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Adenoid cystic carcinoma of the salivary glands: an immunohistochemical study.

Twenty-four cases of adenoid cystic carcinoma from the Salivary Gland Registry of the University of Hamburg were analysed with respect to their differentiation and subclassification. With immunohistochemical methods, several groups of marker substances were analysed in these tumors: marker for a glandular function; immunoglobulins; metalloproteins; tumor markers; substances associated with the basal membrane and carbohydrate chains. The following patterns of histological differentiation were found: cribriform pattern with typical pseudocysts; tubular pattern with ductal elements; trabecular pattern with predominance of hyalinized stromal elements; basaloid pattern with low differentiated cells. For every pattern, a special immunohistochemical profile could be established. The morphological and immunohistochemical analysis revealed the following relation between the different patterns: Origin of the malignant proliferation is presumably the terminal ductal system of the salivary glands (indifferent cell of the reserve cell type). This cell can differentiate in 2 directions: a myoepithelial and a ductal cell type. Immunohistochemically, the presence of basement membrane-associated substances is accompanied by the appearance of myoepithelial-like cells. The presence of secretory products is a feature of ductal cells.

Antibodies, Neoplasm↗

BIOLOGICAL FORMATION OF MOLECULAR HYDROGEN.

From a general standpoint, the formation of molecular hydrogen can be considered a device for disposal of electrons released in metabolic oxidations. We presume that this means of performing anaerobic oxidations is of ancient origin and that the hydrogen-evolving system of strict anaerobes represents a primitive form of cytochrome oxidase, which in aerobes effects the terminal step of respiration, namely the disposal of electrons by combination with molecular oxygen. We further assume that the original pattern of reactions leading to H(2) production has become modified in various ways (with respect to both mechanisms and functions) during the course of biochemical evolution, and we believe that this point of view suggests profitable approaches for clarifying a number of problems in the intermediary metabolism of microorganisms which produce or utilize H(2). Of special general importance in this connection is the basic problem of defining more precisely the fundamental elements in the regulatory control of anaerobic energy metabolism. Among the more specific aspects awaiting further elucidation are: the relations between formation of H(2) and use of H(2) as a primary reductant for biosynthetic purposes; the various forms of direct and indirect interactions between hydrogenase and N(2) reduction systems; and the transitional stages between anaerobic and aerobic energy-metabolism patterns of facultative organisms.

Bacteria↗

Mutational enzymatic resistance of Enterobacter species to beta-lactam antibiotics.

Mutants with enhanced beta-lactam resistance were selected from strains of Enterobacter cloacae and E. aerogenes by using three antibiotics. High-level beta-lactamase-producing mutants had similar degrees of increased resistance, enzyme substrate profiles, and isoelectric (pI) values irrespective of the selective agent. Reverse mutants from a resistant E. cloacae mutant regained the susceptibility pattern originally exhibited by the wild type, or were of enhanced susceptibility, and no longer expressed increased beta-lactamase production. beta-Lactamases of the mutants were similar in pI values to the wild-type enzyme. The increased resistance of the mutants therefore appeared to be accounted for by increased beta-lactamase production.

Anti-Bacterial Agents↗

DNA fingerprinting of Enterococcus faecium by pulsed-field gel electrophoresis may be a useful epidemiologic tool.

Pulsed-field gel electrophoresis was used to compare 34 isolates of Enterococcus faecium from six different geographic locations. This procedure generated an average of 13 discernible fragment bands per isolate (range, 10 to 19 fragment bands) of 34 to 485 kb. The resulting restriction endonuclease digestion patterns were quite heterogeneous and were able to differentiate 27 of 34 isolates from each other, as defined by one or more mismatched fragment bands. Five patterns were shared by two or more isolates, and each set of isolates with matching patterns (shared pattern) originated in the same medical center, suggesting a common epidemiologic background, including highly penicillin resistant isolates in Richmond and Philadelphia. We conclude that pulsed-field gel electrophoresis of DNA digested with low-frequency-cleavage restriction enzymes offers a relatively simple method of comparing E. faecium for the purpose of epidemiologic study.

Bacterial Typing Techniques↗

tRNA-like structure regulates translation of Brome mosaic virus RNA.

For various groups of plant viruses, the genomic RNAs end with a tRNA-like structure (TLS) instead of the 3' poly(A) tail of common mRNAs. The actual function of these TLSs has long been enigmatic. Recently, however, it became clear that for turnip yellow mosaic virus, a tymovirus, the valylated TLS(TYMV) of the single genomic RNA functions as a bait for host ribosomes and directs them to the internal initiation site of translation (with N-terminal valine) of the second open reading frame for the polyprotein. This discovery prompted us to investigate whether the much larger TLSs of a different genus of viruses have a comparable function in translation. Brome mosaic virus (BMV), a bromovirus, has a tripartite RNA genome with a subgenomic RNA4 for coat protein expression. All four RNAs carry a highly conserved and bulky 3' TLS(BMV) (about 200 nucleotides) with determinants for tyrosylation. We discovered TLS(BMV)-catalyzed self-tyrosylation of the tyrosyl-tRNA synthetase but could not clearly detect tyrosine incorporation into any virus-encoded protein. We established that BMV proteins do not need TLS(BMV) tyrosylation for their initiation. However, disruption of the TLSs strongly reduced the translation of genomic RNA1, RNA2, and less strongly, RNA3, whereas coat protein expression from RNA4 remained unaffected. This aberrant translation could be partially restored by providing the TLS(BMV) in trans. Intriguingly, a subdomain of the TLS(BMV) could even almost fully restore translation to the original pattern. We discuss here a model with a central and dominant role for the TLS(BMV) during the BMV infection cycle.

Base Sequence↗

Colocalization of microtubules and mitochondria in the yeast Schizosaccharomyces japonicus var. versatilis.

Both living and fixed cells of Schizosaccharomyces japonicus var. versatilis showed thread-like mitochondria when studied by phase-contrast and fluorescence microscopy. In the interphase cells, mitochondria extended from pole to pole and converged towards the growing tips. The mitochondrial threads did not disrupt but persisted during mitosis and, subsequently, their bundle was split between the two daughter cells by a concentrically growing septum. Mitochondria in the interphase cells were accompanied by cytoplasmic microtubules. These disappeared during mitosis and, instead, spindle microtubules were formed in the nucleus. The cytoplasmic microtubules reappeared after anaphase B, again in coaligment with mitochondria. Protoplasting as well as the action of microtubule inhibitors methyl-1-(butylcarbamoyl)-2-benzimidazolecarbamate (benomyl) and 2-methylbenzimidazole (MBC) resulted in rapid disintegration of microtubules and, suprisingly, also in disruption of mitochondria into small bodies. Removal of the inhibitors or a short regeneration of protoplasts allowed both the cytoplasmic microtubules and the thread-like mitochondria to reaggregate into the original pattern. Cytochalasin D treatment caused a complete disintegration of actin filaments, while the cytoplasmic microtubules and mitochondria remained intact. These findings of a transient close association of mitochondria and microtubules and their relative independence of the arrangement of actin filaments suggest that microtubules, but not actin cables, form supports for positioning or movement of mitochondria along the cylindrical cells. The persistence of mitochondria in the cell centre during mitosis may be accounted for by the fact that disrupted microtubules fail to provide support for mitochondrial movement towards the cell poles.

Benomyl↗

The effect of reinnervation on the distribution of muscle fibre types in the tibialis anterior muscle of the mouse.

The distribution of fibre types in the tibialis anterior (TA) muscle of adult mice was examined by means of an immunohistochemical approach, using monoclonal antibodies that recognize different myosin heavy chain isoforms. As has been reported previously, the superficial portion of TA contains almost exclusively type IIB fibres and is almost entirely glycolytic in nature. Following section of the lateral popliteal nerve and rotation of the proximal stump to prevent rematching, it was found that the original pattern was virtually restored within 2 months. One possible explanation for this observation is that the activity pattern of peripheral and deep muscle fibres differs and that this aids in specification of muscle fibre type. Alternatively, the muscle fibres of the superficial portion of TA may be inherently resistant to an alteration of their phenotype with regard to expression of myosin heavy chain.

Adenosine Triphosphatases↗

Intermittent flow in tendon capillary bundles.

The capillary bed has been observed in the Achilles tendon of 40 bullfrogs and 10 guinea pigs for periods of up to 2 h. The opening and closing of adjacent capillaries in a perfused area follows the pattern originally described by Krogh for skeletal muscle but the frequency is slower, as anticipated from the lower metabolic rate of tendon. However, superimposed on this "flickering is a much slower process whereby whole bundles of 20-147 capillaries open and close with little overlap in the tissue areas perfused by each. Periods of no flow averaged 39 min in 70 bundles followed in bullfrogs and 43 min in 34 bundles followed in guinea pigs, although a few failed to open in 100 min. This bundle phenomenon is discussed in relation to the serious implications in mathematically modeling the exchange of gases and nutrients between blood and tissue and the possible errors in assuming time averaging when determining blood perfusion rates. Also mentioned are the likely effects of decompression on closed bundles and the notion is introduced that the bundle phenomenon may be a factor determining which tissues can be injured by decompression.

Achilles Tendon↗

A tissue culture model of the hypophysiotrophic CRF producing neuronal system.

To investigate functional and chemical properties of anatomically characterized corticotropin-releasing factor-41 (CRF-41) producing neurons in vitro, hypothalamic slices of 6-day-old rats were maintained in culture for up to 6 weeks using a modified roller culture technique. This technique yields thick (100 microns) slices that contained an average of 300-400 CRF-41-immunostained neurons. The majority of CRF-41-positive cells were of small size (12-15 microns in diameter), and contained CRF-41-labeled dense core vesicles of 100 nm diameter as detected by electron microscopic postembedding immunocytochemistry. These cells represented the only CRF-41-positive cell population in the culture. Light microscope double immunolabelling of colchicine-treated cultures kept in a serum-containing media (SCM) indicated that about 60% of these CRF-41-positive neurons contains detectable levels of vasopressin-associated neurophysin (VP-NP). Culturing slices in serum-free, chemically defined media (SFM) resulted in an increased VP-NP immunostaining: parvicellular neurons labeled for both CRF-41 and VP-NP could be detected without colchicine treatment, and practically all CRF-41-positive neurons expressed VP-NP immunoreactivity. At the electron microscopic level there was a significant increase in VP-NP labeling density in the dense core vesicle compartment of CRF-41-positive varicosities. Adding dexamethasone (10 nM) to the SFM restored the staining pattern originally observed in SCM. Hence, the increased VP-NP and CRF-41 immunostaining after culturing CRF-41 neurons in SFM is most likely due to the absence of inhibitory glucocorticoids. The capacity of cultured paraventricular cells to release CRF-41 was assessed using an immunoassay. Unstimulated (basal) secretion of CRF-41 was not altered by five successive samplings at 2-hour intervals and stimulation of the same culture with 56 mmol K+ significantly increased (2-3 times) the CRF-41 content in the medium. The presence of dexamethasone (10 nM) in SFM induced a 6-fold reduction of K(+)-stimulated CRF-41 release and a 5 times reduction in tissue content in relation to cultures maintained in SFM without dexamethasone. In summary, we have demonstrated that cultured CRF-41 cells display morphological and biochemical features, as well as responsiveness to glucocorticoids, that is reminiscent to the situation in vivo. Thus, the model is well suited for studies of hypophysiotrophic CRF-41 cell functions.

Animals↗

Nodular lymphoma eventuating into lymphoplasmocytic lymphoma with monoclonal IgM/lambda cold agglutinin and Bence-Jones proteinuria.

A case of nodular lymphocytic (centroblastic/centrocytic) lymphoma that developed within 5 months after the initial diagnosis of lymphoplasmocytic lymphoma is described. The change in the histopathological picture, consisting of the development of a functionally more differentiated B cell neoplasm, occurred in the abdominal lymph nodes while the original pattern persisted in the bone marrow, liver and spleen. The patient was also found to have a serum IgM/lambda monoclonal immunoglobulin exhibiting cold agglutinin activity with specificity for the 'non-I' erythrocyte antigens.

Agglutinins↗

Gm allotypes as indicators of non-atopic and atopic bronchial asthma.

69 Caucasian children, 34 with non-atopic and 35 with atopic bronchial asthma, demonstrated different, Gm-associated IgG antibody responsiveness. The non-atopic bronchial asthma group showed a preponderance of the Gm(a,'',g) haplotype, while the atopic study group showed a preponderance of the haplotype with the alternative allotypes on all IgG subclass loci, namely Gm(f,n,b). Patients with non-atopic bronchial asthma showed a significantly increased frequency of the phenotypes containing the Gm(a,'',g) haplotype, namely the Gm(a,'',g/a,'',g) and Gm(a,'',g/f,'',b), and an increased number of individuals were homozygous G2m('','') on the IgG2 locus. The 2 asthma groups showed different characteristic IgG subclass patterns, the non-atopic group with significantly decreased IgG2 and IgG3, especially those of the Gm(a,'',g/a,'',g) phenotype, and the atopic group with significantly increased IgG1 and IgG4, especially those of the Gm(f,n,b/f,n,b) phenotype. The characteristic IgG subclass patterns originate from the different Gm phenotypes found in the 2 groups. The results emphasize the presence of qualitatively and quantitatively different IgG molecules in non-atopic and atopic bronchial asthma patients and show the interest in studying IgG genes and IgG molecules as markers of pathogenesis. G2m('','') homozygosity is a new important marker of non-atopic bronchial asthma.

Adolescent↗

Self-destructive behavior in battered children.

Fifty-nine physically abused children demonstrated a significantly higher incidence of self-destructive behavior than two control groups of nonabused children, one neglected and one normal. The self-destructive behavior, including suicide attempts and self-mutilation, was potentiated by interrelated variables operating in the abused child and his environment. Often enhanced by the ego deficits and impaired impulse control of the abused children, this behavior seemed to represent a learned pattern originating in early traumatic experiences with hostile primary objects.

Adolescent↗

Effectiveness of switching antipsychotic medications.

OBJECTIVE: Changing antipsychotics is common despite the dearth of information on risks and benefits associated with medication changes. The authors examined phase 1 findings from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study to explore whether it was more advantageous to continue taking the medication being received at baseline or to switch to a different antipsychotic. METHOD: First, for patients randomly assigned to treatment with olanzapine (N=314) or risperidone (N=321), the authors assessed the impact of being assigned to stay with the medication they were receiving at entry into the study versus being assigned to switch to these medications from a different antipsychotic. Second, for patients whose baseline antipsychotic was olanzapine (N=319), risperidone (N=271), or quetiapine (N=94), the authors examined the impact of being randomly assigned to stay with the same antipsychotic versus switch. Finally, the authors assessed the impact of removing the data of 209 patients whose random assignment was to stay with their baseline antipsychotic. The authors followed analysis strategies for CATIE; primary outcome was time until all-cause treatment discontinuation. RESULTS: Individuals randomly assigned to olanzapine and risperidone who were continuing with their baseline medication had significantly longer times until discontinuation than did those assigned to switch antipsychotics. When these "stayers" were removed, differences seen in the original CATIE phase 1 analyses were attenuated, although the original pattern of results remained. CONCLUSIONS: Comparisons of medication effectiveness should take into account whether medications being compared were each newly initiated. Further, unless the clinical situation requires a medication change, prescribers may want to take steps to optimize current medication regimens (e.g., dosage adjustments, behavioral or psychosocial interventions) before switching medications.

Adolescent↗

A method for evaluating vestibular control of posture.

Tests that measure the patient's ability to control his posture generally have failed to yield clinically useful information about vestibular function. The primary reason for this failure is that postural control does not depend on vestibular function when visual and proprioceptive cues are available. To test vestibular function, one should use a procedure that forces the patient to rely on vestibular cues by eliminating cues from these other sensory systems. Such a procedure is described. Vision is eliminated by eye closure, and proprioceptive cues are minimized by rotating the supporting surface to null changes in ankle angle. Data are presented which show that postural responses are complex, but that they appear to conform to the pattern originally observed by Nashner. A method potentially capable of separately evaluating semicircular canal and otolith function is described.

Ankle Joint↗

Deoxyribonucleic acid hypomethylation of male germ cells by mitotic and meiotic exposure to 5-azacytidine is associated with altered testicular histology.

Genomic methylation patterns originate during gametogenesis and are postulated to be involved in important developmental events, including gene regulation, embryogenesis, and genomic imprinting. In previous work, treatment of male rats with 5-azacytidine, a drug that blocks DNA methylation, resulted in abnormal embryo development when germ cells were exposed throughout spermatogenesis, encompassing mitotic, meiotic, and postmeiotic development, but not if they were only exposed postmeiotically. To explore the mechanisms underlying the effects of 5-azacytidine on sperm function, we determined the effects of the drug on testicular morphology, assessed whether exposure of meiotic spermatocytes resulted in abnormal pregnancy outcome, and examined the role of germ cell genomic demethylation in mediating the effects of 5-azacytidine on spermatogonia and spermatocytes. Male Sprague Dawley rats were treated three times a week with saline or 5-azacytidine (2.5 and 4.0 mg/kg) for 6 weeks (meiotic and postmeiotic germ cell exposure) and 11 weeks (mitotic, meiotic, and postmeiotic exposure). Six weeks of paternal treatment with the highest dose of 5-azacytidine resulted in an increase in preimplantation loss (corpora lutea minus implantation sites) without affecting testicular morphology or altering sperm DNA methylation levels. Eleven weeks of 5-azacytidine treatment at doses that cause preimplantation loss resulted in severe abnormalities of the seminiferous tubules, such as degeneration and loss of germ cells, atrophy of seminiferous tubules, presence of multinuclear giant cells, and sloughing of immature germ cells into the lumen, and a 22-29% decrease in genomic methylation levels in epididymal sperm. On closer evaluation of testicular histology using terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end-labeling detection in situ, both 6 and 11 weeks of 5-azacytidine treatment resulted in an increase over the control value in the number of apoptotic germ cells in the seminiferous tubules. Analysis of DNA methylation levels in isolated germ cells of treated males indicated that spermatogonia were more susceptible to the hypomethylating effects of 5-azacytidine than were spermatocytes. These studies provide evidence of an association between demethylation of germ cell DNA and alterations in testicular histology.

Animals↗

Subacute sclerosing panencephalitis: atypical absence attacks as first symptom.

Subacute sclerosing panencephalitis was diagnosed in a 10-year-old girl who had suffered from atypical absence attacks for 3 months; diagnosis was made after 5 months of these attacks. Characteristic EEG findings included diffuse spike and wave complexes of about 2.5 Hz associated with desynchronization during the absence attacks, and recruiting rhythm during the tonic seizure. As the lesion responsible for these EEG patterns originated in the brainstem, subcortical structures were probably affected early in the disease. The SSPE complexes may have originated chiefly in the brainstem since, in this case, they were recognized even during the period of absence attacks.

Brain Stem↗

Modeling of digestive tract lesions using silicone rubber RTV (KE-12).

In order to produce life-size models of digestive tract lesions, we applied silicone rubber RTV (KE-12) over the surface of the resected fresh, half-fixed or completely-fixed specimens to achieve their impressions. Into these impressions, super-hard plaster, acrylics and lysine base were separately poured, with the resultant casts realizing faithful replicas of the original patterns, finely reproducing their mucosal micro-structures. A photofluorogram of the silicone rubber pattern taken by using softex could reveal roentgenographic micromucosal features on a single plane. Clinically, endoscopic casting of lesions in similar procedures could produce their models, providing data available for estimation of the size and depth of an ulcer. Our method would be of help in dynamical pursuit of digestive tract lesions, as well as for comparison of the vital realities of lesions and their histopathological findings. The method may further contribute to reducing the dosage of x-ray bombardment in gastric fluoroscopy.

Animals↗

Modification of a response bias through differential amount of reinforcement.

A procedure is described for assessing response bias to either the form or color dimension of a compound standard stimulus. Responding was assessed under conditions of equal reinforcement (three tokens) for responding to either the form or color dimension. Under these conditions, the four male subjects (aged 7 to 11 yr) differentially responded to the form dimension. After a bias was assessed, the number of tokens delivered contingent upon form responses was reduced. After a reversal in differential responding, the equal-reinforcement condition was reintroduced. Two of the subjects returned to their initial response bias when equal reinforcement for either dimensional response was reintroduced, and two maintained the reversal established during the differential-reinforcement phase. For the latter two subjects, differential reinforcement was again imposed, in favor of form. This partial replication reinstated their original pattern of response bias.

Color Perception↗