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Biomedical subjects

J Mark

Publications and source records attributed to J Mark.

At least 37 records · Page 2Linked to original sources

Submicroscopic deletions of 3p sequences in pleomorphic adenomas with t(3;8)(p21;q12).

A subgroup of benign pleomorphic adenomas of the salivary glands is characterized by translocations, or on rare occasions deletions, with breakpoints at 3p21. We have applied restriction fragment length polymorphism (RFLP) analysis to assess the frequency of allelic losses at four different loci located within 3p21-->p25 in 35 pleomorphic adenomas, 18 of which were also karyotyped. Parallel analysis of constitutional and tumor DNAs in informative tumors revealed that all patients retained heterozygosity in their tumor DNA at the D3S2 and RAF1 loci. Among the 29 tumors informative for THRB three showed loss of heterozygosity (LOH). All three tumors had a t(3;8)(p21;q12). Of the 23 tumors informative for D3F15S2, one showed LOH. This tumor also had a t(3;8)(p21;q12). To further map the deletions in relation to the 3p21 translocation breakpoint, we also sublocalized the THRB locus. Using in situ hybridization we assigned the gene to 3p24.1-3. The fact that none of the tumors with loss of 3p alleles showed cytogenetic evidence of deletions indicates that the losses are submicroscopic, probably interstitial, and in most cases distal to the 3p21 breakpoint. This was confirmed in one case with loss of a THRB allele where both proximal (D3F15S2) and distal (RAF1) markers retained heterozygosity. Our results suggest that deletion of 3p sequences might be of progressional importance in a subset of pleomorphic adenomas with t(3;8)(p21;q12).

Adenoma, Pleomorphic

Implants of pure titanium for internal fixation of the peripheral skeleton.

In a multicentre study, a clinical evaluation of the new titanium implants of the sizes 2.7, 2.0 and 1.5 mm was done. In seven centres, 133 patients were operated on and the personal, subjective opinions of the surgeons were recorded. In the opinion of these surgeons experienced in using steel implants, the outcome of the internal fixations was the same for titanium as for steel implants. Three metal-related complications occurred in the smallest size screw type (1.5 mm), namely, one screw broke and two bent. In the cases in which the implant had been removed, good tissue contact with the implant could be seen. Only in one case was there discolouring of the soft tissue due to titanium. It is recommended that surgeons who are used to handling stainless steel screws should be aware of the slightly different behaviour of titanium screws.

Adolescent

Cytogenetic observations in 13 cystadenolymphomas (Warthin's tumors).

The cytogenetic findings in 13 cultured Warthin's tumors (papillary cystadenoma lymphomatosum) are reported. Only one case showed an abnormal stemline. This was pseudodiploid and characterized by three different reciprocal translocations and one deletion. Small abnormal sidelines, however, were seen in three additional cases. All except one of the 12 tumors with a normal stemline contained variant cells. These showed a variety of numerical and/or structural aberrations. From this study it is obvious that to determine whether or not cytogenetically distinctive subgroups actually exist in cystadenolymphomas (as in pleomorphic adenomas) the number of cases must be greatly amplified.

Adenolymphoma

Aggressive angiomyxoma of the vulva: an unusual, deceptive and recurrence-prone tumour with evidence of estrogen receptor expression. Case report.

Positive staining for estrogen receptors is reported in a new case of aggressive angiomyxoma of the vulva. Clinical, light- and electron microscopic features as well as immunohistochemical reactions in this case are compared with the 28 earlier published cases, and the main differential diagnosis, angiomyofibroblastoma of the vulva, is discussed.

Female

Beta-nerve growth factor levels in newborn cord sera.

This study was designed to examine beta-nerve growth factor (NGF) levels in human cord blood by a two-site enzyme immunoassay using MAb 27/21 to mouse NGF and to determine whether beta-NGF levels show developmental changes. Blood was collected at delivery from 61 newborns, 55 neonates appropriate for gestational age (46 term infants and 9 premature infants), 5 neonates small for gestational age, and 1 neonate with congenital hydrocephalus. In addition, samples were collected from 2 microcephalic children (microcephaly vera) aged 15 and 18 mo, 2 control children, and 4 healthy adults. Mean levels of NGF in preterm infants (n = 9; 13.7 +/- 8 pg/mL) were significantly lower than levels in term infants (n = 47; 21.2 +/- 8.8 pg/mL; p = 0.034 by Mann-Whitney U test). There was no correlation between birth weight, length, head circumference, and beta-NGF levels. In microcephalic children, NGF levels were low (8 pg/mL) compared with control infants' values (22 pg/mL). In adults, beta-NGF levels were higher and ranged between 238 and 292 pg/mL. Our study demonstrates that beta-NGF levels can be assessed in human newborn sera using a two-site enzyme immunoassay with MAb 27/21 to mouse beta-NGF, that beta-NGF levels are extremely low in newborns compared with adults, that beta-NGF levels seems to show developmental changes, and that beta-NGF levels may be used to assess NGF utilization under normal and pathologic conditions such as cerebral malformations.

Adult

The 12q13-q15 translocation breakpoints in pleomorphic adenoma and clear-cell sarcoma of tendons and aponeuroses are different from that in myxoid liposarcoma.

The transcription factor gene CHOP was recently shown to be rearranged in myxoid liposarcoma with t(12;16)(q13;p11). We have analyzed whether the CHOP gene is the target of rearrangements in pleomorphic adenoma and clear-cell sarcoma of tendons and aponeuroses with chromosome abnormalities of 12q13-q15. Restriction fragment analysis showed that the CHOP gene and its flanking sequences were not rearranged in any of these tumor types, indicating that the 12q translocation breakpoints in pleomorphic adenoma and clear-cell sarcoma are different from that in myxoid liposarcoma.

Adenoma

Isotretinoin therapy for acne vulgaris: a re-evaluation of the need for measurements of plasma lipids and liver function tests.

A retrospective analysis of patients receiving isotretinoin for acne was performed, in order to determine the necessity for routine testing of lipid profiles and liver function tests during therapy. Data were analysed from 209 individuals, 113 (69 males, 44 females) of whom had been treated with 1 mg/kg/day, and 96 (67 males, 29 females) with 0.5 mg/kg/day. There were no significant changes in any of the tests of liver function. There were significant elevations in both plasma cholesterol and triglycerides at 8 and 16 weeks (P < 0.01) for both dose schedules, which were significant in both male and female subjects (P < 0.001). All the individuals with elevated cholesterol (> 6.5 mmol/l) at 16 weeks had elevated cholesterol at the onset of therapy. Triglyceride concentrations were elevated at 8 weeks, but there was no further increase thereafter. It was not possible to predict which subjects would become hypertriglyceridaemic from pretreatment lipid estimations. In conclusion, there appears to be little evidence to support the previously recommended regular biochemical monitoring of liver function and lipid profiles in patients who are treated with isotretinoin for 16 weeks. It would appear prudent to ensure that there is neither liver disease nor hyperlipidaemia prior to the onset of therapy, and to determine the triglyceride response to therapy on one occasion after 4 weeks' treatment. This change in patient management should result in considerable savings both in patient time and in blood collection and analysis.

Acne Vulgaris

gamma-Hydroxybutyrate ligands possess antidopaminergic and neuroleptic-like activities.

The action of agonists or antagonists at the gamma-hydroxybutyrate (GHB) receptor represents a possibility to modulate dopaminergic activities in brain. In the present study, GHB and six structural analogs were tested for their ability to displace [3H] GHB binding from striatal membranes. All the analogs tested exhibited higher affinity for GHB as compared with GHB itself. Parallel experiments were carried out on striatal slices in order to determine IC50 values for inhibition of dopamine release in the presence of these compounds. All substances inhibited dopamine release with higher potency as compared with GHB itself. These antidopaminergic activities were confirmed in several neuropharmacological tests, usually used to predict neuroleptic activities in vivo. There appears to be a relationship between the affinity for the GHB striatal low-affinity receptor and the inhibition of dopamine release on one hand, and the antidopaminergic activity (as revealed by the in vivo tests) on the other hand. Thus, it is suggested that GHB agonists possessing antidopaminergic activities, may represent potential drugs endowed with neuroleptic properties.

Animals

Multiple unrelated chromosome abnormalities in a metastatic mucoepidermoid carcinoma of the parotid gland.

We describe cytogenetic findings in a poorly differentiated, metastatic mucoepidermoid carcinoma of the parotid gland. The tumor was characterized by multiple, unrelated chromosome abnormalities. Except for two small aberrant clones showing t(1;7) and t(2;15), respectively, all other abnormal cells showed unique, mostly structural rearrangements peculiar to each cell. No less than 34 different abnormal karyotypes were observed. A similar karyotypic heterogeneity was also described recently in squamous cell carcinomas of the head and neck.

Carcinoma

A unique hydrophobic domain of rat brain globular acetylcholinesterase for binding to cell membranes.

Both salt-soluble and detergent-soluble rat brain globular acetylcholinesterases (SS- and DS- AChE EC 3.1.1.7) are amphiphiles, as shown by detergent dependency of enzymatic activity and binding to liposomes. Proteinase K and papain treatment transformed SS-AChE and DS-AChE into forms that, in absence of detergent, no longer aggregated nor bound to liposomes. In contrast, phosphatidylinositol-specific phospholipase C had no effect on these properties. Labeling DS-AChE with 3-(trifluoromethyl)-3-(m-(125I)-iodophenyl) diazirine ([125I]TID) revealed, by polyacrylamide gel electrophoresis under reducing conditions, one single band of 69 kD apparent molecular mass. The same pattern was previously obtained with Bolton and Hunter reagent-labeled enzyme. Proteinase K treatment transformed the 11 S [125I]TID labeled AChE into a 4 S form which no longer showed 125I-radioactivity and was unable to bind to liposomes. These results are compatible with the existence of a hydrophobic segment present both on salt-soluble and detergent-soluble 11 S AChE as well as on the minor forms 4 S and 7 S. This segment is not linked to the catalytic subunits by disulfide bounds in contrast to the 20 kD non-catalytic subunit described by Inestrosa et al.

Acetylcholinesterase

Human benign chondroblastoma with a pseudodiploid stemline characterized by a complex and balanced translocation.

The chromosomes of a human benign chondroblastoma of the jaw were studied by in vitro technique. Approximately one-third of the analyzed cells had a normal karyotype. The remaining two-thirds constituted an abnormal monoclonal population with a complex and balanced translocation. The observations are different from those in previously studied benign primary bone tumors. The breakpoint in 22q, however, is similar or very close to that observed in two extraskeletal myxoid chondrosarcomas earlier reported.

Adolescent

INT1 and GLI genes are not rearranged or amplified in benign pleomorphic adenomas with chromosome abnormalities of 12q13-15.

A subgroup of pleomorphic adenomas of the salivary glands is characterized by translocations involving chromosome 12, with consistent breakpoints at 12q13-15. Two proto-oncogenes, INT1 and GLI, have been assigned to this region of chromosome 12. We studied the possible involvement of these genes in pleomorphic adenomas with different karyotypic abnormalities, including cases with involvement of 12q13-15. Using detailed restriction fragment analysis of tumor DNAs from 25 cases, we found no evidence of rearrangement or amplification of INT1 or GLI. Because we previously found an adenoma with a del(12)(q13q15), we also analyzed normal and tumor DNAs from the 25 tumors separately to identify possible allelic losses at the GLI locus. Thirteen of the 25 tumors were informative, and none of these showed evidence of allelic losses. Collectively, these findings indicate that neither the INT1 nor the GLI gene appears to be the primary target gene for the translocations and deletions involving the 12q13-15 region in pleomorphic adenomas.

Adenoma, Pleomorphic

Long-term effects of topical corticosteroids in the nose.

In a prospective study, biopsies were taken from the septal mucosa in 21 patients of whom 11 had been using topical nasal corticosteroids. In contrast to the effect of long-term treatment with corticosteroids in the skin, but in accordance with previous investigations of the nasal mucosa, no histopathological changes of significance were found, although the biopsies were taken from different sites. These findings do not suggest that topically corticosteroids are harmful to the nasal mucosa.

Administration, Topical

Expression, characterization, and serologic reactivity of recombinant surface antigen P22 of Toxoplasma gondii.

The utility of recombinant Toxoplasma gondii surface antigen P22 for the detection of specific T. gondii antibodies in human sera was evaluated. Polymerase chain reaction was used to produce a 438-bp fragment of the P22 gene; the fragment corresponded to the amino acids predicted to be in the processed, native antigen. The fragment was subcloned into pGEX-2T and was expressed in Escherichia coli as a glutathione-S-transferase (GST) fusion protein. The fusion protein was purified in a soluble form and was found to be recognized by sera from infected individuals in immunoblots and an enzyme-linked immunosorbent assay. Immunoglobulin G antibodies in sera from 31 acutely infected patients in general reacted more strongly to the fusion protein than did those in sera from 31 patients with the chronic infection. None of the sera from a panel of 26 seronegative controls reacted with the fusion protein was separated from the GST partner by cleavage with thrombin, it retained its immunoreactivity and its electrophoretic mobility in polyacrylamide gels was found to be similar to that of native P22. By a modification of the published method for purification of the foreign polypeptide from the GST carrier, the recombinant P22 was readily purified to homogeneity by thrombin cleavage of the fusion protein while it was adsorbed to glutathione agarose.

Animals

Expression of the ERBB2 protein in benign and malignant salivary gland tumors.

Fifty-two primary human salivary gland tumors were analyzed for expression of the p185ERBB2 protein using immunohistochemical and immunoblotting techniques. About 63% (33/52) of the tumors expressed the ERBB2 protein. The highest expression levels were detected among the carcinomas, where 32% of the tumors showed intense membrane staining in 25-100% of the tumor cells. In benign pleomorphic adenomas, the corresponding figure was only 12%. Clinical follow-up data available for 18 of the 19 patients with carcinomas suggested an association between high ERBB2 protein levels and poor prognosis as measured by recurrence of disease and/or the appearance of metastases. These results indicate that ERBB2 activation and overexpression could be an important genetic event with possible prognostic implications in a subset of malignant salivary gland tumors.

Adenoma

Functionalized membrane supports for covalent protein microsequence analysis.

Methods were developed for high yield covalent attachment of peptides and proteins to isothiocyanate and arylamine-derivatized poly(vinylidene difluoride) membranes for solid-phase sequence analysis. Solutions of protein or peptide were dried onto 8-mm membrane disks such that the functional groups on the surface and the polypeptide were brought into close proximity. In the case of the isothiocyanate membrane, reaction between polypeptide amino groups and the surface isothiocyanate moieties was promoted by application of aqueous N-methylmorpholine. Attachment of proteins and peptides to the arylamine surface was achieved by application of water-soluble carbodiimide in a pH 5.0 buffer. Edman degradation of covalently bound polypeptides was accomplished with initial and repetitive sequence yields ranging from 33 to 75% and 88.5 to 98.5%, respectively. The yields were independent of the sample load (20 pmol to greater than 1 nmol) for either surface. Significant loss of material was not observed when attachment residues were encountered during sequence runs. Application of bovine beta-lactoglobulin A chain, staphylococcus protein A, or the peptide melittin to the isothiocyanate membrane allowed for extended N-terminal sequence identification (35 residues from 20 pmol of beta-lactoglobulin). A number of synthetic and naturally occurring peptides were sequenced to the C-terminal residue following attachment to the arylamine surface. In one example, 10 micrograms of bovine alpha-casein was digested with staphylococcal protease V8 and the peptides were separated by reverse-phase chromatography. Peptide fractions were then directly applied to arylamine membrane disks for covalent sequence analysis. From as little as 2 pmol of initial signal it was possible to determine substantial sequence information (greater than 10 residues).

Amines

Karyotypic variability and evolutionary characteristics of a polymorphous low grade adenocarcinoma in the parotid gland.

The chromosomes of a polymorphous low-grade adenocarcinoma originating from a pleomorphic adenoma of the parotid gland were studied. Three successful preparations were performed. A minor fraction of cells showed normal karyotypes and some cells only inconsistent, usually numerical, deviations. The remaining cells constituted an abnormal monoclonal population with an unusual and very extensive karyotypic variability. The origin of most marker chromosomes could be wholly or partly clarified. Five different subclones could be distinguished on basis of different specific marker chromosomes. The characteristics of the marker sets suggested a closely interrelated derivation of the subclones. The results also provide insight as to the influence of random factors and/or differential growth rate on the chromosomal picture observed in in vitro systems. The present chromosomal observations showed no similarities either to the cytogenetical findings in the five previously reported salivary gland adenocarcinomas or to the deviations seen in the single studied case of carcinoma ex-pleomorphic adenoma.

Adenocarcinoma