Tobacco smoke toxicity: loss of human oral leukocyte function and fluid-cell metabolism.

The human mouth has been utilized as a new and significant in vivo open bioassay system for tracing undesirable substances present in tobacco smoke, in an exact milieu where the smoking "problem" begins and must be dealt with directly. The associated in vitro closed test systems described herein have provided new, sensitive bioassays that help to explain the in vivo effects.

Influence of a deficiency of the second component of complement on the bactericidal activity of neutrophils in vitro.

Serum from three patients with a complete, selective deficiency of the second component of complement (C2) did not promote optimal killing of Staphylococcus aureus, 502A by neutrophilic polymorphonuclear leukocytes (PMN) in vitro. The addition of C2 reagent or the presence of heat-stable opsonin in the C2-deficient serum corrected the defective killing of S. aureus that was observed with patient or control PMN. PMN from the patients or control subjects killed bacteria with equal efficiency under conditions of optimal opsonization (normal pooled serum). However, twice-washed control PMN were better than patient PMN in killing S. aureus under circumstances of suboptimal opsonization (C2-deficient serum, heated C2-deficient serum, heated normal pooled serum, or no replacement of serum). The latter finding was due to residual C2 on the surface of twice-washed control cells. As repeated washing of control PMN progressively removed cell-associated C2, the staphylocidal effectiveness of the control RMN decreased to the level of patient PMN. In contrast to the findings with S. aureus, triply-washed PMN from patients or controls killed normal numbers of Escherichia coli, ON2, in C2-deficient serum.

Studies on the pathogenesis of acute inflammation. IX. The influence of hyperosomolality secondary to hyperglycemia upon the acute inflammatory response induced by thermal injury to ear chambers of rabbits.

The inflammatory reaction induced in ear chambers of rabbits by heat injury was studied in nondiabetic animals made hyperglycemic with continuous infusions of glucose. Hypertonic solutions of glucose administered intravenously to rabbits induced the following triad: hyperglycemia, hyperosmolality, and metabolic lactic acidosis. It was found that relatively short periods of this metabolic abnormality were associated with a significant reduction in the intensity of the inflammatory reaction. There was no evidence microscopically of circulatory impairment within ear chambers; and since neither arterial hypotension nor oxygen deficit was recorded during experiments, it appeared most likely that decreased leucocytic margination per se best explained the inhibited exudative response. Hyperglycemia seemed the dominant factor responsible for this anti-inflammatory effect. It was found subsequently that hyperglycemia and hyperosmolality without metabolic acidosis impaired cellular exudation just as well.

Normal UV-induced DNA repair synthesis in peripheral leukocytes from patients with malignant melanoma of the skin.

Seventeen patients with malignant melanoma were compared to 24 control subjects regarding UV-induced DNA repair synthesis. Peripheral leukocytes were irradiated with different UV-doses and the DNA-repair synthesis was measured in presence of hydroxyurea. A dose response curve was established for each individual. No statistical differences were observed when melanoma patients were compared to the controls.

The pathologic characteristics of leukostasis and leukemic nodules occurring in the central nervous system of guinea pigs with L2C/NB leukemia.

Leukostasis and leukemic nodules are found in the central nervous system (CNS) of at least 75% of guinea pigs during the terminal stages of untreated L2C/NB leukemia, a transmissible, acute lymphocytic leukemia. The CNS lesions develop after extensive visceral leukemic infiltration at a time when the white cell count is rising to 10(5)-5 x 10(5) cells/mm3, and the differential examination shows predominantly blasts. Leukostasis precedes formation of the nodule. Both lesions may be found in any part of the central nervous system including the spinal cord, but are most numerous in the diencephalon and rostral brain-stem. Ultrastructural studies demonstrate that parenchymal leukostasis develops chiefly within capillaries, and is associated with endothelial cell degeneration and necrosis. Fibrin deposits are not seen within affected capillaries. The sequence of development, pathologic and hematologic characteristics of leukostasiss and leukemic nodules in human and L2C/NB leukemia are virtually identical. The CNS lesions of untreated L2C/NB leukemia are a precise, convenient model for the study of intracerebral leukostasis and leukemic nodules.

Functional significance of growth retardation in malnutrition.

Various functional parameters involved in resistance to infection were investigated in children suffering from varying grades of protein-calorie malnutrition. It was observed that the phagocytic function was impaired in children whose weights were below 80% of the Indian Council of Medical Research standard, whereas the cell-mediated immune response was altered in those with weights below 70% of the standard. Antibody response to typhoid antigen was impaired in children with severe protein-calorie malnutrition, while the response to diphtheria and tetanus toxoids was normal in all. These observations suggest that malnourished children whose weights are below 80% of the Indian standard are likely to suffer from at least one functional handicap which may increase the risk of infection. In any action-oriented program, priority should, therefore, be given to this group of children.

Retinal blood velocity in patients with leukocyte disorders.

The blue light entoptic phenomenon was used to measure retinal blood velocity in eight patients with chronic granulocytic leukemia, six patients with leukopenia, and matched control subjects. The retinal leukocyte velocity of the leukemic patients was 0.53 +/- 0.26 (mean +/- SD) mm/s, whereas that of the matched control subjects was 0.46 +/- 0.14 mm/s. There was no significant difference between these two groups (power: 96% for a difference of 0.2 mm/s and 66% for 0.1 mm/s). There was also no significant difference between the leukocyte velocities of the leukopenic patients and control subjects (0.47 +/- 0.19 mm/s and 0.55 +/- 0.14 mm/s, respectively; 89% power for a difference of 0.2 mm/s, 59% for 0.1). There was a correlation between the leukocyte count and the number of leukocytes seen in the entoptoscope. The results suggest that retinal vascular autoregulation can compensate for changes in leukocyte numbers that might have been expected to alter retinal blood flow.

Leukocyte abnormalities.

Certain qualitative abnormalities in neutrophils and blood monocytes are associated with frequent, severe, and recurrent bacterial infections leading to fatal sepsis, while other qualitative defects demonstrated in vitro may have few or no clinical sequelae. These qualitative defects are discussed in terms of the specific functions of locomotion, phagocytosis, degranulation, and bacterial killing.

Cerebrospinal fluid shunts interfere with host defenses.

Despite advances in neurosurgical therapeutics, cerebrospinal fluid shunt infections have continued to complicate the management of patients with shunted hydrocephalus. Although various factors have been proposed to explain the pathogenesis of these infections, they have remained poorly understood. This in vitro study determined the ability of human neutrophils and monocytes to adhere to two types of shunt catheters and to phagocytose bacteria. These white blood cells failed to adhere in normal numbers to the catheters and failed to ingest fully a bacterial inoculum on the catheters' surfaces. While in contact with the shunt apparatus, the neutrophils also exocytosed myeloperoxidase, a major component of the intracellular microbicidal system. These observations suggest that the shunt apparatus may diminish the effectiveness of the hosts' defenses at the site of implantation.

Measurement of retinal blood flow in diabetes by the blue-light entoptic phenomenon.

Retinal blood flow velocity was measured in 24 normal volunteers and compared with the results obtained in 101 diabetics at different stages of retinopathy. The blue-light entoptic phenomenon was used to measure retinal flow velocity. Results showed that there was a significantly higher capillary flow velocity in those patients with background retinopathy (0.74 +/- 0.32 mms/s) over the group of normals (0.54 +/- 0.19 mm/s) and those diabetics with no retinopathy (0.51 +/- 0.24 mm/s). Retinal flow velocity was reduced at the preproliferative stage of retinopathy to 0.37 +/- 0.2 mm/s. Proliferative retinopathy showed a slightly greater flow velocity (0.56 +/- 0.27 mm/s), which was reduced following photocoagulation (0.42 +/- 0.14 mm/s).

Chemotactic ability of dental plaque upon autologous or heterologous human polymorphonuclear leukocytes.

The chemotactic effect of pooled human plaque suspension, supernatant, and ultrafiltrate upon heterologous human PMNs was investigated using the Boyden chamber technique. It was observed that pooled plaque suspensions (20 mg/ml) were consistently chemotactic for heterologous human PMN cells. Whole plaque suspensions were most chemotactic, and the supernatant was approximately half as active, while the bacteria-free ultrafiltrate induced a negligible chemotactic response. Chemotactic assays of individual plaque suspensions were also performed. Twelve male subjects were paired according to age and PDI scores to assess whether the PMN cells of certain individuals responded differently to their autologous plaque. When comparing subjects with high or low PDI scores, there were no significant differences in the chemotactic responses. However, a trend of reduced chemotaxis was observed in most subjects with a high PDI. When the subjects were arbitrarily divided into groups with high and low plaque indices, a greater overall chemotactic response was generated by the higher plaque formers. The differences between the two groups, however, were not statistically significant.