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Biomedical subjects

T C Wright

Publications and source records attributed to T C Wright.

At least 19 recordsLinked to original sources
PubMed1992

Relationship of human papillomavirus type to grade of cervical intraepithelial neoplasia.

OBJECTIVE--To determine the relationship of human papillomavirus (HPV) type to grade of cervical intraepithelial neoplasia (CIN) in a large series of cases. DESIGN--A survey of HPV types in CIN lesions detected using a new, highly accurate method for typing HPV that is based on restriction fragment length polymorphism analysis of amplimers produced during polymerase chain amplification of the conserved L1 region of HPV using consensus primers. SETTING--Private gynecologists' offices and inner-city colposcopy clinics. PATIENTS--A convenience sample of 276 HPV DNA-positive cervical biopsy specimens or samples from patients undergoing colposcopy for abnormal Papanicolaou smears. INTERVENTION--None. MAIN OUTCOME MEASURE(S)--Human papillomavirus type(s). RESULTS--Cervical intraepithelial neoplasia 1 lesions were relatively heterogeneous with regard to associated HPV types. Nineteen percent of CIN 1 lesions were associated with HPV types 6 or 11; 29% contained HPV types 16, 18, or 33; and 19% were associated with "novel types" of HPV. It was also found that 22% of CIN 1 lesions were associated with more than one HPV type. In contrast to CIN 1, both CIN 2 and CIN 3 were relatively homogeneous with regard to associated HPV types. Eighty-eight percent of CIN 2 and 3 lesions contained HPV types 16, 18, or 33. Unlike CIN 1 lesions, which often contained multiple types of HPV, only 7% of CIN 2 and 3 lesions were associated with multiple HPV types. CONCLUSIONS--Cervical intraepithelial neoplasia should be classified into two separate categories--low-grade and high-grade CIN. Since only 29% of low-grade lesions are associated with HPV types 16, 18, or 33, HPV type could potentially play a role in determining the most appropriate clinical management of patients with low-grade CIN. However, prospective follow-up studies of lesional behavior based on HPV type are required before clinical recommendations can be made.

DNA, Viral↗
PubMed1992

Heparin inhibits the attachment and growth of Balb/c-3T3 fibroblasts on collagen substrata.

In investigating the role of cell-extracellular matrix interactions in cell adhesion and growth control, the effects of heparin on cell-collagen interactions were examined. Exponentially growing Balb/c-3T3 fibroblasts were radiolabelled with 3H-thymidine and detached from tissue culture surfaces using EDTA, and cell attachment to various types of collagen substrata was assayed in the presence or absence of heparin or other glycosaminoglycans (GAGs) or dextran sulfate (40 K). Cells attached readily (70-90%) to films of types I and V, but not to type III collagen. The number of cells bound to types I and V collagen films was inhibited by 10-50% when heparin was present from 0.1-100 micrograms/ml. Cell-collagen attachment was also inhibited by dextran sulfate, and to a lesser extent by dermatan sulfate, but chondroitin sulfates A and C and hyaluronic acid showed no effect. Heparin was active even at early time points in the adhesion assay, suggesting it may disrupt cell-collagen attachment. To study the effects of heparin in modulating cell growth on collagen, growth arrested cells cultured on type I collagen films were serum stimulated in the presence of heparin or other GAGs for 3 days. Growth was inhibited (greater than 40%) only by heparin and dextran sulfate. Interaction of heparin fragments (Mr less than or equal to 6KD) with type I collagen was analyzed by affinity co-electrophoresis (Lee and Lander, 1991) and showed higher affinity heparin binding to native as compared with denatured collagen. These data suggest that sites within native collagen may mediate Balb cell-collagen and heparin-collagen interactions, and such interactions may be relevant towards understanding heparin's antiproliferative activity in vivo and in vitro.

3T3 Cells↗
PubMed1992

Typing of human papillomaviruses by polymerase chain reaction amplification with L1 consensus primers and RFLP analysis.

Human papillomaviruses (HPV) cause benign and malignant lesions of the epithelial and mucosal surfaces. Certain virus types are associated with cervical carcinomas, while others are associated with benign condylomata. We have developed a rapid method for determining HPV type that is based on restriction fragment length polymorphism (RFLP) analysis within the L1 region of HPVs that is amplified by PCR using the consensus primers described by Manos et al. Analysis of the product generated by PCR amplification of plasmids containing cloned HPV genomes and of 88 clinical specimens, known to contain HPV viral DNA by previous hybridization analysis, revealed that this method is useful for typing HPV sequences amplified from a variety of sources including cervical lavages, fresh tissue, and paraffin-embedded formalin-fixed biopsy material. The method can differentiate between most known types of HPV and discriminate between infections with single, multiple or novel HPV types. A high correlation (86%) was obtained when this method was compared with PCR amplification and Southern blot hybridization analysis of PCR product, or Southern blot hybridization analysis of total genomic DNA. Differences in typing occurred mostly for specimens that contained multiple or new/unknown HPV types. However, RFLP typing easily identified repeated patterns for new HPV types that were not detected by the other methods. In summary, PCR-RFLP typing is a sensitive and specific method to identify and characterize rapidly HPV DNA in clinical specimens from a variety of sources.

Blotting, Southern↗
PubMed1992

Human papillomavirus.

In the past year, new data have been published on the molecular biology of human papillomavirus infections and their relationship to cervical neoplasia. As molecular techniques have become more sophisticated and as the molecular knowledge of human papilloma-virus infections has been pursued in greater depth, it is increasingly apparent that this human tumor DNA virus is similar to a number of other oncogenic DNA viruses that have been described and well studied. These viruses appear to act through a common pathway of producing oncogenic proteins that interfere with key signalling elements that normally control the process of cell division. With a better mechanistic knowledge, it should be possible to design new therapeutic approaches to treating human papillomavirus-associated disease that are directed toward specific cellular events such as turning off the production of E6 and E7 proteins or restoring the activity of pRB or p53. Increased attention has also been turned to immunologic aspects of HPV infections, and a number of groups are eagerly pursuing the possibility of using simple office-based procedures to detect specific proteins encoded for by the human papillomavirus open reading frames in an attempt to determine who has been infected, is actively infected, and has proteins being produced that are indicative of neoplasia. From the clinical point of view, the use of outpatient excisional techniques such as the loop electrosurgical excision procedure is rapidly supplanting ablative techniques because of their superior ability to identify early invasive carcinomas and adenocarcinomas in situ that have not been detected by colposcopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Localization of cellular retinoid-binding proteins in human cervical intraepithelial neoplasia and invasive carcinoma.

Cellular retinoic acid-binding protein (CRABP) and cellular retinol-binding protein (CRBP) were localized in biopsies of normal squamous epithelium, cervical intraepithelial neoplasia (CIN), and invasive squamous cell cancer of the cervix uteri by immunohistochemistry. In both the normal stratified squamous epithelium of the exocervix and low-grade CIN, CRABP I was present predominantly in the basal layer of the epithelium. The more superficial, differentiated cell layers lacked immunoreactive protein. In high-grade CIN (CIN2-3), the distribution of CRABP I was altered. Immunoreactive CRABP I was detected in all layers of high-grade CIN. In squamous cell carcinoma of the cervix, CRABP I was detected in cells throughout the tumor but was minimal in cells demonstrating squamous differentiation. In contrast to CRABP I, CRBP was diffusely present throughout the cervical epithelium irrespective of the state of differentiation or the presence of disease.

Adolescent↗
PubMed1992

Loop electrosurgical excision procedure for CIN.

The loop electrosurgical excision procedure, also referred to as large loop excision of the transformation zone, is gaining acceptance in the United States as a method for treating cervical intraepithelial neoplasia. Loop excision of cervical tissue is accomplished using a high-frequency alternating current (radiofrequency) and thin wire loop electrodes. Loop excision may be in the form of simple excision of the transformation zone or electrosurgical loop conization. The specimens obtained using this technique are suitable for histologic evaluation. Loop excision, which is usually performed under local anesthesia, is associated with minimal short-term and long-term morbidity. Patient acceptance is high. Family physicians who perform colposcopy should consider using loop electrosurgical excision to treat cervical intraepithelial neoplasia in the outpatient setting.

Ambulatory Surgical Procedures↗
PubMed1992

Comparison of specimens removed by CO2 laser conization and the loop electrosurgical excision procedure.

A comparison is made of the histologic changes in the cervical epithelium and stroma following CO2 laser conization and office excisional biopsy of cervical tissue using the loop electrosurgical excision procedure. In both types of specimens, two zones of thermal injury were detected. The zone at the margin of resection measured approximately 50 microns in thickness and was characterized by extensive carbonization and charring. The other zone was much more variable in thickness and characterized by tissue coagulation, but lacked charring. No significant difference in the biocharacteristics or extent of thermal damage was detected between the methods. For 11 specimens obtained with the CO2 laser, the coagulated zone ranged from 130-750 microns in greatest thickness; the mean thickness was 411 microns. For 40 specimens obtained using the loop procedure, the range of thickness of the coagulated zone was 150-830 microns, and the mean thickness was 396 microns. The difference in the mean value of thermal injury (measured in microns) between the laser and loop procedures was not significant (Student t test; P = .79). Extensive areas of carbonization and epithelial distortion at the margins of excision were only occasionally present in specimens obtained by the electrosurgical excision procedure but almost invariably present in CO2 laser specimens. However, in all cases it was possible to evaluate the epithelium and the stroma both histologically and cytologically.

Carbon Dioxide↗
PubMed1992

Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure.

In selected patients with cervical intraepithelial neoplasia (CIN), outpatient ablative procedures represent a readily accepted and highly effective treatment modality. The recently introduced loop electrosurgical excision procedure offers a quick and simple alternative to cryotherapy and laser ablation for treating CIN, and has the distinct advantage of allowing both diagnosis and treatment of selected patients at a single visit. This report presents our clinical experience treating 432 patients with CIN using the loop electrosurgical excision procedure on an outpatient basis. Small loop electrodes were used to excise CIN lesions in 275 patients, and large loop electrodes were used in 157. When performed on an outpatient basis under local anesthesia, loop excision was well tolerated by patients with only minimal discomfort. Post-treatment bleeding occurred in less than 2% of the subjects and responded to either recauterization or packing of the cervix. Post-treatment stenosis occurred in less than 1%. The success rate of the loop electrosurgical excision procedure, as defined by absence of cytologic, histologic, or colposcopic lesions 4-48 months after therapy, was 80% for women treated using the small loop electrodes. Ninety percent of all patients treated using the large loop electrodes were free of disease during 6-12 months of follow-up. For women being treated for primary (as opposed to recurrent) disease, the success rate with large loop electrodes was 94%.

Carcinoma in Situ↗
PubMed1991

Avascular necrosis and vascular anatomy of the metacarpals.

Aseptic necrosis of the metacarpal head is extremely rare and has been described in association with systemic lupus erythematosus, steroid use, trauma, and other sites of bone infarction. The long metacarpal is the most commonly involved. The extrinsic and intrinsic vascular anatomy of the metacarpal is described in fifty metacarpal specimens. No definite conclusions can be drawn about anatomic variations in blood supply between the different metacarpals. However, in 35% of the specimens, a main arteriole in the distal epiphysis was absent, making these metacarpal heads solely dependent on small circumferential pericapsular arterioles. This group of metacarpals, when associated with other risk factors, such as trauma, systemic lupus erythematosus, or steroid use, may be at increased risk for the development of aseptic necrosis.

Adolescent↗
PubMed1991

Pathology of the cervix.

Over the last year, the majority of research on the pathology of the cervix has been focused on the human papillomavirus (HPV) and its role in the pathogenesis of cervical neoplasia. Several major points emerged from these studies. First, the incidence of latent HPV infection in the general population is greater than previously thought. Up to 31% of a college-aged population has HPV DNA detected in cervical swabs. Second, in situ hybridization to detect HPV has been found to be a useful quality control measure for laboratories diagnosing cervical lesions. Finally, it is now recognized that many different HPV types can infect the cervix and be associated with cervical neoplasia. With regard to treatment, the introduction of loop electrosurgical excision procedures for treating cervical intraepithelial neoplasia lesions promises to have a significant impact on the management of cervical disease.

Female↗
PubMed1991

Pearly penile papules: absence of human papillomavirus DNA by the polymerase chain reaction.

Pearly penile papules clinically resemble the sexually transmitted papular variant of genital condylomata. Histologically, however, pearly penile papules consist of fibropapillomata that lack the characteristic morphologic features of human papillomavirus (HPV) infection. To study the possible association of HPV infections with pearly penile papules, we examined tissue specimens from 13 men with pearly penile papules with and without associated penile condylomata. Biopsy specimens were tested for the presence of HPV DNA by the polymerase chain reaction. None of the pearly penile papules contained HPV DNA sequences, whereas four of seven cases clinically suspected of being condylomata associated with pearly penile papules contained HPV DNA. These results confirm that pearly penile papule lesions do not contain HPV DNA; therefore, the distinction between pearly penile papules and penile condylomata is clinically significant.

Adult↗
PubMed1990

Role of human papillomavirus in the pathogenesis of genital tract warts and cancer.

During the last decade a large number of clinical, epidemiological, and experimental studies have elucidated the role of HPV in the pathogenesis of anogenital cancer. Although the clinical and epidemiological studies have been criticized for a variety of technical and design shortcomings, for the most part they have independently reached the same conclusion--there is a strong association between the presence of specific types of HPV and the development of anogenital cancer. Similarly, laboratory studies clearly indicate that specific types of HPV act in concert with other cellular changes to transform a variety of cell types in vitro, including human cervical epithelial cells. Over the next decade the challenge is twofold. First we need to define precisely the mechanisms by which HPV either by itself or in concert with other factors, acts to transform anogenital epithelial cells. These studies will, it is hoped, identify important cofactors in the transformation process and determine the role of host immunity. Second, we need to determine the clinical applicability of the association between HPV and anogenital cancer. Large clinical studies will determine whether HPV testing of asymptomatic patients facilitates the detection of patients at risk for developing cervical cancer and whether the presence of a specific type of HPV in a cervical cancer actually affects a patient's prognosis. As the answers to these and other questions become available, we will be in a better position to assess the clinical importance of the associations between HPV and anogenital cancer.

Female↗
PubMed1990

Heparin inhibits c-fos and c-myc mRNA expression in vascular smooth muscle cells.

Heparin is a potent inhibitor of vascular smooth muscle cell (VSMC) growth. In this paper we show that heparin suppressed the induction of c-fos and c-myc mRNA in rat and calf VSMC. This effect of heparin is closely associated with its growth-inhibitory activity, as shown by isolating and characterizing a strain of rat VSMC that was resistant to heparin's antiproliferative effect; heparin did not suppress c-fos mRNA induction in these cells. Moreover, neither a nonantiproliferative heparin fragment or other glycosaminoglycans that lack growth-inhibitory activity repressed c-fos or c-myc mRNA levels. The effect of heparin on c-fos mRNA induction was selective for specific mitogens, as heparin inhibited c-fos mRNA induction in phorbol 12-myristate 13-acetate (TPA) stimulated but not epidermal growth factor (EGF) stimulated VSMC. The effect of heparin on gene expression is independent of ongoing protein synthesis, and inhibition of c-fos mRNA is at the transcriptional level. These results suggest that heparin may selectively inhibit a protein kinase C-dependent pathway for protooncogene induction and that this may be one mechanism used by heparin to inhibit cell proliferation.

Animals↗
PubMed1989

Heparin suppresses the induction of c-fos and c-myc mRNA in murine fibroblasts by selective inhibition of a protein kinase C-dependent pathway.

Heparin is a complex glycosaminoglycan that inhibits the proliferation of several cell types in culture and in vivo. To begin to define the mechanism(s) by which heparin exerts its antiproliferative effects, we asked whether heparin interferes with the expression of the growth factor-inducible protooncogenes c-fos and c-myc. We show that heparin suppressed the induction of c-fos and c-myc mRNA by serum in murine (BALB/c) 3T3 fibroblasts. Using purified mitogens, we further show that suppression was most marked when protooncogene expression was induced by phorbol 12-myristate 13-acetate, an activator of protein kinase C. By contrast, there was little or no suppression when the cells were stimulated by epidermal growth factor, which, in these cells, utilizes a protein kinase C-independent pathway for the induction of gene expression. Heparin also inhibited the change in cell morphology induced by the phorbol ester but had no effect on the morphological change induced by epidermal growth factor and agents that raise intracellular cAMP. Heparin did not inhibit intracellular protein kinase C activity, phorbol ester-induced down-regulation of protein kinase C, or phosphorylation of the 80-kDa intracellular protein kinase C substrate. These results suggest that heparin inhibits a protein kinase C-dependent pathway for cell proliferation and suppresses the induction of c-fos and c-myc mRNA at a site distal to activation of the kinase.

Animals↗
PubMed1989

Heparin selectively inhibits a protein kinase C-dependent mechanism of cell cycle progression in calf aortic smooth muscle cells.

The proliferation of arterial smooth muscle cells (SMCs) plays a critical role in the pathogenesis of arteriosclerosis. Previous studies have indicated that the glycosaminoglycan heparin specifically inhibited the growth of vascular SMCs in vivo and in culture, although the precise mechanism(s) of action have not been elucidated. In this study, we have examined the ability of specific mitogens (PDGF, EGF, heparin-binding growth factors, phorbol esters, and insulin) to stimulate SMC proliferation. Our results indicate that SMCs derived from different species and vascular sources respond differently to these growth factors. We next examined the ability of heparin to inhibit the proliferative responses to these mitogens. In calf aortic SMCs, heparin inhibits a protein kinase C-dependent pathway for mitogenesis. Detailed cell cycle analysis revealed several new features of the effects of heparin on SMCs. For example, heparin has two effects on the Go----S transition: it delays entry into S phase and also reduces the number of cells entering the cycle from Go. Using two separate experimental approaches, we found that heparin must be present during the last 4 h before S phase, suggesting a mid-to-late G1 heparin block. In addition, our data indicate that heparin-treated SMCs, while initially blocked in mid-to-late G1, slowly move back into a quiescent growth state in the continued presence of heparin. These results suggest that heparin may have multiple targets for its antiproliferative effect.

Animals↗
PubMed1987

Characterization of keratins from rat cervical epithelial cells in vivo and in vitro.

The keratins expressed in cultured rat cervical epithelial cells were analyzed by using two-dimensional gel electrophoresis and monoclonal antikeratin antibodies and were compared with those expressed in the rat cervix in vivo in the presence and absence of estrogen stimulation. The cervical epithelium in vivo responds to estrogen stimulation with alterations in keratin composition. In response to estrogen, the epithelium undergoes proliferation and stratification and begins expressing increased amounts of two basic Mr 57,000 and 58,000 keratins and two acidic Mr 51,000 and 52,000 keratins. Cultured rat cervical epithelial cells were found to express only small amounts of the basic Mr 57,000 and 58,000 keratins and the two acidic Mr 51,000 and 52,000 keratins characteristic of the estrogen-stimulated cervix. In addition to the keratins found in the cervical epithelium in vivo, rat cervical epithelial cells in vitro begin expressing two Mr 55,000 and 56,000 keratins of the basic keratin family (type II) and an acidic component with a molecular weight of 40,000. Although these components are not detected in the rat cervix in vivo, they migrate similarly on two-dimensional electrophoretic gels to proteins expressed by the rat endometrial epithelium in vivo. These findings indicate that alterations in keratin expression could serve as markers for studying the effects of steroid hormones on the differentiation of rat cervical epithelial cells in vitro and during the development of squamous metaplasia.

Animals↗
PubMed1987

Metabolic effects of heparin on rat cervical epithelial cells.

The glycosaminoglycan heparin inhibits the growth of a number of different cell types in vitro including smooth muscle cells, mesangial cells, fibroblasts, and rat cervical epithelial cells (RCEC). Studies investigating the antiproliferative effects of heparin on smooth muscle cells have demonstrated the site of the cell cycle block and revealed several metabolic alterations that could be causally associated with growth inhibition. We have investigated these metabolic parameters in RCEC to determine whether they are also associated with the antiproliferative effects of heparin in epithelial cells. Heparin acts rapidly to inhibit RCEC growth with inhibition detectable by autoradiography 7 h after the addition of heparin. Heparin treated RCEC begin to enter S-phase 12 h after the removal of heparin. These findings suggest that heparin blocks RCEC in the early-to-mid G1 phase of the cell cycle rather than late in G1 or early in S-phase as has previously been demonstrated for smooth muscle cells. Unlike smooth muscle cells, the uptake of thymidine and uridine is not inhibited by heparin in RCEC. Treatment of medium with heparin-Sepharose does not reduce the subsequent growth of RCEC; heparin inhibits the growth of RCEC in heparin-Sepharose treated medium in a manner identical to that in nontreated medium. Therefore the growth inhibitory effects of heparin cannot be explained by the inactivation of mitogens present in serum. In contrast to its effects on smooth muscle cells, heparin treatment of RCEC does not result in a reduction in the binding of epidermal growth factor (EGF) to the cells. These results indicate that although heparin inhibits the growth of a variety of cell types, significant differences exist in the responses of the different cells to heparin.

Animals↗