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Biomedical subjects

M Mitchell

Publications and source records attributed to M Mitchell.

At least 91 records · Page 5Linked to original sources
PubMed1987

Pseudosarcoma botyroides in pregnancy: report of a case with ultrastructural observations.

A case of pseudosarcoma botryoides of the vagina diagnosed in advanced pregnancy is described. The cellular characteristics (atypical cells and abnormal mitoses) suggested malignancy, but ultrastructural studies demonstrated the fibroblastic nature of the cells, thus confirming the diagnosis of pseudosarcoma. Local excision and subsequent cesarean section was the method of treatment. Three years later, another pregnancy was terminated by repeat cesarean section and uncontrollable hemorrhage requiring emergency hysterectomy. The histologic study of the bleeding area revealed very edematous areas and lacunaelike endothelium-lined vessels. No cellular abnormalities were observed.

Adult↗
PubMed1986

Regional assignment of Y-linked DNA probes by deletion mapping and their homology with X-chromosome and autosomal sequences.

A series of Y recombinants have been isolated from Y-specific DNA libraries and regionally located on the Y chromosome using a Y deletion panel constructed from individuals carrying structural abnormalities of the Y chromosome. Of twenty recombinants examined twelve have been assigned to Yp and eight to Yq. Five of the Yp recombinants map between Yp11.2 and Ypter and one can only be assigned to Yp. Of the former, four detect homologies on the X chromosome between Xq13 and Xq24 and the latter one between Xp22.3 and Xpter. The sixth recombinant detects autosomal homologous sequences. The six remaining Yp probes are located between Ycen and Yp11.2. One of these detects a homology on the X chromosome at Xq13-Xq24 and a series of autosomal sequences, two detect uniquely Y-specific sequences and three a complex pattern of autosomal homologies. The remaining eight recombinants have been assigned to three intervals on Yq. Of three recombinants located between Ycen and Yq11.21 two detect only Y sequences and one additional autosomal homologies. Two recombinants lie in the interval Yq11.21-Yq11-22, one of which detects only Y sequences and the other an Xp homology between Xp22.3 and Xpter. Finally, the three remaining Yq recombinants all detect autosomal homologies and are located between Yq11.22 and Yq12. The divergence between homologies on different chromosomes has been examined for three recombinants by washing Southern Blots at different levels of stringency. Additionally, Southern analysis of DNA from flow sorted chromosomes has been used to identify autosomes carrying homologies to two of the Y recombinants.

Chromosome Deletion↗
PubMed1986

Variable transfer of Y-specific sequences in XX males.

A series of twelve XX males and their relatives have been examined by Southern blot analysis with fourteen different Y recombinants. The pattern of Y sequences present shows considerable variation between XX males. Furthermore, on the basis of the terminal transfer model, anomalous patterns of Y sequences are evident in certain XX males in that sequences located as proximal Yp by means of a Y deletion panel are found to be present in the absence of distal sequences. These anomalies can be resolved by proposing that the order of Yp sequences varies in the population in the form of inversion polymorphisms in the Y chromosomes of normal males. Alternatively, it is necessary to invoke multiple recombination events between the X and Y chromosomes to explain the patterns of Y sequences in these XX males. Southern analysis on DNA prepared from flow sorted X chromosomes of XX males indicates that the Y sequences in these patients are linked to X chromosomes.

Chromosome Mapping↗
PubMed1986

Regulation of prostaglandin biosynthesis by human ovarian follicular fluid: a mechanism for ovulation?

We have studied the effect of human ovarian follicular fluid on PG production by bovine seminal vesicles in vitro and found that hFF1 contains a factor of high molecular weight (Mr greater than 30,000) which inhibits PG synthase in a dose-dependent manner. Exposure of this substance to protease activity produced a factor of lower molecular weight (Mr less than 1000) which stimulated PG synthase activity. If this is true of ovarian follicles in vivo, it is possible that increased follicular protease activity stimulates PG synthesis at the time of ovulation.

Animals↗
PubMed1986

Multiple C4/Slp genes distinguished by expression after transfection.

The S region of the murine major histocompatibility complex contains two closely related genes: C4, encoding the fourth component of complement, and Slp, encoding sex-limited protein. We cloned these genes from a cosmid library of the B10.W7R strain that does not show androgen regulation of the Slp protein. Restriction site polymorphisms revealed at least four C4-like genes within the Sw7 locus, indicating evolutionary amplification of this region. Transfection of these genes into L cells resulted in expression, processing, and secretion of immunologically correct C4 and Slp proteins. At least two different Slp genes and one C4 gene were capable, after transfection, of expressing C4 and Slp indistinguishable from macrophage-derived protein. A third Slp gene exists within this locus whose recombinant cognate did not express in L cells. Thus, the B10.W7R S region includes one C4 gene and at least three Slp-like genes.

Animals↗
PubMed1986

Primary drug-resistant tuberculosis in children. Emergence of primary drug-resistant strains of M. tuberculosis to rifampin.

A prospective study of primary drug-resistant strains of Mycobacterium tuberculosis among children was begun at the Kings County Hospital Medical Center of Brooklyn in 1961 and reported at 5 4-yr periods through 1980. The present report extends our observations of primary drug-resistant tuberculosis in children through 1984. The salient finding in the present report was the increase in primary drug resistance to rifampin, 3 of 19 strains resistant in the last period of study (1981 to 1984) as compared with 1 of 96 strains isolated in the previous 3 periods of study (1969 to 1980). This increase was significant (p less than 0.02) even though the number of strains isolated was small. There were continued low resistance rates to ethambutol and para-aminosalicylic acid and stable resistance rates for isoniazid and streptomycin.

Adolescent↗
PubMed1985

1,4-Dideoxy-1,4-imino-D-mannitol inhibits glycoprotein processing and mannosidase.

1,4-Dideoxy-1,4-imino-D-mannitol (DIM) was synthesized chemically from benzyl-alpha-D-mannopyranoside [Fleet et al (1984) J. Chem. Soc. Chem. Commun., 1240-1241], and was tested in vitro as an inhibitor of various alpha-mannosidases and in cell culture as an inhibitor of glycoprotein processing. DIM proved to be an effective inhibitor of jack bean alpha-mannosidase, with 50% inhibition requiring 25 to 50 ng/ml inhibitor. It also inhibited lysosomal alpha-mannosidase, but in this case 50% inhibition required about 1 to 2 micrograms/ml. In both cases, the inhibition was of the competitive type when p-nitrophenyl-alpha-D-mannopyranoside was used as the substrate. The inhibition was better at higher pH values, suggesting that DIM was more effective when the nitrogen in the ring was in the unprotonated form. In addition, rat liver processing mannosidase I was also inhibited by DIM as measured by the release of [3H]mannose from [3H]mannose-labeled Man9GlcNAc. Glycoprotein processing was examined in influenza virus-infected MDCK cells. Infected cells were incubated in various concentrations of DIM and labeled with [2-3H]mannose. Viral and cell pellets were digested with Pronase and glycopeptides were isolated by gel filtration on columns of Bio-Gel P-4. The glycopeptides were then treated with endoglucosaminidase H (Endo H) and rechromatographed on the Bio-Gel column in order to distinguish complex from high-mannose structures. As the DIM concentration in the medium was raised, more and more of the [3H]mannose was incorporated into high-mannose oligosaccharides, and less and less radioactivity was in the complex chains. Most of the Endo H-released oligosaccharides induced by DIM were of the Man9GlcNAc structure, as determined by gel filtration, HPLC, and digestion by alpha-mannosidase. Thus, DIM also appears to inhibit mannosidase I in cell culture. However, about 15% of the Endo H-released oligosaccharides appear to be hybrid types of oligosaccharides, suggesting that DIM may also inhibit mannosidase II.

Animals↗
PubMed1985

Controlled study of withdrawal symptoms and rebound anxiety after six week course of diazepam for generalised anxiety.

A group of patients suffering from anxiety, as assessed by general practitioners and psychologists using research criteria for generalised anxiety, were treated with either diazepam or placebo double blind for six weeks. This active treatment period was preceded by a one week single blind placebo "wash in" period and followed by a two week single blind placebo "wash out" period. The results suggest that diazepam can produce rebound anxiety and withdrawal symptoms when used in moderate doses and for what has previously been regarded as a safe length of time. If replicated these results have implications for the therapeutic use of benzodiazepines.

Adult↗
PubMed1985

Primary drug-resistant tuberculosis in children. Correlation of drug-susceptibility patterns of matched patient and source case strains of Mycobacterium tuberculosis.

The purpose of this study is to compare the drug-susceptibility patterns of Mycobacterium tuberculosis isolated from patients (children) and from their corresponding adult contacts. We wished to ascertain if the susceptibility pattern of the isolate from the adult contact could be used as a guide in the initial selection of the antituberculous drug regimen in the child. Strains resistant to one or more antituberculous drugs were emphasized in our study. For 120 children with positive cultures, adults were identified who had positive cultures and who were the source of the children's infections. All strains had susceptibility tests for isoniazid, streptomycin, aminosalicylic acid, ethionamide, and, when they became available, ethambutol and rifampin. There were 29 instances in which either the adult's and/or the child's strain were resistant to one or more antituberculous drugs. In 111 (92.5%) instances the organism isolated from the child and that from the adult contact had identical drug-susceptibility patterns. Fourteen (93%) of 15 of the adult/child pairs were both resistant to isoniazid. The drug-susceptibility pattern of isolates obtained from the source of a child's illness is useful as a guide in planning initial drug therapy. In addition, knowledge of isoniazid-resistant strains in adult contacts may alert the physician to the potential failure of isoniazid prophylaxis.

Adolescent↗
PubMed1985

Rapid plasma digoxin assay in outpatients--a useful routine technique?

In 25 outpatients taking digoxin for chronic atrial fibrillation (established for at least six months) a prospective study identified only one case in which rapid availability of the results of a plasma digoxin assay altered the dose which had already been selected on the basis of simple clinical assessment. No patient received more than 375 micrograms digoxin per day and none showed clinical evidence of toxicity even though seven had renal impairment. Six other patients had poorly controlled ventricular rates requiring larger doses of digoxin, but even in these patients the dose could be selected on clinical grounds alone. Despite the availability of a very rapid fluorescence polarisation immunoassay for digoxin, simple but careful clinical monitoring is an adequate basis for the selection of a suitable dose in most patients taking digoxin for atrial fibrillation.

Aged↗
PubMed1985

Stimulation of ovine placental lactogen secretion by arachidonic acid.

To determine whether arachidonic acid stimulates the secretion of ovine placental lactogen (oPL), arachidonic acid was infused as an intravenous bolus into pregnant ewes and fetuses. Plasma oPL concentrations were determined in mothers and fetuses before and for 5 h after infusion. The administration of 12.5 mg arachidonic acid (0.15-0.2 mg/kg, n = 11 experiments) to the pregnant ewes caused an increase in maternal plasma oPL concentrations of 73.9 +/- 15.6% (S.E.M.) and 60.8 +/- 18.1% above the pretreatment concentrations at 4 and 5 h respectively (P less than 0.01 in each instance). The infusion of 25 mg arachidonic acid (n = 8) caused increases of 96.0 +/- 19.1% and 100.3 +/- 26.4% (P less than 0.005), and the stimulation was not inhibited by the cyclo-oxygenase inhibitors indomethacin and ibuprofen. In contrast to arachidonic acid, vehicle alone or palmitic acid had no effects on plasma oPL concentrations. Despite the increase in maternal plasma oPL concentrations, plasma oPL concentrations in the fetus remained unchanged after the maternal infusions. The infusion of arachidonic acid (0.5-1.5 mg/kg) directly into six fetuses had no effects on either fetal or maternal oPL concentrations. These studies indicate that arachidonic acid stimulates maternal plasma oPL concentrations but has no effect on fetal oPL concentrations and the stimulation of oPL secretion is not due to the conversion of arachidonic acid to prostaglandins or other cyclo-oxygenase products.

Animals↗
PubMed1984

The pyrrolidine alkaloid, 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine, inhibits glycoprotein processing.

2,5-Dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP) is a pyrrolidine alkaloid that was isolated from the plant, Lonchocarpus sericeus. In the present study, DMDP was tested as an inhibitor of glycoprotein processing. MDCK cells were infected with influenza virus and the virus was raised in the presence of various amounts of DMDP. The glycoproteins were labeled by the addition of [2-3H]mannose or [1-3H]galactose to the medium. The virus was isolated by differential centrifugation and treated with Pronase to obtain glycopeptides. These glycopeptides were isolated by chromatography on Bio-Gel P-4, then digested with endoglucosaminidase H (Endo H) and rechromatographed on the Bio-Gel P-4 column. In the control virus, more than 70% of the glycopeptides were resistant to Endo H and were previously characterized as complex types of oligosaccharides. The remaining 20-25% are sensitive to Endo H and are of the high-mannose type. However, in the presence of DMDP (250 micrograms/ml), more than 80% of the glycopeptides are susceptible to digestion by Endo H. The oligosaccharide released by this treatment sized like a hexose11-12GlcNAc on a calibrated column of Bio-Gel P-4, and was only slightly susceptible to alpha-mannosidase treatment. This oligosaccharide was also labeled in the glucose moieties by growing the virus in [1-3H]galactose in the presence of DMDP. Following isolation, the oligosaccharide was subjected to complete methylation. Acid hydrolysis of the methylated oligosaccharide gave three methylated glucose derivatives, corresponding to 2,3,4,6-tetramethylglucose, 3,4,6-trimethylglucose, and 2,4,6-trimethylglucose in almost equal amounts. These data indicate that the oligosaccharide is a Glc3Man8-9-GlcNAc and that DMDP inhibits glucosidase I. Similar results were obtained with the cellular glycoproteins. DMDP did not inhibit the incorporation of [3H]leucine into protein in MDCK cells, nor did it inhibit virus production as measured by plaque counts or hemagglutination assays. DMDP did cause some inhibition of mannose incorporation into the lipid-linked monosaccharides, but incorporation into lipid-linked oligosaccharides was not greatly affected, and incorporation into protein was stimulated. These results suggest that the pyrrolidine alkaloids are a new class of processing inhibitors.

Alkaloids↗
PubMed1984

Uptake of heterologous DNA by Haemophilus influenzae.

With the use of highly competent Haemophilus influenzae cells, it was possible to demonstrate the uptake of heterologous DNAs. However, these DNAs, as expected, were only 1% or less as effective when competing for uptake with Haemophilus DNA. Escherichia coli DNA was removed from solution by competent cells to the extent expected if all the E. coli DNA particles contained at least one uptake recognition signal. The data were consistent with a model in which there was one uptake signal per 20 X 10(6) to 30 X 10(6) daltons of E. coli DNA. Since H. influenzae DNA has many more recognition signals, approximately one per 2 X 10(6) daltons (Danner et al., Gene 77:311-318, 1980; K. Vogt and S. H. Goodgal, submitted for publication), it has been suggested that the slower rate of E. coli DNA binding and the so-called specificity of Haemophilus DNA binding are due to the number of recognition signals per molecule of DNA as well as the nature of the DNA receptor (Vogt and Goodgal, submitted for publication). The specificity of native H. influenzae DNA binding does not apply to the uptake of denatured DNA in the transforming system (low pH) for denatured DNA.

Binding Sites↗
PubMed1984

Effect of castanospermine on the structure and secretion of glycoprotein enzymes in Aspergillus fumigatus.

Aspergillus fumigatus secretes a number of glycosidases into the culture medium when the cells are grown in a mineral salts medium containing guar flour (a galactomannan) as the carbon source. At least some of these glycosidases have been reported to be glycoproteins having N-linked oligosaccharides. In this study, we examined the effect of the glycoprotein processing inhibitor, castanospermine, on the structures of the N-linked oligosaccharides and on the secretion of various glycosidases. Cells were grown in the presence of various amounts of castanospermine; at different times of growth, samples of the media were removed for the measurement of enzymatic activity. Of the three glycosidases assayed, beta-hexosaminidase was most sensitive to castanospermine; and its activity was depressed 30 to 40% at 100 micrograms of alkaloid per ml and even more at higher alkaloid concentrations. On the other hand, beta-galactosidase activity was hardly diminished at castanospermine levels of up to 1 mg/ml, but significant inhibition was observed at 2 mg/ml. beta-Galactosidase was intermediate in sensitivity. Cells were grown in the presence or absence of castanospermine and labeled with [2-3H]mannose, [6-3H]glucosamine, or [1-3H]galactose to label the sugar portion of the glycoproteins. The secreted glycoproteins were digested with pronase to obtain glycopeptides, and these were identified on Bio-Gel P-4 (Bio-Rad Laboratories). The glycopeptides were then digested with endoglucosaminidase H to release the peptide portion of susceptible structures, and the released oligosaccharides were reisolated and identified on Bio-Gel P-4. The oligosaccharides from control and castanospermine-grown cells were identified by a combination of enzymatic and chemical studies. In control cells, the oligosaccharide appeared to be mostly Man8GlcNAc and Man9GlcNAc, whereas in the presence of alkaloid, the major structures were Glc3Man7GlcNAc and Glc3Man8GlcNAc. These data fit previous observations that castanospermine inhibits glucosidase I.

Alkaloids↗
PubMed1984

Midazolam and fentanyl-fluanisone: assessment of anaesthetic effects in laboratory rodents and rabbits.

The anaesthetic effects of a combination of midazolam, a water-soluble benzodiazepine, and fentanyl-fluanisone were assessed in laboratory rodents and rabbits. This combination of drugs produced good surgical anaesthesia in all of the species investigated. An important advantage of the combination was that it could be administered as a single intraperitoneal injection.

Anesthesia, General↗
PubMed1984

Accuracy versus speed in the generalized effort of learning-disabled children.

Reinforcement of effortful performance in a given academic task has been found to increase the subsequent performance of other academic tasks. The learned-effort hypothesis assumes that individuals learn which dimensions of task performance are correlated with reinforcement of high effort, and generalize across tasks. Therefore, reinforcement of increased effort in a given dimension of one task should result in greater generalized effort in the same dimension of transfer performance than in another dimension. In accord with this view, preadolescent learning-disabled students who received points for high reading accuracy subsequently produced more accurate drawings and stories than did students whose points had been based upon high reading speed or upon mere completion of the reading task. Students who received points for high reading speed subsequently constructed stories more quickly than did children whose points had been based upon high reading accuracy or upon reading-task completion. Consistent with the more explicit and frequent feedback for accuracy than for speed in most academic tasks, generalized accuracy was much more durable than generalized speed.

Child↗