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On the Formulation of Lagrangian Stochastic Models for Heavy-Particle Trajectories.

The modeling approach of B. L. Sawford and F. H. Guest ("8th Symposium of Turbulence and Diffusion; San Diego, CA," pp. 96-99. Am. Meteorol. Soc., Boston, MA, 1990) is extended to encompass the formulation of Lagrangian stochastic models for fluid velocities along heavy-particle trajectories in inhomogeneous turbulent flows. The approach ensures consistency with prescribed Eulerian fluid velocity statistics. Models are formulated and then used in conjuction with the equations of motion for heavy particles to simulate the trajectories of heavy particles in vertical turbulent pipe flow. Model predictions for particle-velocity statistics, particle deposition velocities, and mean particle concentrations are shown to be in good agreement with experimental results. In contrast with "eddy-interaction" models but in accord with the results of direct numerical simulations, the models predict a buildup of mean particle concentration within the viscous sublayer at y(+) approximately 0.2. It is suggested that Lagrangian stochastic models for fluid-particle motions provide a good description of fluid velocities along the trajectories of heavy particles, when Lagrangian timescales are appropriately modified. Copyright 2000 Academic Press.

Journal Article↗

Experimental Q fever in sheep.

The aim of the present investigation is the complex study of experimental infection in pregnant ewes by means of clinical, serological, biological, histological and Electron microscopy methods. Four ewes, pregnant from the 2nd to 5th month, were infected by intravenous (in one case by intraperitoneal) routes with a C. burnetii strain at 10(6) ID 50/ml. The clinical illness in all of the animals was characterized by fever and two-phase temperature reaction on the 5th and 12th days. The clinical symptoms were as follows: torpidity, reduced appetite, thirst, conjuctivitis, rhinitis, rapid breathing. As a result of the developed latent infection, after the acute stage, the animals gave birth to three unviable lambs who died within 24 h. Another lamb was still-born. The lambs showed cachexia, arthritis, ataxia, wrinkled skin. The highest CF-titers (1:256-1:512) were reached on the 40th day, but serum antibodies (1:8-1:32) first appeared on the 8th day. The titers began to decrease on the 60th day. The pathomorphological changes testify to a latent infection characterized by placentitis, lymphocellular proliferation of the lamb's parenchymal organs and lymph nodes, multiple thromboses, interstitial pneumonia and plural proliferative changes. The EM exam showed rickettsiae in placentas mainly in the form of inclusions in cytoplasm of leukocytes and epithelial cells.

Abortion, Veterinary↗

Evaluation of two nonculture antigen tests and three serotests for detection of anti-chlamydial antibodies in the diagnosis of ocular chlamydial infections.

BACKGROUND: Diagnosis of chlamydial conjuctivitis is difficult in chronic diseases because chlamydial elementary bodies are mostly undetectable in conjunctival scrapings by cell culture. We therefore compared two nonculture antigen tests and three different serotests for anti-chlamydial antibodies with McCoy cell culture, the "gold standard" of chlamydial diagnosis. Conjunctival scrapings and serum samples of 93 patients attending the outpatient eye clinic in Graz because of chronic follicular conjunctivitis were tested. METHODS: A total of 558 conjunctival scrapings and 93 serum samples were investigated. Chlamydial antigen detection was done by McCoy cell culture, polymerase chain reaction (PCR; Amplicor, Roche), and direct immunofluorescence assay (DFA; Microtrak, Syva). Antichlamydial IgA and IgG antibodies in the sera were detected by an immunoperoxidase assay (IPAzyme, Savyon) and two different enzyme-linked immunosorbent assays (SeroELISA, Savyon and rELISA, medac). RESULTS: Cell culture and PCR yielded identical results. The positivity rate for chlamydial conjunctivitis was 8.6% (8 of 93 patients). PCR proved most sensitive and most specific. IPAzyme was 75% sensitive for IgA and 100% for IgG; SeroELISA and rELISA were less sensitive. IPAzyme was 81% specific for IgA and 47.3% for IgG. SeroELISA and rELISA were less specific for IgA, but more specific for IgG. Post-test likelihood of disease was greatest in IPAzyme. CONCLUSIONS: PCR proved to be a good alternative to cell culture; DFA is useful for quick diagnosis. Genus-specific serotests cannot compete with chlamydial antigen detection. They differ in sensitivity and specificity because of the antigen type they present. They are still of only supportive value in cases where chlamydial antigen detection is not possible. Recently introduced species-specific antibody tests should be of greater value.

Adolescent↗

An unstable donor-recipient DNA complex in transformation of Bacillus subtilis.

In re-extracted DNA obtained shortly after uptake of transforming DNA by Bacillus subtilis, increased amounts of donor DNA radioactivity banding at the position of donor-recipient DNA complex (DRC) are observed in CsCl gradients, if the cells are irradiated with high doses of UV prior to reextraction of the DNA. Qualitatively, the same phenomenon is observed if lysates of transforming cells are irradiated. UV-irradiation of lysates of competent cells to which single-stranded DNA is added after lysis, does not result in linkage of this DNA to the chromosomal DNA. Two observations argue in favour of the formation of a specific labile complex between donor and resident DNA during transformation. Firstly, heterologous donor DNA from Escherichia coli, although being processed to single-stranded DNA in competent B. subtilis, does not seem to be linked to the recipient chromosome upon UV-irradiation, and secondly, the labile complex of donor and recipient DNA can be stabilized by means of treatment of the lysates of transforming cells with 4, 5(1), 8-trimethylpsoralen in conjuction with long-wave ultra violet light irradiation. This indicates that basepairing is involved in the formation of the complex. On the basis of these results we assume that the unstable complex of donor and recipient DNA is an early intermediate in genetic recombination during transformation.

Bacillus subtilis↗

Neurological manifestations of rhabdomyosarcomas in the head and neck in childhood. Neuroradiological study.

Two cases of rhabdomyosarcoma in the head and neck with neurological manifestations are presented. Brain scan demonstrated an apparent area of increased uptake of 99mTc in the tumor. Cerebral angiography revealed a sharply demarcated but rather faint tumor stain. The contributing vessels were hypertrophied branches of the external carotid artery, a dural branch of the internal carotid artery, and branches of the vetebrobasilar systes emphasized because the recent combination of chemotherapy in conjuction with surgery and irradiation seems to be encouraging.

Adolescent↗

A comparison of various procedures for fine grain development in electron microscopic radioautography.

Fine grain development for electron microscopic radioautography was investigated with two types of radioactive specimens: sections of tritiated methacrylate, which provide a homogeneously labeled source for quantitative evaluation of the radioautographic reaction, and sections of 125I-labeled thyroid. Radioautographs were prepared with Ilford L4, Sakura NR-H2, Agfa-Gevaert NUC 307 or Kodak NTE emulsions. The radioautographs were developed with one of several "solution physical" development procedures (Agfa-Gevaert, phenidone-ascorbic acid, p-phenylenediamine developers) or with arrested "direct" developments (D-19b, Elon-ascorbic acid developers). By arresting each development at an early stage of the reaction and at progressively longer time intervals, it was possible to examine the sequence of shapes in the growth of developed silver deposits for each emulsion-development combination. Thus, conditions which resulted in the development of small, round, compact silver deposits were defined for each emulsion. These developments were used in conjuction with gold latensification, a treatment which increases the sensitivity of the emulsions and thus compensates for the lowered sensitivity of fine grain development procedures. The location of the silver deposits in relation to the silver bromide crystals from which they derive was investigated. The emulsion gelatin surrounding the crystals was stained whereas the spaces, which remained after the crystals were dissolved in the photographic fixer, appeared transparent. This analysis permitted the selection of development procedures in which the single or multiple round silver deposits originating from a single crystal will remain within or on the boundary of this crystal. By this method, quantitation of radioautographic reactions composed of small, round silver deposits was studied by using the uniformly labeled 3H-methacrylate sections as a standard source of radiation. The conditions under which grain counting is feasible are discussed.

Autoradiography↗

The aldehyde fuchsin and colloidal iron staining reactions in the canine thyroid C cell.

The cytochemically reactive groups which are responsible for Aldehyde Fuchsin (AF) and colloidal iron (CI) staining of C cells were investigated in the canine thyroid gland. To this end, stains for proteoglycans and peptide groups were utilized in conjuction with hydrolysis of glycosidic and amide bonds. In addition, the following procedures were used: acetylation, benzoylation, nitrozation, aldehyde blockade, sulphydryl blockade, methylation and mild acid hydrolysis. No acidic proteoglycan, sialic acid, polyphosphate or polysaccharide ester sulphate were detected in C cells; the results suggest that AF staining, after an oxidation step, and CI staining are due to polypeptides. Sulphydryl and carboxyl groups together are necessary for mediating the attachment of AF in C cells and it is adduced that this attachment is due to the combined charges of sulphonic and carboxylic acids. Methylation and acetylation inhibit CI staining and those staining reactions that depend upon carboxylic acid (TB) and hydroxyl groups (PAS) for their dye attachment in C cells. Acid hydrolysis, which increases the demonstration of carboxylic acid in C cells, decreases the attachment of hydroxyferric ions. I speculate that this inhibition is due to extraction of iron sites in the C cell and conclude that it is not solely carboxylic acids in C cells that are responsible for CI staining.

Animals↗

Conjoined twins--the Cape Town experience.

This paper records our experience in the management of 25 sets of conjoined twins seen over a 32 year period (1964 - 1996). The twins were classified into 14 complete and symmetrical sets and 11 incomplete or heteropagus. The 14 symmetrical sets included 9 thoracopagus, 2 ischiopagus, 1 craniopagus and 1 omphalopagus twins. In the incomplete heteropagus group there was 1 ischiopagus, one twin being anencepahlic, 2 dipygus, 5 parasitic, 2 fetus-in-fetu and I cranial and caudal. The management is detailed case by case. Overall 10 of 14 symmetrical sets underwent attempts at separation with 16 surviving the procedure, but there were 3 late deaths. In the incomplete group 10 of 11 were operated on with 9 survivors. The importance of a multi-disciplinary approach, the extensive investigations required pre-operatively to define areas of organ and bony conjunction, congenital anomalies of each twin and surgical teamwork is emphasized. Specific problems encountered were identified. In thoracopagus twins the hearts were of paramount importance as conjuction was usually fatal, being associated with major congenital defects. The greater the extent of thoracic cage fusion the greater the chance of associated severe anomaly. Skin expansion to assist coverage of the defects after separation was of great assistance, as was the use of collagen coated vicryl. Evaluation of the liver and pancreatico-biliary systems with isotope excretion scanning was crucial to pre-operative planning. Where there was fusion of the duodenum a single pancreatico-biliary system could be expected and prior strategies for separation and Roux-en-Y enteric drainage of both pancreatic and biliary secretion should be planned. Gastro-oesophageal reflux led to considerable morbidity in both twins of a thoraco-omphalopagus set. In ischiopagus and dipygus conjoined twins bilateral posterior iliac osteotomies were an essential component to anatomic reconstruction of the pelvic ring and wound closure. Also in this group, due to the frequency and extent of shared genital, urinary and ano-rectal structures, long-term morbidity was expected and a component of this might be due to spinal cord tethering, or as in one of our cases, a progressive hydrosyringomyelia. Timing of separation was ideally set at between 5 and 9 months with 6 to 8 weeks of prior tissue expansion but earlier operation was frequently required because of cardio-respiratory problems or organ failure in one twin. In most cases the goal of obtaining separate, independent and intact individuals was achieved.

Abnormalities, Multiple↗

Intraoperative measurement of the bile flow resistance in the terminal portion of the common bile duct and its clinical significance in biliary surgery.

A practical method, safe and relatively simple to perform, which we have developed for the intra-operative measurement of the resistance to bile flow in the terminal portion of the common bile duct is described. This method performed routinely in conjuction with the operative cholangiography in the operating room, proved to be a powerful diagnostic acid for detecting abnormalities in the terminal portion of the common bile duct. In gallstone disease, the results by this method were compared with the operative results. It was found that minimal organic changes or functional disturbances in the terminal portion of the common bile duct, even those without jaundice, can be detected, and unnecessary choledochotomy or sphincteroplasty avoided. This method has a further advantage in that it gives universality to the resistance R and the residual pressure P as quantitative discriptive indices for the qualitative state of bile flow in the terminal portion of the common bile duct, and, if adopted as a standard and routine method, should make the comparison of works by different investigators easier and more significant.

Bile↗

Brain lysosomal hydrolases in neuronal ceroid-lipofuscinoses.

Although the neuronal ceroid-lipofuscinoses (NCLs) are often referred to as lysosomal storage disorders, information on brain lysosomal hydrolases in NCLs is not available. We have determined the specific activities of several acid hydrolases in postmortem brain gray matter of infantile (INCL), late infantile (LINCL), juvenile (JNCL), and adult (ANCL) forms of NCL, patients affected with other neurological disorders (ON), and normal controls. The specific activities of beta-hexosaminidase A and B were significantly high in JNCL gray matter, whereas in LINCL, the increase is significant only in beta-hexosaminidase compared to the controls. A significant increase in the activities of alpha-mannosidase, beta-glucuronidase, and acid phosphatase was also observed in LINCL and JNCL patients compared to the control values. beta-galactosidase activity was also found to be elevated in JNCL brains over the controls. In contrast, activities of beta-glucosidase and sialidase appeared to be lowered in INCL and LINCL. On the other hand, alpha-fucosidase, beta-mannosidase, and sulfatase were unaffected in NCLs brains. Thus, the present data indicate NCLs related abnormalities in some of the acid hydrolases in brain gray matter, which are primarily glycoproteins of lysosomal origin. These data in conjuction with the reported association of sphingolipid activator proteins (SAP) A and D and lysosomal glycoproteins with NCL storage bodies imply abberations in the glycoconjugate metabolism and lysosomal function.

Acid Phosphatase↗

Scoparone from Artemisia capillaris inhibits the release of inflammatory mediators in RAW 264.7 cells upon stimulation cells by interferon-gamma Plus LPS.

Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In the present study we observed that, scorparone exhibited no cytotoxic effect in unstimulated macrophages, but reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) upon stimulation by IFN-gamma/LPS or LPS. The inhibitory effects were found to be in conjuction with the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-gamma/LPS stimulated RAW 264.7 cells. Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in LPS-stimulated RAW264.7 cells. These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and PGE2 in macrophages by inhibiting iNOS and COX-2 expression.

Animals↗

Characterization of rainbow trout terminal deoxynucleotidyl transferase structure and expression. TdT and RAG1 co-expression define the trout primary lymphoid tissues.

One component of antigen receptor diversity shared by all gnathostomes characterized to date is mediated by a unique DNA polymerase, terminal deoxynucleotidyl transferase (TdT), which generates significant functional diversity during immunoglobulin and T-cell receptor rearrangement. To gain further insight into the evolutionary origin(s) of this unique enzyme and the immune system, a thymic cDNA clone encoding TdT was isolated from rainbow trout. The 2.3 kilobase (kb) full-length clone contained an open reading frame of 1 506 base pairs with a deduced protein product of Mr 57 000. Sequence comparisons demonstrate that TdT has been highly conserved in both sequence (>70% aa similarity, >50 aa identity) and overall structure during the course of vertebrate evolution. An amino acid alignment of all known TdT sequences (chicken, Xenopus, mouse, human, cattle, and trout) reveals that some, but not all, structural motifs believed to be critical for TdT activity have been conserved. The TdT alignment, in conjuction with the recently solved crystal structure for rat beta-polymerase, supports the hypothesis that both may have evolved from a common ancestral repair gene. In addition, four PKC phosphorylation sites are conserved, and hence may be involved in TdT regulation. Because TdT contributes to the generation of junctional diversity in antigen receptors of immature lymphocytes, its expression serves as a developmental marker for the sites of teleost lymphopoiesis. Northern blot (2.3 kb message) analysis shows that TdT mRNA is highly expressed within the thymus and to a lesser extent in the pronephros. In addition, reverse transcriptase-polymerase chain reaction analysis detected transcipts of both RAG1 and TdT in the thymus, pronephros, mesonephros, spleen, and intestine, but not within muscle, liver, or brain. Finally, TdT cDNA was amplified from embryos at 20 days post-fertilization (pf), which correlates with the appearence of the thymus and pronephros anlage during trout ontogeny.

Amino Acid Sequence↗

The tuning of a model-based estimator for the specific growth rate of Candida utilis.

Control of microbial conversion processes is frequently inhibited by the infeasibility of measuring important process variables. In order to circumvent this lack of measurements, an accurate or valuable and conveniently measurable on-line hardware measurement can be combined with the balance equations describing the process to obtain estimates of less easily measurable variables. In this article the on-line estimation of the specific growth rate of Candida utilis is evaluated. The observer-based estimator requires a hardware measurement of the biomass during fermentations in conjuction with a model of the process; therefore the Biomass Monitor, giving an on-line measurement of viable biomass, is used in the bioreactor experiments described. The optimal tuning of the estimation for the experimental conditions is described and several alternative adaptations of the design of the estimator are presented. The influence of implemented time intervals for discretization of the estimator on the reliability of the estimated growth rate values is discussed. Additionally, the necessary choice of an initial value of the estimated specific growth rate has proven to be of great importance in practice.

Journal Article↗

Gene therapy: future therapy for erectile dysfunction.

Advances in molecular biological techniques, completion of the Human Genome Project, and the ensuing age of molecular medicine, in conjuction with the sum of a decades-long accumulation of knowledge of the physiology of erection and the pathophysiology of erectile dysfunction have converged to make gene therapy for erectile dysfunction a distinct possibility. In short, both the intrinsic complexities of mechanisms responsible for ensuring normal erection and the multifactorial nature of erectile dysfunction ensure that there is a relatively vast number of physiologically relevant molecular targets for gene therapy. As such, perhaps it is not surprising that virtually every preclinical gene therapy strategy/target examined thus far has been largely successful in ameliorating conditions associated with compromised erectile function in vivo and/or in vitro. This report highlights the goals and strategies of gene therapy for erectile dysfunction and reviews the strategies that initially have been employed. In short, the preclinical data, while still quite preliminary in many regards, are nonetheless quite impressive and encouraging. If similar success is obtained in clinical trials, gene therapy for erectile dysfunction may provide the first concrete "proof of concept" for using gene therapy in the treatment of human smooth muscle disorders.

Erectile Dysfunction↗

Tumors of the submaxillary gland.

This study reviews a thirty year experience with 217 patients who had a tumor of the submaxillary gland, comprising about 9 per cent of all patients with salivary neoplasms seen during the same period. Most of the tumors were malignant (56 per cent), with adenoid cystic carcinoma predominating, but the histologic type most frequently encountered was benign mixed tumor (43 per cent). Median age was fifty-four years in patients with malignant tumors compared with forty-six years in those with benign tumors, and 58 per cent were women. Asymptomatic swelling was the usual presenting complaint, and the clinical findings are summarized using a staging system recently proposed for patients with parotid tumors. Cervical lymph node metastasis occurred in at least 50 per cent of patients who had an adenocarcinoma or epidermoid, mucoepidermoid, or anaplastic carcinoma. Treatment was surgical and complete gland excision proved adequate in those with benign tumors. Radical neck dissection was performed in conjunction with submaxillary resection in most patients with malignant lesions, but radical en bloc resection was reserved for those few who had extensive or fixed disease. Net determinate "cure" rates at five and ten years (30 and 20 per cent, respectively) are distressingly low and compare unfavorably with those previously reported in patients treated for carcinoma of the parotid. The high local recurrence rate and the greater incidence in the submaxillary gland of more aggressive tumor types which metastasize readily suggest that current treatment should be more radical. It seems reasonable to expect that results might be improved if en bloc resections were more often performed in patients with less advanced disease, possibly in conjuction with intensive postoperative irradiation in selected cases.

Adenocarcinoma↗

The rise in chlorophyll a fluorescence yield and decay in delayed light emission in tris-washed chloroplasts in the 6-100 microseconds time range after an excitation flash.

Parallel measurements of the rise in chlorophyll a fluorescence yield and delayed light emission decay, after a 10 ns saturating excitation flash, have been made in tris (hydroxymethyl)aminomethane-washed chloroplasts. Various electron donor systems (Mn2+; ascorbate; reduced phenylenediamine and benzidine) were used in conjuction with different preillumination regimes to alter [P+-680], the oxidized form of the Photosystem II reaction center chlorophyll a. Conditions giving rise to high [p+ -680] resulted in only a small rise in fluorescence yield, an inhibition of a 6 microseconds component of delayed light emission. These results confirm the hypothesis that P+-680 acts as a quencher of fluorescence and that delayed light emission in the microsecond time range is due to the back reaction of P+-680 and Q-. (Q is the first "stable" electron acceptor of Photosystem II.) Two preillumination flashes are required before the full effect of Tris washing is observed in the delayed light emission decay and fluorescence yield rise; this suggests that a capacity to hold two charges exists between the Tris block and P+-680. Tris washing has no direct effect on the movement of electrons from Z (the first electron donor to P+-680. Finally, Mn2+ donates electrons to P+-680 via Z.

Ascorbic Acid↗

The contingent negative variation and psychological findings in chronic hepatic encephalopathy.

Early diagnosis of chronic hepatic encephalopathy (CHE) in the latent stage before the appearance of clinical signs, should reduce both morbidity and mortality as deterioration is often preventable by treatment. Since existing diagnostic procedures are inadequate, we have investigated a test in which morphine is used as a provocative agent and any resulting change in cerebral function assessed by measurement of the CNV in conjuction with a psychological trail test. Twenty six patients were studied, 6 of whom had clinically overt CHE. A significant correlation (P less than 0.05) between the change in CNV amplitude with morphine and the initial CNV amplitude, consistent with the theoretical model of Tecce (1972), was found. However, the CNV and trail test results taken as a whole did not allow even those patients with overt CHE to be distinguished and we conclude that it is unlikely that differing degrees of latent CHE could be detected.

Chronic Disease↗

A refinement of the concept "reticence".

This report has 1. Made a distinction between speech disorders involving defects and those that are primarily reticence, but in any case identified speech disorders as negotiated states as opposed to fixed disease states. 2. Argued that there is a clear analytical separation between speech disorders and speech behaviors which are indicative of neurotic disorders. 3. Attempted to remove anxiety as a component of the communication process by according it its rightful place, which is central in human personality. Furthermore, we have attempted to dispel the notion that anxiety is evil and the perennial (and sole) cause of speech disorders. 4. Identified a specialist known as the rhetoritherapist (a specially trained speech teacher) as the particular king of professional qualified to deal with speech disorders (in conjuction with speech pathologists and/or psychotherapists where necessary). We have accorded to the rhetoritherapist the province of instruction and training in all aspects of invention, delivery, and reception of rhetorical speech without reference to its moral intent. 5. Identified "reticence" as the most useful of the various imprecise terms used to refer to people with speech problems, because it is devoid of connotations that go beyond the speech process. Further refinement of specific categories of speech disorders is necessary to order to expand the repertoire of available treatment strategies. Such refinement will probably include reference to the various subprocesses of human speech identified earlier in this paper as they are related to the rhetorical situation. The rhetoritherapist thus emerges as the trouble-shooter, but not the "psychotherapist," of speech pedagogy.

Adolescent↗