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Biomedical subjects

F H White

Publications and source records attributed to F H White.

At least 37 records · Page 2Linked to original sources
PubMed1993

A histological morphometric study of nuclear size in benign and malignant neoplasms of the human cheek.

This report describes the application of simple morphometric methods to generate quantitative data on nuclear size from tissue sections of normal, benign and malignant oral epithelium of the cheek. Measurements of nuclear areas of basal and spinous cells from cheek mucosa were made on haematoxylin and eosin-stained sections using a Zeiss VIDAS image analyser. The lesions examined comprised benign squamous cell papillomas and islands of cells from invasive squamous cell carcinomas. Normal control epithelium was obtained from the biopsy margins of non-neoplastic lesions. The nuclear areas (AN) were obtained by direct measurement whereas the nuclear diameters (DN) were determined automatically. In both basal and spinous strata, values for both these nuclear parameters were lowest in normal tissue and increased progressively through benign papillomas, with the highest values being found invariably in carcinomas. Statistically significant differences were detected between both normal and carcinoma and between papilloma and carcinoma. The morphometric parameters AN and DN are of value in distinguishing benign from malignant lesions of the human cheek.

Carcinoma, Squamous Cell↗
PubMed1993

Bovine bone morphogenetic protein-induced dentinogenesis.

Differentiation of odontoblasts is important for dentin formation in tooth germs and mature teeth. Although previous reports have indicated that there may be a kind of inductive agent that could induce mesenchymal cells in dental pulps to differentiate into odontoblasts, and secrete dentin matrix, the primary inductive factor of odontoblasts has not been found. Bone morphogenetic protein (BMP), which induces the formation of cartilage and bone when implanted in muscle tissue, is found in dentin matrix. The relationship between the differentiation of odontoblasts and BMP was observed by means of immunohistochemical staining with monoclonal antibody (MAb) against BMP in dental pulp tissue and cell culture; [3H]thymidine incorporation; and measurement of alkaline phosphatase activity. The conclusions are: (1) BMP exists in odontoblasts, ameloblasts, and dentin matrix (the positive reaction in ameloblasts appeared earlier and remained stronger); (2) BMP promotes incorporation of [3H]thymidine and increases the activity of alkaline phosphatase in cultured dental pulp cells; (3) BMP-induced dental pulp cells in dental pulp tissue cultures differentiate from mesenchymal to odontoblast-like cells; and (4) BMP induces formation of osteodentin and tubular dentin when used as a dental capping agent of dogs' teeth. Bone morphogenetic protein plays an important role in differentiation of odontoblasts and might be one of the inductive agents of odontoblasts. Further investigations of BMP as a biologic dental capping agent are warranted.

Animals↗
PubMed1992

A morphometric study of histological variations during cellular differentiation of normal human colorectal epithelium.

Quantifiable variations existing in the colorectal crypt during cellular differentiation were detected by using simple computer-aided morphometric techniques applied to routinely prepared H&E stained and semithin toluidine blue stained sections of normal colonic mucosa. Generally, most of the morphometric parameters including nuclear volume, nuclear volume weighted mean volume, cytoplasmic volume, cellular volume, nuclear axial ratio (a/b), mean nuclear diameter, nuclear shape factor (NSF) and nuclear maximum angle (Agmax) showed an increasing trend between basal and surface segments. Conversely, the nuclear-cytoplasmic (N/C) ratio, NSF and nuclear circularity index (NCI) decreased between these segments. Epithelial cells in the basal segment had the highest N/C ratio and the lowest cell volume due to their low volumes of cytoplasm. However, substantial increases of cytoplasmic volume occurred in the intermediate segment, thereby expanding the cell volume to 136% of that of the basal segment cell. Data for a/b, NSF, NCI and Agmax suggest that the epithelial nuclei were more ellipsoidal in shape and were aligned more perpendicular to the basement membrane as they reached the surface epithelium. Numerical densities for epithelial cell nuclei were highest in the basal segment, indicating more nuclear profiles at this region per unit area or volume. This also suggested that the basal segment was the active proliferating zone. Such observations agree with previously reported cell kinetic and autoradiographic studies.

Aged↗
PubMed1992

Studies on cell-clearing activity in alpha-lactalbumin. Effects of calcium removal on activity and conformation.

Effects of calcium removal on the cell-clearing activity of alpha-lactalbumin (alpha-LA) and concomitant changes in conformational structure have been investigated as part of a continuing study of the activity found earlier [McKenzie, H.A. & White, F.H., Jr. (1987) Biochem. Int. 14, 347]. This activity is similar to that of lysozyme, whereby lysis of the bacterial cell wall is catalyzed. However, the specific activity of alpha-LA is on the order of 10(-6) that of lysozyme. Under conditions where activities of apo and native alpha-LA were approximately linear functions of the protein concentration, the maximal ratio of apo to native activity was 5.7:1, determined by comparison of second order velocity constants. The CD spectrum of apo alpha-LA is intermediate between that of the A state and the native protein. By NMR, the conformation of apo alpha-LA is similar to, but distinctly different from, that of the native protein. The apo form did not revert completely to the native state when Ca(II) was resupplied, consistent with a role for this cation in folding. It is suggested that the activity increase may result from a diminished constriction of the "cleft" region in alpha-LA.

Calcium↗
PubMed1991

Morphometric and stereological study of the glandular epithelium of the lateral prostate of the intact and castrated guinea pig.

The glandular epithelium of the lateral prostate of the guinea pig was described within the framework of a morphometric model in terms of relative densities and absolute dimensions. A combination of direct measurement and point and intersection counting techniques was used. The quantitative data generated in the intact animals were compared with those of castrated controls. Castration was accompanied by a significant decrease in height of the glandular epithelium and in sizes of secretory and basal cells and their corresponding nuclei. On a per cell basis, significant decreases in total volume and surface area of granular endoplasmic reticulum were detected after castration. This was accompanied by a significant reduction in the total volume of Golgi cisternae. The total volume, surface area, and number of highly electron-dense and clear granules decreased significantly compared with the intact control animals. However, no significant changes in these parameters of low electron-dense granules were found. Significant reductions in the total volume and surface area of condensing granules, lysosomes, and mitochondria, but not their number, were detected. The average sizes of condensing granules, secretory granules, lysosomes, and mitochondria were decreased significantly after castration. The present study showed that the alterations in the secretory function of the secretory cells of the lateral prostate was reflected by the quantitative changes in granular endoplasmic reticulum, Golgi complexes, and secretory granules on a per cell basis. The data generated in the present study will serve as a baseline for further studies of the lateral prostate of the guinea pig.

Animals↗
PubMed1991

Morphometric and stereological analysis of the effects of 17 beta-estradiol on the glandular epithelium of the castrated guinea pig lateral prostate.

Upon administration of pharmacological doses of estradiol to castrated guinea pigs, the secretory cells of the lateral prostate underwent hypertrophy which resulted from significant increases in nuclear and cytoplasmic volume. There were quantitative increases in the small highly electron-dense granules and multivesicular bodies when compared with the castrated control. The dramatic increase in the number of highly electron-dense granules probably occurred at the expense of the low electron-dense granules. The average size of the condensing granules and mitochondria decreased significantly after estradiol administration. However, significant increase in the number of mitochondria was detected when compared with the castrated control. Ultrastructural data revealed no significant changes in the absolute dimensions of granular endoplasmic reticulum or of the Golgi complex, suggesting that estradiol exerted no significant stimulatory effects on these organelles. Pharmacological doses of estrogen appear to regulate the expression of secretory granules and multivesicular bodies in the lateral prostate of castrated guinea pigs.

Animals↗
PubMed1988

Studies on a partially purified bovine milk lysozyme.

Bovine milk lysozyme has been partially purified by a method developed in this laboratory. We have shown, by preliminary sequential analysis, and by gel filtration on HPLC, that the product is a mixture of two components. One of these, the enzymically active one, differs in its N-terminal sequence from that of "lysozyme 2", a bovine stomach mucosal enzyme, by 7 residues within the first 39 residues. However, some of its properties differ markedly from those of lysozyme 2. The other component, comprising 70% by weight of the total mixture, bears no sequential resemblance to any protein known to us. Our two component system appears to be the same as the preparation of Chandan et al. (Biochim. Biophys. Acta 110, 289 (1965], which they concluded was an homogeneous preparation of lysozyme.

Amino Acid Sequence↗
PubMed1987

Studies on a trace cell lytic activity associated with alpha-lactalbumin.

alpha-Lactalbumin (alpha-LA) has been examined with a new and sensitive method for determination of lysozyme activity. Samples of bovine, human, equine, and rat alpha-LA exhibited cell lytic activity, from 2 X 10(-6) to 45 X 10(-6) of the specific activity of hen eggwhite lysozyme. The activity was chromatographically inseparable from bovine and human alpha-LA. Bovine serum albumin and purified beta-lactoglobulin were inactive. The pH profiles and reaction kinetics of bovine and human alpha-LA showed differences from those of the corresponding milk lysozymes, indicating that their lytic activities were not likely to have resulted from trace lysozyme content. Thus, it appears that a weak cell lytic activity is inherent to alpha-LA.

Animals↗
PubMed1986

Determination of lysozyme activity at low levels with emphasis on the milk enzyme.

A method is described for the determination of lysozyme (muramidase) activity, whereby sensitivity is maximized by incubation of the reaction mixture (sample, buffer, and substrate (Micrococcus luteus] over an extended period. This approach is made feasible by exploiting our observation that the lytic reaction follows simple kinetic order during this time (e.g., 700 min for bovine lysozyme and 960 min for the eggwhite enzyme at low concentrations). After this period, the reaction rates diminish, indicating biphasic behavior, and eventually become negligible. The kinetic order may vary with both the type of lysozyme and the buffer system used. The limit of detection for bovine milk lysozyme is 100 pg/ml reaction mixture, equivalent to 6 ng/ml milk, for a 50-microliters sample (with reference to hen eggwhite lysozyme). With these limits, the method has proven valuable in our comparative studies, particularly for low levels of activity in bovine milk, but also in secretions and tissue extracts from various other eutherian, metatherian, and prototherian mammals. The method may also be applied to investigation of structure and function in modified forms of the enzyme.

Animals↗
PubMed1986

The Golgi apparatus during epithelial differentiation: a quantitative morphological study of maturation compartments in keratinised epithelium from hamster cheek pouch mucosa.

Stereological and other morphometric techniques have been used to investigate the quantitative morphological characteristics of the Golgi complex in defined basal, spinous and granular layers of hamster cheek pouch epithelium. As the cell migrates between basal and granular layers, there are reductions in the volumetric, numerical and surface densities of Golgi per unit volume of epithelial cell cytoplasm. When these density estimates are related to the average cell, the average granular cell has a higher number of Golgi complexes with a greater cisternal and associated vesicular volume and membrane surface area than the average basal cell. Both the volume and surface area of individual Golgi systems are smaller in the average granular cell when compared with the average basal cell. We suggest that these structural alterations are associated with the increased secretory activity of spinous and granular cells which is primarily effected by the production of membrane-coating granules, organelles which are probably responsible for producing the intercellular permeability barrier. These changes are also accompanied by increases in the amounts of rough endoplasmic reticulum and plasma membrane, supporting the proposition that the epithelial cell becomes increasingly metabolically active as it differentiates.

Animals↗
PubMed1986

Reclassification of North American leptospiral isolates belonging to serogroups Mini and Sejroe by restriction endonuclease analysis.

The genomes of North American strains of leptospires belonging to serogroups Mini and Sejroe were analyzed and compared with those of reference strains by cleavage with restriction endonucleases. The isolates selected for this study, when typed by the serologic method, were identified as serovars szwajizak, hardjo, and balcanica. However, the results of restriction endonuclease analysis (REA) indicated that a different classification existed. The 2 isolates typed as serovar szwajizak seem to be georgia by REA. Isolates belonging to serovars balcanica and hardjo had REA patterns that differed from both reference strains. Differences were not observed in the REA patterns between balcanica and hardjo isolates. All hardjo and balcanica isolates examined are suggested to be classified into a previously described hardjo, REA subtype hardjobovis. Using the enzyme Hha1, these isolates were subdivided into 3 subgroups. When examining the REA pattern of the 17 reference strains in serogroup Sejroe, 3 identical pairs were observed: wolffi and roumanica; sejroe and polonica; and istrica and nyanza. The REA again indicated that it will be a valuable method for the classification of leptospires.

DNA Restriction Enzymes↗
PubMed1985

A quantitative ultrastructural study of alterations in the area of the basal cell-stromal interface during experimental oral carcinogenesis.

Because of its topographical location, the basal cell in carcinomas must play a significant role in the invasion of adjacent tissues. We have analysed the proportion of the basal cell plasma membrane in direct contact with the adjacent lamina propria during in vivo oral carcinogenesis. Samples of hamster cheek-pouch mucosa treated with DMBA were assigned to hyperplasia, dysplasia and carcinoma groups using strictly defined histopathological criteria. Electron micrographs of basal cells were subjected to stereological intersection counting to provide estimates of the proportion of the total basal cell membrane in contact with the connective tissue (SSBM,PM). In untreated controls, a mean value of 9% was obtained, whereas, for DMBA-induced hyperplasias, dysplasias and carcinomas, values were 8%, 12% and 16% respectively. Statistically, SSBM,PM values were significantly elevated in dysplasias and carcinomas. The changes in this parameter may reflect an increased motility in the transforming basal cell prior to and concomitant with cellular invasion, and may prove to be of value as a structural indicator of malignant transformation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Studies on equine recurrent uveitis. II: The role of infection with Leptospira interrogans serovar pomona.

An enzyme linked immunosorbent assay was developed for the detection of immunoglobulin class specific antibodies to Leptospira interrogans serovar pomona in the serum and aqueous humor of horses. Serum antibody was also assayed by microscopic agglutination tests. Although higher levels of antibody were found in sera from horses with signs of uveitis, the association was not statistically significant. Antibodies to pomona were detected in the aqueous of 12 eyes from the 101 horses sampled at a slaughterhouse, and in most instances, a comparison of the aqueous/serum antibody level with that of the total aqueous/serum IgG level indicated intraocular antibody synthesis. Antibodies were also found in 4 aqueous (or vitreous) samples out of 9 obtained from horses with clinically documented uveitis and the above comparison again indicated intraocular antibody synthesis. The data point to an important role for pomona as an etiology of equine recurrent uveitis but also emphasize that the initiating cause for this disease is often obscure in that association with leptospirosis cannot be shown in many instances.

Agglutination Tests↗
PubMed1985

An ultrastructural morphometric study of cellular and nuclear volume alterations during experimental oral carcinogenesis.

Cellular and nuclear pleomorphism are features of epithelial dysplasia, a premalignant alteration found in many stratified squamous epithelia including those of the oral mucosa. In the present report we have applied morphometric techniques to evaluate alterations in cellular and nuclear volume during epithelial differentiation in experimentally-induced oral carcinogenesis. Hamster cheek pouches treated with DMBA were biopsied and assigned to hyperplasia, dysplasia and carcinoma groups with untreated pouches being used as controls. Following a rigorous sampling scheme, electron micrographs from defined basal, spinous and granular strata were obtained and cellular and nuclear volumetric estimates obtained by a combination of direct measurement and stereological intersection counting. In all strata, nuclear, cytoplasmic and cellular volumes were lowest in the normal control group and were increased in all experimental groups. Volumetric estimates obtained for carcinogen-treated groups were generally between 2 to 3 times higher than for the control group which indicates that cellular and nuclear hypertrophy occurs in conjunction with the epithelial hyperplasia and proliferation induced by the chemical carcinogen. We also describe the application of the pathological alteration ratio (PAR), a parameter which is independent of methodological variables, and which was consistently elevated in our experimental study. This was also applied to a number of reports in the literature which describe morphometric alterations in cellular or nuclear parameters in a variety of human lesions. Within any particular group of lesions, PAR values were generally higher for carcinomas than for other benign conditions. We conclude that cellular and nuclear hypertrophy occurs not only during experimental carcinogenesis but also in human benign and malignant lesions. With the advent of computer-based automated image analysers, measurements of certain structural features on sectioned tissues may have a role in histopathological diagnosis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

A morphometric study of alterations in rough endoplasmic reticulum during differentiation in stratified squamous epithelium.

Stereological techniques were applied to investigate several structural parameters characterising the rough endoplasmic reticulum (RER) during differentiation in hamster cheek-pouch epithelium. Mucosal samples from five Syrian golden hamsters were obtained and processed for electron microscopy. Following a strict sampling regime, micrographs were obtained from defined basal, spinous and granular layers, and subjected to stereological point and intersection counting procedures. This enabled volume and surface densities, and volume-to-surface ratios of RER to be determined for each cellular layer. From previous estimates of the mean cytoplasmic volume of the "average" basal, spinous and granular cell in this tissue, it was possible to calculate the absolute volume and surface area of RER present in these average cells. Both volume and surface densities of RER decreased between basal and granular layers, whereas the total volume and surface area present in the average spinous and granular cell were both higher than in the average basal cell. These data suggest that RER is being synthesised during epithelial differentiation. In view of the role of the RER in the production of exportable proteins, it is possible that increased amounts of this organelle are required to synthesise the enzymes and glycoproteins found in membrane-coating granules, since these are also seen with increasing frequency in successively higher strata.

Animals↗
PubMed1984

Ultrastructural morphometry of collagen from lamina propria during experimental oral carcinogenesis and chronic inflammation.

Stereological point-counting methods were used to determine the volumetric alterations in collagen from the lamina propria immediately beneath the epithelial-connective tissue junction in hamster check-pouch mucosa treated with the chemical carcinogen DMBA. In addition, a non-neoplastic inflammatory control was evaluated in which a delayed hypersensitivity reaction was induced by the contact-sensitising agent DNCB. DMBA-treated tissues were assigned to histopathologically defined hyperplasia, dysplasia and carcinoma stages. The volume densities of collagen present in unit volume of extracellular lamina propria were found to decrease progressively and significantly in DMBA-treated tissues when compared with values obtained from normal untreated mucosa. Values from the inflammatory control were comparable with those from the dysplasia stage of carcinogenesis. The mechanisms responsible for these decreases in collagen volume density are unknown, but contributory factors might include collagen destruction by enzymes originating in either the epithelium or the cells of the inflammatory infiltrate, dilution of collagen produced by inflammatory oedema or alterations in the synthetic capabilities of fibroblasts.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Hemidesmosomal dimensions and frequency in experimental oral carcinogenesis: a stereological investigation.

Connective tissue invasion by carcinomas results in a variety of morphological changes at the epithelial-connective tissue junction. In this report, hemidesmosomal size (-delta) and frequency (Ns) were quantified using established stereological methods. Following treatment of hamster cheek pouches with the chemical carcinogen DMBA, lesions defined as hyperplasias, dysplasias and carcinomas were evaluated using electron microscopical techniques. Untreated pouches served as controls. Stereological intersection counting procedures were used to quantify hemidesmosomes at the epithelial-connective tissue junction. During carcinogenesis, hemidesmosomal diameter decreased progressively, although the reductions were not statistically significant. Hemidesmosomal frequency also decreased progressively between control and carcinoma groups. Normal basal plasma membranes possessed approximately 8 hemidesmosomes/micron 2 whereas values were reduced to approximately 3/micron 2 in the carcinoma group. The reductions in hemidesmosomal frequency during carcinogenesis may reflect an increased motility of basal epithelial cells and a decreased adherence of basal cells to the adjacent lamina propria. The specificity of this alteration in the pathogenesis of malignancy can be readily determined by the application of stereological methods to various neoplastic and non-neoplastic lesions.

9,10-Dimethyl-1,2-benzanthracene↗