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Biomedical subjects

J H Gibbs

Publications and source records attributed to J H Gibbs.

At least 19 recordsLinked to original sources
PubMed1995

Delayed hypersensitivity and HLA in smear-positive pulmonary tuberculosis.

Tuberculin responses were quantified by induration of the skin, velocity of blood flow in dermal microcirculation and composition of the cellular infiltrate in 125 patients with tuberculosis and 39 healty controls. The diameters of the tuberculin responses were greater in HLA-DR15-positive patients than in DR15-negative patients. The density of infiltrating CD(4+)-positive cells showed a positive correlation with induration in DR15-negative subjects (r = 0.54). A fraction of DR15-positive patients gave large tuberculin responses (> or = 15 mm) but with few CD4+ cells in the test site (< 500/mm2); these patients had a greater percentage of cells in the diffuse dermal infiltrate than in the perivascular region, greater blood flow velocities in the tuberculin response but more frequently with central relative slowing of blood flow and had higher total IgG and specific antimycobacterial antibody levels compared to other DR15-positive patients. If the inflammatory infiltrate in the lungs parallels that in the tuberculin skin test, the lack of immunocompetent cells and tissue hypoxia could permit pulmonary cavitation and explain the association of HLA-DR15 with smear-positive pulmonary tuberculosis.

Blood Flow Velocity↗
PubMed1994

Effect of hyperoxia at 1 and 2 ATA on hypoxia and hypercapnia in human skin during experimental inflammation.

Transcutaneous PO2 and PCO2 measurements and estimates of skin respiration were monitored at different levels of inspired PO2 in 20 healthy adults during the first 4 days of the tuberculin reaction, a convenient model of acute inflammation. Hyperoxia at 1 and 2 ATA significantly increased transcutaneous PO2 levels in undisturbed and in inflamed skin but did not fully correct the relative hypoxia at the site of inflammation. Hypercapnia was reduced with O2 breathing at 2 ATA. The apparent rate of O2 consumption at the reaction site was raised during hyperoxia, most prominently at 2 ATA. The most intense reactions showed a central relative slowing of laser-Doppler blood flow indicative of microcirculatory impairment. The extent of the relative hypoxia and hypercapnia was greatest in these strongest reactions. The density of lymphocytes and monocytes in biopsies of 48-h reactions was loosely related to the corresponding transcutaneous PO2 measurements. The present study provides evidence that diffusion barriers, in addition to increased local respiration, can contribute to the apparent hypoxia and hypercapnia of this inflammatory model.

Adult↗
PubMed1992

Measurements of blood flow and histometry of the cellular infiltrate in tuberculin skin test responses of the typical Koch type and the non-turgid variant form (Listeria-type) in pulmonary tuberculosis patients and apparently healthy controls.

The typical turgid Koch type and the non-turgid variant form (Listeria-type) of the tuberculin skin test responses were studied in 76 newly diagnosed pulmonary tuberculosis patients and 29 apparently healthy factory worker controls from Surabaya in Indonesia; in general, the patients had more intense responses than the controls. The blood flow velocity (RBCflux) at the centre of the reaction was similar in all groups, but central relative slowing (a presumed forme fruste of severe ischaemia) was much more common in the Koch-type reactions in tuberculosis patients. In both groups of subjects, the overall density of cellular infiltrate (and the major populations of inflammatory cells) was greater in the typical Koch-type reactions than in the non-turgid variant reactions. Thus the Koch-type reactions were indubitably more intense in inflammatory terms than the non-turgid variant form, but the results of this study do not exclude the possibility that there were underlying qualitative differences in pathogenesis between reactions of the two types as well as the obvious difference in severity.

Adult↗
PubMed1992

Circulatory adaptation to the increased metabolism in the skin at the site of the tuberculin reaction.

The sequence of changes at the site of a positive tuberculin test response were studied in 19 healthy young adults who had been immunised with BCG in childhood. The development of erythema preceded that of induration and both were most intense at 48-72 h. The strongest reactions showed higher laser Doppler (LD) flux at the periphery than at the center (central relative slowing). All showed a substantial reduction in steady-state (ss) tcpO2 from 24 h onwards and the oxygen consumption rate (mlO2.kg-1.min-1), calculated from the rate of fall in tcpO2 during temporary cuff occlusion of arterial input, was raised (greater than two-fold) throughout the period of study (to 96 h). The density of lymphocytes and macrophages in the inflammatory infiltrate in the dermis was related to the fall in tcpO2.ss and to the extent of thickening of the dermis. These experiments showed that the previously healthy dermal microcirculation can adapt to temporary increase in metabolic demands of leucocytes emigrated from the circulation into the tissue: in intense delayed hypersensitivity (DHS) reactions there is considerable hypoxia and respiratory debt, but maintenance of viability in the short-term. It is likely that similar adaptations occur in the period of establishment of microbial infection.

Adaptation, Physiological↗
PubMed1991

Early delayed hypersensitivity responses in tuberculin skin tests after heavy occupational exposure to tuberculosis.

The early (six hours) reaction to tuberculin skin testing was studied in 33 Indonesian hospital workers with frequent occupational exposure to M tuberculosis and compared with responses maximal at the usual time (48 hours) in factory workers, from the same locality but with only occasional occupational exposure, to determine the nature of the early reaction. The early reaction had the same general histopathological appearance as that seen in the conventional (48 hour) reaction, and both had an infiltrate consisting largely of T lymphocytes and macrophages. The cell densities were lower in the six hour reactions, but the relative concentration of macrophages was greater in the earlier response. These histometric measurements suggested that the six hour reaction was an accelerated delayed hypersensitivity reaction. Moreover, the absence of a specific IgE response or of particulate masses of Ig or complement, made it unlikely an anaphylactoid or Arthus-type reaction could have been responsible. It is concluded that those with frequent occupational exposure to M tuberculosis have larger numbers of circulating T cells reactive with mycobacterial antigens, so that the development of the skin test response to tuberculin is less dependent on "by-stander" cell infiltration to mediate the delayed hypersensitivity reaction than the reactions in those with less intense and less frequent natural exposure. The skin test response maximal at six hours is probably a hyperimmune reaction to an antigen recognised by T cells.

Adult↗
PubMed1991

Histometric studies on cellular infiltrates of tuberculin tests in patients with sarcoidosis.

The density and microanatomical location of CD4 and CD8 lymphocytes and of monocytes/macrophages at the site of a tuberculin test were measured in 13 patients with sarcoidosis, and the results were compared with those seen in a group of healthy controls. The cellular infiltrate was significantly reduced in the sarcoid subjects compared with the controls for all cell phenotypes studied; the ratio of CD4 positive:CD8 positive lymphocytes was significantly increased in the sarcoid group. Clinically negative reactions showed substantial numbers of infiltrating mononuclear cells, although not as great as in clinically apparent reactions. A clinically negative tuberculin reaction does not necessarily imply anergy to the test substance and should not be termed "negative".

Adult↗
PubMed1990

Assessment of the respiratory metabolism in the skin from transcutaneous measurements of pO2 and pCO2: potential for non-invasive monitoring of response to tuberculin skin testing.

A method is described for non-invasive transcutaneous (tc) measurement of tissue respiratory gas tensions in the skin on the forearm for study of delayed hypersensitivity reactions in man. Steady state values for tcpO2 and tcpCO2 were measured, and the skin respiratory rate (oxygen consumption) and the tissue pH were estimated from the changes in tcpO2 and tcpCO2 observed after interruption of the arterial circulation by cuff occlusion for 4 minutes. The extent of within-experiment and between subject variation in the steady-state measurements was not great (coefficient of variation 10%): tcpCO2.ss (steady state) was higher in men and tcpO2.ss was higher in women, but the extent of these sex differences was also small. Reference ranges have been established for tc measurements and calculated indices of tissue respiration in the undisturbed forearm skin of normal volunteers, against which the changes induced by tuberculin testing can be assessed. Severe changes, indicative of profound hypoxia and acidosis, are seen in intense delayed hypersensitivity reactions. Similar, but less severe changes were seen at the site of skin tests on BCG-vaccinated subjects who were 'negative' by conventional criteria of measurement of dermal induration and they became greatly exaggerated after successful re-vaccination. Intradermal injection of saline did not induce hypoxia or local acidosis. These new methods are very sensitive indicators of the tissue response in the DHS reaction.

BCG Vaccine↗
PubMed1989

Histometric studies on biopsies of tuberculin skin tests showing evidence of ischaemia and necrosis.

In a study of tuberculin skin tests in 216 consecutive untreated pulmonary tuberculosis patients, one showed central necrosis at 48 h: there was no effective blood flow at the centre of this lesion, but the periphery was markedly hyperaemic. Many dermal capillaries and venules contained deposits of fibrin, but none was occluded completely: the surviving cells in the dermal infiltrate were almost all macrophages. Five patients with strongly positive reactions at 48 h showed slower blood flow at the centre of the reaction than at the periphery (central relative slowing, CRS), possibly indicating central ischaemia short of necrosis: no fibrin deposits were seen in the dermal vessels of these skin test sites. The cellular infiltrate in the dermis was similar in distribution, but more abundant than that seen in uncomplicated positive reactions of comparable clinical size and with blood flow velocity maximal at the centre. At 48 h, lymphocytes were more numerous than macrophages in both groups, CD8 lymphocytes were more abundant in CRS reactions, but CD4 and CD25 (activated) T-lymphocytes and macrophages had a similar density in both groups. Epidermal CD1 cells were less frequent in CRS reactions than in uncomplicated positive reactions. Although CRS reactions showed more intense inflammation than the uncomplicated controls, none of the histometric measurements correlated with the extent of CRS. Follow-up studies showed that CRS reactions reverted to a normal hyperaemic blood flow pattern 5 days after antigen injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

The relation between cutaneous blood flow and cell content in the tuberculin reaction.

The relationship of velocity of blood flow to density and microanatomical distribution of inflammatory cells in the dermis was studied in 20 human tuberculin tests. Most positive reactions showed maximal blood flow velocities (measured as red blood cell (RBC) flux) at the centre of the reaction, but the two most intense responses showed 'central relative slowing' (CRS) with higher RBC flux at the periphery. Two of the four clinically negative reactions showed a considerable acceleration of blood flow, but the other two showed no such acceleration. The packing density of lymphocytes/monocytes in the perivascular zone was greater in the stronger positives than in the weaker reactions. The density of cells in the intervening dermis was markedly lower than in the foci: the lesions with CRS had the highest density of cells in the diffuse infiltrate of the reticular dermis. At the centre of the reaction, blood flow velocity was generally related to density of cellular infiltrate, except in those with CRS, which had a disproportionately lower blood flow velocity. The finding that the circulatory adaptation to a delayed hypersensitivity reaction can be inadequate may explain the dermal acidosis previously observed in intense skin test reactions, and may be the underlying mechanism of necrosis in hypersensitivity reactions.

Blood Flow Velocity↗
PubMed1989

Histometric studies on cellular infiltrates of tuberculin tests in patients with haemophilia.

The number of microanatomical location of CD4 and CD8 lymphocytes, of cells bearing receptors for I12 and transferrin, and of monocyte/macrophages in the dermis at the site of a tuberculin test were measured in 13 patients with haemophilia (10 seronegative and three seropositive for human immunodeficiency virus (HIV]. The overall density of lymphocytes in the perivascular and diffuse parts of the infiltrate was similar to that reported in other groups of subjects without evidence of immunosuppression. The CD4:CD8 ratio of the infiltrating lymphocytes throughout the section showed an inverse relation with clotting factor consumption. There was no significant change in the CD4:CD8 ratio in the diffuse infiltrate at various levels into the dermis in tuberculin reactions in patients with haemophilia, unlike healthy controls and other groups with no evidence of immunosuppression, who have previously been shown to have increasing CD4:CD8 ratio with increasing depth into the dermis. The number of cells bearing receptors for I12 and transferrin and of monocyte/macrophages was related to total lymphocyte density in the infiltrate. There was no evidence of serious impairment of the cell mediated response to a long term recall antigen, but the relatively low preponderance of CD4 lymphocytes in the diffuse infiltrate, particularly in the deeper dermis, may be the earliest indicator of impending immunosuppression.

CD4-Positive T-Lymphocytes↗
PubMed1988

Diversity in migration of CD4 and CD8 lymphocytes in different microanatomical compartments of the skin in the tuberculin reaction in man.

The lymphocytes in the perivascular foci of tuberculin skin tests have a similar CD4:CD8 ratio to those in the peripheral blood, suggesting that these subsets do not show bias in their initial emigration. By contrast, the diffusely infiltrating lymphocytes show a relative preponderance of CD4 cells which is progressively greater in successive 250 micron layers into the dermis. A generally similar pattern is seen in healthy controls and in patients with untreated pulmonary tuberculosis, treated leprosy, haemophilia A and chronic obstructive lung disease (COLD) patients treated with prednisolone, but the gradient of increasing CD4:CD8 ratio with depth into the dermis is significantly less steep in patients with tuberculosis, haemophilia and prednisolone-treated COLD than in the healthy controls. Selective migration results in a relative preponderance of CD4 cells in the diffuse infiltrate and it is suggested that this is a mechanism likely to potentiate defensive reaction to Mycobacterium tuberculosis: any deficiency in selective migration may make immunological defences less effective and so contribute to the chronicity of the lesions of tuberculosis.

Cell Movement↗
PubMed1987

Skin test responsiveness to four new tuberculins in patients with chronic obstructive airways disease receiving short term high doses of, or long term maintenance treatment with, prednisolone: clinical appearances and histometric studies.

The response to skin testing with tuberculins extracted from various species of mycobacteria was studied in 49 patients from Dundee with chronic obstructive airways disease. Seventeen had never been treated with steroids (group 1), 17 were receiving short term high doses of prednisolone (group 2) and did not have impaired Synacthen tests; 15 were receiving long term maintenance treatment and did have impaired Synacthen tests (group 3). Erythematous and indurated reactions were seen in a few patients, more commonly to antigens from Mycobacterium tuberculosis than to the other species: neither of the latter treatment groups showed appreciable reduction in reactivity compared with that of the group 1 patients. The number and microanatomical distribution of the T4 and T8 lymphocytes and the M3 bearing monocytes and macrophages was studied immunocytochemically in cryostat sections of biopsy specimens from the antigen injection sites. The density of these cells was significantly less in clinically negative reactions than in those with erythema or induration, but was unrelated to the presence or absence of a history of treatment with prednisolone. The T4:T8 ratio in the section as a whole was similar to that of the peripheral blood, but T8 cells were relatively more common in the perivascular and periappendicular foci, and T4 lymphocytes were predominant in the diffuse component of the infiltrate. I12 receptor bearing lymphocytes were uncommon: such cells were least common in the clinically negative reactions, but the number and distribution were apparently unrelated to the presence or absence of prednisolone treatment. It was concluded that currently accepted regimens of treatment with prednisolone did not reduce the effector arm of type IV (delayed type hypersensitivity) responses and so are unlikely to compromise this aspect of protective immunity.

Aged↗
PubMed1986

Measurement of skin swelling in the tuberculin test by ultrasonography.

A new method is described for non-invasive measurement of the thickness of the skin at the site of a skin test from the echo pattern of a pulsed ultrasonic (15 MHz) A-mode scanner. In tuberculin tests on normal volunteers, the skin thickness increased rapidly during days 1 and 2 and was usually greatest at day 4. The echogram measurements can be used to calculate the increase in skin volume and this is disproportionately greater than would be expected from measurements of the diameters of erythema and induration.

Adult↗
PubMed1986

The cellular responses of tuberculosis and leprosy patients and of healthy controls in skin tests to 'new tuberculin' and leprosin A.

The density and distribution of T4 and T8 lymphocytes and of monocyte/macrophages at the site of skin tests with mycobacterial antigens was studied in pulmonary tuberculosis and leprosy patients and in healthy controls. Most of the inflammatory cells were located in perivascular and periappendicular foci in the dermis: the percentage of the dermis occupied by focal infiltrate was unrelated to the clinical measurement of the area of induration. There was a less intense diffuse infiltrate in the dermis between the foci, most marked in the papillary dermis and lessening progressively in deeper layers. In patients, diffusely infiltrating lymphocytes were more numerous (mainly due to an excess of T8 cells) in relation to extracts of the pathogen causing their disease than to extracts of the other organism: T8 cells were particularly numerous in reactions to Leprosin A in three of four partly treated leprosy patients who had been classified as tuberculoid at the time of diagnosis. The density of diffusely infiltrating macrophages showed a similar density gradient and selective concentration in response to active disease pathogens. However these cells were less numerous in partly treated leprosy patients than in controls and most frequent in untreated pulmonary tuberculosis patients. Selective migration of monocyte/macrophages and, to a lesser extent T8 cells, appears to be a prominent feature in the reaction of patient with active mycobacterial disease to antigens derived from the causative organisms: this suggests that it might become possible to distinguish direct reactions from cross-reactions in human delayed hypersensitivity reactions by identification of these histological features.

Adult↗
PubMed1985

Lymphocyte subsets and Langerhans cells in allergic and irritant patch test reactions: histometric studies.

This study has attempted to distinguish between allergic and irritant reactions to patch tests by semiquantitative histological methods. The extent of perivascular chronic inflammatory infiltrate at 72 h in irritant patch test reactions to sodium lauryl sulphate was shown to be small and very consistent, whereas in allergic reactions to nickel sulphate it was generally larger and more variable in size (p less than 0.02). The two major lymphocyte subsets (T4 and T8) were randomly intermixed in both types of reaction and formed the major component of both the perivascular and diffuse dermal infiltrate, without any evidence of selective migration. The T4:T8 ratios were similar in focal and diffuse infiltrates. The number of T6 dendritic (putative Langerhans) cells in the epidermis (per mm inner epidermal length) was usually greatly reduced in irritant reactions (5-16 mm-1, mean 10 mm-1) but remained within normal limits in allergic reactions (6-33 mm-1, mean 21 mm-1) (p less than 0.001). Comparable results were seen with other irritants (mercuric chloride and benzalkonium chloride) and other allergens (neomycin sulphate, ethylene diamine and potassium dichromate). In additional experiments, pairs of biopsies were taken from the reaction and from adjacent unaffected skin. The T6 cell density in the epidermis did not significantly differ between allergic reactions and control skin. By contrast, the irritant reactions had fewer T6 cells than the control skin (p less than 0.001).

Dermatitis, Atopic↗
PubMed1984

Histometric study of the localisation of lymphocyte subsets and accessory cells in human Mantoux reactions.

Intradermal injection of purified protein derivative produced typical delayed type hypersensitivity reactions in five healthy human subjects. The major subpopulations of lymphocytes and certain accessory cells were located in frozen sections of biopsies of the lesions with monoclonal antibodies and immunohistochemical staining. The densities (expressed as number/unit area for comparison) of the different types of cells were counted at various microanatomical locations in the tissue. The inflammatory cells were concentrated in narrow zones, initially (24 h) only surrounding small blood vessels but later (48-96 h) also around sweat ducts. Lymphocytes were the predominant cell type at these sites with T4 and T8 cells randomly intermixed at a ratio similar to that in the mononuclear cell fraction of the peripheral blood samples removed at the time of biopsy. There was also a scanty diffuse infiltrate in the intervening dermis, but here the T4:T8 ratio was significantly lower than that in the peripheral blood or perivascular cuffs. There was considerable intersubject variation in the relative preponderance of T8 cells in the diffuse infiltrate. The results suggest that there is no subset selection in the initial emigration of lymphocytes through vascular endothelium in the delayed hypersensitivity reaction, but that the subsets behave differently during the subsequent migration through the tissues. It remains to be determined whether the extent to which T8 cells migrate more rapidly than T4 cells through the tissues may influence the reaction at the site of entry of organisms or antigens into the body by altering the balance of the immunoregulatory lymphocyte subsets. This may underlie some of the differences in susceptibility to infection between subjects and determine the type of granuloma that develops in a particular patient.

Adult↗
PubMed1983

The sensitivity of peripheral blood lymphocytes to growth inhibition by hydrocortisone is not determined by their OKT4:OKT8 ratio.

Normal adult human subjects show considerable variation in sensitivity to depression of the activation phase of mitogen-induced lymphocyte growth by the natural glucocorticoid, hydrocortisone. In a study of 21 subjects, the slope of the log-dose response to hydrocortisone was unrelated to the relative numbers of cells in the two major T-cell subpopulations stained by the OKT4 and OKT8 monoclonal antibodies. It is concluded that the extent of the glucocorticoid-induced suppression of early mitogen-stimulated lymphocyte growth is probably not determined by relative numbers of the various immunoregulatory lymphocytes.

Adult↗