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Biomedical subjects

H Cheng

Publications and source records attributed to H Cheng.

At least 451 records · Page 25Linked to original sources

Dynamics of lymphocyte-endothelial interactions in vivo.

The dynamics of the attachment of lymphocytes to the endothelium of high endothelial venules in murine Peyer's patches were studied in vivo. Lymphocytes adhered readily to the endothelium lining these vessels, but most of the adhering cells detached within a few seconds. Many lymphocytes, however, experienced multiple collisions with the high endothelial venules, and this substantially increased the efficiency of lymphocyte collection by these vessels.

Animals↗

Scanning electron microscopy of isolated epithelium of the murine gastrointestinal tract: morphology of the basal surface and evidence for paracrinelike cells.

By using the method of Bjerknes and Cheng, isolated murine gastrointestinal epithelial sheets were prepared for scanning electron microscopy. Examination of isolated epithelium from fundic stomach revealed numerous branched gastric glands. Parietal cells were easily detected bulging from the basal surface of the glandular epithelium. The basal surface membrane of parietal cells appeared smooth, with only sparse microvilluslike projections, whereas adjacent glandular cells had numerous 1- to 2-micron fingerlike projections which interdigitated laterally with similar processes from adjacent cells. Occasionally, paracrinelike cells having long cytoplasmic processes ranging from 10 to 20 micron in length were observed on the basal epithelial surface of the stomach and the colon, but not the small intestine. In isolated intestinal epithelia, the basal surface of crypt epithelial cells showed extensive cytoplasmic interdigitations, but no distinct morphology permitting recognition of individual cell types. Various stages of intestinal crypt bifurcation were seen. Craterlike spaces in the basal surface of crypt epithelium, presumably due to migrating leukocytes, were also numerous. Examination of the luminal surface of the isolated intestinal epithelium revealed that intimate associations between epithelium and mucosal-associated microorganisms were maintained, thus suggesting that minimal alterations in surface morphology were incurred by epithelial isolation. These observations on epithelial structure suggest that isolated gastrointestinal epithelia may be well suited for physiological studies of epithelial function and interactions with the microbial flora.

Animals↗

Effects of 30% intestinal resection on whole population cell kinetics of mouse intestinal epithelium.

The intestine remaining after resection undergoes a well known compensatory response. Crypts and villi grow in size, and the number of proliferating cells in a crypt increases. The crypt labeling index, however, is unchanged, which is thought to suggest that the growth fraction also remains unchanged and hence that the system is enlarged, but otherwise the new steady-state is similar to that of the controls. It is also generally accepted that no new crypts or villi are added to the adapting bowel. In this study we applied recently developed tools to study the response of the intestinal epithelium as a whole. Thus, the effects of 30% intestinal resection on whole population cell kinetics were determined by using flow cytometry, Coulter particle counting, and simple morphometric techniques. In addition to the classic response, we found an increase in the rate of crypt production, which was due mainly to a shorter crypt replication cycle. Thus, new crypts were produced at a faster rate in the resected animals than in the transected controls. This resulted in an expansion of the crypt cell population in the epithelium following resection. There was a corresponding expansion of the cycling cell population and thus an increase in the growth fraction of the resected epithelium. We conclude that for the crypt population, the classic story is correct with the exception that new crypts are added to the epithelium after resection. However, for the epithelium as a whole, the classic story is misleading as there appears to be an increase in the growth fraction of the epithelium after intestinal resection.

Animals↗

Crypt production in normal and diseased human colonic epithelium.

New crypts are added continuously to the adult mouse intestinal epithelium by a process of crypt replication. Branching crypts found in the epithelium represent a stage in the process of crypt replication. In "normal" human colonic epithelium we found a small but definite percentage of branching crypts, 0.44 +/- 0.16, indicating that new crypts are being produced at a low rate in this epithelium. Significantly higher (P less than .001) percentages of branching crypts, 30.4 +/- 5.75, 15.1 +/- 1.08, and 13.2 +/- 1.05, were found in diseased colonic epithelium from patients with ulcerative colitis, Crohn's disease, and multiple polyposis, respectively. These results may be interpreted as suggesting that the rate of crypt production in human colonic epithelium is increased in a number of disease states. We concluded that, as in the mouse intestinal epithelium, the rate of the crypt replication process in human colonic epithelium is plastic and may respond to a variety of conditions.

Aged↗

Ageing, exercise and food restriction: effects on body composition.

This study was undertaken to reevaluate the effect of ageing on body composition and to compare the effects of exercise and food restriction on body fat content in rats. Body fat content increased progressively between ages 12 and 28 months in sedentary freely eating male Long-Evans rats. A program of 3 h of swimming/day caused body weight to plateau at a level approximately 20% below that of the freely eating sedentary rats, primarily due to a more than 100 g lower body fat content in the swimmers. Lean body mass and protein content decreased progressively with ageing; in the sedentary animals, this decrease was significant by 18 months. The swimming protected against the decline in lean body mass and protein content up to age 18 months, but did not prevent a large decrease in lean body mass between ages 18 and 24 months. Food restriction that kept the sedentary rats at the same weight as the swimmers had its major effect on body fat content, which was approximately 40% lower than in the sedentary freely eating rats at all ages. The differences in body composition between the swimmers and food restricted sedentary animals were relatively small and consisted primarily of a lower body fat content in the swimmers. In conclusion, our results show that lean body mass declines with ageing in rats and that this loss of lean tissue is counterbalanced by an increase in fat. Exercise is highly effective in minimizing the increase in body fat, and may delay the decline in lean body mass, with ageing.

Aging↗

Cataract and retinopathy: screening for treatable retinopathy.

Diabetes causes cataract and certain physical changes in the lens. The diabetic lens is larger than the non-diabetic and shows greater light scatter and fluorescence. Both hyperglycaemia and lowering of blood glucose case refractive changes and hypermetropia is the most common. Classical 'snow-flake' juvenile cataract associated with hyperglycaemia is now rare. It has an osmotic mechanism. Diabetes is a risk factor for cataract in adults which is duration dependent, more frequent in women and leads to earlier surgery. It resembles non-diabetic senile cataract. Extracapsular cataract extraction is the method of choice for diabetic cataract with a better visual result and less risk of rubeosis iridis. A posterior chamber implant may still permit retinal photocoagulation if necessary. Diabetic retinopathy is still the leading cause of blindness in the working age group. The beneficial effect of photocoagulation has been shown by randomized controlled trials to be long-lasting for both proliferative retinopathy and maculopathy. Therefore there is a need for screening, especially for those with proliferative disease which may be present without symptoms. A knowledge of risk factors will enhance detection rate with duration as the strongest determinant for retinopathy. Any screening modality should be highly sensitive as well as specific. The role of different professionals as potential screeners should be considered. Adequate provisions include facilities for checking vision and for dimming ambient lighting. Mydriasis and a good ophthalmoscope light will increase detection rate. The use of a 45 degrees non-mydriatic camera is unlikely to supplant the use of an ophthalmoscope as a single field is likely to miss important lesions. A 60 degrees camera may confer a large enough field and the use of transparencies will provide magnification when films are projected but the camera is more difficult to use. A list of features chosen by a recent study to characterize sight-threatening retinopathy is included and their presence indicates the need for referral to an ophthalmic clinic for treatment or close observation.

Adolescent↗

Evaluation of the functional maturity of newborn T8+ suppressor cells and the resistance of newborn lymphocytes to suppression.

Concanavalin A (Con A) was used to study the suppressor function of human umbilical cord blood T cells. The suppressor activity and the phenotype of Con A-activated adult and cord T cells were compared using allogeneic adult mononuclear cell (MNC) response to pokeweed mitogen (PWM), phytohemagglutinin (PHA), and alloantigen as indicator culture systems. It was found that Con A-activated adult suppressor T cells were predominantly T8+ cells and suppressed PWM-induced IgG production by adult lymphocytes, as well as PHA- and alloantigen-induced proliferation of allogeneic adult MNC. Con A-activated cord T cells, however, exhibited no significant suppression in any of the three indicator systems. Furthermore, using Con A-activated adult T8+ cells as a source of suppression, the proliferative response of cord lymphocytes to PHA and alloantigen were as susceptible to suppression as those of adult lymphocytes. These results, together with previous findings that PWM-induced cord suppressor T cells were predominantly T4+ cell-mediated suppression, suggest that fetus/newborn lymphocytes achieved their selective inhibition on adult lymphocytes through the T4+ suppressor cell circuit.

Adult↗

Human cord blood suppressor T lymphocytes. II. Characterization of inducer of suppressor cells.

Previously, we reported an antigen nonspecific inducer of T suppressor cell factor (TisF) produced by cord blood mononuclear cells (MNC) in 48-hr, two-way mixed lymphocyte cultures (MLC). The target of this factor was a radiosensitive, T4+ (T8-) adult suppressor T cell subset. The cellular origin of this TisF was examined in the present study. IgG production by pokeweed mitogen (PWM)-stimulated adult MNC was used as an assay for TisF activity. It was found that TisF-producing cells formed rosettes with sheep erythrocytes (E+) and were independent of adherent cells (AC) in the production of TisF. They were resistant to irradiation (2500 rads) and phenotypic characterization with T cell reactive monoclonal antibodies indicated that they resided in the T8- (T4+) population. Furthermore, both TQ1- and TQ1+ cells were required for the production of TisF activity and such activity could not be reconstituted by supernatants from TQ1- MLC and TQ1+ MLC. These results indicate that the production of TisF is dependent upon interactions between radioresistant E+, T8-, TQ1- and radioresistant E+, T8-, TQ1+ cells.

Antibodies, Monoclonal↗

Freeze frame analysis on high speed cinematography of Nd/YAG laser explosions in ocular tissues.

High speed colour cinematography at 400 frames per second was used to photograph both single and train burst Nd/YAG laser applications in ox eyes at threshold energy levels. Measurements of the extent and speed of particle scatter and tissue distortion from the acoustic transient were made from a sequential freeze frame analysis of the films. Particles were observed to travel over 8 mm from the site of Nd/YAG application 20 milliseconds after a single pulse at initial speeds in excess of 20 km/h. The use of train bursts of pulses was seen to increase the number of particles scattered and project the wavefront of particles further from the point of laser application.

Animals↗

Pseudophakic bullous keratopathy: relationship with endothelial cell density and use of a predictive cell loss model. A preliminary report.

Patients involved in a clinical trial of cataract surgery who developed pseudophakic bullous keratopathy were studied. They did not differ from the trial population as a whole with respect to their age or pre-operative endothelial cell density. Bullous keratopathy occurred within a narrow range of endothelial cell density. Examination of endothelial cell loss profiles over four years of follow-up after cataract surgery, in patients who developed bullous keratopathy and others, suggested that there was a predictable pattern. A mathematical model is described which gave good agreement between predicted and measured endothelial cell density. The model is now being used to identify parameters which may predict susceptibility to development of bullous keratopathy.

Aged↗

In situ cross-linking of androgen receptors to nuclear acceptor sites of rat prostate with formaldehyde.

Androgen receptors were attached covalently in situ to their nuclear acceptor sites with the contact site cross-linker, formaldehyde. Chromatin, prepared from sonicated nuclei of rat prostate, was labeled by isotope exchange with [3H]dihydrotestosterone and found to contain 19,000 +/- 900 (mean +/- S.E.) salt-extractable androgen receptors/nucleus which sedimented in the 3-4 S region of 7.6-76% (v/v) glycerol gradients and at a density of approximately 1.28-1.35 g/ml in CsCl gradients. After incubation of the chromatin with 0.5% (w/v) formaldehyde for 1 h at 4 degrees C, there was a 90% reduction in the concentration of free androgen receptors and an increase in the density of the androgen binding sites recovered from CsCl gradients. Extensive digestion of the cross-linked chromatin with micrococcal nuclease liberated 18% of the androgen receptors as 3-4 S entities and caused an overall decrease in the density of the receptor-acceptor complexes. Ribonuclease digestions had no effect on the androgen receptors cross-linked to chromatin. Mild digestion of the cross-linked preparations with trypsin, alone or in combination with micrococcal nuclease, resulted in the release of 74% and 97% of the androgen receptors, respectively. Together, these findings imply that two classes of receptor-acceptor complexes are present in prostatic chromatin--one, containing about 20% of the androgen receptors in which the receptors are in direct contact with DNA but not with proteins and the other, containing most of the androgen receptors in which the receptors are adjacent to acceptor proteins but not to DNA.

Animals↗

Precision of cell density estimates and endothelial cell loss with age.

The precision of estimating endothelial cell density of the cornea, using a noncontact method of specular microscopy, was assessed by asking eight individuals with known densities in one operated-on and one unoperated-on eye to have photography on two occasions in the same day. Three photographs of each eye were assessed by two individuals using masking procedures. Interobserver differences were negligible and estimates were similar except for one eye with low density values. The method was applied to a natural history study in which 103 eyes had cell-density estimates at zero and two years, and mean cell loss was found to be 2%. A collateral study using only good photographs that were available at both zero and two years showed a similar loss of 1.86% and reduced the number of counts showing unexpectedly high gains and losses.

Aging↗

Whole population cell kinetics and postnatal development of the mouse intestinal epithelium.

Measurements of whole population cell kinetics of mouse intestinal epithelium during postnatal development are reported. Swiss albino mice aged 1, 2, 3, 4, 6, 8, 10, 12, 16, 19, 24, and 28 weeks were studied. Isolated epithelial preparations of jejunum and colon were used. Most kinetic parameters studied either increased or decreased with age to reach a steady level sometime after weaning. For example, before weaning about 30% of crypts were observed to be branching, while after weaning, the population of crypts that were branching decreased to adult levels of 5-10% in jejunum and 1-2% in colon. Thus, there was very active crypt formation before weaning, which likely continued into adult life but at a lower level. Villus formation appeared to be occurring in animals before weaning (i.e., 1-3 weeks), while it stopped with weaning, and thus the mean villus height increased to a plateau, which was constant with age after 4 weeks. In contrast, the mean villus width increased steadily with age. As the width of villi increased with age, the number of crypts associated with a villus also increased (presumably as a result of net crypt production in the adult). These measurements and many others (proportion of cells in S phase, number of cells/cm2, number of cells/villus, number of cells/crypt, etc.) are described.

Animals↗

Mucous cells and cell migration in the mouse duodenal epithelium.

The distribution of mucous cells in the mouse duodenum was used to determine whether or not intestinal epithelial cells move as a sheet during their migration from crypts to villi. The experiments took advantage of the probable symmetry of mucous-cell divisions (symmetry in the sense that each mucous-cell division produces two mucous cells). Since approximately 50% of newly formed mucous cells are derived from mucous-cell divisions, at least 50% of newly formed mucous cells in the crypt should be found in mucous-cell pairs. It follows that if the epithelium moves as a firmly interconnected sheet, at least 50% of mucous cells found in the villus should also be in pairs. On the other hand, if a significant amount of cell mixing occurs during migration, the pairing tendency of mucous cells would be lost. Mucous-cell pairing was determined by two independent methods: 1) direct observation of mucous-cell pairs and 2) the application of Poisson statistics to the mucous-cell distribution to determine a "pairing tendency." We found that in the crypt at least 75-80% of newly formed mucous cells occur in pairs, while in all regions of the villus (base, middle, and top) mucous cells are distributed randomly. These results strongly indicate the existence of a significant amount of cell mixing in the epithelium at some point between the site of mucous-cell formation in the crypts and the villus base. Since the mucous-cell population was randomly distributed in all regions of the villus we were unable to determine whether or not additional cell mixing occurs in the villus epithelium.

Animals↗