Identification of 3,4-dihydroxyphenylalanine, 5,6-dihydroxyindole, and N-acetylarterenone during eumelanin formation in immune reactive larvae of Drosophila melanogaster.

3,4-Dihydroxyphenylalanine, 5-6-dihydroxyindole, and N-acetylarterenone were detected by electrochemical methods in the hemolymph of immune reactive larvae of Drosophila melanogaster following parasitization by the wasp Leptopilina boulardi. Determinations of the catechols were made after separation by reverse phase, ion-pairing high pressure liquid chromatography with electrochemical detection. The presence of 5,6-dihydroxyindole unequivocally establishes the eumelanin pathway in the defense response of Drosophila, and confirms previous investigations which have implicated certain catecholamine metabolizing enzymes in insect immunity. The occurrence of N-acetylarterenone, a derivative of the principal sclerotizing agent N-acetyldopamine, verifies the existence and proposed involvement of quinone methide isomerase in the regulation of catecholamine metabolism, and suggests that the cellular capsule formed by Drosophila in immune reactions against parasites is most likely a composite of both eumelanin and sclerotin. The absence of 3,4-dihydroxyphenylacetic acid in hemolymph samples from immune reactive hosts suggests that during parasitization certain catecholamines and metabolic precursors may be re-employed in alternate pathways, some of which may be used in defense reactions.


A FMRFamide-like peptide is associated with the myotropic ovulation hormone in Rhodnius prolixus.

The protocerebral neurosecretory cells previously shown to be the source of the myotropin controlling ovulation in Rhodnius prolixus react in an immunocytochemical assay using an antiserum against FMRFamide. When the same antiserum was injected into fed mated females at the appropriate time the timing of oviposition was delayed, but the total number of eggs developed was unaffected compared to controls injected with pre-immune rabbit serum. The titer of FMRFamide-like peptide (assayed by RIA) in the hemolymph of mated and virgin females was found to fluctuate with the egg laying cycle, and to reflect earlier determinations of the titer of myotropic activity. Western blots of SDS-PAGE revealed a FMRFamide-immunoreactive peptide of approximately 8.5 kDa in both hemolymph and extracts of the ovulation hormone cells.


The gonad of the desert snail Eremina ehrenbergi Roth, 1839 (Stylommatophora-Gastropoda) and its role in the production of the male gametes.

Specimens of Eremina ehrenbergi Roth, 1839, were collected in the El-Omayed area of the Sahara Desert, west of Alexandria. This simultaneously hermaphrodite snail has a comparatively small gonad enclosed in a thin membrane. The gonad is composed of a mass of branched tubules, each differentiated to a generative proximal half and a conducting distal half. The primitive germ cells proliferate from germinal cells forming a discontinuous layer in the germinal wall of each tubule; they undergo spermatogenesis or oogenesis at the original site of their proliferation. A cluster of spermatogonia may be derived from one primitive germ cell and it develops round a "Sertoli" cell. The division and differentiation of the cells in each cluster are strictly synchronized. The role of the gonad in formation of the spermatophore is restricted to the production of clusters of mature spermatozoa, which are discharged, without the "Sertoli" cell, via three efferent ductuli connecting the conducting portions of the gonadal tubules with the hermaphrodite duct. The sperm has the same appearance as in vertebrates and can be studied in smears prepared from the gonad or the middle of the hermaphrodite duct, where they are collected and stored for a time.


A study of the formation of the neural network in the lungs of Perdicula asiatica, as revealed by the cholinesterase technique.

The investigation was undertaken to investigate the formation and association of neural network and their fibres with nerve cells and ganglia in the parenchyma. The staining of the neural network was done by the cholinesterase technique under the maintained pH 5.2, temperature 40 degrees C and incubation period 30 hrs. The neural network was formed by a good number of tortuous thick nerves and was related either with nerve cells or ganglia. At times, it was formed by a good number of thick nerves and a few thin nerves in the connective tissue space.


Histoenzymological demonstration of glycerol-3-phosphate dehydrogenase and succinate dehydrogenase in the telencephalic nuclei and fibre tracts of hillstream cyprinoid, Barilius bendelisis (Hamilton).

The authors studied the regional localization of two dehydrogenases--glycerol-3-phosphate dehydrogenase and succinate dehydrogenase--in the telencephalic nuclei and fibre tracts of Barilius bendelisis by histoenzymological methods. The activity of these dehydrogenases varied from moderately positive to strongly positive in the nuclear areas and from intensely to strongly positive in the fibre tracts, except those related to the olfactory tubercle. G3PD appears to play an important role in the biosyntheses of phospholipids and to form a link between glycolysis and the pathway of the hexose-monophosphate shunt, in addition to its usual role in the degradation of glucose, along with other dehydrogenases, including succinate dehydrogenase.


Studies of the histoenzymological mapping of acid and alkaline phosphatases in the hindbrain of Barilius bendelisis (Hamilton).

The regional localization of acid and alkaline phosphatase (EC 3.1.3.2. and 3.1.3.1. respectively), determined histoenzymologically, is described in the cerebellum and medulla oblongata of Barilius bendelisis (Hamilton). Acid phosphatase activity in nuclear areas was observed to be moderately positive, whereas alkaline phosphatase activity varied from weak to strongly positive. The localization pattern of these enzymes in the fibre tracts differed. One interesting finding in this study was that the Purkinje cells in the cerebellum and the Mauthner cells in the medulla oblongata contained these enzymes in a high concentration. The contrasting cytological distribution patterns of the two enzymes indicate that their roles in the neurons and fibre tracts are probably different.


Wallagotrema indicus n.sp., a new monogenean from the freshwater sheat-fish Wallagu attu Bloch and Schneider.

The paper describes Wallagotrema indicus n.sp., a freshwater monogenean recovered from the gill filaments of the freshwater sheat-fish Wallago attu Bloch and Schn. It is characterized by the number of head organs, an accessory piece on the cirrus, wings on the anchors and a beak-like outgrowth on the dorsal anchors, together with numerous other differences in the shape and size of various body parts. On the basis of these findings, the generic diagnosis of Wallagotrema is amended and a key to the various species of this genus is appended.


Variability of the v. cava caudalis and its tributaries in some laboratory animals. II. The laboratory rat (Rattus norvegicus v. alba).

Duplication of the v. renalis was found in 11 of the regions examined (18.3%), when it was more frequent on the right side. A v. capsularis was found in 35 regions (58.3%), usually as a single vein. There were 1-3 vv. suprarenales (but mostly two; on the right they usually joined the v. cava caudalis and on the left the v. renalis sinistra). A v. spermatica was present on the right side in every case, but on the left side in 11 cases only; in one case it was duplicated. In the rat, the v. spermatica was rather thin; if absent, it was replaced by the v. deferentialis. In nine cases (60.0%) the v. uterina cranialis dextra opened into the v. cava caudalis, while in 12 cases (80.0%) the left vein opened into the v. renalis sinistra. A v. uterina media, draining blood from the caudal third of the cornu uteri, was found in only five cases (16.7%). The v. uterina caudalis drained blood from the corpus and cervix uteri. The v. ovarica was a constant finding; it was mostly joined by the v. lumbalis--and on the left side by the v. phrenica sinistra. In males, the vv. lumbales occurred mostly as a pair of veins lying just below the vv. renales. In females, they were present on both sides. As a rule, the v. iliolumbalis occurred as a single vein on both sides. The v. cava caudalis originated at the level of the transition between the lumbar and the sacral spine, usually at the confluence of the two vv. iliacae communes, which in 14 cases (46.7%) were joined by the v. sacralis mediana. Duplication of the v. cava caudalis was found in only one case (a female). Comparison of the morphology of the v. cava caudalis and its tributaries in the rat and the guinea pig showed more slight differences between the two species.


Effect of testosterone on the ovotestis of the land snail Theba pisana.

The effect of testosterone on the histological pattern of the gonads of the land snail Theba pisana was studied. It was found that testosterone accelerated spermatogenesis, as indicated by the large increase in the number of spermatozoa and the decrease in the number of primary spermatocytes. The diameter of the acini in treated snails was greater than in the normal controls. Conversely, testosterone led to reduction of the number of mature ova.


What we have learned about uremia from peritoneal dialysis.

Weekly clearances of small solutes such as urea are relatively low on continuous ambulatory peritoneal dialysis (CAPD) compared to those of thrice weekly hemodialysis (HD); large solute clearances are more comparable. Some believe that good clinical outcomes with chronic peritoneal dialysis support the importance of larger molecular weight toxins. However, CAPD patients of large size or approaching an anephric state occasionally develop uremic symptoms that can be reversed with an increased exchange volume or an increased number of exchanges. Increasing exchange volume or the number of exchanges increases small solute clearances by an amount near the increase in drain volume, but clearances of larger molecular weight substances are minimally affected. Thus, peritoneal dialysis experiences initially focused attention on large molecules and now appear to confirm the importance of small solutes in uremic toxicity but at lower clearance requirements than needed in HD.


Implantable pumps. Recent progress and anticipated future advances.

The implantable pump field is now more than 20 years old. The original goal of developing a totally artificial beta-cell remains unrealized, but programmable insulin pumps that contain all of the elements of the artificial beta-cell except the glucose sensor are involved in clinical trials in the United States and are commercially available in Europe. Currently, both single-rate and programmable implantable pumps are in general clinical use in the United States for the treatment of pain and spasticity, cancer, and osteomyelitis. Only a few of the potential applications of implantable pumps have been developed to the stage of commercial availability. This is, in part, because drug companies have traditionally developed parenteral drug applications only as a last resort and, in part, because of the complexity of the regulatory process for implantable pumps, often requiring review by both the drug and device branches of the Food and Drug Administration.


ECMO in the management of cardiac failure.

Extracorporeal membrane oxygenation (ECMO) can provide univentricular or biventricular cardiac, as well as respiratory, support; it has extended the application of ECMO to infants and children who develop refractory cardiogenic shock before or after repair of congenital heart defects. The Pediatric Cardiac ECMO Registry, recently established by the Extracorporeal Life Support Organization, reports an overall survival rate of 47%. All were believed to have little chance of survival without mechanical support. ECMO has also been used for perioperative cardiac support after cardiac transplant. Hemorrhage remains the most common complication of ECMO. The future of ECMO for cardiac support depends on development of methods to prevent cardiac failure, improved ECMO techniques, and increased pediatric cardiac transplantation.


Effects of the Berlin Heart biventricular assist device on microvascular responses in pre-transplant patients.

Microcirculatory forearm cutaneous blood flow was monitored continuously and noninvasively by laser doppler flow-metry (LDF) in 15 patients treated with the Berlin Heart biventricular assist device system (BVAD) for end-stage heart failure under stable hemodynamic states (BVAD pts, n = 10) and norepinephrine therapy (BVAD nor pts, n = 5). Ten healthy human subjects served as controls (C). Cutaneous blood flow was measured before, during, and after external brachial artery occlusion to evaluate the post-occlusive reactive hyperemia (PORH) as a standardized response. To examine microvascular responses to macrohemodynamic changes, the cardiac output (CO) was decreased by a 20% reduction in BVAD pump rate. No significant differences in baseline LDF measurements (in millivolts) were observed among the three groups (C, 470.7 mV +/- 177.3; BVAD pts, 328.0 mV +/- 122.7; BVAD nor pts, 360.0 mV +/- 160.0). After cuff pressure release (1 min later), a significant (p < 0.004) three-fold to four-fold blood flow increase (PORH) occurred in each group (C, 1113.6 mV +/- 469.2; BVAD pts, 813.0 mV +/- 190.1; BVAD nor pts, 498.0 mV +/- 191.8). The difference in PORH between the BVAD pts and BVAD nor pts was significant (p < 0.01), and the time to peak PORH values was different (p < 0.05) among the three groups (C, 22.2 s +/- 10.7; BVAD pts, 11.3 s +/- 12.5; BVAD nor pts, 7.0 s +/- 5.8). A markedly delayed return to baseline occurred in the BVAD pts. The 20% reduction in BVAD pump rate decreased CO significantly (p < 0.05) and increased (p < 0.01) systemic vascular resistance (SVR).(ABSTRACT TRUNCATED AT 250 WORDS)


Where should the hemofiltration circuit be placed in relation to the extracorporeal membrane oxygenation circuit?

Patients requiring extracorporeal membrane oxygenation (ECMO) frequently experience hypervolemia and metabolic abnormalities that can be effectively managed by hemofiltration. Although several options for hemofiltration circuit placement exist, some may have the disadvantage of recirculation or shunting of poorly oxygenated blood to the patient. Attachment of the entire hemofiltration circuit to the pre-ECMO pump region is described. Despite the absence of pump generated pressure and a low blood flow rate, effective hemofiltration and diafiltration were achieved. This article examines whether placement of the hemofiltration circuit proximal to the ECMO pump has advantages over other hemofiltration circuit placements.


Current functional status of Symbion total artificial heart recipients after transplantation.

This multicenter study examines long-term data from the five most experienced North American centers (> 8 total artificial heart [TAH] implants), investigating the functional status of 37 patients who received a Symbion TAH followed by a heart transplant (TX) with post-TX survival > or = 1 year. Primary indications for TAH use included acute cardiogenic shock in 38% (14/37) of patients and deterioration while on the TX waiting list in 35% (13/37). At the time of this study, 86% (32/37) of patients were alive, 94% of whom were functioning at a New York Heart Association (NYHA) classification of I (75% [24/32]) or II (19% [6/32]). NYHA classification before death was I for all five patients who died 40 +/- 17 (r = 14-58) months after transplant. Of the 32 surviving patients, 47% (15) were working, 16% (5) were retired, 12% (4) chose not to work, and 9% (3) were in school. The remaining 16% (5) were unable to work due to surgical limitations. After TX, significant infections occurred in 81% (26/32) of patients and rejection in 72% (23/32). At 1 year after TX, creatinine was within normal limits (< or = 1.4 mg/100 ml or 65-125 mol/L) for 41% (13/32) of patients, 1-2 times normal for 56% (18/32), and > 2 times normal for 3% (1/32). Although TAH is not required for most patients awaiting TX, the device allows excellent long-term functional status in patients otherwise at risk for death. No long-term problems related to the use of temporary mechanical circulatory support were found.


Simple membrane models for peritoneal dialysis. Evaluation of diffusive and convective solute transport.

Currently used mathematical models to estimate parameters describing diffusive (diffusive mass transport coefficient, KBD) and convective (sieving coefficient, S) solute transport during peritoneal dialysis, as proposed by Pyle, Popovich, and Moncrief (PPM model) and Babb, Randerson, and Farrell (BRF model), require nonlinear regression and advanced numerical methods for parameter estimation. In this study, a simplified approach to the evaluation of KBD and S, using the same transport equation used in the PPM and BRF models but based on two-dimensional linear regression, is proposed. This new approach can be extended to generate a family of membrane models that differ in assumption concerning the average solute concentration (c) inside the peritoneal membrane. In particular, c was assumed to be equal to the arithmetic mean value of the dialysate and blood concentrations (PPM model), the blood concentration (BRF model), or the dialysate concentration (D model). The investigated family of models was used to study the transport of urea, creatinine, glucose, sodium, potassium, and total protein in 20 single, 6 hr dwell studies carried out in 20 nondiabetic patients in stable clinical condition using hypertonic (3.86%) glucose solution. For the PPM model, the linear and nonlinear regressions were able to provide almost identical values of KBD and S. The theoretical dialysate to plasma concentration ratio (D/P) was adequately fitted to experimental D/P for both the PPM and BRF models, but the fit was worse for the D model. However, unphysiologic (i.e., out of the 0-1 range) values of S were found for urea, potassium, and glucose independent of the version of the model used.


Accuracy of intravenous infusion pumps in continuous renal replacement therapies.

Most extracorporeal continuous renal replacement therapies (CRRT) require inflow pumping of either dialysate, filtrate replacement solution, or both. Outflow of spent dialysate and ultrafiltrate can be accomplished by gravity drainage or pump. Intravenous infusion pumps have been commonly used for these purposes, although little is known about the accuracy of these pumps. To evaluate accuracy of two different types of intravenous infusion pumps used in CRRT, we studied flow rates at nine different pressure variations in three piston type and three linear peristaltic pumps. The results showed that error of either pump was not different for flow rates of 4 and 16 ml/min. Both types of pumps were affected by fluid circuit pressures, although pressure conditions under which error was low were different for each pump type. The linear peristaltic pumps were most accurate under conditions of low pump inlet pressure, whereas piston pumps were most accurate under conditions of low pump pressure gradient (outlet minus inlet) of 0 or -100 mmHg. The magnitude of error outside these conditions was substantial, reaching 12.5% for the linear peristaltic pump when inlet pressure was -100 mmHg and outlet pressure was 100 mmHg. Error may be minimized in the clinical setting by choosing the pump type best suited for the pressure conditions expected for the renal replacement modality in use.


Oxalate removal by differing dialysis techniques.

Secondary hyperoxalemia is a common feature in patients with chronic renal failure, but oxalate removal is not adequately accomplished by regular dialysis treatment. Oxalate removal in two groups of patients, 11 on continuous ambulatory peritoneal dialysis (CAPD) and 12 on hemodialysis (HD), was investigated. HD patients were studied during a regular bicarbonate dialysis and during hemodiafiltration (HDF) with a high convective component (UF = 66 mL/min) and AN69 filter (Hospal Filtral 12, 1.2 m2, Hospal Industrie, Meyzieu, France). All HD and HDF spent dialysate and all 24 hr CAPD effluents were collected; oxalate concentration was measured by high performance liquid chromatography (HPLC) using an ion exchange column. Both oxalate flux and total extraction were statistically higher during HDF treatments (HDF = 1.87 +/- 0.77 mg/min and 335.9 +/- 131.5 mg/session, respectively; HD = 0.99 +/- 0.74 mg/min, 226 +/- 153 mg/session, respectively; p < 0.02). The positive interaction of convective and diffusive fluxes probably played a major role in oxalate removal during treatment with a high convective component; solute-membrane interactions can occur by using either cellulosic or synthetic fibers. In CAPD patients, oxalate removal (76.42 +/- 50.85 mg/day) was lower than in patients on either HD or HDF, although weekly oxalate extraction was statistically no different between CAPD (535.46 +/- 356 mg/week) and HD (677.72 +/- 460.82 mg/week). It was concluded that HDF is more effective than HD or CAPD in oxalate removal. Long-term studies are needed to demonstrate whether these kinetic findings have clinical relevance.


Disordered breathing patterns during bicarbonate hemodialysis in COPD. Effect of cuprophane versus polysulfone membranes.

This study explored the breathing patterns and arterial blood gases before and during cuprophane (CU) bicarbonate and polysulfone (PS) bicarbonate dialysis in six chronic dialysis patients with mild chronic obstructive pulmonary disease (COPD). The studies were performed in random order during two consecutive dialyses. Breathing patterns were monitored by respiratory impedance plethysmography. Apneic episodes, defined as a decrease in tidal volume of 75% lasting 10 sec, were present before and during hemodialysis. In these patients with COPD a high number of apneic episodes (17 +/- 6 [SE]) were observed during CU bicarbonate hemodialysis. Most of these episodes were central rather than obstructive in character. There were fewer events when the same patients were dialyzed with PS membranes (10 +/- 5; p = 0.05). The decrement in PO2 (baseline to 60 min) was 17 +/- 7 during CU and 4 +/- 5 mmHg during PS dialysis (p = 0.10). Minute ventilation decreased in four of six patients on CU bicarbonate and increased in all six patients on PS bicarbonate. It was concluded that bicarbonate hemodialysis does not completely prevent hypoxemia or apnea during dialysis in patients with COPD. Apneic episodes and hypoxemia appear to be less severe during PS bicarbonate than during CU bicarbonate hemodialysis.


Prevention of hemodialysis associated hypoxemia by use of low-concentration bicarbonate dialysate.

Hypoxemia during acetate dialysis is caused by hypoventilation due to bicarbonate loss across the dialyzer and its regeneration from acetate by a CO2 consuming process. Loss of bicarbonate is prevented by using a bicarbonate containing dialysate, but hypoxemia is still found by many authors. In the current study, ten patients were dialyzed twice against acetate dialysate, high concentration bicarbonate (36 mmol/L), and low concentration bicarbonate (29 mmol/L) dialysates. A significant decrease in PO2 was found during both acetate and high concentration bicarbonate dialysis. Hypoxemia was prevented by low concentration bicarbonate dialysate. A possible explanation for the hypoxemia in high concentration bicarbonate dialysis may be hypoventilation induced by alkalosis. It was concluded that low concentration bicarbonate dialysate prevents hypoxemia during hemodialysis.


Effect of endotoxin clearance using whole body rinse-out on some blood-gas and metabolic parameters in rats.

Conscious and unrestrained male Wistar rats were infused over a 10 min period with 60 mg/kg Escherichia coli endotoxin (LD100) and observed for 6 hr. Hypotension, metabolic acidosis, hyperlactemia, hypoglycemia, and elevated oxygen extraction from blood developed in the rats. Another group of rats was subjected to blood substitution with FC-43 emulsion (artificial blood) 30 min after endotoxin application until hematocrit dropped to 3%, after which 6-9 ml of donor blood was exchange transfused with the emulsion. This method resulted in 98% endotoxin clearance, improved blood alkaline reserves, preserved blood glucose, and normalized arterial mixed venous oxygen gradient and O2 extraction from the blood (which implies preserved blood circulation status). Side effects included hypotension, a transitory rise in blood lactate level, and a fall in arterial oxygen content due to the lower hemoglobin (erythrocyte) level.


Influence of aspirin and carbacyclin on bovine platelet function.

Cows, calves, and sheep are the animals of choice for in vivo studies on total artificial hearts. In this study, the response of human and bovine platelets to agonists and antagonists was followed. Epinephrine and arachidonate failed to cause aggregation of bovine platelets. Exposure of bovine platelets to prostaglandin E1 (PGE1) resulted in inhibition of response to the action of adenosine diphosphate (ADP). Although epinephrine restored the response of PGE1 treated human platelets, it failed to restore the sensitivity of bovine platelets to the action of ADP. Exposure of bovine platelets to aspirin (100.0 mumol/L) or administration to calves intravenously (10.0 mg/kg) inhibited platelet cyclo-oxygenases. Infusion of carbacyclin (U55185) inhibited the ex vivo platelet response to the action of ADP. Results of this study demonstrate that the response of bovine platelets to agonists such as epinephrine, arachidonate, and the endoperoxide mimetic, U46619, is severely compromised. The authors' observations in this study, as well as earlier findings demonstrating the inability of bovine platelets to fully spread on a surface, suggests that the cow may not be an appropriate "model" for evaluating thrombogenicity caused by artificial organs and implants.


Peritoneal transfer of carbon dioxide in the rat.

In the authors' previous rat studies (Kidney Int 39: 608-617, 1991), peritoneal clearances (Cp) representing near exclusively diffusive CO2 transfer were evaluated: for isosmotic (0.37% dextrose) and hyperosmotic (15% dextrose) solutions with pH 7.2-7.3, Cp CO2 were 1.20 +/- 0.08 and 1.84 +/- 0.04 ml/min, respectively. In the present studies peritoneal transfer parameters (D/B, Cp) of CO2 gas, HCO3-, and total CO2 (tCO2) in anesthetized rats have been compared (n = 22) using solutions with dextrose contents as mentioned above but with a pH of 6.5 or 7.6; how much Cp CO2 measurements obtained with solutions at these pH values differ from Cp shown earlier with solutions of pH 7.2-7.3 has also been evaluated. When the pH was the same, transfer parameters of CO2 gas, HCO3-, and tCO2 were significantly higher under hyperosmotic conditions. The use of solutions with a pH different from 7.2-7.3 resulted in higher Cp of CO2 gas: with isosmotic solutions at pH 6.5 and 7.6, mean increases were 25 and 75%, respectively; with hyperosmotic solutions respective increases were 45 and 134%. The authors conclude that dialysis solution pH, especially under hyperosmotic conditions, significantly changes parameters of diffusive CO2 transfer in the rat. For evaluation of peritoneal blood flow from diffusive transfer parameters of CO2 gas, smaller overestimation can be expected when dialysis solution pH is slightly under than overadjusted compared to blood pH.


Influence of recombinant interleukin-2 and tumor necrosis factor-alpha on the development of ethyl nitrosourea-induced brain tumors.

Using the experimental model of brain tumors induced by ethyl-nitrosourea (ENU), human recombinant interleukin-2 (rIL-2) and tumor necrosis factor-alpha (TNF-alpha) were administered to Wistar rats in early stages of carcinogenesis. The results obtained suggest that IL-2 does not influence the development of nervous system tumors. In contrast, TNF-alpha was capable of modulating the development of ENU-induced tumors, producing a reduction in the number of schwannomas and a delay in the appearance of intraparenchymatous brain tumors.


Cardiac output regulation in the moving actuator total artificial heart without a compliance chamber.

A new cardiac output regulation method for the moving actuator total artificial heart (TAH) has been developed without using an extra compliance chamber or any transducer. The left and right ventricular sacs are alternately pumped by the pendulous moving actuator, with the left sac attached to the actuator and a free right ventricle. Preload sensitive cardiac output response is achieved by adjusting heart rate just below the level needed to generate atrial collapse, while maintaining full-fill and full-ejection conditions. The motor current waveform analysis detects mild atrial suction related to the amount of venous return. In addition, the structural characteristic of the pendulous moving actuator allows for manipulation of the left and right ventricular output difference by adjusting the asymmetry of stroke angle to either the left or right. In mock circulatory system tests, cardiac output increased from 5 to 9 L/min, with left atrial pressure (LAP) maintained at approximately 5 mmHg higher than right atrial pressure (RAP) over a physiologic range of preload (0-12 mmHg of RAP) and afterload [80-120 mmHg of aortic pressure (AoP)].


HL-60 cells isolated for resistance to vincristine are defective in 12-O-tetradecanoylphorbol-13-acetate induced differentiation and the formation of a functional AP-1 complex.

HL-60 cells isolated for resistance to vincristine are multidrug resistant and defective in the cellular accumulation of drug. Further studies demonstrate that these cells are also highly defective in 12-O-tetradecanoylphorbol-13-acetate (TPA) induced differentiation to macrophages. Analysis of this system demonstrates that certain protooncogenes which may contribute to differentiation are expressed at similar levels in sensitive and resistant cells. Thus, treatment of cells with TPA results in a reduction in the levels of c-myb and c-myc mRNA, while the expression of c-fos, c-jun, and junB is greatly enhanced. Immunoprecipitation experiments also demonstrate a TPA induced increase in the c-jun protein in both sensitive and resistant cells. Gel mobility shift assays show that TPA induces AP-1 formation in sensitive cells, whereas in parallel experiments with the HL-60/Vinc isolate, AP-1 is essentially absent. It has been found, however, that in resistant cells which have reverted to drug sensitivity, the levels of TPA inducible AP-1 is essentially identical to that of sensitive cells. Revertant and sensitive cells differentiate at similar levels in the presence of TPA. These studies therefore demonstrate that HL-60/Vinc cells are defective in the TPA induction of a functional AP-1 complex and that this may account for the inability of these cells to differentiate to macrophages. The molecular basis of the finding that AP-1 is not formed in resistant cells remains to be determined.


Hepatocytes from rat liver perfusions. Physicochemical effects on polyribosome size.

Hepatocytes have been used extensively both in vitro and in vivo for a wide variety of studies. Although isolated hepatocytes appear similar to their in vivo counterparts, they are different in some respects. One aspect in which they differ is their ability to translate proteins. The isolation process appears to inflict sufficient damage to reduce the average polyribosome size within the isolated hepatocytes and this size reduction correlates with a lower rate of protein production. Two methods of liver perfusion that better maintain the normal distribution of polyribosomes are described in this report. It is clear from these studies that new isolation methods that result in high yields of viable hepatocytes that function maximally are needed.


Measurement of folylpolyglutamate synthetase activity in head and neck squamous carcinoma cell lines and clinical samples using a new rapid separation procedure.

The activity of folylpolyglutamate synthetase was measured in extracts of head and neck squamous carcinoma cell lines and in surgical specimens utilizing a new rapid method to separate free [3H]glutamate from [3H]glutamate incorporated into methotrexate, used as a substrate for the enzyme. The validity of this new method, based on reversed phase chromatography via a Sep-Pack C18 cartridge, was observed between both methods, but the Sep Pack C18 assay has the advantage that it can be accomplished in less than 5 min, whereas the DE-52 procedure requires approximately 2 hr. In seven head and neck cell lines, activity of folylpoly-glutamate synthetase varied from 335-1305 pmol [3H]glutamate incorporated/mg protein/hr. In nine head and neck tumor biopsies, a broad range in activity of folylpolyglutamate synthetase was observed (25-1827 pmol/mg/hr) which partly overlapped the enzyme activity in 'normal' tissue (7-297 pmol/mg/hr). For six patients, folylpolyglutamate synthetase was measured in the center of the tumor, in the transitional region from tumor to 'normal' tissue, and in the 'normal' tissue. The enzyme activity was higher in tumor tissue vs 'normal' tissue in four of six cases, whereas in all cases, the enzyme activity in the transitional region was higher than in 'normal' tissue. The results of this study provide further support for the concept that putative differences in folylpolyglutamate synthetase activity between tumor tissue and normal tissue can be exploited to improve the effectiveness of antifolate-based chemotherapy in general, and in head and neck cancer in particular.


Comparison of a new venous control device with a bladder box system for use in ECMO.

During extracorporeal membrane oxygenation (ECMO), forward pump flow must not be allowed to exceed the rate of blood drainage from the patient so that excessive negative pressure does not develop within the ECMO circuit or in the patient's right atrium. A distensible reservoir ("bladder") and mechanically actuated electronic switch ("bladder box"), has typically been used for this purpose. If the rate of blood flow from the patient to the pump is insufficient to support the perfusion rate desired and adjustments in volume status and catheter position do not increase blood drainage, the only recourse is to increase the siphon pressure by elevating the patient. At the author's institution, a novel venous control module (VCM), without a reservoir, that can provide increased venous drainage without elevating the patient is used. Using an in vitro model of neonatal ECMO, the authors' compared their VCM to a commercially available "bladder box" system. Pressures were monitored in a collapsible chamber inside a water bath (simulating the right atrium), at the gravitational high point of the ECMO circuit ("neck site") and at the low point of the circuit ("venous site") at flow rates of 100, 450, 900, and 1,300 cc/min. Pump shut-off characteristics for both systems were also measured with either sudden interruption of venous drainage ("cross-clamping") or restriction of venous inflow ("hypovolemia"). Under continuous flow conditions, higher flows could be achieved with the VCM. With acute venous catheter occlusion, instantaneous ("trough") pressures at the neck site were lower, and venous monitoring site pressures were higher with the bladder box system.(ABSTRACT TRUNCATED AT 250 WORDS)


Therapeutic trials on progressive muscular dystrophy.

The special medical care in the National Sanatorium prolonged the life span of the patients with progressive muscular dystrophy from 15.8 years to 20.4 years over the last 20 years. Various new drug trials for muscular dystrophy have been implemented in the last 12 years in Japan. Bestatin and Loxistatin, protease inhibitors, showed definite improvement on dystrophic mice or hamsters, animal models of muscular dystrophy. However clinical application of these drugs failed to prove the effects on patients with Duchenne muscular dystrophy. The difficulty of clinical evaluation and judgement of effects in progressive neurological diseases is discussed.


Glucose-insulin kinetics of the extravascular bioartificial pancreas. A study using microencapsulated rat islets.

The success of the extravascular bioartificial pancreas (BAP) is contingent on the rapid transfer of the glycemic signal across both an extravascular compartment and a semipermeable membrane and of insulin from the BAP to the recipient. To examine the possibility of microencapsulated islets such as the BAP to achieve satisfactory in vivo glucose-insulin kinetics, islets were isolated from Lewis rats, encapsulated in poly-L-lysine-alginate membranes, and isogenically transplanted into the peritoneal cavity of 14 streptozotocin induced diabetic rats. Fasting blood glucose (BG) was measured and intravenous glucose tolerance was tested at 8-10 weeks and compared with three control groups: 1) normal Lewis rats (n = 6); 2) untreated diabetic rats (n = 5); and 3) diabetic rats that received intraperitoneal implants of empty capsules (n = 4). Ten animals that received microencapsulated islets (5,271 +/- 431) promptly became normoglycemic, with a mean BG of 128 +/- 17 ng/dl 3 days after transplantation and maintained this level > 100 days. Intravenous glucose tolerance K-value for the group was 3.84 +/- 0.32 compared with 3.96 +/- 0.39 (p = 0.83) for the normal control group, and 0.60 +/- 0.12 (p < 0.01) and 0.40 +/- 0.15 (p < 0.01) for the diabetic control groups with and without empty capsules. The authors conclude from these results that, given sufficient beta-cell mass, a BAP without any vascular access can respond appropriately to an increase in blood glucose concentration, without overshoot hypoglycemia and within a lag lapse compatible with normal physiologic insulin delivery.(ABSTRACT TRUNCATED AT 250 WORDS)


Acute and chronic eosinophilic pneumonia: clinical evaluation and the criteria.

The clinical courses of 11 cases of eosinophilic pneumonia which were clinico-pathohistologically diagnosed and found to be unassociated with organic disorders producing peripheral blood eosinophilia were extensively investigated and compared with various types of eosinophilic pneumonia previously reported. Five cases of acute eosinophilic pneumonia fulfilled the following criteria: 1) less than a one-month history of symptoms prior to diagnosis, 2) a short clinical course and 3) no recurrence. Six cases of chronic eosinophilic pneumonia fulfilled the following criteria: 1) more than a two-month history of symptoms prior to diagnosis, 2) a prolonged clinical course and 3) recurrence. The results suggested that various types of previously reported eosinophilic pneumonia classified by sex, the presence or absence of peripheral blood eosinophilia, the degree of clinical symptoms or peripheral blood eosinophilia, and the degree of abnormalities on chest X-ray films should be extensively reevaluated.


Selective IgM deficiency: functional assessment of peripheral blood lymphocytes in vitro.

The functional aspects of the peripheral blood lymphocytes from 6 patients with primary selective IgM deficiency (sIgMD) were analyzed to elucidate its pathogenesis. The surface IgM positive B cells were present at almost the same percentage as in controls, but the percentage of cluster of differentiation (CD)4+ T cells was higher and that of CD8+ T cells was low. The patient B cells showed a significantly lower proliferative response to Staphylococcus aureus Cowan strain I (SAC) than control B cells and did not produce a significant amount of IgM when co-cultured with control T cells. Interestingly, mitomycin C (MMC)-treated patient T cells induced a greater amount of IgM production by control B cells. In addition, patient B cells treated with SAC and B cell differentiation factors (BCDF) failed to secrete IgM. These results suggest that the pathogenesis of sIgMD may be mainly due to an intrinsic defect in B cell maturation.


Administration of GSH has no influence on the RBC membrane: oxidative damage to patients on hemodialysis.

In patients on hemodialysis, a metabolic block of the pentose phosphate shunt has been described that impairs the reduction of oxidized glutathione. The block results in lack of detoxication of the free hydroxyl radicals produced inside the red blood cell (RBC) and causes oxidative damage to the polyunsaturated fatty acids of the RBC membrane that results in formation of aldehydes. Malonyldialdehyde has been used as an index of the oxidative damage. In a study group of 13 patients on hemodialysis, the authors have tested whether administering reduced glutathione (GSH) at 1200 mg/day for 1 month could minimize oxidative damage to the RBC membranes and improve the hematologic parameters. Treatment with GSH was followed by significant improvement of hematocrit (P = 0.008), hemoglobin (P = 0.03), and RBC count (P = 0.0037); however, oxidative damage to the membranes was increased (P = 0.0004), which suggests that improvement of the hematologic parameters is not related to reduction of the oxidative damage. This is because oxidized glutathione, formed in the oxidative process, cannot be reduced back to GSH because of alteration of the pentose phosphate shunt.


Identification and certification of extracorporeal membrane oxygenation specialists in the United States.

Extracorporeal membrane oxygenation (ECMO) is a highly specialized technique widely practiced in many hospitals. Despite the proliferation of ECMO, little information has been generated relating to ECMO specialists, a new professional group responsible for managing the extracorporeal life support (ELS) system. A telephone survey of ECMO centers in the United States was conducted to determine the number of ECMO specialists, team composition by profession, and clinical components of ECMO specialist certification. Data were obtained in May 1991 from all 63 (100%) active ELS centers. The survey found that the average ECMO program performs 3,770 +/- 1,019 clinical hours of ELS per year with a team of 23 +/- 11 specialists. There are 1,431 practicing ECMO specialists in the United States: 73% registered nurses, 22% respiratory therapists, and 5% others. Most ECMO specialist teams (56%) are comprised of a single profession, with 44% of programs using a mixture of professions. The average ECMO specialist manages the ELS system 171 +/- 91 hr/yr. Thirty-six (57%) programs have a mean yearly clinical requirement of 77 +/- 23 ELS hours per specialist. These results represent the first complete report identifying the number of ECMO specialists in the United States. In addition, program demographics demonstrate variability in ECMO experience and certification requirements.


Ten-year follow-up of Japanese overweight subjects with impaired glucose tolerance: identification of a diabetes-prone subpopulation.

Ninety-four overweight subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) were followed for 10 years. No one from the NGT group developed diabetes, however 32% of the IGT subjects did develop diabetes. Initial data of the IGT subjects who developed diabetes were significantly different from those who did not develop diabetes. Fasting, peak and/or sigma plasma glucose (PG), IRI and CPR at 180 minutes and CPR/IRI at 0 and 180 minutes were increased, and the peak time of PG was delayed; also the prevalence of a positive family history was higher, and the body weight heavier. Seventy-nine percent of IGT subjects with the initial sigma PG of greater than or equal to 40 mM or a positive family history developed diabetes whereas only 3% of those with sigma PG of less than 40 mM and a negative family history developed diabetes. Therefore, it might be considered that among the overweight adults with IGT, those with sigma PG of greater than or equal to 40 mM or a positive family history are diabetes prone and those with sigma PG of less than 40 mM and a negative family history are diabetes resistant.


The role of recombinant human tissue-type plasminogen activator in the treatment of acute pulmonary thromboembolism.

The effect of intravenous recombinant human tissue-type plasminogen activator (tPA) on arterial blood gases was compared with the effect of heparin treatment in acute pulmonary thromboembolism. Fifteen patients received heparin alone (group A), 5 cases were treated with 7.7 x 10(6) I.U. of tPA (group B) and 10 cases with 15 x 10(6) I.U. of tPA (group C) combined with heparin treatment. Arterial oxygen tension before treatment was not significantly different among the three groups. PaO2 was dramatically improved on the 1st day in group C. By the 7th day, PaO2 of group B had improved to the level of group C. However, the PaO2 of group A on the 7th day was not significantly different compared to the pre-treatment value. In group C, post-treatment perfusion lung scintigrams were improved compared to the pre-treatment images, but this was not the case in group B. Treatment with tPA is more effective for acute pulmonary thromboembolism than heparin alone and a high dose of tPA (15 x 10(6) I.U.) leads to rapid improvement in arterial blood gases and lung perfusion images.


Ataxic hemiparesis following thalamic lacunar infarction.

A 60-year-old man developed left hemiparesis and homolateral ataxia with normal sensation and normal somatosensory evoked potentials. A lacunar infarct with gadolinium enhancement in the right dorsolateral part of the thalamus was demonstrated on magnetic resonance imaging. Thalamic lesion is a relatively rare cause of ataxic hemiparesis; most of the reported cases of ataxic hemiparesis caused by thalamic lesion were accompanied by sensory disturbances. This is an interesting case which suggested that the thalamic lesion could be responsible for the ataxic hemiparesis without a sensory disturbance.


Periodic fever compatible with familial Mediterranean fever.

A 55-year-old male presented with a recurrent fever of over 38 degrees C, occurring at irregular intervals 1-6 times a month with chest, back or abdominal pain. After admission to our hospital, we found the following characteristics: 1) the febrile attacks were accompanied by obvious inflammatory findings and pleuritis or peritonitis; 2) the patient's elder sister had a similar periodic fever; and 3) there were no apparent causative factors responsible for his symptoms. Therefore, we diagnosed this as a case compatible with familial Mediterranean fever. The febrile attacks have been completely suppressed by daily colchicine. This is the seventh case of familial Mediterranean fever reported in Japan.


Portal hepatic venous shunt via an intrahepatic portal vein aneurysm.

A rare case of portal hepatic venous shunt (PHVS) via an intrahepatic portal vein aneurysm (PVA) is presented. A 66-year-old man was admitted for examination of a mass in the liver. Ultrasonography demonstrated a cystic lesion (15 mm in diameter) at the posterior superior segment of the right hepatic lobe which communicated with the right portal vein (RPV) and right hepatic vein (RHV). Superior mesenteric portography showed a biloculate aneurysm in RPV and PHVS. Color doppler ultrasonography indicated that flow in the tracts entered the aneurysmal cavity from RPV and drained into RHV.


Hyperparathyroidism associated with parkinsonism.

A 70-year-old woman with hyperparathyroidism associated with parkinsonism is reported. Her primary initial symptom was parkinsonism, but it was levodopa-resistant. Chemical and hormonal findings revealed that she had hyperparathyroidism. The symptoms were relieved after the surgical removal of a parathyroid adenoma. Although this type of case has been reported only rarely, it suggests that hypercalcemia might be an aggravating factor in levodopa-resistant parkinsonism.


Noonan syndrome presenting growth hormone neurosecretory dysfunction.

Noonan syndrome has been diagnosed by the characteristic physical stigmata for more than two decades. Recent studies of growth hormone secretory pattern provide a new category of growth hormone neurosecretory dysfunction to characterize short stature. We describe herein a case of growth hormone neurosecretory dysfunction in a 16-year-old boy with Noonan syndrome. Growth hormone neurosecretory dysfunction was diagnosed primarily based on the low amplitude and small numbers of the spontaneous bursts of growth hormone secretion during 12-hour nocturnal growth hormone sampling. Treatment with synthetic human growth hormone has markedly accelerated the growth velocity for one year and a half. This case notes the wide spectrum of short stature in Noonan syndrome and the effectiveness of treatment with human growth hormone.


Klinefelter's syndrome accompanied by diabetes mellitus and diabetes insipidus.

The first case of Klinefelter's syndrome accompanied by diabetes insipidus and diabetes mellitus is reported. A 41-year-old man admitted for hyperosmolar diabetic coma with a past history of diabetes insipidus was diagnosed as having Klinefelter's syndrome by endocrinological examination and sex chromosome analysis. In this case, glucose tolerance test was normalized half a year later and blood glucose was well controlled with diet therapy alone.


Quadriceps myositis.

A young woman with slowly progressive muscular weakness and atrophy localized in both thighs is reported. Laboratory, electromyographic and histological findings suggested that the patient suffered from chronic myositis with a background of autoimmune disorder. Quadriceps myositis is a rare condition. The previously reported cases of this disease in the literature are reviewed.


Fatal pneumonia caused by Corynebacterium group JK after treatment of Staphylococcus aureus pneumonia.

A 76-year-old man who was admitted to the hospital because of chronic renal insufficiency and chronic hepatitis died of Corynebacterium group JK pneumonia, after showing a slight improvement by treatment of Staphylococcus aureus with sulbactam/cefoperazone and minocycline. Transtracheal aspiration (TTA) just before his death revealed numerous gram-positive bacilli phagocytized by many neutrophils and more than 10(8) colony forming units (CFU)/ml of Corynebacterium group JK. A drug susceptibility test showed Corynebacterium group JK was resistant to many antibiotics, with the exception of vancomycin and amikacin.


Pseudomembranous bronchitis (non-diphtherial) resulting in sudden death: an autopsy report.

A 69-year-old woman was admitted because of dyspnea. Thereafter, she fell into a state of shock. Resuscitation was attempted but she did not respond to it and died on the second hospital day. According to the autopsy findings, a wide range of area from the larynx to the trachea was covered with pseudomembrane. In the culture of bacteria, alpha Streptococcus and Corynebacterium genus (non-diphtherial) were all that was detected. These findings suggest that pseudomembranous lesion, an endogenous foreign matter of the air passage should be suspected when a patient presents with sudden dyspnea.


Multiple myeloma complicated by congestive heart failure following first administration of recombinant alpha-interferon.

A 59-year-old female was admitted to Tsukuba University Hospital and diagnosed as IgA-lambda multiple myeloma (stage IIIA). No cardiovascular disorder with the exception of minor ischemic changes in ECG was revealed before treatment. Recombinant human alpha-interferon (IFN) at a dose of 3 million units combined with melphalan and prednisolone was administrated. Sixteen hours after the first administration of IFN, IFN was suspended by the symptoms of congestive heart failure (CHF). Treatment with diuretics and catecholamine products showed almost complete recovery from CHF in 3 weeks. An adverse reaction to IFN was strongly suspected as the cause of CHF.


Inflammatory pseudotumor of the spleen.

The case of a 39-year-old man with inflammatory pseudotumor of the spleen is presented. This is an extremely rare benign lesion with histologic features of non-specific inflammatory and reparative changes. The literature is reviewed and this case is compared clinically and radiologically with the previously reported cases.


Pulmonary intralobar sequestration accompanied by aneurysm of an anomalous arterial supply.

A 47-year-old woman presented with hemoptysis and her chest X-ray films showed an opacity suggesting a mass in the left lower lung field. Based on radiographic investigations, the mass was diagnosed as an aneurysm develop in an anomalous vessel and was considered to be a Pryce type I pulmonary intralobar sequestration. Resection of the left lower lobes was performed and the aneurysm was found to be filled with thrombus. It is rare for an aneurysm to form in an aberrant vessel. This complication may have been the result of regional sclerosis affecting the anomalous artery as well as systemic atherosclerosis.


Rheumatoid nodules of the lung in a patient with palindromic rheumatism.

We report a case of rheumatoid nodules of the lung seen in a patient with palindromic rheumatism. A 54-year-old man with palindromic rheumatism was admitted for evaluation of three nodules in the right upper lobe on chest roentgenogram. Wedge resection was performed for the purpose of confirmative diagnosis and treatment. Histology of these lung lesions revealed palisaded histiocytic cells surrounding a layer of central necrosis, which were considered to be characteristic findings of rheumatoid nodule. Such a case is extremely rare. To our knowledge, only one other case has been reported before in the literature.


Serum interleukin-2 receptor and interferon-alpha levels in a patient with allergic granulomatous angiitis (Churg-Strauss).

A patient with allergic granulomatous angiitis accompanied by increases in serum interleukin-2 receptor (IL-2R) and interferon-alpha (IFN-alpha) levels is reported. Laboratory findings revealed leukocytosis with eosinophilia and increased serum IgE and IgG. The serum IL-2R and IFN-alpha were increased. The serum immune complex, interferon-beta, -gamma and complements remained at normal levels. The serum IgE, IgG, IL-2R and IFN-alpha correlated with disease activity. Immunofluorescent studies using frozen sections obtained from the dermal lesion showed no immunoglobulin or complement deposits on vascular walls. Measurements of serum IL-2R and IFN-alpha might be considered reliable serologic indicators of disease activity.


Hybridization fingerprinting of high-density cDNA-library arrays with cDNA pools derived from whole tissues.

As part of an integrated mapping and sequencing analysis of genomes, we have developed an approach allowing the characterization of large numbers of cDNA library clones with a minimal number of experiments. Three basic elements used in the analysis of cDNA libraries are responsible for the high efficiency of this new approach: (1) high-density library arrays allowing thousands of clones to be screened simultaneously; (2) hybridization fingerprinting techniques to identify clones abundantly expressed in specific tissues (by hybridizations with labeled tissue cDNA pools) and to avoid the repeated selection of identical clones and of clones containing noncoding inserts; and (3) a computerized system for the evaluation of hybridization data. To demonstrate the feasibility of this approach, we hybridized high-density cDNA library arrays of human fetal brain and embryonal Drosophila with radiolabeled cDNA pools derived from whole mouse tissues. Fingerprints of the library arrays were generated, localizing clones containing cDNA sequences from mRNAs expressed at middle to high abundance (> 0.1-0.15%) in the respective tissue. Partial sequencing data from a number of clones abundantly expressed in several tissues were generated to demonstrate the value of the approach, especially for the selection of cDNA clones for the analyses of genomes based on expressed sequence tagged sites. Data obtained by the technique described will ultimately be correlated with additional transcriptional and sequence information for the same library clones and with genomic mapping information in a relational database.


Mouse microsatellites from a flow-sorted 4:6 Robertsonian chromosome.

Twenty microsatellites were generated from a previously characterized lambda gt10 library containing C57BL/6J mouse DNA from a flow-sorted 4:6 Robertsonian chromosome. These sequences were analyzed for size variation between different strains of mice with the polymerase chain reaction (PCR) and mapped by use of either strain distribution patterns (SDPs) in recombinant inbred (RI) strains, or intra- and interspecific backcrosses. Eighty-five percent of the sequences showed allelic variations between different inbred strains of mice and the wild mouse, Mus spretus, and 70% were variant between inbred strains. Eight (62%) of the 13 repeats that have been mapped lie on Chromosomes (Chr) 4 and 6. This approach is an effective way of generating informative markers on specific chromosomes.


Genomic mapping by single copy landmark detection: a predictive model with a discrete mathematical approach.

One of the goals of the Human Genome Project is to produce libraries of largely contiguous, ordered sets of molecular clones for use in sequencing and gene mapping projects. This is planned to be done for human and many model organisms. Theory and practice have shown that long-range contiguity and the degree to which the entire genome is covered by ordered clones can be affected by many biological variables. Many laboratories are currently experimenting with different experimental strategies and theoretical models to help plan strategies for accomplishing long-range molecular mapping of genomes. Here we describe a new mathematical model and formulas for helping to plan genome mapping projects, using various single-copy landmark (SCL) detection, or "anchoring", strategies. We derive formulas that allow us to examine the effects of interactions among the following variables: average insert size of the cloning vector, average size of SCL, the number of SCL, and the redundancy in coverage of the clone library. We also examine and compare three different ways in which anchoring can be implemented: (1) anchors are selected independently of the library to be ordered (random anchoring); (2) anchors are made from end probes from both ends of clones in the library to be ordered (nonrandom anchoring); and (3) anchors are made from one end or the other, randomly, from clones in the library to be ordered (nonrandom anchoring). Our results show that, for biologically realistic conditions, nonrandom anchoring is always more effective than random anchoring for contig building, and there is little to be gained from making SCL from both ends of clones vs. only one end of clones.(ABSTRACT TRUNCATED AT 250 WORDS)


Mapping of the structural gene for S-adenosyl homocysteine hydrolase to mouse chromosome 2, and related sequences to chromosomes 8 and X.

Comparative mapping studies in human and mouse have shown that, to date, human Chromosome (Chr) 20 is completely syntenic with distal mouse Chr 2. The structural locus for S-adenosyl-L-homocysteine hydrolase (EC 3.3.1.1) in human, AHCY, maps to 20 qter-->q13.1, and we report here that the homologous locus in the mouse, Ahcy, maps to distal mouse Chr 2 with gene order Pcna-Ahcy-Ada. Analysis of 123 progeny of an interspecific backcross between a laboratory stock, AN, and Mus spretus using a rat cDNA probe revealed the presence of at least two other Ahcy-related sequences segregating independently in the mouse genome. One, Ahcy-rs1, was mapped to Chr 8 in the BXH recombinant inbred strains, and the other, Ahcy-rs2, shows a pattern of inheritance consistent with X-linkage.


Factors in biological fluids affect gel filtration behavior of epidermal growth factor.

There have been conflicting reports on the presence of multiple forms of epidermal growth factor (EGF) in human saliva. The present study was initiated to study the gel filtration behavior of EGF in saliva and other biological fluids. In addition, studies were performed to determine if there were factors in saliva or other biological fluids that would influence the gel filtration behavior of EGF. Gel filtration studies with saliva and urine demonstrated EGF migration consistent with a molecular weight of 35 kDa with no heterogeneity observed. The addition of radiolabeled EGF to either saliva or urine resulted in an altered migration on gel filtration. These results provide evidence for a protein-peptide interaction in saliva and other biological fluids that alters the apparent physical properties of mature EGF.


Compatibility of the S-(3-nitro-2-pyridinesulfenyl) protecting group with DCC/HOBt coupling chemistry.

Two recent reports on the partial lability of the 3-nitro-2-pyridinesulfenyl (Npys) thiol protecting group towards 1-hydroxy-benzotriazole (HOBt) have prompted a rechecking of the chemical behavior of this group. Using both soluble and polymer-bound forms of Cys(Npys) as test materials, the complete stability of this protection against HOBt has now been definitively established, and its compatibility with Boc-benzyl-based solid-phase synthesis strategies has been clearly confirmed by stability assays against a wide range of reagents, as well as by the successful synthesis of several Cys(Npys)-containing peptides.


Preference of human cdc2 kinase for peptide substrate.

Human cyclin B1-bound cdc2 kinase phosphorylated the threonine residue in the sequence -Thr-Pro-Lys-Lys-Ala- but hardly phosphorylated it in the sequence -Thr-Pro-Lys-Ala-Lys. The sequence -Thr-Pro-Ala-Pro-Lys-, as found in p53 protein, was also phosphorylated by this enzyme, but less efficiently than in the sequence described above. When the threonine residue in -Thr-Pro-Lys-Lys-Ala- was changed to a serine or a tyrosine residue, the enzyme phosphorylated the serine, but not the tyrosine residue. Changing the lysine next to the proline to alanine reduced its efficiency as a substrate. The peptide, Ala-Ala-Ala-Ala-Lys-Thr-Pro-Ala-Lys-Ala-Ala, containing the -Thr-Pro-Ala-Lys- sequence, but not the other lysine residues, was not used as a substrate by the kinase.


[Education and continued education in public health. Wishes and reality at the present time; demands for the future].

Sociomedicine in research and practice, i.e. in universities and in public health services, has experienced an upswing many had not expected. The health requirements of society and not only those of the individual have gained a new topicality as social factors were rediscovered in connection with health. Public health services can be advisors to politicians and defence attorneys for the population by assuming a new role and a new measure of self-understanding in the realisation of old but always fresh topics such as environmental medicine (formerly known as environmental hygiene). To translate the multitude of sociomedical tasks effectively into reality, the practically active sociomedical officer in public health services stands in need of the backing and help by sociomedical researchers in the relevant university departments. It will be imperative to achieve in future a greatly improved and closer cooperation between research and practice in sociomedicine.


N alpha-trifluoroacetylation of N-terminal hydroxyamino acids: a new side reaction in peptide synthesis.

In the synthesis of the double-chain bis-cystinyl hinge fragment 225-232/225'-232' of the human IgG1, which contains two N-terminal threonine residues, the final acidolytic deprotection step, with 99% aqueous trifluoroacetic acid, was accompanied by formation of remarkable amounts of an unknown side product. This has been identified as the N alpha-mono-trifluoroacetylated product; however, even bis-trifluoroacetylation was found to occur by prolonged exposure of the parallel dimer to the reaction medium. Similarly, the model compounds H-Thr(tBu)-Phe-OH, [Boc-Thr(tBu)-Cys-OH]2 and Boc-Thr(tBu)-Cys(StBu)-Ala-OH were acylated by treatment with trifluoroacetic acid at rates that suggest a rather pronounced sequence dependency. Since, on the other hand, the model compound [Boc-Ala-Cys-OH]2 was not trifluoroacetylated at all under identical conditions, the reaction has to proceed prevalently via intermediate formation of the trifluoroacetyl ester of N-terminal hydroxyamino acids, followed by O-->N shift according to the hydroxyoxazolidine mechanism. The experimental data indicate also that under favored conditions aminolysis of the trifluoroacetyl ester via an inter- or intramolecular pathway may contribute to the overall reaction rate.


[Educational emphasis at university centers].

In Germany four postgraduate courses in public health were set up since 1989. They all offer a public health training including research activities, field experience and international perspectives. The public health administration should decide in the near future whether this new training could be passed by the public health officers instead of the compulsory courses in the academies in Düsseldorf and München.


Use of 6 M HCl for removal of the N-alpha-tert-butyloxycarbonyl group during solid-phase peptide synthesis.

We describe the use of 6 M HCl to remove the Boc group in solid-phase peptide synthesis. Three peptides, 4-10 amino acid residues in length, have been successfully synthesized using 6 M HCl and were found to be comparable in purity to the same peptides prepared using the standard 50% trifluoroacetic acid in dichloromethane method of N-alpha-Boc removal.


Suppression of interleukin-1 action by phospholipase-A2 inhibitors in helper T lymphocytes.

The mechanism by which interleukin 1 (IL-1) and T cell receptor (TCR) activation co-stimulate T helper (Th) cells is not clear. In chondrocytes, fibroblasts and several other cell types, much of the evidence suggests a linkage between IL-1 action and increased phospholipase-A2 (PLA2) activity. Although Th cells have very low levels of PLA2, they are well known targets for IL-1. We studied the effects of PLA2 inhibitors, i.e., lipocortin-1 (LC-1) and the synthetic peptide antiflammin-P2 (AF-2), on the enhancing effect of IL-1 upon activation of TCR. When murine D10.G4.1 Th2 cells were stimulated by their clonotypic anti-TCR antibody 3D3, both LC-1 and AF-2 inhibited the biological response to IL-1. This blockade was not seen when D10 cells were induced to proliferate with interleukin-2 (IL-2) and 3D3 in the presence of the same inhibitors, LC-1 or AF-2. These results strongly suggest that PLA2 also plays a central role in mediating the actions of IL-1 in the helper T cell.


[Quality assurance: introduction and legal principles].

Quality assurance has been part of clinical medicine and public health for decades, but only recently have structured and well documented procedures of quality assurance been introduced. Industry has been a model. Since 1. 1. 1989 quality assurance in Germany has been a legal requirement for a wide range of health services. Structure, process and outcome as part of quality assurance is defined as well as criteria, standards and norms. The development of quality assurance in Germany is described. The importance of quality assurance for the efficacy, efficiency and the aim-orientated work of the public health services and for the medical service of the compulsory health insurance is stressed.


Solution synthesis of calciseptine, an L-type specific calcium channel blocker.

Calciseptine, an L-type specific calcium channel blocker consisting of 60 amino acid residues with four intramolecular disulfide bonds, was synthesized by the solution procedure applying our maximum protection strategy. The recently developed solvent systems used were a mixture of chloroform or dichloromethane and trifluoroethanol; they were useful for the synthesis of slightly soluble protected peptides. After removal of all the protecting groups by our two-step HF procedure followed by treatment with mercuric acetate, the peptide was folded into its native form by air oxidation, in which redox reagents were necessary to accelerate the correct disulfide bond formation. The product was purified to homogeneity and found to block contractions of the rat thoracic aorta induced by 40 mM K+ with the same potency as that of the natural product. In addition, this peptide was found to block contractions of various rat smooth muscle preparations as well as increase in cytosolic free calcium concentration induced by a high concentration of extracellular K+.


Copper (II) complexes as a laccase model in the catalytic removal of the phenylhydrazide protecting group under mild oxidative conditions.

Copper (II) complexes, with nitrogen-containing ligands (pyridine and imidazole), simulate perfectly the catalytic activity of laccase in the oxidative removal of the phenylhydrazide protecting group. Deblocking occurs under mild conditions, preventing the oxidation of labile amino acids. The effect of certain factors on the rate of deblocking and the degree of conversion were studied, and optimal conditions providing 100% yield of the deblocked products were chosen.


[Quality assurance in the public health office].

Quality is assured not only by long-standing experience; it must be continually safeguarded. Preconditions are as follows: qualified training with scientific background and continual scientific supervision; regular continuing education via exchange of experience; standardising of methods on a intra-office level and by inter-office exchange on Lander level; internal and external cooperation; validity and plausibility controls; interdisciplinary cooperation. These principles are discussed by means of examples of health protection--health protection on environmental protection principles--expertising--medical statistics/health planning--health care aid/health advisory service.


[Health promotion by the public health service (with special reference to promoting the self help movement)].

During the last decade there has been a new orientation in public health policies. The question of prevention is gaining importance and has assumed social and political dimensions alongside the traditional medical issues. In future the public health service will increasingly recognise the value of an interdisciplinary approach, as was emphasised in a Resolution by the 64th German State Health Ministers' Conference. The need for cooperation and coordination in important future fields of action--especially the area of Self-Help--is presented as a major challenge for the Public Health Department. Details are given on the new requirements in terms of organisation, staffing and facilities.


[High immunization rates--how can they be achieved at all?].

High rates of immunization are achieved not only by compulsory vaccination. Strict discipline is necessary as well as motivation of medical assistants and of patients in their social environment. All people have a natural instinct for protecting themselves against risks of life. This instinct can in fact be stimulated by repeated motivation and can be enforced by propaganda. The process of propaganda alone cannot stimulate urges. Strategy of immunization must be standardised in all districts of the Federal Republic. This means: immunisation schedule, information of patients, children and of their parents. This is part of discipline of vaccination, same as is the permanent training of medical staff. They should be sent to seminars and training workshops. Specialist opinions must be differentiated as to whether they are scientists or articulate their own and personal opinion or whether their attitude is conditioned by general medical considerations. Any legal claims arising from vaccination accidents would be decided 'in dubio pro aegroto'.


[Vaccination against Haemophilus influenzae B and rubella].

Haemophilus influenzae B was the most frequent pathogen of bacterial meningitis in childhood during the mid-eighties to the end of the eighties of the present century, taking the place of meningococci since approximately 1984 at about twice the rate of that pathogen, as shown by the records kept during 1980-1990 in Bavarian Departments of Paediatrics. In fact, in 1990 the incidence of HIB meningitides was about 2.5 times that of meningococcus meningitides (85 vs. 34, respectively). For practically 2 years now vaccination against HIB is being publicly recommended and should be made use of as intensively as possible to prevent all HIB infections. For several years the principle of on-target rubella vaccination has been applied to schoolgirls in Lower Saxony, Bremen and Hamburg to prevent rubella embryopathy, a procedure that has proved much more successful than blank vaccination. None of the other Federal German Laender have been following this procedure to date; in consequence there of, although the strategy of on-target vaccination will be continued in Lower Saxony, greater uniformity and greater efficiency are being aimed at throughout Germany by public recommendation of rubella vaccination at an infant age.


[Between isolation and acceptance--hepatitis B and AIDS in community facilities].

Both Hepatitis B and the HIV-infection are spread either through blood or sexual contact. The danger of these infections spreading in day nurseries and schools is very remote but nonetheless there are confused fears. These fears lead to isolation and enormous problems for the carriers, who, for the most part, are children but can also be adults. As far as Hepatitis B, HIV and AIDS are concerned there are clear scientific recommendations for those attending these social institutions. Such recommendations have been published in decrees by the responsible ministries of the Länder of the Federal Republic of Germany. These decrees enable infected children and adolescents to lead an accepted life within the community. They reduce the remaining extremely small risk of transmitting the diseases to a level that is in fact lower than the general risk of every-day life and can be tolerated in an empathic society.


[The epidemiology of whooping cough].

Due to a low acceptance of active immunisation against Bordetella pertussis, whooping cough continues to be a frequent childhood disease in parts of Germany. The age distribution in the lower Rhine area showed a peak incidence at 4.3 years of age, whereas 11% of all cases were observed in infants, and 6% were observed in adults. A significant sex difference was not found in children suffering from pertussis; in adult patients, however, women were more often affected. Whooping cough occurred during the whole year, its peak incidence was found during early winter. In children, paroxysmal coughing fits, vomiting and whooping were the primary symptoms of disease; adults and infants, however, developed these symptoms only in reduced frequency. About 25% of all cases showed an atypical course, and could only be diagnosed by laboratory tests. While leukocyte count and ESR did not have diagnostic significance, a combination of microbiological and serological tests showed a high diagnostic sensitivity and specificity. In contrast to the former GDR and to most European neighbours, the former Federal Republic overrated the side effects of active vaccination as compared to the various risks of natural infection. This resulted in a decline of vaccine acceptance to less than 10% in several areas of the former FRG. It is anticipated that the altered recommendation in favour of vaccination, and especially the future application of acellular vaccines with less side effects, will result in the elimination of whooping cough in all areas of Germany.


[Rehabilitation of handicapped children as the combined responsibility of medicine and pedagogics--approach and contradictions in the process of integrated education].

The development of common education of handicapped and non-disabled children in kindergartens and schools has removed all doubt that disabled children are encouraged and helped to a considerable degree whereas non-disabled children acquire more social aptitude. In no case need one fear that their learning performance is negatively affected by integrated education. This is of course conditional on the availability of suitable conditions under which such integrated education takes place. The medical profession as a whole did not participate in the development and testing of integrative models and test projects. The main reasons for this are difficulties in communication between physicians and educationists, which require to be discussed. The article describes the need for cooperation by physicians in further development of integrative measures, their possibilities of influencing the development, and their special task in cooperating with educational experts, from a paedogical aspects; finally, the sociopolitical and medicopolitical tasks of the medical profession in Public Health services are pointed out.


[Responsibilities of pediatric medicine in integrated rehabilitation of handicapped children in Bremen].

Integrated education of handicapped children in Bremen is both goal and method. In the case of infants (0-3 years old) integration means integrating the child into the family by working with and within the family; for pre-school children (3-6 years old) this means education with non-handicapped children in a pre-school setting; integration in school settings using various approaches is still a goal. Integrated education is understood as a multi-disciplinary approach with the necessary inclusion of sociopaediatric competencies. The contribution to the concept of integration by paediatricians in Bremen is presented in this article. The work described is viewed as a perfect fit for paediatricians in the Public Health Services if they have the necessary preliminaries in self-understanding and qualification.


[Psychological testing within the scope of social psychiatric service].

As a psychologist working within the Social Psychiatric Service I find myself exposed to certain assignments and methodological expectations. One of the most common images is that of a "trick- and test specialist" that most of the time would appear along with multitude of open and hidden fantasies towards psychological methods of testing. It's not always easy to meet such expectations appropriately. But due to the severe consequences that may arise from statements of the Service we have to emphasise the limitations of such means of assistance. The mathematical operations of test constructors may be extraordinarily brilliant; the possibilities of transforming psychic phenomena into abstract numbers create however, as many complications as the choice of social scales and standards we have to make for our measurements. Hence, psychological results will still have to follow several different steps of examination that are reciprocally related to each other, even when using methods that seem to provide more comfortable, easier solutions.


[Prostitution--a sequela of sexual abuse].

AIDS has consolidated the isolated state of prostitutes and stigmatized them as HIV carriers. Due to the threat of AIDS, the Berlin senate has worked out a programme for prostitutes. For the programme to succeed, knowledge of the causes of prostitution is a prerequisite, such as sexual abuse during childhood and adolescence. The sexually abused who have gone without psychological help are prone to prostitution. The work and its evaluation by a psychologist is presented to help counselling Services on Venereal Diseases in their work.


[AIDS counseling in social welfare for prostitutes in the rural area].

Prostitute welfare and AIDS counselling are in the hands of one person in the rural area of the Westerland district. This offers the opportunity of continuously preventing this disease and giving guidance and the "human touch" in close care in case of a possible infection, especially in view of the lower number of cases examined and advised compared with the figures in the big cities. An anonymous poll among 41 prostitutes shows that they approve of and are satisfied with the concept of the "G-welfare". It also shows that the prostitutes themselves are hardly aware of the HIV-risk, that their customers only rarely accept condoms and that there are problems in the use and the toleration of condoms. These difficulties are the main aspects of the preventive work, as well as the psycho-social care and the personal relationship to those examining.


[Results from the Frankfurt a.M. AIDS counseling unit 1988 and 1989].

An AIDS counselling office of the Public Health Service has been available to the public of Frankfurt a.M. since September 1985. 6969 blood samples were examined for HIV antibodies between January 1988 and the end of December 1989. The prevalence of positive tests was 1.9% (n = 141). Until now most of the HIV-positive clients are homo- and bisexual persons. Security and partnership were the most frequent reasons stated by heterosexual clients at the AIDS-counselling office.


[Yes to sex education, but comprehensive, please. The health fair medium in health promotion, 6 years experiences exemplified by AIDS education].

The basic conditions for HIV/AIDS prevention have been changing during the last years. The interdisciplinary approach must be emphasised very clearly nowadays. Models of cooperation within the community must be enhanced. AIDS counselling in Bremen underwent various stages: from a critical analysis of the risk factor theory to the life-style concept and to a call for community action. The paper points out how the 6 years of experience with a special AIDS exhibition can be utilised for health education in other fields.


[Special characteristics of physician involvement in AIDS counseling].

Characteristic features of medical work at an AIDS Information Centre are pointed out with particular regard to the present situation in the city and district of Crenter? Hannover. Persons infected with HIV are reviewed, drawing particular attention to the extreme stress of living with the knowledge of being HIV-infected. The arising social problems of HIV-positive patients are described together with the doctor's adviser of easing the patient's stress and guiding him into accepting the necessary changes in life. Intensive cooperation hospital doctors, GP's and social workers is described.


[Medical management of HIV infected and AIDS patients in the Hannover metropolitan area as an interdisciplinary construct].

Two wards for consultation of AIDS have opened in Hannover in 1987, one in the Public Health Department for the city of Hannover, the other in the Public Health Department for the surroundings. It was a big step towards prevention of AIDS. At the same time a centre, especially for AIDS, was opened at the Medical college of Hannover, consisting of an ambulance and beds in a ward. An official laboratory tests the medical analyses. Today the doctor in the Public Health Department plays an important part: he is the first partner with whom the infected patient can talk. He must also maintain contact with all institutions including the family doctor for optimum patient care.


[Effect of air pollutants on the organism of the child].

The Institute of Hygiene at Rostock initiated studies in 1980 on schoolchildren (1st to 4th form) in air-hygienically differently affected areas of the former GDR, as well as studies on probationers of the same age in non-polluted areas. The spectrum of methods included besides clinical, sensorial and psycho-diagnostical investigations, also haematological, immunological and pulmonary functions tests. The results indicate that the state of health of children living in industrial areas is impaired. After a recuperating for four weeks under clean air conditions the changed values were normalised and adapted to the values of the non-exposed control group. The long-term effect of the recuperating stay lasts for 9 months.


[Incidence of leukemia in the Elbmarsch area].

The extremely conspicuous excess of leukaemia in the immediate neighbourhood of the world's largest boiling water reactor Krümmel is shown in its temporal and spatial context. An early extensive Lower Saxony state research programme gives no hint what so ever for a cause beyond three known risks of the region: 1. the main point is that the radiation exposure is well-known for causing leukaemia; 2. contamination of drinking water with an unknown substance containing nitrogen; 3. emissions from a chemical factory (according to a brief toxicological report, however, without potential for causing leukaemia). The leukaemia cluster is discussed against the background of a new valuation of radiation risk derived from recent Hiroshima data and the Mainz Leukaemia Study published in February, which points out in analogy to late British studies a significant increase in the leukaemia risk for the most radiation-sensitive group of infants and young children (aged 0-4) in the proximity of nuclear power plants.


[Legionella contamination in warm water systems of a large German city].

Since 1988 the Frankfurt City Health Department examined the hot water systems of all public indoor swimming pools, old age homes and hospitals, and made subsequent checks on the corrective measures introduced. In the 6 public indoor swimming pools the percentage of positive legionella findings, after corrective measures has dropped since 1988: at the central hot-water supply units from 47% to 23%, and at the peripheral tap connections from 66% to 22%. The number of negative samples rose from 43% to 77%. Thus the favourable effect of the corrective measures is demonstrated. Since 1988 samples have been taken from the shower water at old age homes. An increase in negative findings could be shown (from 58% to 70%). From 1990, however, an increase of high-level legionella contamination (> 10,000 Legionella colonies per litre) was detected as well. In one home with a generally high legionella contamination level (up to 75,000 legionella colonies per litre) an investigation of the legionella antibodies was done in the blood of 44 residents whose medical history included fever or bronchial symptoms. In no case a previous infection could be demonstrated. However, there was one patient with a definite legionella pneumonia in the home: this patient usually had been showering for at least 20 minutes a day. Legionella were found in the hot water systems of 16 of the 17 hospitals in Frankfurt. In 1991 more than half to the 204 samples were legionella positive. 5% of the samples had legionella contamination levels of more than 100,000 per litre. Corrective measures have been taken.(ABSTRACT TRUNCATED AT 250 WORDS)


[Ethical judgments in environmental medicine].

Among the main tasks of environmental medicine within the framework of the German Public Health Service are the assessment and management of risks involved in environmental problems. The article points out that both tasks involve ethical judgments in crucial matters. An important part of risk management is to establish limit and guiding values. The examples of drinking water regulations and WHO Air Quality Guidelines show that these values depend mainly on decisions on standard settings. It is pointed out that these cannot be derived from knowledge gained from research in natural science and that our present heterogeneous civilization is not conductive to a generally recognised basis for an evaluation. It is suggested to solve this dilemma by a process of mutual agreement on a reciprocal basis. The models of "proxy consent" and "presumed intent" are discussed. Public Health Service must therefore systematically reflect, expose and develop the standard settings of its judgments and actions.


[Regional service for senior citizens--a responsibility of the public health office].

At present the share of persons over 60 years of age in the total population is about 20 per cent. The number of persons of very advanced age and of persons in need of permanent care is increasing. Planning care of such persons is one of the major problems of society in the coming decades. This means that Public Health offices will have to tackle important problems in planning, in an advisory capacity and in expertising. The article describes the activities of the "Planning Group Concerned with Care for Persons of Advanced Age" under the supervision of the Public Health Office in Schleswig-Holstein district.


[Assistance for the aged from the viewpoint of the public health office].

Problems of old age and ways of helping the old were discussed with various social and age groups, among them secondary pupils as well as people living in old people's homes. The main questions which arose were: "How can one give a purpose to one's old age?"--"How does one win sufficient recognition?"--"What can be done to avoid, or overcome, isolation?" Most senior citizens were in favour of spending their old age in their familiar surroundings--either on their own or with their families, in whose life they wanted to participate. Our inquiries have shown that there are more institutions than generally assumed which offer advice and help and can be consulted by those in particular who have decided against living in an old people's home. With the support of other institutions and authorities, the staff of the local Health Service drew up a brochure on "Assistance in Old Age", which covers the Kulmbach area. Then we tried to find ways of improving the quality of our senior citizens' lives without spending too much money. The key issue which emerged was prevention.


[Social medicine aspects in expert assessment according to the new long-term care legislation].

According to the new German 'Betreuungsgesetz' (BtG) legislation concerning care for the mentally and or physically disabled, instituting a "case of care" requires an expert opinion on the patient's mental and physical impairments as well as on the question as to what degree the patient lacks the ability to manage his or her own affairs. The respect for the personal autonomy has to be weighed against the need to take action for the patient's benefit. The concept of 'neglect' ('Verwahrlosung') plays an important role in judging a patient's situation. Criteria for the use of this term are derived from a study carried out by the author, and lead to a questionnaire designed for preparatory investigations. As to the question of who should act as an expert in BtG cases, the author argues that the public health offices qualify best for this task.


[Expert assessment for long-term care--starting point for comprehensive help in medical and social rehabilitation].

Based on the various definitions of people in need of constant care the authors describe the needs and chances of professional assessment in the process of financing care at home and in nursing homes. They stress the often neglected point of rehabilitation and plead for participation of social workers and nurses in the assessment process. The precarious situation for many relatives of people in need of care is pointed out. The authors come to the conclusion that public health offices in Germany should--as an important task in the future--concentrate more intensively on the actual problems of people in need of care and participate in local strategies to improve their living conditions.


Free radical theory of aging: history.

Aging is the accumulation of changes responsible for the sequential alterations that accompany advancing age and the associated progressive increases in the chance of disease and death. These changes can be attributed to disease, environment, and the inborn aging process. The aging process is now the major risk factor for disease and death after about age 28. The free radical theory of aging arose in 1954 from a consideration of aging phenomenon from the premise that a single common process, modifiable by genetic and environmental factors, was responsible for the aging and death of all living things. The theory postulates that aging is caused by free radical reactions, i.e., these reactions may be involved in production of the aging changes associated with the environment, disease and the intrinsic aging process. The origination of the theory and its application to the problem of increasing the functional life span are discussed. Support for the free radical theory of aging has increased progressively and now includes: 1) studies on the origin of life and evolution, 2) studies on the effect of ionizing radiation on living things, 3) dietary manipulations of endogenous free radical reactions, 4) the plausible explanations it provides for aging phenomena, and 5) the growing numbers of studies that implicate free radical reactions in the pathogenesis of specific diseases. The rapidly growing number of scientists involved in studies on the role of free radical reactions in biological systems should assure future significant increases in the healthy, useful, life span of man.


Relationship between antioxidants, lipid peroxidation and aging.

Experiments performed on species as different as flies, rats and frogs are not conclusive about the possibility that antioxidant defenses decrease in old animals. Even when these decreases are found, their physiological meaning is far from clear. Furthermore, a constancy of antioxidant capacity in old age is consistent with the fact that aging is a progressive phenomenon which occurs at a rather constant rate from the mature young to the very old animal, without showing a great acceleration rate in the aged. Nevertheless, experimental results strongly suggest that the maintenance of an appropriate antioxidant/prooxidant balance does have an important role in maintaining health in the aging animal. It is possible that the continuous presence of small amounts of free radicals in the adult tissues of both mature adults and old animals is an important factor in aging (a progressive phenomenon) and susceptibility to disease. Since, similarly to what occurs in procariota, the whole antioxidant system seems to be under homeostatic control in vertebrates, it is imperative to perform comprehensive and detailed studies on the effects of carefully controlled doses of antioxidants on biomarkers of health as well as on the different endogenous cellular antioxidant and prooxidant systems. These studies should have as a final goal the knowledge of which doses of antioxidants are high enough to increase antioxidant protection but low enough to avoid feedback depression of other endogenous antioxidants; this could further improve the health state of humans situated in the middle and last phases of their life span.


Free radical theory of aging: view against the reliability theory.

The reliability theory approach to the free radical theory of aging is presented. First, the structural and functional inhomogeneity - hierarchy - of living systems has been taken into account. Hence, the existence of the finite number of critical structures - supervisors - in the system has been postulated. Second, I have postulated the stochastic nature of age-changes in the supervisors, paying particular attention to oxygen free radicals as the by-products of normal oxidative metabolism. Third, according to the cooperativity of main processes in biological systems, the existence of the threshold values of the reliability parameters of the supervisors has been postulated. In the terms of this reliability free radical theory of aging it becomes possible to explain the character of age-changes in mortality data for humans and animals; to explain how the linear kinetics of accumulation of free radical damages in the cellular targets (supervisors) can lead to the exponential kinetics of the mortality rate growth with age, i.e., to deduce the so-called Gompertz law of mortality; to explain the nature of the well-known empiric interspecies correlations between the maximum life span values and metabolic factors; to estimate species-specific life span potentials of humans and animals. The chromosomes of neural postmytotic cells have been suggested to function as the supervisors. In the terms of the theory it has been estimated that the life span of primates could run up 250 years but for the damages due to the oxygen free radicals.


The metabolism of 4-hydroxynonenal, a lipid peroxidation product, is dependent on tumor age in Ehrlich mouse ascites cells.

4-Hydroxynonenal is a major product formed by lipid peroxidation from omega 6-polyunsaturated fatty acids as linoleic acid and arachidonic acid. This aldehyde is cytotoxic at high concentrations (in the range of 100 microM), disturbs cell proliferation at low concentrations and exhibits genotoxic effects. Furthermore, in the submicromolar range 4-hydroxynonenal is chemotactic and stimulates phospholipase C. 4-Hydroxynonenal is rapidly metabolized in eucaryotic cells. Here the metabolism of 4-hydroxynonenal was studied in suspensions of Ehrlich mouse ascites cells at different periods of the tumor age. The Ehrlich ascites tumor is a convenient biological model for the investigation of tumor cells in different age and proliferation phases of the tumor. The main products of 4-hydroxynonenal which were identified in the Ehrlich ascites cells were glutathione-HNE-conjugate, hydroxynonenoic acid and 1,4-dihydroxynonene. The formation of glutathione conjugates following the addition of 4-hydroxynonenal was higher in cells of the early phase in comparison with cells of the late phase of tumor growth. That was in accordance with the increased consumption of the reduced form of glutathione during 4-hydroxynonenal utilization. The degradation of 4-hydroxynonenal and other aldehydic products of lipid peroxidation is postulated to be an important part of the intracellular antioxidative defense system.


Effect of aging on glutathione metabolism. Protection by antioxidants.

The free radical theory of aging suggests that oxygen free radicals may be involved in the aging process. Thus, changes in antioxidant mechanisms may occur with aging. Since glutathione is one of the most effective antioxidant systems in the cell, its metabolism may change with aging. In this chapter we describe experiments which show the involvement of glutathione in the aging process and which provide a rationale for the administration of antioxidants to old organisms to protect them against some of the changes that occur with aging.