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Biomedical subjects

W C Lambert

Publications and source records attributed to W C Lambert.

At least 37 records · Page 2Linked to original sources

Identification of early apoptosis in feulgen-stained cultured cells in situ by computerized image analysis.

A method is presented in which Feulgen-stained apoptotic cells are identified among cultured cells in situ using computerized image analysis of their nuclei. Images of either control (untreated) human lymphoblastoid cell nuclei or of similar cells treated with 3mM methyl methanesulfonate for 1 h, which induces apoptosis in 100% of the cells, were converted to a standard size (80 x 80 pixels) and Fourier transforms and boundary images based on 21 proportional mean gray-level thresholds obtained. The perimeter and the mean fractal dimension of the latter and 39 selected coefficients of the former were then obtained from which data were chosen heuristically and subjected to multivariate linear discrimination analysis. Eighty-two percent of a teaching set of 50 nuclei and 69% of a test set of 29 nuclei were correctly identified as apoptotic versus nonapoptotic by the computer, compared with 57% identified correctly by a panel of 7 pathologists. This study shows the feasibility of using this type of analysis to directly identify apoptotic cells in culture, and probably also in tissues, by direct observation using computerized imaging technology.

Apoptosis↗

Binding properties of bovine ocular lens zeta-crystallin to right-handed B-DNA, left-handed Z-DNA, and single-stranded DNA.

Bovine zeta-crystallin has the ability to bind with different DNAs. Initially, this protein was named regulatory factor 36 (Kang et al., 1985), but it has been shown to be an ocular lens zeta-crystallin (Jörnvall et al., 1993), which is considered an enzyme-crystallin (Rodakanaki et al., 1989). The enzyme-linked immunosorbent assay (ELISA) was used to quantitate the binding of bovine zeta-crystallin to purified high molecular weight double-stranded (ds-) and single-stranded (ss-) DNA (bovine and synthetic DNA). ELISA quantitation was achieved by the addition of anti-zeta-crystallin antibodies to the DNA-zeta-crystallin complex, using a novel immunochemical avidin-biotin method. Zeta-crystallin shows much greater binding intensity for ss-DNA and for ds-Z-DNA than for ds-B-DNA. It also reacts slightly more with ds-Z-DNA than ss-DNA. Therefore, we speculate that zeta-crystallin may act as a transcriptional enhancer (outer lens cortex), possibly binding to Z-DNA regulatory elements within lens crystallin genes. It may also act to protect DNA from endogenous DNase activity and as a DNA unwinding (destabilizing) protein also involved with transcription, occurring in normal adult bovine lens nucleated secondary fiber cells.

Animals↗

Correction of the DNA repair defect in Fanconi anemia complementation groups A and D cells.

We have previously isolated from Fanconi anemia, complementation groups A (FA-A) and D (FA-D) cells, a DNA endonuclease complex which is defective in its ability to incise DNA containing interstrand cross-links produced by psoralen plus UVA light. The repair capabilities of the FA complexes, compared with those of the corresponding normal complex, have now been examined using two types of complementation analysis. First, introduction of the normal complex, by electroporation, into 8-methoxypsoralen (8-MOP) plus UVA treated FA-A and FA-D cells resulted in correction of their repair defect, determined by measuring repair-related unscheduled DNA synthesis (UDS). The FA-A and FA-D complexes could similarly complement the repair defect in each others' cells, but not in their own. Second, mixing the normal with the FA-A and FA-D complexes, or the FA-A with the FA-D complex, in a cell-free system resulted in correction of the defect in ability of these FA complexes to incise damaged DNA. These results indicate that the normal complex contains the proteins needed to correct the DNA repair defect in FA-A and FA-D cells and that the FA-A and FA-D complexes contain the protein needed to complement the repair defect in each other.

Cell Line, Transformed↗

Localization of B-DNA and Z-DNA in terminally differentiating fiber cells in the adult lens.

We examined histochemically and immunohistochemically the distribution of B- and Z-DNA in the epithelium and terminally differentiating dog lens fiber cells. On the basis of anti-DNA antibody reactivity, qualitative and quantitative data on B- and Z-DNA in cells were determined. Anti-B-DNA immunoreactivity gradually declined throughout nucleated fibers, with a precipitous decrease at approximately 90 microns. Anti-Z-DNA antibody binding decreased with a sudden loss of immunoreactivity at approximately 90 microns. The pattern of anti-B- and Z-DNA staining correlates with the loss of alpha-crystallin immunoreactivity, the major lens crystallin, and decreased eosin staining of proteins. Germinative zone cell nuclei showed the highest DNA probe binding values, followed by the superficial fibers, central zone, middle fibers, and deep fibers. The presence of single-stranded (ss)DNA in deeper fibers was detected by anti-ss-DNA antibodies. This is indicative of DNA degradation. These observations suggest that a dramatic reorganization of lens fiber cells' supramolecular order occurs at approximately 90 microns, the phase transition zone.

Adult↗

Echogenicity of hepatic versus portal vein walls revisited with histologic correlation.

The portal vein wall typically is hyperechoic over a wide range of beam-vessel angles, whereas the hepatic vein wall is hyperechoic only when the incident beam and the vessel are perpendicular. This has been attributed to marked discrepancies in mural thickness, collagen content, or perivascular fat between portal and hepatic veins. We evaluated histologically the walls of portal and hepatic veins using three cadaveric livers. For vessels with luminal diameter above 2 to 3 mm, hepatic vein and portal vein wall thicknesses were similar such that portal vein walls were not more than 50% thicker than those of hepatic veins of comparable size. Hepatic vein walls were mostly composed of parallel, tightly packed collagen fibers. In contrast, portal vein walls were composed of loosely arrayed, nonparallel connective tissue fibers which were separated by multiple intervening spaces and only a minority of which were collagenous. Perivascular fat was not identified adjacent to intrahepatic vessels beyond the liver hilus. The marked differences in echogenicity between portal vein and hepatic vein walls typically observed at ultrasonography thus cannot be attributed to differences in mural thickness, collagen content, or perivascular fat between these vessels. Rather, the distinct composition of the hepatic vein wall renders it a specular reflector, which is hyperechoic only when the angle between the ultrasound beam and the vessel wall is close to 90 degrees, whereas the composition of the portal vein wall enables it to appear hyperechoic at a wide range of beam-vessel angles.

Aged↗

Bacillary angiomatosis: presentation of six patients, some with unusual features.

Bacillary angiomatosis (BA) is an unusual systemic vascular proliferation seen predominantly in patients with the acquired immunodeficiency syndrome. These vascular lesions are probably due to infection with a Bartonella species, most often B. henselae and, in some patients, B. quintana. BA is treatable and often curable, but without therapy, may be life-threatening. Clinically, the lesions, when superficial, are said to often resemble pyogenic granulomas, appearing polypoid histologically with an epidermal collarette. We now report six patients, three of whom showed lesions of BA morphologically and histologically distinct from the other patients reported to date. Two patients lesions appeared clinically as violaceous plaques and tumours resembling Kaposi's sarcoma; one of them had lesions histologically reminiscent of a papular angiokeratoma; and the other had lesions histologically suggestive of a combination of Kaposi's sarcoma and BA. Another patient presented with soft subcutaneous nodules which histologically showed extensive acute inflammation characteristic of an acute abscess, but which also displayed proliferating dilated small blood vessels with bulbous endothelial cells adjacent to numerous bacteria and also containing them. The Grocott-methenamine silver stain and the Warthin-Starry stain showed the organisms to better advantage in lesions of all six patients, although bacteria were also evident with the haematoxylin and eosin, periodic acid-Schiff and alcian blue stains.

AIDS-Related Opportunistic Infections↗

Surgical management of mycosis fungoides.

Mycosis fungoides (MF) is a type of cutaneous hyperproliferative T-cell disorder that may be localized. Although there is considerable controversy regarding whether MF may originate as a non-neoplastic condition, or even whether MF is a neoplastic condition until late in its course, we have seen a few cases undergo what appeared to us to be a clear progression from an inflammatory disorder to MF. We now report a 32-year-old man with MF most prominent on his right flank and buttock who developed his patches several weeks following, and in the precise locations in which he had experienced, exposure to toxic chemicals in an industrial accident. Because of this history, and because all lesions were transient except for these sites, these permanent lesions were treated with local surgical excision. There was no recurrence of disease at the treated sites, and the progression of MF markedly slowed following surgery, although he has continued to experience multi-focal transient recurrent disease, controlled by a combination of topical and systemic treatments, until the present time. Destructive methods such as excisional surgery or carbon dioxide laser may be considered a therapeutic option for localized MF.

Adult↗

Bacillary angiomatosis in an HIV seronegative patient on systemic steroid therapy.

Bacillary angiomatosis is an unusual systemic vascular proliferation seen predominantly in patients with the acquired immunodeficiency syndrome. These vascular lesions are due to infection with a Bartonella species, most commonly B. henselae, but sometimes B. quintana. It is treatable and often curable, but without therapy may be life-threatening. Clinically, the disorder often resembles several different vascular disorders, particularly pyogenic granuloma and Kaposi's sarcoma. We now report a clinically typical patient with bacillary angiomatosis who was HIV seronegative, but who had idiopathic thrombocytopenic purpura, was status-post splenectomy and to whom long-term systemic prednisone had been administered.

Adult↗

Granuloma annulare of the eyelid.

A superficial (dermal) granuloma annulare (GA) of the eyelid developed in a 69-year-old woman who initially had no evidence of precipitating causes, including trauma, tuberculosis, octopus bite, lupus vulgaris, actinic damage, sarcoidosis, diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, or rheumatic fever. She later developed complete bilateral nasolacrimal duct obstruction that led to dacryocystorhinostomy on the right side. Systemic workup showed evidence of a lupus-like syndrome. Although deep, subcutaneous GAs have been reported in the periocular tissues, episclera, and orbit in children and young adults, a superficial dermal GA of the eyelid in an elderly patient is distinctly rare. The characteristic histopathologic feature of both superficial and deep GAs is a necrobiotic granuloma in which necrotic collagen is surrounded by a zone of histiocytes and fibroblasts. This case demonstrates that superficial GA of the eyelid may be associated with an underlying lupus-like syndrome. This case also raises the question of whether GA of the eyelid and lupus erythematosus may be associated with bilateral nasolacrimal duct obstruction.

Aged↗

Cutaneous fibrous dysplasia: an incomplete form of the McCune-Albright syndrome.

A number of genetic disorders have been described in limited form. We report a patient with precocious puberty, large irregularly shaped café-au-lait spots since birth and a diffuse scalp alopecia showing the cutaneous changes of fibrous dysplasia. Histologically, the hair follicles were replaced by convolutions of fibrous tissue. This is to our knowledge the first patient reported with an apparently localized cutaneous form of this syndrome, a pattern predicted by the recently described somatic mutation of the Gs alpha gene. This is the second patient reported to our knowledge with the cutaneous McCune-Albright syndrome and scalp alopecia, and the first with diffuse scalp alopecia, the latter being the presenting sign. We believe that the differential diagnosis of both localized and diffuse alopecia should include the McCune-Albright syndrome.

Alopecia↗

Xeroderma pigmentosum.

Xeroderma pigmentosum is a rare, recessively transmitted disease associated with increased sensitivity to ultraviolet radiation in wavelengths found in sunlight, development of cancers in sun-exposed areas of the body in much larger numbers and much earlier in life than in normal individuals, and in some patients, neurologic deficiencies unrelated to sun exposure. Extensive cellular, biochemical, and molecular genetic studies in numerous laboratories have revealed that cells derived from patients with this disease have defective repair of ultraviolet-light-induced damage in cellular DNA, and that extensive genetic heterogeneity and numerous distinct genes are involved in the genetics of this disease and the etiopathogenesis of its associated changes. A number of these genes and gene products are now being, or have been, cloned, and their gene products characterized.

DNA↗

Ecchymotic Kaposi's sarcoma.

We report two patients with ecchymotic patches that did not suggest the diagnosis of Kaposi's sarcoma. The principal complaint of one patient was facial and periorbital edema with bilateral periorbital ecchymosis. On his trunk were patches resembling pityriasis rosea-like Kaposi's sarcoma. Both types of lesions proved to be Kaposi's sarcoma on histologic examination. The second patient had scattered ecchymotic lesions, with typical lesions of Kaposi's sarcoma elsewhere on his body. The ecchymotic lesions showed a large amount of extravasated red blood cells and no evidence of amyloid. This variant has not been described previously to our knowledge.

Adult↗

Protracted superficial Wegener's granulomatosis.

We describe a patient with protracted superficial Wegener's granulomatosis. On the basis of nasal mucosa and conjunctival biopsy specimens, a diagnosis of sarcoidosis was originally made. However, later biopsy specimens and the clinical condition indicated a rare variant of Wegener's granulomatosis, one with a protracted course of granulomatous ulcers localized to the skin and mucosa.

Adult↗

Keloidal Kaposi's sarcoma: report of three patients.

Kaposi's sarcoma is a unique neoplasm which has emerged as an important element of AIDS in homosexuals but not in others at high risk for AIDS. The biology of this important tumor may be related to cytokines secreted by HIV-infected cells and/or by Kaposi's sarcoma cells themselves. We report 3 patients with multiple keloid-like tumors. These lesions proved to be Kaposi's sarcoma histologically, yet with a unique keloidal component. This variant has not been described previously. It is possible that cytokines that stimulate Kaposi's sarcoma cell growth may also stimulate proliferation of local fibroblasts to produce this variant.

Acquired Immunodeficiency Syndrome↗