Biomedical subjects

Z Chen

Publications and source records attributed to Z Chen.

At least 811 records · Page 45Linked to original sources

PubMed1998

Molecular analysis of DRB and DQB1 alleles in German spina bifida patients with and without IgE responsiveness to the latex major allergen Hev b 1.

BACKGROUND AND OBJECTIVE: Spina bifida patients are at a high risk of developing latex allergy. Recently, we found a relationship between the IgE responsiveness to latex allergen hevein and human leucocyte antigen (HLA) alleles DRB1*04(DR4) as well as DQB1*0302(DQ8). This study was carried out to investigate the association between HLA class II alleles and the specific IgE response to latex allergen Hev b 1 in spina bifida patients. METHODS: Blood samples from 103 unrelated German spina bifida patients exposed to latex products and from 90 unsensitized controls were examined. Genomic DNA isolation followed by HLA-D-specifc polymerase chain reaction (PCR) amplification was used to perform HLA typing of allelic polymorphisms in exon 2 of DQB1 and of DRB1,3,4,5 with sequence-specific oligonucleotide probes (SSOPs). RESULTS: Fifty-one out of 103 spina bifida patients were found to have anti-latex IgE antibodies; 40 had also anti-Hev b 1 antibodies. Further, we observed that 80% of the Hev b 1 responders underwent five or more surgeries whereas 55% of the Hev b 1 non-responders and 75% of the latex-non-responders underwent less than five surgical interventions. From the latex-sensitized group 33% showed an elevated phenotype frequency of DRB1*0701(DR7) when compared with unsensitized patients (12%, P = 0.0095, Pc = NS) and with controls (17%; P = 0.035, Pc = ns). Fifteen out of 40 Hev b 1 responders also exhibited an elevated DR7 frequency when compared with latex-sensitive but Hev b 1-negative patients (38% vs 18%, P = NS) or with unsensitized controls (38% vs 17%, P = 0.013, Pc = NS). CONCLUSIONS: Although we found that the DRB1*0701 (DR7) phenotype frequency was elevated in SB patients with latex- as well as with Hev b 1-IgE responsiveness, the analyses of the other class II alleles clearly demonstrate that the HLA-D region does not play a major role in the pathogenetic way of sensitization to Hev b 1.

Adolescent↗

PubMed1998

Analysis of T-cell reactive regions and HLA-DR4 binding motifs on the latex allergen Hev b 1 (rubber elongation factor).

BACKGROUND: The rubber elongation factor in Hevea rubber (Hev b 1) is one of the important latex-allergenic proteins inducing the production of specific IgE antibodies in latex-exposed subjects. In addition, Hev b 1 induces lymphocyte proliferation responses. A study about detailed T-cell epitope analysis of major latex allergens has not been published yet. OBJECTIVE: The aim of this study was to define the T-cell reactive regions on the latex allergen Hev b 1. METHODS: Nine overlapping peptides with 19 or 17 amino acid lengths representing the complete sequence of Hev b 1 were used for T-cell epitope mapping. Peripheral blood mononuclear cells (PBMCs) of latex-sensitized patients and healthy subjects were isolated and stimulated with the synthetic peptides to determine the specific proliferation response. The examined patients were sensitized to latex by occupational exposure (n=14) and suffered from rhinitis, conjunctivitis, contact urticaria and/or asthma. Two control groups of non-sensitized subjects were studied, one occupationally exposed to latex (n=4), the other one not exposed to latex (n=4). RESULTS: Positive proliferation response induced by one or more peptides was detected in 10 of the latex-sensitized patients and in two of the latex-exposed non-sensitized subjects. Each patient exhibited an individual epitope reactivity pattern. The whole protein was found to be immunogenic, but the intensity of lymphocyte responses induced by the peptides was different. The majority of the patients' PBMCs (more than 66%) responded to the peptides 31-49 and 91-109. Using the peptide selection of Stille's algorithms, three epitopes were predicted covering region 38-74 and two others covering region 82-104; the two peptides 31-49 and 91-109 are part of these regions. A strong HLA-DR4Dw4 (DRB1*0401)-binding motif according to published DR4w4 binding motifs was predicted in the region of 102-110 including peptide 91-109 to which the majority of tested HLA-DR4-positive patients responded. CONCLUSIONS: Our data indicate that the whole 14 kDa protein Hev b 1 is immunogenic having regions that demonstrate individual and varying PBMC stimulation. Experimental data of T-cell reactive regions based on PBMC-stimulation complement the information on T-cell epitope prediction. In addition, the Hev b 1 molecule contains a HLA-DR4Dw4 (DRB1*0401)-binding motif.

Adult↗

PubMed1998

Exposure-response relationships of occupational inhalative allergens.

Only a few threshold limit values exist at present for allergens in the workplace known to cause bronchial asthma. This contrasts with the great number of occupational asthma cases observed in industrialized countries. Recently published studies provide clear evidence for exposure intensity response relationships of occupational allergens of plant, microbiological, animal or man-made origin. If allergen exposure levels fall short of determined limit values, they are not associated with an increased risk of occupational asthma. Corresponding data are available for wheat flour (1-2.4 mg/m3), fungal alpha-amylase (0.25 ng/m3), natural rubber latex (0.6 ng/m3), western red cedar (0.4 mg/m3) and rat allergens (0.7 microg/m3). It is suggested to stipulate legally binding threshold limit values (TLV/TWA) on this basis in order to induce more effective primary preventive measures. If no reliable data on the health risk of an occupational airborne noxa exist, the lowest reasonably practicable exposure level has to be achieved. Appropriate secondary preventive measures have to be initiated in all workplaces contaminated with airborne allergens. Verified exposure-response relationships provide the basis for risk assessment and for targeted interventions to reduce the incidence of occupational asthma also in consideration of cost benefit aspects. 'Occupational asthma is a disease characterized by variable airflow limitation and/or airway hyperresponsiveness due to causes in a working environment. These causes can give rise to asthma through immunological or non-immunological mechanisms. Up to 15% of all asthma cases are of occupational origin or have at least a significant causal occupational factor. According to the New Zealand part of the European Respiratory Health Survey, an increased risk of asthma prevalence was found for several occupations such as laboratory technicians, food producers, chemical workers, plastic and rubber workers. The Spain part of this study comprising 2646 Spanish subjects showed an asthma risk to be attributed to occupational exposures between 5 and 6.7%. Main asthma-inducing agents in the workplace are flour, grain and feed dust, animal dander/urinary proteins and isocyanates. Further, several inhalative irritants such as chlorine, acid or alkaline aerosols play a pivotal role. Many low molecular weight chemicals have irritative as well as allergenic effects on the airways, e. g. isocyanates and acid anhydrides. In addition to chronic or repetitive exposures, also singular accidental exposure to high concentrations of irritative or toxic airborne substances can cause occupational asthma. This condition is frequently called reactive airways dysfunction.

Allergens↗

PubMed1998

HLA class II phenotype controls diversification of the autoantibody response in primary Sjögren's syndrome (pSS).

The coexistence of anti-La (SS-B) and anti-Ro (SS-A) autoantibodies in pSS is probably explained by intermolecular spreading of autoimmunity toward different components of the La/Ro ribonucleoprotein (RNP). In order to evaluate the role of the HLA class II phenotype in controlling diversification of this autoantibody response, 80 patients with pSS were typed by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) at the HLA class II loci DRB1, DQA1 and DQB1. Serum samples were examined for anti-La and anti-Ro by counterimmunoelectrophoresis and by ELISA using purified recombinant La and 60-kD Ro proteins. Patient sera were classified according to the extent of diversification of the anti-La, anti-Ro response including the presence or absence of precipitating anti-La antibodies. Immunogenic characteristics of these stratified groups were then studied. All patients with pSS, with or without autoantibodies to Ro and La, were found to have at least one of the HLA-DRB1 types DR2, DR3 or DR5. The HLA DR3-DQA1*0501-DQB1*02 (DR3-DQ2) haplotype was primarily associated with a diversified La/Ro RNP response containing precipitating autoantibodies to La (P<0.001); whereas the haplotype HLA DR2-DQA1*0102-DQB1*0602 (DR2-DQ1) was associated with a less diversified La/Ro RNP response containing non-precipitating (restricted epitope) anti-La autoantibodies (P<0.001). Anti-La-positive patients lacking both HLA-DR2 and HLA-DR3 all expressed the HLA-DQA1*0501 allele, which was present at increasing frequency with greater diversification of the anti-La/Ro autoantibody response. The association of distinct HLA haplotypes with different degrees of autoantibody diversification in patients with pSS suggests a model of HLA-restricted presentation of La/Ro peptide determinants to autoreactive helper T cells. We propose that non-precipitating anti-La responses are driven by limited intermolecular help from DR2-DQ1-restricted T helper cells recognizing Ro determinants. On the other hand, we speculate that the more diversified, precipitating anti-La responses obtain more efficient cognate T help from DR3-DQ2-restricted T helper cells recognizing La determinants, where HLA-DQA1*0501 may be a critical determinant for antigen presentation.

Alleles↗

PubMed1998

Prednisone and low-dose activated prothrombin complex concentrates for FVIII inhibitor in nonhaemophilic patients.

Eight nonhaemophilic patients with factor VIII (FVIII) inhibitors were reported. There was no difference in sex distribution. Median age at diagnosis was 62 years (ranging from 14 to 73 years). No associated disorders were revealed and all the patients were presented with severe muscular or arthral bleeding. Inhibitor titre was measured by the Bethesda method, which were 6.4, 126.0, 155.0, 4.8, 56.0, 13.5, 35.0 and 150.0 BU mL-1, respectively, at diagnosis. FVIII:C levels were less than 1 U dL-1 in seven patients and less than 2 U dL-1 in one patient. The median vWF:Ag level was 210% (ranging from 80% to 340%). All the patients had good response to activated prothrombin complex concentrates for acute bleeding episodes and prednisone for inhibitor elimination. Inhibitors completely eliminated in seven patients within a follow-up duration over 1 year, and one patient died of intracranial haemorrhage when her inhibitor titre decreased to 4.5 BU mL-1 and FVIII:C increased to 21 U dL-1.

Adolescent↗

PubMed1998

Analysis of cytokine production and V beta T-cell receptor subsets in irradiated recipients receiving portal or peripheral venous reconstitution with allogeneic bone marrow cells, with or without additional anti-cytokine monoclonal antibodies.

Irradiated (800 rads) AKR mice received intravenous (i.v.) reconstitution with a mixture of B10.BR T-depleted bone marrow cells and spleen cells. Only in groups of mice treated additionally with i.v. cyclophosphamide (Cy; 150 mg/kg), 24 hr before transplantation, was long-term (> 60% at 50 days) survival seen. In mice receiving only irradiation all animals died by 30 days post-transplantation. Histological changes consistent with graft-versus-host disease (GVHD) were seen in the liver of reconstituted mice at 30 days, along with an organ-specific increase in V beta 3 T-cell receptor-positive (TCR+) cells. No such increase in V beta 3 TCR+ cells was seen in the spleen from the same mice. These data are consistent with a tissue antigen-driven expansion of V beta 3 TCR+ cells associated with GVHD in the liver in this model. When we analysed cytokine production in vitro from CD3+ cells restimulated with 'host' (AKR) antigen-presenting cells (APC), we found a transition in cytokine production from preferential synthesis of type-1 cytokines [interleukin-2 (IL-2) and interferon-gamma (IFN-gamma)] at early times (day 15) post-reconstitution to increased production of type-2 cytokines [IL-4, transforming growth factor-beta (TGF-beta) and IL-10] at later times (day 30) post-reconstitution in Cy-treated recipients. Animals not receiving Cy did not show this 'switch' in cytokine production at later time points. We have observed a similar polarization in cytokine production, along with increased graft survival, in recipients of vascularized and non-vascularized allografts after portal venous (p.v.), but not i.v., pretransplant donor-specific immunization. We next studied AKR mice receiving 800 rads and subsequently reconstituted with B10.BR stem cells via the p.v. route. Again these mice showed prolonged survival (> 50% at 50 days), with polarization to IL-4, IL-10 and TGF-beta on restimulation of CD3+ cells in vitro at 30 days post-transplant and increased V beta 3 TCR+ cells in the liver. Infusion of anti-IL-12 monoclonal antibodies into irradiated mice receiving i.v. cell reconstitution produced a similar pattern of changes to those seen after p.v. reconstitution, while a combination of anti-IL-10 and anti-TGF-beta monoclonal antibodies reversed the changes seen after p.v. reconstitution. These data are consistent with an important role for differential cytokine production in the regulation of GVHD following allogeneic bone marrow transplantation.

Animals↗

PubMed1998

An oligo selection procedure for identification of sequence-specific DNA-binding activities associated with the plant defence response.

Sequence-specific DNA-binding (SSDB) factors play central roles in transcription, DNA replication, recombination and repair. This report describes a simple procedure for high-throughput identification of SSDB activities without prior knowledge of their target genes or binding sequences. The procedure starts with a population of completely random oligo(nucleotide) sequences and selects for those oligo molecules that specifically bind to cellular SSDB factors by use of common gel-retardation assays and PCR. Amplification and subsequent cloning of these selected oligo molecules result in the establishment of oligo DNA libraries enriched in DNA molecules containing specific sequences recognized by SSDB factors. These oligo libraries can be rapidly screened to identify a large number of SSDB activities, including those that are differentially regulated by developmental and environmental signals. With identified oligo DNA as probes, the corresponding SSDB factors can be isolated and analysed with respect to their structures, regulation and functions. Using this procedure, we have identified approximately 100 SSDB activities from tobacco leaves, including seven that are differentially regulated during the tobacco mosaic virus-induced hypersensitive response in resistant tobacco plants.

Amino Acid Sequence↗

PubMed1998

Histochemical mapping of NADPH-diaphorase in monkey and human eyes.

PURPOSE: To localize nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in normal human and monkey eyes. METHODS: NADPH-d activity in ocular tissue sections was revealed by histochemical staining. RESULTS: NADPH-d staining was found in the anterior and posterior ocular segment of both species. In the anterior segment, reaction product was present in the corneal epithelium and endothelium, iris dilator and sphincter, lens capsule, ciliary muscle, and non-pigmented epithelial cells and stroma of the ciliary processes. Staining density in the longitudinal ciliary muscle was higher than in the other ciliary muscle regions in the human; such regionalization was less apparent in the monkey. The trabecular meshwork stained minimally if at all in both species. In the posterior segment, staining was seen around choroidal blood vessels and choroidal nerves, and in the retinal pigment epithelial, photoreceptor, bipolar, inner plexiform and ganglion cell layers. CONCLUSIONS: NADPH-d is widespread in human and monkey eyes, indicating significant and presumably functionally relevant NO production in the various ocular structures.

Adolescent↗

PubMed1998

Evidence for a Turner syndrome locus or loci at Xp11.2-p22.1.

Turner syndrome is the complex human phenotype associated with complete or partial monosomy X. Principle features of Turner syndrome include short stature, ovarian failure, and a variety of other anatomic and physiological abnormalities, such as webbed neck, lymphedema, cardiovascular and renal anomalies, hypertension, and autoimmune thyroid disease. We studied 28 apparently nonmosaic subjects with partial deletions of Xp, in order to map loci responsible for various components of the Turner syndrome phenotype. Subjects were carefully evaluated for the presence or absence of Turner syndrome features, and their deletions were mapped by FISH with a panel of Xp markers. Using a statistical method to examine genotype/phenotype correlations, we mapped one or more Turner syndrome traits to a critical region in Xp11.2-p22.1. These traits included short stature, ovarian failure, high-arched palate, and autoimmune thyroid disease. The results are useful for genetic counseling of individuals with partial monosomy X. Study of additional subjects should refine the localization of Turner syndrome loci and provide a rational basis for exploration of candidate genes.

Adolescent↗

PubMed1998

Signal attenuation and localization in optical coherence tomography studied by Monte Carlo simulation.

A Monte Carlo model has been developed for optical coherence tomography (OCT). A geometrical optics implementation of the OCT probe with low-coherence interferometric detection was combined with three-dimensional stochastic Monte Carlo modelling of photon propagation in the homogeneous sample medium. Optical properties of the sample were selected to simulate intralipid and blood, representing moderately (g = 0.7) and highly (g = 0.99) anisotropic scattering respectively. For shallow optical depths in simulated intralipid (<3 scattering mean free path (mfp) units), the number of detected backscattered photons followed the extinction-single-backscatter model, and OCT was found to detect only minimally scattered photons. Within this depth range the backscatter positions of detected photons corresponded well with the nominal focus position of the probe. For propagation to deeper positions in intralipid, localization of backscattering was quickly lost due to detection of stray photons, and the number of detected photons remained constant with increasing depth in the non-absorbing medium. For strongly forward-directed scattering in simulated blood, the number of detected photons approached the extinction-single-backscatter model only for very shallow depths (<2 mfp units). However, backscattering positions for detected photons correlated well with the nominal focus position of the probe even for optical depths greater than 40 mfp units.

Blood↗

PubMed1998

Accuracy and noise in optical Doppler tomography studied by Monte Carlo simulation.

A Monte Carlo model has been developed for optical Doppler tomography (ODT) within the framework of a model for optical coherence tomography (OCT). A phantom situation represented by blood flowing in a horizontal 100 microm diameter vessel placed at 250 microm axial depth in 2% intralipid solution was implemented for the Monte Carlo simulation, and a similar configuration used for experimental ODT measurements in the laboratory. Simulated depth profiles through the centre of the vessel of average Doppler frequency demonstrated an accuracy of 3-4% deviation in frequency values and position localization of flow borders, compared with true values. Stochastic Doppler frequency noise was experimentally observed as a shadowing in regions underneath the vessel and also seen in simulated Doppler frequency depth profiles. By Monte Carlo simulation, this Doppler noise was shown to represent a nearly constant level over an investigated 100 microm interval of depth underneath the vessel. The noise level was essentially independent of the numerical aperture of the detector and angle between the flow velocity and the direction of observation, as long as this angle was larger than 60 degrees. Since this angle determines the magnitude of the Doppler frequency for backscattering from the flow region, this means that the signal-to-noise ratio between Doppler signal from the flow region to Doppler noise from regions underneath the flow is improved by decreasing the angle between the flow direction and direction of observation. Doppler noise values from Monte Carlo simulations were compared with values from statistical analysis.

Diagnostic Imaging↗

PubMed1998

On the use of unshielded cables in ionization chamber dosimetry for total-skin electron therapy.

The dosimetry of total-skin electron therapy (TSET) usually requires ionization chamber measurements in a large electron beam (up to 120 cm x 200 cm). Exposing the chamber's electric cable, its connector and part of the extension cable to the large electron beam will introduce unwanted electronic signals that may lead to inaccurate dosimetry results. While the best strategy to minimize the cable-induced electronic signal is to shield the cables and its connector from the primary electrons, as has been recommended by the AAPM Task Group Report 23 on TSET, cables without additional shielding are often used in TSET dosimetry measurements for logistic reasons, for example when an automatic scanning dosimetry is used. This paper systematically investigates the consequences and the acceptability of using an unshielded cable in ionization chamber dosimetry in a large TSET electron beam. In this paper, we separate cable-induced signals into two types. The type-I signal includes all charges induced which do not change sign upon switching the chamber polarity, and type II includes all those that do. The type-I signal is easily cancelled by the polarity averaging method. The type-II cable-induced signal is independent of the depth of the chamber in a phantom and its magnitude relative to the true signal determines the acceptability of a cable for use under unshielded conditions. Three different cables were evaluated in two different TSET beams in this investigation. For dosimetry near the depth of maximum buildup, the cable-induced dosimetry error was found to be less than 0.2% when the two-polarity averaging technique was applied. At greater depths, the relative dosimetry error was found to increase at a rate approximately equal to the inverse of the electron depth dose. Since the application of the two-polarity averaging technique requires a constant-irradiation condition, it was demonstrated than an additional error of up to 4% could be introduced if the unshielded cable's spatial configuration were altered during the two-polarity measurements. This suggests that automatic scanning systems with unshielded cables should not be used in TSET ionization chamber dosimetry. However, the data did show that an unshielded cable may be used in TSET ionization chamber dosimetry if the size of cable-induced error in a given TSET beam is pre-evaluated and the measurement is carefully conducted. When such an evaluation has not been performed, additional shielding should be applied to the cable being used, making measurements at multiple points difficult.

Biophysical Phenomena↗

PubMed1998

Sleep-associated changes in interleukin-1beta mRNA in the brain.

Much evidence implicates interleukin-1beta (IL-1beta) in sleep regulation. Two previous studies indicated that levels of IL-1beta in mRNA were affected by sleep. In the current study, levels of IL-1beta mRNA and IL-1 receptor assessory protein (IL-1RAP) mRNA were determined 1 h after the beginning of light and dark periods and after sleep deprivation, using the reverse transcriptase-polymerase chain reaction (RT-PCR) and mutated internal standards. Daytime samples contained relatively more IL-1beta mRNA than nighttime samples, and levels of IL-1beta mRNA were higher after sleep deprivation. These changes occurred in the hypothalamus, hippocampus, cerebral cortex, and mesencephalon/pons. In contrast, the IL-1 RAP mRNA level did not seem to be affected by sleep.

Animals↗

PubMed1998

Effective treatment of experimental uveitis with interleukin-1 blockers, CK 123 and CK 124.

Interleukin-1 (IL-1) blockers are known to inhibit IL-1-induced uveitis. CK 123 and CK 124 are new IL-1 blockers which showed potent anti-uveitis actions that are more potent than the classic corticosteroid, prednisolone. In addition to anti-inflammation, CK 123 and CK 124 were also found to inhibit proliferation of fibroblast-like corneal and conjunctival cells, indicating that these compounds could be used not only as anti-uveitis agents but also as useful agents to prolong the functional period of aqueous humor outflow after trabeculectomy. It was also found that DNA and mRNA synthesis were markedly inhibited by CK 123 and CK 124, yet the protein synthesis was either untouched or enhanced.

Animals↗

PubMed1998

A human vascular endothelial cell model to study angiogenesis and tumorigenesis.

Endothelial cell biology has recently been the subject of considerable interest in thrombosis and cancer research. However, the successful establishment of immortalized human endothelial cells which retain differentiated cell characteristics has been rare. We have successfully established immortalized human umbilical vein endothelial cells (HUVECs) by human papilloma virus (HPV)-16 E6-E7. HPV-16 E6, E7 and E6-E7 were successfully introduced into HUVEC cells. Both E6 and E7 cultures had an extended lifespan but eventually underwent senescence. E6-E7 cultures 4-5-2G, however, acquired an indefinite lifespan in culture but did not undergo malignant conversion. Telomerase activity was not detected in either E6 or E7 cultures; however, telomerase was detected in E6-E7 4-5-2G cells. The cells exhibited a 'cobblestone' morphology and developed a capillary-like tube structure upon reaching confluence. The 4-5-2G line expressed Factor VIII related antigen and took up DiI-Ac-LDL as markers of endothelial origin. The line expressed integrin subunits (alpha(v)beta3, alph(v)beta5, beta1, alpha2, alpha3, beta4 and alpha6) consistent with an endothelial origin. The higher passage of 4-5-2G line showed a similar intensity of integrin immunostaining to that of primary HUVECS. Subsequent infection of these immortal cells with the Kirsten murine sarcoma virus which contains an activated K-ras oncogene induced morphological transformation that led to the acquisition of invasion capability and neoplastic properties. Telomerase was also detected in the tumorigenic v-Ki-ras transformed cell line. These cell lines should be useful for studies of the molecular mechanisms underlying normal and neoplastic endothelial cell proliferation and migration, and might also provide an in vitro model for development of pharmacologic and gene therapy for cardiovascular thrombosis and cancer.

Cell Line, Transformed↗

PubMed1998

Malignancy may adversely influence the quality and behaviour of oocytes.

A case series of eight cycles of in-vitro fertilization (IVF) in five women diagnosed with malignant disorders is presented. These patients chose to defer definitive treatment for a chance for preservation of potential fertility. The response of these patients to ovarian stimulation, and the outcome, was compared with 17 IVF cycles in 12 age-matched patients with isolated tubal infertility. An apparent adverse influence of malignant disease on the quality and behaviour of oocytes was observed. Despite a comparable total number of oocytes per cycle in the two groups, a significantly reduced percentage of mature oocytes was retrieved per cycle from patients with malignant diseases. The oocytes from patients with malignant disorders were of a poorer quality and exhibited a significantly impaired fertilization rate compared to the controls. We propose that neoplastic processes, irrespective of the site or cell of origin, may have a detrimental impact on the biology of oocytes, an effect akin to that seen on spermatozoa in men with certain malignancies.

Adenocarcinoma↗

PubMed1998

Differentiation and cathepsin D expression in human oral tumors.

OBJECTIVES/HYPOTHESIS: This study aimed to ascertain whether cathepsin D expression could be related to the stage of differentiation of oral tumors. STUDY DESIGN: Human oral biopsies of 10 squamous cell carcinomas and of the corresponding perilesional normal tissues were used. The tumors had all been clinically graded as advanced stage but nonmetastatic; five were classified histopathologically as poorly differentiated. METHODS: The gene expression of cathepsin D and keratin K13 in the biopsies was measured by reverse transcription polymerase chain reaction. Ratios of tumor-to-control readings helped compensate for sample variability. RESULTS: Keratin K13, as a suprabasal cell marker, tended to confirm the histological grading of the tumors (but was not otherwise useful in distinguishing tumors from normal tissue). Substantial overexpression of cathepsin D was found in the poorly differentiated tumors. CONCLUSIONS: Cathepsin D overexpression is considered a prognostic indicator of metastasis. In this sample, it was also associated with dedifferentiation. Cathepsin D might serve as a valuable gauge in clinical exploration of the connection between dedifferentiation and metastasis.

Adult↗

PubMed1998

Risk assessment to improve targeting of HIV counseling and testing services for STD clinic patients.

BACKGROUND AND OBJECTIVE: To determine whether self-administered risk assessment could improve targeting of HIV counseling and testing in an STD clinic. STUDY DESIGN: Computerized records from the Prince George's County, Maryland, STD clinic from 1993 through 1996 were used to develop and test models for predicting a positive HIV test. In 1996, a self-administered risk assessment was compared with a counselor's risk assessment of the same patient. RESULTS: Testing the 10% of patients at highest risk would identify 39% of those who were HIV-positive; testing 70% of the patients could identify 92% of those who were HIV-positive. In 1996, 2,288 patients completed the self-administered HIV risk assessment. The same number of HIV-positive persons (7 [28%]) were identified using either self-assessment or face-to-face interview. CONCLUSIONS: Selectively offering voluntary HIV testing based on risk assessment would not be useful because it would miss many infected persons. If prevention counseling cannot be offered to everyone, it could be targeted to those who report a risk by self-assessment.

Adolescent↗