Interrelationships and functions of the pyruvate kinase isozymes and their variant forms: a review.

The relationships among and the properties of the pyruvate kinase isozymes are reviewed, emphasizing their potential role in carcinogenesis. Particular consideration is given to evaluation of the concept that the three major nonreadily interconvertible forms are the products of distinct genes, the relationship of these forms to additional separable forms of pyruvate kinase, the types and possible functions of interconvertible forms of the major isozymes, and mechanisms affecting the genetic expression of the isozymes. Emphasis is placed upon the apparent derepression of the fetal isozyme in hepatomas and the influence of neoplasms and their extracts on the expression of pyruvate kinase in the liver of host animals.

Extraction of a factor from Ehrlich ascites tumor cells that increases the activity of the fetal isozyme of pyruvate kinase in mouse liver.

Isoelectrofocusing studies of mouse tissue extracts show mice to have a pyruvate kinase isozyme pattern very similar to that of the rat. Moreover, electrofocusing or kinetic assays conducted on liver extracts from normal mice and from mice bearing Ehrlich ascites tumors show that the latter have a higher proportion of the fetal K-isozyme of pyruvate kinase. Serial injection of the supernatant remaining after centrifugation of homogenized tumor cells at 100,000 x g, or of the phenolic extracts from the latter, produced a similar shift in the liver isozyme pattern involves both a decrease in L-isozyme activity and an increase in K-isozyme activity. However, only the increase in activity of the K-isozyme appears to be a specific response to injection of the extracts. The presence of a specific factor in these extracts was confirmed by the observation that similar extracts prepared from normal adult tissues did not increase activity of the K-isozyme. On the other hand, phenolic extracts from fetal mice did increase K-isozyme activity as did injections of serum from tumor-bearing mice or of the cell-free ascites fluid. Evidence is presented supporting the concept that the factor is proteinaceous in a nature, and that it acts by deprepressing synthesis of the K-isozyme.

Expression of multimolecular forms of pyruvate kinase in normal, benign, and malignant human breast tissue.

The levels of multimolecular forms of pyruvate kinase present in four normal human breast specimens, nine benign tissues, and 13 malignant breast carcinomas were determined. The different enzymatic forms were separated by isoelectrofocusing, quantitated photometrically, and characterized further by kinetic studies using phosphoenolpyruvate as the variable substrate in the presence of different effectors. A correlation between specific activity and malignancy was found. The mean specific activities (+/- S.E.) of the normal, benign, and malignant tissues were: 0.078 +/- 0.006, 0.36 +/- 0.072, and 3.50 +/- 0.696 IU/mg protein, respectively. A form of pyruvate kinase with an isoelectric point (pI) of 7.0 predominated in the breast tissues. The properties of this form were consistent with it being the K4 isozyme, known to be widely distributed in mammalian tissues. Higher pI forms were also found. The M4 isozyme, expressed by normal muscle and brain, has a pI value similar to the highest pI form found in the breast tissues. Therefore, the pI data alone suggest that the breast specimens also express some M-type subunits. This conclusion was not supported by the kinetic data. The higher pI forms are thought to be a posttranslationally modified K isozyme. Although this modified form is found in normal specimens, it seems more prevalent in neoplasms.

Essential hypertension: sodium-lithium countertransport in erythrocytes from patients and from children having one hypertensive parent.

This report deals with the possibility that there is a specific change of the lithium transport across the membrane of erythrocytes from patients with essential hypertension. Sodium-lithium countertransport was significantly increased (p less than 0.005) in erythrocytes from 17 males with essential hypertension (mean 0.7 mmole (liter cells X hr)-1, range 0.4-1.6) compared to a group of 16 normotensive males (mean, 0.4 mmole (liter cells X hr)-1, range 0.3-0.6). A considerable overlap between the values from patients and controls was found. No significant increase of the transport function was found in a group of 14 female patients (mean 0.4 mmole (liter cells X hr)-1, range 0.2-0.6) compared with 10 normotensive female controls (mean 0.3 mmole (liter c hr)-1, range 0.3-0.6). A considerable overlap between the values from patients and controls was found. No significant increase of the transport function was found in a group of 14 female patients (mean 0.4 mmole (liter cells X hr)-1, range 0.2-0.6) compared with 10 normotensive female controls (mean 0.3 mmole (liter c hr)-1, range 0.3-0.6). A considerable overlap between the values from patients and controls was found. No significant increase of the transport function was found in a group of 14 female patients (mean 0.4 mmole (liter cells X hr)-1, range 0.2-0.6) compared with 10 normotensive female controls (mean 0.3 mmole (liter cells X hr)-1, range 0.1-0.6). Determination of sodium-lithium countertransport in red blood cells from nine children with and 14 without known familial disposition for essential hypertension did not demonstrate a close coupling between genetic disposition and the membrane transport function. In spite of the very small intraindividual variability of the transport function, studies of changes in sodium-lithium counter-transport are hampered by considerable interindividual variability of the transport in red cells from apparently normal individuals.

Blood pressure in childhood: pooled findings of six European studies.

In an attempt to study and prevent the development of hypertension, there is a growing interest in measuring blood pressure in children. The aim of this is to detect and monitor those with a relatively high level of blood pressure. Until now, reference values on blood pressure in children are based on data from North-American youngsters. The present study provides percentile charts based on pooled data from studies on blood pressure conducted in six North-West European countries among 28,043 children. These blood pressure centiles are presented as age-, height- and gender-specific. Brief guidelines for blood pressure measurements in childhood and for detection of children with a relatively high blood pressure are included.

Maternal smoking during childhood and increased risk of smoking in young adulthood.

BACKGROUND: Effective prevention of smoking depends on the identification of factors that determine smoking onset. We examined the influence of family factors during childhood (household income, parents' education and smoking behaviour) on the subsequent risk of smoking in young adults. METHODS: In 1979, 1300 children aged 6-18 years, whose parents were randomly selected for participation in the Copenhagen City Heart Study were invited to a health examination. Information about health and smoking behaviour was obtained from 73% of the children. A random sample of 579 of the children were invited to a follow-up examination 13 years later. In all, 486 (84%) participated in the follow-up. RESULTS: The influence of household income, parents' smoking behaviour and education on the child's risk of becoming a smoker in young adulthood was estimated. Household income and parents' education did not significantly affect the risk of adult smoking. Maternal smoking during childhood increased the risk in comparison with the mother being a non-smoker (adjusted odds ratio = 1.95; 95% confidence interval: 1.07-3.58). CONCLUSION: Maternal smoking during childhood increases children's risk of becoming young adult smokers, independent of age and smoking behaviour in childhood, gender and social background. In Denmark 28% of smoking in young adults could be attributed to maternal smoking.

Intensive dynamic back exercises with or without hyperextension in chronic back pain after surgery for lumbar disc protrusion. A clinical trial.

Sixty-two patients with chronic low back pain occurring 14-60 months after undergoing discectomy for the first time were randomized to two physical treatment groups: 24 sessions of intensive dynamic back exercises with hyperextension or 24 sessions of intensive dynamic back exercises without hyperextension. At the conclusion of therapy and at one-year follow-up, no difference was seen between the randomized groups, with regard to the combined assessments of pain, disability and objective measurements. A difference for back exercises without hyperextension to be superior to the other treatment regimen was statistically significant at the three-month follow-up. In the patient's qualitative assessment of treatment outcome there were seen no significant differences between back exercises with or without hyperextension. There was a similar and significant improvement of the isometric endurance of back muscles in both groups, but the flexibility of the spine was significantly improved only in the group using hyperextension exercises. The overall response rate of an earlier published investigation was reproduced. It is concluded that chronic back patients after first time discectomy may benefit from an intensive rehabilitation protocol including intensive exercises. The added use of hyperextension exercises does not confer any independent benefit. Furthermore, the training had to continue for more than 2-3 months before a statistical significant decrease in back pain was reported in the patient pain diary.

A process economic approach to develop a dilute-acid cellulose hydrolysis process to produce ethanol from biomass.

Successful deployment of a bioethanol process depends on the integration of technologies that can be economically commercialized. Pretreatment and fermentation operations of the traditional enzymatic bioethanol-production process constitute the largest portion of the capital and operating costs. Cost reduction in these areas, through improved reactions and reduced capital, will improve the economic feasibility of a large-scale plant. A technoeconomic model was developed using the ASPEN Plus modeling software package. This model included a two-stage pretreatment operation with a co-current first stage and countercurrent second stage, a lignin adsorption unit, and a cofermentation unit. Data from kinetic modeling of the pretreatment reactions, verified by bench-scale experiments, were used to create the ASPEN Plus base model. Results from the initial pretreatment and fermentation yields of the two-stage system correlated well to the performance targets established by the model. The ASPEN Plus model determined mass and energy-balance information, which was supplied to an economic module to determine the required selling price of the ethanol. Several pretreatment process variables such as glucose yield, liquid: solid ratio, additional pretreatment stages, and lignin adsorption were varied to determine which parameters had the greatest effect on the process economics. Optimized values for these key variables became target values for the bench-scale research, either to achieve or identify as potential obstacles in the future commercialization process. Results from this modeling and experimentation sequence have led to the design of an advanced two-stage engineering- scale reactor for a dilute-acid hydrolysis process.

[Purulent myofasciitis in a patient with diabetes treated with a vacuum boot by a zone therapist]. / Purulent myofasciitis hos en diabetiker efter vacuumstøvleterapi hos zoneterapeut.

Diabetic peripheral neuropathy is one of the most common complications of diabetes. We present a case of necrotizing fasciitis in a 38 year old man with insulin dependent diabetes, who had been treated by an alternative therapist with a vacuum boot. The treatment resulted in ulcerations and later infection of the foot and ankle, which had to be treated by acute amputation. The story illustrates the risk of consulting alternative treatment when suffering from diabetic neuropathy or circulatory disturbances. We can therefore not recommend that patients of this kind receive treatment from any person without medical experience.

[Body height in a population of children in Greater Copenhagen 7 to 18 years of age in 1981 and 1985. The Osterbro child study]. / Højde hos en population af storkøbenhavnske børn i alderen 7-18 år, 1981 og 1985. Osterbro-undersøgelsens børneundersøgelse.

As part of the childrens' section of the Osterbro investigation, a quantity of standard health information concerning 736 boys and girls in 1981 and 892 in 1985 was collected. Review of these values revealed a significantly greater average height (greater than 3 cm) for boys in the age group 8-16 years and for girls aged 7-15 years than in previously published materials. The final height at about the age of 18 years for both girls and boys was not found to deviate significantly from previous results. The height/weight relationship remained unchanged. Current adjustments of the normal curves for childrens' growth should be made and/or an assessment of how well the subpopulation concerned is in agreement with the national average.

[Optic nerve atrophy with particular attention to perinatal damage]. / Synsnervesvind. Med specielt henblik på perinatale skader.

We reviewed the records of children born between 1983 and 1987 reported to the Danish National Register for the Visually Impaired Children and with a diagnosis of optic atrophy. Known or presumed etiology was found in 53 of 55 children. Perinatal stress factors were found in 32 patients (58%), with prematurity, low birth-weight and perinatal asphyxia as the most common findings. 78% of the children in the perinatal damage group were boys. We found that all children with optic atrophy caused by perinatal difficulties had one or more additional handicap. The types of handicaps were cerebral palsy, epilepsy and psychomotor retardation. The importance of paying attention to the fact that multiply handicapped children may be visually impaired on account of optic atrophy is emphasized. Early diagnosis is important in order to start educational stimulation as early as possible. It is concluded that visual impairment caused by perinatal damage to some extent is preventable. The strategy for prevention should be based upon better identification of specific etiologies as well as a better understanding of the pathogenesis of infantile optic neuropathy.

[Food composition and serum lipids in children]. / Kostsammensaetning og serum-lipider hos børn.

The composition of the diet is considered to be one of the factors which may be of significance in development of ischaemic heart disease. In order to investigate whether the composition of the diet has a greater influence on the cholesterol levels in children than in adults, af 24-hour dietary interview was carried out on 42 children aged 7-11 years who had previously been examined in the childrens' section of the Osterbro investigation. The children were selected in three groups with low, average and high serum cholesterol levels, respectively. The dietary content of energy-providing substances was compared with the cholesterol values measured. In addition, the composition of the diet in other respects was described and was found to contain, on an average, 40% fat, 14% protein and 42% carbohydrate (of which 14% was sugar). The cholesterol intake was 146 mg/1,000 Kcal. The sugar consumption was low as compared with the national average, approximately 62 g/day. The protein consumption was approximately 2 g per kg body-weight per day. The median total energy intake was 8,024 KJ for girls and 8,569 KJ for boys lower than the recommended daily values and corresponded to a low levels of physical activity. This investigation showed a definite linear connection between the fat energy percentage and the serum cholesterol (alpha = 5.26 p less than 0.005) and that intake of saturated fatty acids, in particular can be related to the cholesterol level (alpha = 2.88 and p less than 0.005). A significantly greater fat energy intake was demonstrated in girls (p less than 0.05) in the group with high serum cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ethical problems of the emergency room work]. / Etiske problemer i skadestuearbejdet.

We studied the incidence of ethical problems occurring in the emergency room of a large Danish provincial hospital. During a period of two months, 3620 unselected patients were treated, and in 190 (5.2%) of these cases the attending physician identified one or more ethical problems. The three most common problems identified were a. potentially suboptimal treatment due to communication difficulties, b. potentially suboptimal treatment due to a high work-load in the emergency room, and c. questions raised by patients who presented with minimal lesions not requiring any treatment. It is suggested that a reduction of the number of ethical problems encountered in the emergency room can be obtained by allocation of more resources, education of the staff, and education of the general public explaining the role of the emergency room.

[Smoking as social heritage. Children whose mothers are smokers are more likely to become smokers as adults]. / Rygning som social arv. Børn, hvis mor er ryger, har øget risiko for at blive rygere som voksne.

Effective prevention of smoking depends on the identification of factors that determine smoking onset. We examined the influence of family factors during childhood (household income, parent education and smoking behaviour) on the subsequent risk of smoking in young adults. In 1979, 1300 children aged 6-18 years, whose parents were randomly selected for participation in the Copenhagen City Heart Study were invited to a health examination. Information about health and smoking behaviour was obtained from 73% of the children. A random sample of 579 of the children were invited to a follow-up examination 13 years later. Four hundred and eighty-six (84%) participated in the follow-up. The influence of household income, parent smoking behaviour and education on the child's risk of becoming a smoker in young adulthood was estimated. Household income and parent education did not significantly affect the risk of adult smoking. Maternal smoking during childhood increased the risk in comparison with the mother being a non-smoker (Adjusted Odds Ratio 1.95 (95% CI 1.07-3.58). Maternal smoking during childhood increases children's risk of becoming young adult smokers, independent of age and smoking behaviour in childhood, gender and social background. In Denmark 28% of smoking in young adults could be attributed to maternal smoking.