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Biomedical subjects

J F Schmitt

Publications and source records attributed to J F Schmitt.

At least 19 recordsLinked to original sources
PubMed2001

The contribution of inhibins and activins to malignant prostate disease.

The normal human prostate expresses inhibin and activin subunits. In prostate cancer, the inhibin alpha subunit gene is down regulated and this is associated with loss of heterozygosity (LOH) at the gene locus and methylation of the promoter. These data support the hypothesis that the inhibin alpha subunit is tumor suppressive in the prostate. The pluripotent effects of activins and the similarities to transforming growth factor beta (TFGbeta) suggest a role for activins in progression to malignancy, whereby, the normal growth inhibitory action of activin A observed on benign cells is lost with the acquisition of activin resistance in prostate cancer cells. The mechanisms of rendering tumor cells resistant to activin A may include: alteration in activin binding protein (follistatin) synthesis and/or dimerisation with activin beta(C) to form novel activin dimers. The contribution of the activin signalling cascade to malignancy requires further evaluation to identify the synergies and differences to other members of the TGFbeta superfamily.

Activins↗
PubMed2001

Activins and inhibins in endocrine and other tumors.

Inhibin and activin are members of the TGF beta superfamily of growth and differentiation factors. They were first identified as gonadal-derived regulators of pituitary FSH and were subsequently assigned multiple actions in a wide range of tissues. More recently, the inhibin alpha subunit was considered as a tumor suppressor based on functional studies employing transgenic mouse models. This review evaluates the functional and molecular evidence that the inhibin alpha subunit is a tumor suppressor in endocrine cancers. The evaluation highlights the discrepant results from the human and mouse studies, as well as the differences between endocrine tumor types. In addition, we examine the evidence that the activin-signaling pathway is tumor suppressive and identify organ-specific differences in the actions and putative roles of this pathway in endocrine tumors. In summary, there is a considerable body of evidence to support the role of inhibins and activins in endocrine-related tumors. Future studies will define the mechanisms by which inhibins and activins contribute to the process of initiation, promotion, or progression of endocrine-related cancers.

Activins↗
PubMed1999

Design of a muscle cell-specific expression vector utilising human vascular smooth muscle alpha-actin regulatory elements.

The facility to direct tissue-specific expression of therapeutic gene constructs is desirable for many gene therapy applications. We describe the creation of a muscle-selective expression vector which supports transcription in vascular smooth muscle, cardiac muscle and skeletal muscle, while it is essentially silent in other cell types such as endothelial cells, hepatocytes and fibroblasts. Specific transcriptional regulatory elements have been identified in the human vascular smooth muscle cell (VSMC) alpha-actin gene, and used to create an expression vector which directs the expression of genes in cis to muscle cells. The vector contains an enhancer element we have identified in the 5' flanking region of the human VSMC alpha-actin gene involved in mediating VSMC expression. Heterologous pairing experiments have shown that the enhancer does not interact with the basal transcription complex recruited at the minimal SV40 early promoter. Such a vector has direct application in the modulation of VSMC proliferation associated with intimal hyperplasia/restenosis.

Actins↗
PubMed1999

Tissue-selective expression of dominant-negative proteins for the regulation of vascular smooth muscle cell proliferation.

The transcription factors c-myb and c-myc are essential for vascular smooth muscle cell (VSMC) replication and are rapidly induced following mitogenic stimulation of quiescent VSMCs in vitro and in vivo following balloon catheter injury. Consequently, interference with c-myb and c-myc function provides a possible avenue for the prevention of VSMC proliferation associated with intimal hyperplasia. We have carried out studies focused on the inhibition of VSMC proliferation using dominant-negative gene constructs incorporating the DNA-binding domains of the c-myb or c-myc genes fused to the repressor domain of the Drosophila engrailed gene. Transient transfection of rat, rabbit and human vascular SMCs results in a dramatic inhibition of proliferation for at least 72 h after transfection. Furthermore, this inhibition of cellular proliferation was found to be due, at least in part, to the induction of apoptosis. Coupling expression of the chimeric dominant-negative proteins to transcriptional regulatory elements of the human vascular smooth muscle alpha-actin gene allows specific targeting of vascular smooth muscle cells.

Actins↗
PubMed1997

High efficiency reporter gene transfection of vascular tissue in vitro and in vivo using a cationic lipid-DNA complex.

Efficient transfection conditions for a number of human, rat and rabbit primary cells and established lines of vascular origin have been determined using a complex of a commercially available cationic lipid transfection agent (Tfx-50) and luciferase reporter plasmid constructs. The optimised conditions have also been successfully applied to rabbit carotid arteries in vivo and a series of human arteries in vitro. The most critical factors influencing the efficiency of gene transfection with this protocol are: DNA concentration; ratio of lipid reagent to DNA; transfection time and the presence or absence of serum. Immunohistochemical analysis shows that a high percentage of cells (approximately 30-80% dependent on lineage) were transfected under optimal conditions with minimal toxicity effects. Similar analyses performed on undamaged rabbit carotid vessels transfected in vivo and human arteries transfected in vitro show high-efficiency transfer and strong expression of the luciferase vector as demonstrated by reporter gene expression. The optimisation of gene transfer into vascular cells with this cationic lipid complex will be valuable for molecular studies of genes implicated in cardiovascular diseases and as a possible method of gene delivery with therapeutic intent.

Animals↗
PubMed1996

The use of crude tissue section lysates for PCR assessment of gene copy number with human tumour biopsy samples.

This paper reports the development of experimental procedures for the use of crude tissue section lysates, in conjunction with a non-radioactive polymerase chain reaction-high performance ion-exchange chromatographic (PCR/HPIEX) method, for the quantitative assessment of gene copy number in human biopsy samples. In particular, these methods have been established for the assessment of gene amplification with the FGF-2, FGF-3, FGF-4 and c-erb-B2 genes with the a single copy IFN-gamma gene used as an internal control. In principle, the same procedures could, in general, be simultaneously applied for monitoring the amplification or deletion of other oncogenes as well as normal genes in mammalian cells. Procedures to optimise the precision of the analysis have been examined, including the influence of the oligonucleotide primer concentrations, cycle number, extension temperature, and method of pre-treatment of the tissue sample with proteinase K. The results confirm that crude tissue lysates, rather than purified DNA samples, can be reliably employed, thus extending the scope of non-radioactive PCR/HPIEX methods for the assessment of aberrant gene copy number to biological samples such as tumour biopsy tissues.

Adenocarcinoma↗
PubMed1996

Expression of fibroblast growth factor-8 in adult rat tissues and human prostate carcinoma cells.

Androgens are essential for normal prostatic and testicular function. However, paracrine and/or autocrine actions of a number of growth factors have been implicated in the function of these tissues. A recent addition to the fibroblast growth factor family, the so called androgen-induced growth factor (AIGF) or fibroblast growth factor-8 (FGF-8), has been proposed to be under strict androgen regulation and induction in the mouse mammary carcinoma cell line SC3. FGF-8, therefore, may have a local role in the prostate, which is known to be an androgen-responsive organ. This study reports, for the first time, the presence of FGF-8 mRNA in normal adult rat tissues (heart, brain, lung, kidney, testis, prostate and ovary), using an optimised reverse transcription and nested polymerase chain reaction (RT-PCR) procedure, although androgen-dependent FGF-8 expression was not demonstrated in these adult tissues. Consistent with the oncogenic characteristics of FGF-8, the corresponding mRNA was detected in the human prostate tumour cell lines LNCaP and DU145. Because the DU145 cell line is known to be androgen-independent, and the expression of FGF-8 mRNA in cultured LNCaP cells also occurred in the absence of exogenous androgens, it can be concluded that the expression of FGF-8 mRNA in these human cell lines, in the rat prostate and in other rat tissues is not under the regulation of androgens as hitherto proposed.

Androgens↗
PubMed1996

Aberrant FGF-2, FGF-3, FGF-4 and C-erb-B2 gene copy number in human ovarian, breast and endometrial tumours.

The important role of oncogene amplification and tumour suppressor gene deletion in human tumours is becoming increasingly apparent. However, extensive screening of human tumours is required before the prognostic significance of such genetic abnormalities can be fully appreciated. The present investigation describes a rapid non-radioactive and largely automated procedure for the analysis of aberrant gene copy number in large numbers of tissue samples of different human tumours. This procedure is based on the sequential use of the polymerase chain reaction (PCR) and high performance ion exchange liquid chromatography (HPIEX). Using this rapid PCR/HPIEX technique, we have identified amplification and deletion of the FGF-2 gene and the FGF-3, FGF-4 and c-erb-B2 oncogenes in human tumours of the breast, ovary and endometrium. Comparison of the data with tumour pathology has revealed possible associations between aberrant gene copy number and tumour type, invasiveness and metastases.

Blotting, Southern↗
PubMed1995

The perceptions of stutterers by people who stutter.

Twenty-five persons who stutter completed a questionnaire asking respondents to list adjectives describing four hypothetical stutterers: a female child, male child, female adult and male adult stutterer. The majority of reported adjectives concerned negative stereotypical personality traits, indicating descriptions of stutterers by a group of persons who stutter that were similar to descriptions given by fluent subject groups. Implications of these findings are discussed.

Adult↗
PubMed1992

A new quantitative polymerase chain reaction-high performance ion exchange liquid chromatographic method for the detection of fibroblast growth factor-beta (FGF-beta) gene amplification.

A method for the quantitative determination of fibroblast growth factor-beta (FGF-beta) genomic amplification based on the use of optimized polymerase chain reaction (PCR) procedures and high performance ion exchange (HPIEX) liquid chromatography has been developed. Co-amplification of a second genomic species permits internal standardization of the techniques during optimization of the reaction conditions, the PCR cycle number and the PCR cycle efficiency, as well as during the analytical HPIEX chromatographic determination of the PCR products. These investigations confirm the versatility of these procedures to quantitatively analyse FGF-beta gene amplification in various cells and tissues.

Base Sequence↗
PubMed1990

Subject descriptions, control groups, and research designs in published studies of language-impaired children.

We reviewed the 1983-1988 issues of six journals that frequently publish papers including specifically language-impaired (LI) subjects. A total of 92 research reports provided data for our review. The research reports included experimental studies, ex post facto studies, and intervention studies. These studies represent a broad spectrum of the theoretical and empirical foundations of knowledge regarding LI children. The analysis of the published research centered on subject descriptions and the use of control groups. A descriptive analysis of the data showed few consistent trends among the studies with respect to subject selection, subject description, and the number and types of control groups. We discuss the importance of more complete subject descriptions in studies of LI children as well as the importance of the choice of matching criteria for control groups in between-subjects designs.

Child↗
PubMed1989

Selected pragmatic features in Spanish-speaking preschool children.

We assessed Spanish-speaking preschool children for the development of seven language functions and three discourse features. Analyses consisted of spontaneous language samples averaging 136 utterances per child, for 18 subjects between 3:0 and 4:5 (years:months). Data for the frequency of occurrence and the percentage of appropriate usage showed that the preschoolers had established communicative competence for the functions and discourse features. Implications include establishing preliminary guidelines for the development of normal pragmatics in Hispanic preschoolers. We also discuss the 10-item taxonomy as a reliable and clinically useful tool with either English-speaking or Spanish-speaking children.

Central America↗
PubMed1989

Natural alteration of speaking rate: the effect on passage comprehension by listeners over 75 years of age.

The purpose of the study was to assess the comprehension performance of "old-old" listeners for naturally rate-altered passages. Fourteen men and 14 women between 75 and 84 years of age responded to comprehension questions after hearing matched passages at four different rates. The listeners' performances were significantly worse under 60% time compression than at normal rate and two rates of time expansion. Comprehension differences between the sexes were not significant. The results are compared with prior findings for old-old listeners responding to electronically altered speech stimuli (Schmitt, 1983a) and for "young-old" listeners (65-74 years of age) who also responded to naturally rate-altered passages.

Aged↗
PubMed1988

Sequence and transcriptional analysis of the vaccinia virus HindIII I fragment.

The complete sequence of the vaccinia virus HindIII I fragment, which is composed of 6,498 base pairs, encodes six complete and two incomplete open reading frames (ORFs). Computer analysis revealed an amino acid sequence homology between ORF I 4 and the large subunit of the ribonucleotide reductase complex. The two small polypeptides derived from ORFs I 2 and I 5, with molecular weights of 8,500 and 8,700, respectively, have a very high hydrophobic amino acid sequence composition. S1 analysis revealed that ORF I 4 is expressed at early stages of infection, ORFs I 1, I 2, I 5, and I 7 are expressed in the late phase of infection, and ORF I 3 is constitutively expressed. Screening a vaccinia virus genomic library revealed a large vaccinia virus insert overlapping the HindIII I and O fragments which contains a previously undetected HindIII P fragment of approximately 300 base pairs. S1 analysis revealed an early (O1) and a late (O2) start site of transcription initiation located within the HindIII O fragment.

Amino Acid Sequence↗
PubMed1986

Variable speech control vs Varispeech: does newer mean better?

Normal-hearing volunteers (N:30, aged 19-28 yrs) yielded intelligibility scores for W-22 word lists and CID sentences at 40 db re each S's SRT, and judgments on a 7-pt scale ("very pleasant"----"very unpleasant") for Sentence 3 of Fairbanks' "Rainbow Passage". Normal and time-altered speeds (60%: compression; 140%: expansion) were compared between the widely-used but obsolescent Lexicon Varispeech (VSp) unit vs the commercially available Variable Speech Control Model A-7 which incorporates a time-sampling technique similar to the VSp. With both VSp and VSC, intelligibility was nearly perfect at all three speeds, and thus both appear equally suitable for intelligibility studies, but at the 60% and 140% speeds the signal clarity was significantly preferable for the VSp system (p less than .01 in both cases), by .6 of a scale interval at 60% and 1.8 interval at 140%. Furthermore, the VSC does not operate beyond the 60-140% range, as occasionally may be desirable in research on the effects of time alteration on speech reception.

Adolescent↗
PubMed1985

Older listeners' ability to comprehend speaker-generated rate alteration of passages.

The purpose of this investigation was to determine the effect of speaker-generated (natural) rate alteration on passage comprehension performance by healthy older listeners. Fourteen men and 14 women between 65 and 74 years of age were tested. The passages were recorded at 60% time compression, 0% alteration (normal rate), and at time expansion values of 140% and 180%. Comprehension was measured by scoring the responses made by subjects to questions that were pertinent to each passage. The data were analyzed for comprehension performance differences among the four rate alteration conditions and between the men and women. The group performed significantly more poorly only at 60% time compression when compared with normal rate; there were no differences among the three slower rates. The findings are compared with prior studies of rate-altered stimuli with older listeners and are discussed relative to potential differences in the responses of older persons to electronically altered as opposed to naturally altered speech rate.

Aged↗
PubMed1983

The effects of time compression and time expansion on passage comprehension by elderly listeners.

The purpose of the investigation was to examine the comprehension performance of elderly listeners in response to rate-altered passages. A group of 56 persons was divided equally into two groups: young-old (65-74) and old-old (75-84). Experimental stimuli included four sets of test passages and questions that had been equalized for difficulty using three trial groups of subjects. Passages were presented at 60% time compression, 0% alteration (normal rate), and at 140% and 180% time expansion. Results indicated that young-old and old-old listeners did not differ significantly in mean passage comprehension scores at the normal rate and that both groups had significantly poorer comprehension at 60% time compression than at each of the other three presentation rates. Young-old subjects had better comprehension at 140% expansion and significantly better comprehension at 180% expansion compared with their performance at 0%. However, old-old subjects experienced nonsignificantly improved comprehension at 140% time expansion and were affected detrimentally by further expansion to 180%. Results are compared with those of prior investigations of sentence comprehension and are discussed with an emphasis on the heterogeneity of elderly listeners.

Aged↗