acidocaldarius (renamed as Alicyclobacillus acidocaldarius) were identified. According to SDS-PAGE, the apparent molecular masses of the enzymes were 90 and 160 kDa. Eight peptide fragments and the N-terminal end of the 90 kDa polypeptide were sequenced. An oligonucleotide, based on the amino acid sequence of a peptide fragment of the 90 kDa protein, was used to screen a lambda gt10 bank of B. acidocaldarius, and the region encoding the 90 kDa protein was cloned. Unexpectedly, the ORF continued upstream of the N terminus of the 90 kDa protein. The entire ORF was 1301 amino acids (aa) long (calculated molecular mass 140 kDa) and it was preceded by a putative ribosomal binding site and a promoter. Computer analysis showed that the 1301 aa protein was closely related to an alpha-amylase-pullulanase of Clostridium thermohydrosulfuricum. We suggest that the starch-degrading 160 kDa protein of B. acidocaldarius is an alpha-amylase-pullulanase, and the 90 kDa protein is a cleavage product of the 160 kDa protein. Another ORF, apparently in the same transcription unit, was found downstream from the amylase gene. It encoded a protein that was closely related to the maltose-binding protein of Escherichia coli.

Carbohydrate deficient transferrin (CDT) has been reported to be one of the best biochemical markers of alcohol abuse. However, a need still exists for a simple and practical method for widespread laboratory use. A semi-automatic (SA) isoelectric focusing (IEF) assay for CDT (SA-IEF-CDT) by a Phast System is introduced here. Different isoforms of transferrin were separated by IEF on polyacrylamide gels (pI 4.0-6.5) and located by immunofixation with an anti-transferrin serum. The precipitation bands were stained with Coomassie Brilliant Blue and quantitated densitometrically. The present method gave a picture of the relative amounts of 10 different transferrin isoforms. The percentage of CDT with pI > or = 5.7 (representing di-, mono- and asialotransferrin) was calculated. For comparisons transferrin bands with pI > or = 5.6 (tri-, di-, mono-, and asialotransferrin), pI > or = 5.8 (mono- and asialotransferrin) and pI > or = 5.9 (asialotransferrin) as well as GGT, ASAT and ALAT were calculated. The method showed good linearity and it identified different isoforms in concentrations of < 10 mg/l of transferrin. The correlation of the present method with a commercially available method employing anion exchange followed by double antibody RIA (AE-RIA-CDT) was good (n = 38, r = 0.924). In 19/20 (95%) of healthy controls, the CDT value was below 4.4% (mean + 2 S.D.) of total transferrin, while higher values were observed in all 20 (100%) alcoholics. In conclusion, the developed semi-automatic method is a practical and reliable alternative for determination of different transferrin isoforms.

Epidemiological studies have consistently shown an apparent protective effect of moderate alcohol consumption on coronary artery disease (CAD). This has been considered to be due to the rise in the high-density cholesterol lipoprotein (HDL-cholesterol). Since the response of the HDL-subfractions to moderate or heavy dose of alcohol is less clear, we now compared the high-density lipoprotein cholesterol status between groups consuming different amounts of alcohol. In this population-based survey serum total high-density lipoprotein cholesterol and its HDL2 and HDL3 subfractions were blindly compared between 264 consecutive middle-aged men (37 teetotallers, 137 moderate drinkers, 90 heavy drinkers) participating in a voluntary health screening and 104 male alcoholics. Alcohol consumption correlated significantly (P < 0.001) with total HDL-cholesterol, HDL2, HDL3 when all subjects (n = 368) were included but the correlation disappeared when alcoholics were excluded (n = 264). In comparison with teetotallers, alcoholics had significantly higher total HDL-cholesterol, HDL2 and HDL3 values (P < 0.001). Moderate or heavy intake of alcohol had no effect on HDL2 but increased the HDL3-fraction. If the protective effect of moderate alcohol consumption is mediated by high-density lipoprotein, it may not be accounted for by changes in the HDL2-fraction. The observed increases in the concentration of the HDL3-fraction, however, suggest that this subfraction may not be inert with respect to coronary disease and could possibly have a role in the protective effect.

Carbohydrate-deficient transferrin, CDT, had previously been reported to be an excellent marker for alcoholism. The present population-based study examined the diagnostic value of CDT among consecutive middle-aged males including 122 social drinkers (mean alcohol consumption 88 +/- 79 g per week) and 77 non-alcoholic heavy drinkers (301 +/- 195 g/wk). Ninety-six men with a well-documented history of chronic alcoholism (> or = 1000 g/wk) were used as a reference group. The CDT (containing mainly isotransferrin with pI = 5.8 and 5.9) was separated by anion exchange chromatography and assayed by RIA. The CDT values of social drinkers (mean +/- SD = 14 +/- 5 U/I) were significantly lower than those of heavy drinkers (19 +/- 13 U/I, p < 0.01) and alcoholics (34 +/- 18 U/I, p < 0.001). In the whole material CDT correlated positively with alcohol consumption (r = 0.53, p < 0.001). At a specificity of 91.8%, CDT found 28.6% of the heavy drinkers and 79.2% of the alcoholics; the best traditional marker, GGT, with a specificity of 86.9%, found 35.1% and 64.6%, respectively. In conclusion, CDT is a specific marker, which is superior to traditional markers for identifying alcoholics. Unfortunately, it does not seem to provide additional power for identifying the important group, non-alcoholic heavy drinkers.

We determined DNA content, S-phase fraction, and estrogen (ER) und progesterone receptor (PR) levels in 36 stage I endometrial adenocarcinomas and in 22 hyperplastic lesions to obtain information on the genesis and progression of endometrial malignancy. DNA aneuploidy was detected in 12/36 (33%) carcinomas and in none of the hyperplastic lesions. DNA aneuploidy was significantly more common in poorly and moderately differentiated carcinomas than in the well-differentiated ones. Similarly, the highest number of cells in S-phase were found in poorly and moderately differentiated carcinomas, whereas well-differentiated carcinomas and all hyperplasias had an equally small S-phase fraction. Mean ER and PR levels were highest in hyperplastic lesions, especially those with atypical features, whereas carcinomas of all grades had significantly lower values. Thus, it is likely that the loss or decreased expression of steroid receptors is an early event during carcinogenesis in human endometrium, whereas an increase in the cell proliferation rate and the formation of DNA aneuploidy occur later during tumor progression.

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.

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.

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).

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.

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.

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.

In the search for potential biochemical markers of value for prognosis after acute hypoxic brain damage, amino acids and glucose were assessed in the cerebrospinal fluid (CSF) and glucose in blood. Samples were taken by lumbar puncture 4, 28, 76 and 172 h after resuscitation from 20 patients and once from 10 control patients. Eight of the resuscitated patients recovered neurologically but 12 remained comatose. The concentrations of alanine (P less than 0.001) and phenylalanine (P less than 0.035) differed most in 4-h samples between the groups. The concentration of alanine was higher in all patient groups with hypoxic brain damage as compared to the controls, the concentrations in patients dying within 76 h (disabled-s group) being higher than in the recovered patients. Phenylalanine in the disabled-s group was significantly higher than the control value. Furthermore, there were significant differences between various patient groups in the concentrations of glutamine, isoleucine, leucine, lysine, serine, tyrosine and valine. When taking into account the permeability of the BBB to these amino acids, alanine, valine and isoleucine most clearly represent brain amino acid metabolism. CSF glucose in the control group and in the recovered patients was lower than in patients dying within 76 h.

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.