The pathogenesis of corneal epithelial defects.
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Biomedical subjects
Publications and source records attributed to M Berman.
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The clinical implications of specific human papillomavirus (HPV) types in invasive cervical carcinomas are only beginning to be appreciated. In this series of 100 women with cervical cancers analyzed for the presence of HPVs 6, 11, 16, 18, and 31 by Southern blot hybridization, a more aggressive clinical behavior was demonstrated for tumors containing HPV 18 than for those with HPV 16 or those in which no HPV was identified. Among 69 stage Ib tumors, no significant differences were found in the size of tumor, presence of parametrial involvement, or lymph node metastasis among patients whose tumor contained HPV 16, HPV 18, or no HPV DNA; however, 45% of the women with HPV 18-containing tumors (five of 11) had recurrence, as compared with only 16% of those with HPV 16 (five of 31) during the 20-month mean follow-up period. This tendency for HPV 18-containing tumors to recur was seen with all histologic subtypes of cervical cancers and with all grades of tumor. In addition, patients with HPV 18-containing tumors were more likely to give a history of recent normal Papanicolaou smears than were those whose tumors contained HPV 16. Forty-four percent of women with HPV 18 in their tumors had a history of three class I Papanicolaou smears in the 3 years before the diagnosis of cancer, whereas a similar history was elicited in only 16% of those with HPV 16 in their tumors, suggesting that HPV 18-containing tumors might progress to invasion without a prolonged preinvasive period.
Eleven pure adenocarcinomas of the cervix were analyzed for human papillomavirus (HPV) types 6, 11, 16, 18 and 31 by Southern blot hybridizations. Seven tumors were positive for papillomavirus DNA. Five hybridized to the HPV 18 specific probe and two tumors hybridized to HPV 16. All tumors were negative for HPV 6/11 and 31, and no additional tumors became positive with hybridizations under nonstringent conditions to a mixture of HPV probes. No papillomavirus DNA was detected in 11 noncervical malignancies or in six hysterectomy specimens in which cancer was not present. The histopathologic and clinical features of the patients were correlated with the presence of HPV. The women with papillomavirus DNA in their adenocarcinomas tended to be younger (mean age, 37.3) than those that were negative for HPV (mean age, 49.0). The findings suggest that papillomaviruses may be an etiologic factor in the development of some adenocarcinomas of the cervix.
A method of deconvolution is illustrated using compartmental models. The approach can be used to determine an arbitrary unknown input function from a measured response and the impulse response of the system. Compartmental models are constructed to specify (a) the function fitting the response data and (b) the impulse response of the system. Simulation of these models is then used to construct the unknown input function.
Of 337 urine specimens evaluated, 75 of the 113 that showed positive readings on the Bac-T-Screen urine-screening instrument were found by subsequent semiquantitative culture to yield either less than 10,000 CFU of mixed bacteria per ml or no growth (less than 100 CFU/ml by our criteria). We tried to determine what factors contributed to the positive Bac-T-Screen results by examining the 75 Bac-T-Screen-positive urine specimens with three visual methods: Gram staining, hemacytometer chamber counting, and filtering through a 5.0-microns-pore-size nitrocellulose filter with subsequent microscopic examination of the stained filter. Somatic cells and other particles present in those urine specimens that yielded positive readings by the Bac-T-Screen included epithelial cells in 43%, crystals and amorphous material in 33%, and leukocytes in 17% of the specimens. There was no relationship between the numbers of particles seen in urine and the magnitude of the relative absorbance reading obtained with the Bac-T-Screen. A retrospective chart review was conducted for patients with positive Bac-T-Screen results and negative cultures. Of the 75 patients, 6 were thought to have urinary tract infections on the basis of clinical criteria; the majority of the remaining 69 patients had clinical histories revealing systemic or urogenital conditions consistent with shedding of particles in the urine. A positive reading by the Bac-T-Screen system seemed to be related to the presence of somatic cells and other particles in urine; bacteriuria was not always detectable in these cases.
Median duration of the chronic phase of chronic myelogenous leukemia (CML) is 3 years; less than 20% of patients have a chronic phase greater than 7 years. It is unknown whether the length of chronic phase is stochastic or is predetermined for each patient. Since molecular abnormalities of bcr and c-abl occur in CML, we sought to determine whether there were differences in bcr and c-abl translocation or transcription in individuals with long v short chronic phase. These studies were performed in six patients with CML in whom chronic phase was 7+ to 26 years and 20 patients in whom chronic phase was less than 7 years. All patients had translocation of c-abl to within bcr. The distribution of breakpoints in bcr were similar in both groups. Transcription of the chimeric bcr/c-abl mRNA was comparable. These data suggest that changes in bcr or c-abl alone do not determine the duration of chronic phase in CML; other factors are likely involved.
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Plasminogen activator (PA) activity during epithelial wound healing in vitamin A-deficient rats was investigated to determine whether a relationship exists between corneal defect formation and PA activity. Uniform, central 3 mm diameter corneal epithelial wounds were made by scalpel debridement in vitamin A-deficient and in pair-fed control rats. Cryostat sections of such corneas, taken at various times post-scrape, were overlaid with fibrin films containing plasminogen to examine the distribution of PA activity; and antibodies to tissue plasminogen activator (tPA) or to urokinase-like activator (uPA) were incorporated into the films so that the immunochemical natures of detected PA activities could be determined. Corneas from pair-fed controls showed tPA-dependent lysis in association with the regenerating epithelium as well as in the defect region during epithelial wound healing. Corneas from vitamin A-deficient rats also demonstrated tPA activity in association with corneal epithelium post-scrape but showed no detectable tPA activity in the defect region. Histological examination of the vitamin A-deficient corneas demonstrated that a pseudomembrane composed of PMNs, cell debris, and fibrinous exudate had formed on the scrape-debrided stromal surface. The migrating edge of regenerating epithelium overlaid this membrane and was, therefore, not in contact with the stromal surface. The formation of the pseudomembrane, which delays reepithelialization, might have resulted from the absence of PA activity in the defect region. Both excessive and inadequate levels of PA activity may result in impaired epithelial wound healing.
We have used the technique of subtractive hybridization to identify a T cell gene selectively expressed during activation via the antigen-receptor pathway. This gene, termed TCA3 (for T cell activation) encodes a mRNA which is expressed following concanavalin A (Con A) activation of T cell clones at levels of approximately 1% total poly(A)-containing mRNA. The cDNA isolate, termed TCA3.0, is 512 bases in length excluding poly(A) and encodes a predicted 92-amino acid protein having the characteristics of a secreted polypeptide of approximately 69 amino acids. The genomic organizations of TCA3 was determined for two lambda phage clones and was found to be a single copy gene containing at least three exons dispersed over less than 4.7 kb. The temporal appearance of TCA3 mRNA in response to several activating agents was examined. It is not transcribed in response to interleukin 2 stimulation, but is transcribed in response to either antigen or Con A stimulation and can be detected as early as 1 hr poststimulation. Expression TCA3 in response to Con A is blocked by cyclosporin A treatment. The combined data suggest that TCA3 may represent a new lymphokine.
An association between myelofibrosis (MF) and chronic granulocytic leukemia (CGL) has been recognized. MF is usually a sign of a poor prognosis but its relation to other important parameters of CGL is not known. We observed a 54-year-old, white male patient who was well until May 1983 when he began developing gradually increasing right hip and left shoulder pain. Clinical evaluation 3 months later revealed splenomegaly and a white blood count of 126,000 with 29 segmented neutrophils, 22 bands, 7 metamyelocytes, 11 myelocytes, 6 promyelocytes, 5 blasts, 2 eosinophils, 5 basophils, and 3 lymphocytes. Cytogenetic analysis by G-banding technique showed a male karyotype with all 20 bone marrow cells examined positive for the Philadelphia chromosome. The patient was placed on busulfan therapy with good symptomatic improvement, but later suffered severe thrombocytopenia. At the end of October 1983, he was admitted with blast crisis and thrombocytopenia and was initiated on vincristine and cytosine arabinoside therapy. His bone marrow was repeatedly inaspirable and the biopsy was characterized by diffuse fibrosis. Chromosome analysis of 16 spontaneously dividing cells in the blood at this time revealed that 86% of cells had a karyotype of 46,XY,t(9;22)(q34;q11),t(1;3)(p32;p21) with the rest of the cells having only the Ph chromosome. The patient died 4 months later of intracranial hemorrhage. Chromosome #3 involvement has been reported in acute MF and essential thrombocytosis, but no specific cytogenetic abnormalities have been found in MF associated with CGL. It is unclear whether t(1;3) in this case represents a cytogenetic marker of MF or blast transformation, but it is certainly associated with poor prognosis and short survival.
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Twenty-seven patients with measurable, advanced nonsquamous cell carcinoma of the cervix were entered into this Phase II study evaluating the efficacy of ICRF-159 (razoxane). Eighteen of the 27 had adenocarcinoma. Thirteen patients had no previous chemotherapy. One patient was ineligible because she was never treated. One patient was inevaluable for response. Thus, 25 evaluable patients were given ICRF-159 orally at a starting dose of 1.5 g/m2 weekly until response could be determined. Grade 4 hematologic toxicity in two patients was the only life-threatening toxicity. One study patient had a partial response, 13 patients were regarded as having stable disease, and 11 had increasing disease. We conclude that ICRF-159 administered at this dose and schedule has no significant clinical activity against advanced adenocarcinoma of the cervix.
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The purpose of this paper is to evaluate the use of an alloplastic material, Gore-Tex Soft Tissue Patch, which when bonded to silicone rubber (Silastic) may represent a more "ideal" implant material. It's use in the rabbit model is compared to Silastic alone, Supramid Mesh, and cartilage control. Grafts were harvested at 3 weeks and 3 months, and the histologic findings were reviewed. Our results demonstrate that the implant is quite inert (minimal tissue reaction), allows for tissue ingrowth with reduced capsule formation, and protects the silicone rubber infrastructure from encapsulation. These findings suggest that Gore-Tex Soft Tissue Patch bonded to silicone rubber is a superior implant material and is worthy of consideration for clinical applications.
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Skin biopsies from the volar aspect of the forearm were studied in 26 patients with progressive systemic sclerosis (PSS) (16 diffuse, 10 CREST) and 4 controls using monoclonal antibodies against Langerhans' cells, T lymphocytes, macrophages, B lymphocytes, NK/K cells and HLA-DR antigen(s). Langerhans' cells were reduced or absent (anti-T6, anti-HLA-DR) in 19 of 20 clinically involved and in all 6 uninvolved PSS skin biopsies. Electron microscopic studies of 3 PSS patients indicated a reduction in the number of Langerhans' cells, with normal morphology of the remaining. HLA-DR antigen(s) on dermal endothelial cells were absent or reduced in 8 of 20 involved and 5 of 6 uninvolved PSS skin biopsies, but were present on the surface of dermal mononuclear cells presumably representing activated T lymphocytes. Increased numbers of dermal macrophages were found in 19% of PSS biopsies compared with controls. Absence of Langerhans' cells appears to represent the most widespread immunopathological feature of PSS. It is also associated with absent endothelial HLA DR surface antigens and activated T lymphocytes within the dermis.
A 45-year-old white male, bisexual, with a 2-year history of acquired immunodeficiency syndrome (AIDS) prodrome, developed a Burkitt cell-like acute lymphoblastic leukemia (ALL). Marker studies of marrow blasts show an unusual and possibly unique pattern, in that an unequivocal monoclonal B cell leukemia, having K-IgM with HLA-DR and B cell subset antigen (BA-1) expression, was superimposed with a mature suppressor T cell marker profile (pan-T, mature T, and suppressor/cytotoxic T antigens). The leukemic blasts were totally negative for terminal deoxynucleotidyl transferase (TdT), human T cell leukemia-lymphoma virus (HTLV) p19 antigen, and other immunoglobulin isotypes. Chromosome analysis of marrow cells disclosed that 70% of the cells had 47,XY, + 12,t(8;14)(q24;q32) chromosome complement, and 30% of the cells had a 47,XY, + 12,dup1q + (q22-31),t(8;14)(q24;q32). The consistent finding of the specific chromosome rearrangement (8/14 translocation) in all abnormal cells suggests that the cells were derived from a common precursor. With regard to the partial T cell marker expression, the significance of these markers in B cell leukemia is unclear, as is their relation to the additional chromosome abnormalities that apparently developed in the process of clonal evolution.