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Biomedical subjects

F Bode

Publications and source records attributed to F Bode.

At least 19 recordsLinked to original sources

Quantitative skin prick and bronchial provocation tests with platinum salt.

Occupational asthma due to platinum salts is a frequent disease in platinum refineries. The diagnosis is based upon a history of work related symptoms and a positive skin prick test with platinum salts. Bronchial provocation tests have not been performed in epidemiological studies because the skin test is believed to be highly specific and sensitive. As no reliable data about this issue currently exist, this study assesses the use of skin prick and bronchial provocation tests with methacholine and platinum salt in platinum refinery workers. Twenty seven of 35 workers, who were referred to our clinic with work related symptoms and nine control subjects with bronchial hyperreactivity underwent a skin prick test and bronchial provocation with methacholine and platinum salt. For skin prick and bronchial provocation tests with platinum salt a 10(-2)-10(-8) mol/l hexachloroplatinic acid solution, in 10-fold dilutions was used. Four of the 27 subjects and all controls showed neither a bronchial reaction nor a skin reaction. Twenty three subjects were considered allergic to platinum salt; 22 of these showed a fall of 50% or more in specific airway conductance after inhalation of the platinum salt solution. Four workers experienced a positive bronchial reaction despite a negative skin prick test. No correlation of responsiveness to methacholine with responsiveness to platinum salt was found, but the skin prick test correlated with the bronchial reaction to platinum salt (rs = 0.50, p less than 0.023, n = 22). One dual reaction was seen in bronchial provocation tests. Side effects of both skin tests and bronchial provocation tests with platinum salt were rare and were not encountered in workers without a skin reaction to platinum salt. It is concluded that bronchial provocation tests with platinum salts should be performed on workers with work related symptoms but negative skin tests with platinum salts.

Adult

Computer analysis reveals changes in renal Na+-glucose cotransporter in diabetic rats.

A novel, computer-assisted program was developed to analyze the time course of Na+-glucose cotransport by rat renal cortical brush-border membrane vesicles (BBMV). Transporter characteristics can be measured, which routine kinetic analyses fail to distinguish: cotransporter membrane density is derived from the picomoles of D-glucose bound per milligram of protein. Binding is stereospecific, blocked by phlorizin, and supported equally well by Na+ or K+ (but not Cs+). Quasi-first-order influx and efflux rate constants for the composite Na+-driven influx and the (presumed) Na+-independent efflux processes were highly dependent on glucose concentration. Either two Na+-glucose transporters exist in proximal tubules or a single mechanism abruptly changes rate when glucose falls to low levels. The major operation mode is slow, has a high capacity but low affinity, and may have a 2 Na+:2 glucose stoichiometry (Hill coefficient is unity). The minor system is a fast, smaller-capacity, higher-affinity operation with a 2 Na+:1 glucose stoichiometry that was not distinguishable when the same data were analyzed in conventional kinetic plots. Results with streptozocin-induced diabetic rats illustrate the method's utility. Low-glucose-affinity cotransporters were upregulated in hyperglycemic, but not in cachectic, ketoacidotic animals. Rate constants, especially for efflux, were decreased in diabetes.

Animals

Amniotic fluid isoamylase activity in uneventful pregnancies.

A kinetic test (Phadebas) was used to determine the isoamylase activity in 50 serum specimens and 159 samples of amniotic fluid. A highly significant difference between the isoamylase patterns of serum and amniotic fluid was ascertained which strongly supports the view that amylase activity in amniotic fluid is not of maternal origin. During the whole course of gestation the activity of pancreatic isoamylase was constantly low whereas there was an increase of nonpancreatic activity (S-type amylase) from 44 +/- 10 U/l in the 18th week of gestation to 445 +/- 170 U/l in week 39/40. A comparison between the dispersion of the ascertained values and the lecithin-sphingomyelin (L/S) ratio showed a clear overlapping. There was a correlation coefficient of r = 0.645 for 115 amniotic fluid specimens examined in our investigation. The findings show that the estimation of nonpancreatic isoamylase (S-type amylase) activity in amniotic fluid is a valuable indirect parameter for determining fetal maturity and fetal lung maturity. The easy and quick determination method will provide even those hospitals with an index of fetal maturity which are presently not in a position to estimate the L/S ratio, thus being of great assistance in the field of premature deliveries.

Amniotic Fluid

Kinetic studies of D-glucose transport in renal brush-border membrane vesicles of streptozotocin-induced diabetic rats.

Renal brush-border membrane vesicles prepared from streptozotocin-induced 4-day-diabetic rats possessed a Na+-dependent D-glucose transport system that exhibited apparent Kt and Vmax values about 2-fold greater than normal. Apparently, hyperglycemia and probably other stimuli cause the induction and membrane incorporation of a low-affinity transporter in these membranes; this increased sugar-transport capacity is retained for at least 4 weeks so long as the animals maintained or increased their body weight. Membranes prepared from 28-day-diabetic, severely ill ketoacidotic animals lose this enhanced transport ability and the decrease in Vmax was found to correlate directly with the weight loss. Furthermore, the transporter in brush-border membranes prepared from these cachectic animals had an even lower affinity for glucose than those from the acute hyperglycemic animals. That these changes in the diabetic animals represent major alterations in renal brush-border membrane construction is further supported by our observation that the specific activity of the marker enzymes, alkaline phosphatase and neutral alpha-glucosidase, are profoundly increased and decreased, respectively, in this condition.

Alkaline Phosphatase

Inhibition of protein reabsorption in the renal proximal tubule by basic amino acids.

The effects of basic and neutral amino acids on the reabsorption of 125I-lysozyme by the renal proximal tubule were examined in rats. In whole animal experiments control animals were given an intravenous (i.v.) injection of 125I-lysozyme alone while experimental animals received an i.v. injection of either a basic or a neutral amino acid prior to the injection of 125I-lysozyme. In control animals the renal content of 125I-lysozyme 30 min after injection was 35% of the injected dose. After injection of basic amino acids there was a significant decrease in the renal uptake of lysozyme. There was no effect of neutral amino acids on the reabsorption of lysozyme. In microperfusion experiments proximal convoluted tubules were perfused in vivo for 3 min with a solution containing 125I-lysozyme and either lysine or alanine. In tubules perfused with lysine there was a significant decrease in the reabsorption of lysozyme, whereas alanine had no effect on lysozyme uptake. Electron microscope autoradiography revealed that lysozyme was located in endocytic vesicles and lysosomes in both experimental groups. However, the autoradiographic grain density was significantly decreased in tubules perfused with lysine as compared with those perfused with alanine. These findings demonstrate that basic amino acids inhibit the reabsorption of the cationic protein lysozyme by the proximal tubule cells.

Absorption

Effect of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on isotonic fluid reabsorption: polarity of proximal tubular cells.

Isotomic fluid reabsorption (JV) of rat renal proximal tubules was examined by the shrinking droplet method in combination with simulatneous perfusion of blood capillaries. Sensitivity of JV measurement was improved by using each punctured tubule for control measurements: 1) Parathyroid hormoen (PTH) on the contraluminal cell side reduced JV in a dose-response behavior. The maximal inhibition was achieved at a PTH concentration of 10(-5) M, the half maximal inhibition at a concentration of 3 X 10(-9) M. PTH on the luminal cell side had a small inhibitory effect. 2) Cyclic AMP inhibited JV preferentially when applied to the luminal cell side. On the luminal cell side, both cyclic AMP and dibutyryl cyclic AMP inhibited JV in a similar dose-dependent behavior. Concentrations of both nucleotides as low as 10(-10) M had a definite inhibitory effect. Tested at a high concentration, N6-butyryl cyclic AMP was almost as effective as cyclic AMP. Deoxy cyclic AMP, 5' AMP, cyclic guanosine monophosphate (cyclic GMP), dibutyryl cyclic GMP had no effect. ATP inhibited JV to a very small extent. 3) The reduction of JV after administration of PTH and dibutyryl cyclic AMP was not additive. The similar inhibitory effect of PTH at the contraluminal cell face and of cyclic AMP at the luminal cell face suggests the following sequence of events in the mediation of the action of PTH: 1) activation of adenylate cyclase by PTH in the contraluminal cell membrane, and 2) action of the generated cyclic AMP on the luminal cell membrane. The interaction of cyclic AMP and the luminal cell membrane is initiated at the luminal cell surface.

Absorption

Diagnosis of obstruction of the upper and central airways.

Patients with obstruction of the upper airways are often treated for long periods of time for other disorders. Correct diagnosis is important since treatment is quite specific. Such patients may present with a characteristic history and findings on physical examination. Certain physiologic tests such as flow-volume loops with and without helium help to prove the diagnosis. Patients with upper airway obstruction may also have sleep apneas and the sleep deprivation syndrome. Methods of diagnosis of upper airway obstruction are presented and three instructive cases are reviewed.

Airway Obstruction

The relationship between symptoms and functional abnormalities in clinically healthy cigarette smokers.

Because a number of "early tests" may now be used to measure abnormalities of lung function in cigarette smokers with normal airflow rates, we evaluated the symptoms of cough, sputum, wheezing, and shortness of breath in 60 nonsmokers and 49 smokers to determine whether these symptoms correlated with measurements of lung function that are believed to be altered by mild obstruction. One or more symptoms were present in 5 per cent of the nonsmokers and 90 per cent of the smokers. Individual symptoms, sums of symptoms (symptoms score), and various combinations of symptoms correlated poorly or not at all to measured values for dynamic lung compliance, closing volume, closing capacity, slope of Phase III, and helium flow-volume curves. The symptoms score correlated negatively (P less than 0.05) with forced maximal expiratory flow at 50 per cent of vital capacity. Inasmuch as the serious consequences of chronic airway obstruction are related to abnormalities of lung function, it is likely the function tests will prove more useful than symptoms to reveal smokers at risk to develop chronic obstructive pulmonary disease. Symptoms cannot be used to detect smokers who are liable to have functional abnormalities suggestive of mild peripheral airway obstruction.

Adult

Effect of cyclic nucleotides on the isotonic fluid reabsorption in the proximal convoluted tubule of rat kidney.

In order to reveal the sidedness of the cyclic AMP action on renal tubules the effect of cyclic nucleotides on isotonic fluid reabsorption was examined in proximal convoluted rat kidney tubules by using advanced micropuncture techniques. Cyclic AMP inhibited isotonic fluid reabsorption preferentially when applied on the luminal cell side. This finding coincides with a predominant distribution of a membrane bound cyclic AMP dependent protein kinase in a luminal cell membrane fraction. On the luminal cell side cyclic AMP and dibutyryl cyclic AMP inhibited isotonic fluid reabsorption in a similar dose dependent behaviour. Concentrations of both nucleotides as low as 10-10M had a definite inhibitory effect. Tested at a high concentration N6-butyryl cyclic AMP was almost as effective as cyclic AMP. Deoxy cyclic AMP, 5' AMP, cyclic GMP and dibutyryl cyclic GMP had no effect. ATP inhibited isotonic fluid reabsorption to a very small extent. The data indicate that the observed inhibition of isotonic fluid reabsorption is specific for cyclic AMP and that the interaction of cyclic AMP and the luminal cell membrane is initiated at the luminal cell surface.

Animals

Is there any transtubular reabsorption of filtered proteins in rat kidney?

The bovine protease inhibitor aprotinin (Trasylol) has a high affinity to the kidney and is preferentially pinocytized in the proximal tubule. After i.v. injection of 1mug 124 I aprotinin the blood content decreases to 2.8% of the primary injected amount within 3 hrs, while simultaneously each kidney contains 29%. This substance was used to test whether or not a peptide which is pinocytized, is released in the intact form into the peritubular blood. By a cross circulation technique with two unilaterally nephrectomized rats we were unable to detect any transport of pinocytized, intact peptide through the proximal tubule cell over the observed cross circulation period of 1-8 hrs even when using 5000 times the above dosage. Since the total amount of aprotinin in the kidney is immunologically reactive (ca. 97%), and 65% of the radioactivity in the blood is not reactive after 6 hrs, we believe that the last step in the absorption process consists in digestion inside the lysosomes and instantaneous release of the split products into the blood.

Animals

Role of inertia in the measurement of dynamic compliance.

Dynamic compliance (Cdyn) was measured at different frequencies (breaths/min) in 30 nonsmoking males and females aged 30-59 yr. In those aged 30-49 yr Cydn at 90 breaths/min was significantly higher than at 15 breaths/min while those aged 50-59 yr showed no significant difference. Assuming an inertance of 0.01 cmH2O/l per s-2, and a sinusoidal breathing frequency, Cydn at 60 and 90 breaths/min was corrected for inertia. In the 30-49 yr age group corrected Cydn did not change with increasing frequency of breathing whereas in the 50-59 yr age group Cydn at 15 breaths/min was significantly higher than at 90 breaths/min (P is less than 0.05). In this age group, four of eight subjects were frequency dependent when corrected for inertia. These findings indicate that inertia influences Cydn at breathing frequencies of 60 per min and above. Unless this is taken into account, frequency dependence of compliance may be missed. The results also indicate that frequency dependence of compliance is normal in some older individuals but is not normal in the younger age group.

Adult

Analysis of the pinocytic process in rat kidney. I. Isolation of pinocytic vesicles from rat kidney cortex.

Pinocytosis was induced in rat kidney by exposure to horseradish peroxidase (HRP). Pinocytic vesicle preparations were enriched after homogenization of kidney cortex by differential centrifugation and free-flow electrophoresis with HRP as an exogenous marker. Vesicles were identified by enzymatic analysis and by electron microscopy, including specific staining procedures. Typical brush-border enzymes such as alkaline phosphatase, aminopeptidase, 5'-nucleotidase, lysosomal acid phosphatase, and mitochondrial succinic dehydrogenase were reduced in the vesicular fraction, compared to the kidney cortex homogenate. Glucose-6-phosphatase and Na(+)-K(+)-ATPase were only slightly increased in the fraction. These results indicate that preparations of pinocytic vesicles from rat kidney cortex can be enriched. They have biochemical characteristics that differ from those of the cell organelles and membranes previously purified from renal tissue.

Acid Phosphatase