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Biomedical subjects

G Whalen

Publications and source records attributed to G Whalen.

34 records · Page 2Linked to original sources
PubMed1985

Flatfishes breathe symmetrically: an experimental reappraisal.

Experimental analysis of the pressure changes in the respiratory cavities of the American winter flounder Pseudopleuronectes americanus, together with electromyographic recordings of key respiratory muscles and cineradiographic observations of the distribution of radioopaque dye, have revealed unequivocally that the respiratory current and underlying mechanisms are symmetrical. The respiratory apparatus, as in other teleosts, is driven by bilaterally symmetrical alternating buccal pressure and opercular suction pumps. An elaborate deflecting apparatus is present in the respiratory cavities of flatfishes to maximize the irrigation of gills of both sides. Functional symmetry is maintained in the morphologically asymmetrical flatfishes and a high premium is put on the bilateral distribution and opercular ejection of the respiratory current during the evolutionary radiation of the Pleuronectiformes.

Animals↗
PubMed1983

Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome.

We studied B-lymphocyte function in 12 homosexual male patients with the acquired immunodeficiency syndrome, 5 healthy homosexual men, and 12 heterosexual controls. In comparison with the heterosexual controls, the patients were found to have elevated numbers of cells spontaneously secreting immunoglobulin, decreased B-cell proliferative responses to T-cell-independent B-cell mitogens, and qualitatively deficient helper T cells. The hyperactive spontaneous B-cell responses as well as the refractoriness to signals for T-cell-independent B-cell activation were highly suggestive of an in vivo polyclonal activation of B cells and may have been responsible for the manifestations of B-cell hyperreactivity, such as hypergammaglobulinemia, seen in these patients. We conclude that the scope of immune dysfunction in the acquired immunodeficiency syndrome involves B cells as well as T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Antigen-induced human T cell help. Precursor frequency, radiation sensitivity, and allogeneic effects.

We have recently noted marked differences between the in vitro responses of human B lymphocytes to stimulation with soluble antigens vs. stimulation with mitogens. In the present study, these differences were analyzed in terms of the precursor frequencies for the T cells and B cells involved and in terms of the radiation sensitivity of the T cells providing help in the two systems. Marked differences were found between antigen-induced and mitogen-induced systems with regard to T cell precursor frequencies and radiation sensitivity. In contrast, the precursor frequencies for the B cells involved in the two systems were approximately the same. In addition, having developed a system for the study of human antigen-specific B cell responses, we were interested in delineating the nature of the allogeneic effects that might be operative in this system. Marked allogeneic effects, both positive and negative, were noted in this system and will need to be taken into account in any studies that try to address the question of the genetic restriction, if any, that exists in human antigen-specific T cell-B cell collaboration. Appreciation of the marked differences between the antigen-specific and mitogen-induced activation and immunoregulation of human B cell responses will be of importance in understanding the relationship between specificity and nonspecificity of antibody production in normal and disease states.

Adolescent↗
PubMed1981

In vitro antigen-induced, antigen-specific antibody production in man. Specific and polyclonal components, kinetics, and cellular requirements.

A highly specific and reproducible antigen-induced, antigen-specific culture and assay system for antibody production by human peripheral blood B lymphocytes has been developed. The system is clearly T cell and monocyte dependent and is independent of exogenous mitogens. The major factors in our ability to trigger specific antibody production with antigen alone have been the use of extremely low concentrations of antigen in vitro (doses several orders of magnitude below those inducing a peak blastogenic response), careful attention to in vitro cell density and culture vessel geometry, and appreciation of the kinetics of the circulating antigen-inducible B cell repertoire. A dichotomy and overlap between antigen-induced, antigen-specific and antigen-induced, polyclonal responses was observed in the study of doubly immunized individuals. Whereas antibody responses highly specific for the antigen in culture were observed under one set of culture conditions (flat-bottomed vessels, 1.5 x 10(6) cells), switching to another culture system (round-bottomed vessels, 5 x 10(5) cells) resulted in polyclonal responses to antigen. Despite these culture condition-related differences in the induction of antibody synthesis, the suppression of specific antibody production that occurred at high concentrations of antigen was specific only for the antigen in culture. The capability to easily and reproducibly look at truly antigen-induced, antigen specific antibody production should be a major tool in furthering the understanding of human B cell activation and immunoregulation.

Adolescent↗
PubMed1981

Effects of verapamil on heart and circulation in hemorrhagic shock in dogs.

Myocardial blood flow and left ventricular oxygen utilization were studied in verapamil-treated and untreated pentobarbital-anesthetized dogs subjected to hemorrhagic shock. Blood loss was similar in both groups. The dogs treated with verapamil (n = 15) during shock had a slower heart rate and lower left ventricular oxygen utilization than the untreated dogs (n = 14). Nevertheless, the treated dogs had a significantly higher myocardial blood flow and were able to maintain a higher cardiac index. Thus, verapamil has beneficial hemodynamic and metabolic effects that preserve myocardial function. These effects may explain the improved survival and protection of the heart against anatomic lesions, which have been demonstrated previously in dogs treated with verapamil during hemorrhagic shock.

Animals↗
PubMed1980

Activation of human B lymphocytes. XV. Spontaneously occurring and mitogen-induced indirect anti-sheep red blood cell plaque-forming cells in normal human peripheral blood.

A system for the development of indirect (IgG, IgA, and IgM) anti-SRBC plaque-forming cells (PFC) after polyclonal stimulation of human peripheral blood lymphocytes with pokeweed mitogen (PWM) is described. Rabbit anti-human polyvalent Ig or Ig class-specific antisera were employed. Most of the indirect PFC were IgG with less being IgM and IgA. The finding of significantly more indirect IgM PFC than direct PFC suggests that many IgM PFC are producing low efficiency hemolysin that requires an anti-globulin to produce lysis. The system is T cell dependent and cultures require selected batches of supplemented fetal calf serum that preferentially yield indirect (1527 +/- 243 PFC/10(6) lymphocytes) as opposed to direct (36 +/- 11 PFC/10(6) lymphocytes) PFC. Batches of human AB sera that were previously chosen to yield optimal direct PFC (approximately 200 to 300 PFC/10(6) lymphocytes) did not yield indirect PFC. Hence, depending on culture conditions, polyclonal stimulation of human lymphocytes can yield antigen-specific direct and indirect hemolytic PFC.

Animals↗
PubMed1979

Altered intestinal fluid movement in response to Trichinella spiralis in immunized rats.

Net intestinal fluid movement was measured in immunized and non-immunized rats infected with the enteric stages of the nematode, Trichinella spiralis. Animals were studied 30 min, 5 days and 30 days after receiving infective larvae. Net water movement across the mucosal surface of the gut was measured in vivo by perfusing a cannulated segment (approximately 30 cm) of proximal small intestine with an isotonic solution containing a nonabsorbable marker, 14C polyethylene glycol, at a rate of 0.5 ml/min. Uninfected rats showed net absorption of water, 25 microliter/h per cm of intestine. This response was unaltered when rats were infected (7 x 10(3) larvae/rat) and examined 30 minutes later. Five days after primary infection net tissue-to-lumen fluid movement, ie. net secretion, occurred at a rate of 45 microliter/h per cm. When rats were studied 30 days after primary infection, net absorption equivalent to the preinfection level was observed once again. Previously infected (immunized) rats, when challenged (secondary infection, 7 x 10(3) larvae/rat) and examined within 30 min showed a significant decrease in net absorption rate as compared with non-immunized rats. Absorption returned to the preinfection level at both 5 and 30 days post challenge. Results support the conclusion that T. spiralis caused a decrease in net lumen-to-tissue fluid movement during primary and secondary infections. The response was initiated faster in previously infected hosts. The rapid induction of net fluid movement in the direction of secretion upon secondary contact with the parasite is associated temporarily with prevention of worm establishment.

Absorption↗
PubMed1979

Treatment of hemorrhagic shock in dogs with verapamil: effects on survival and on cardiovascular lesions.

Dogs were subjected to a standardized hemorrhagic shock procedure. Some were treated with verapamil and others were untreated. It was found that the dogs treated with verapamil were protected from the damaging effects of hemorrhagic shock on the heart. This was true even in treated dogs that had a rapid heart rate maintained by means of an intracardiac pacing electrode. In addition, the treated dogs did not show the intestinal hemorrhage that is usually seen in dogs subjected to hemorrhagic shock. Finally, it was found that verapamil treatment increased the survival rate of shocked dogs in comparison with control dogs which were not treated.

Animals↗
PubMed1978

Activation of human B lymphocytes. VIII. Differential radiosensitivity of subpopulations of lymphoid cells involved in the polyclonally-induced PFC responses of peripheral blood B lymphocytes.

The differential effect of various doses of irradiation on subpopulations of human peripheral blood lymphoid cells involved in the pokeweed mitogen (PWM) induced PFC response against sheep red blood cells (SRBC) was studied. The plaque forming B cells were quite sensitive to low doses of irradiation with complete suppression of responses at 300 to 500 rad. On the contrary, helper T-cell function was resistant to 2000 rad. Co-culture of irradiated T cells with autologous or allogeneic B cells resulted in marked enhancement of PFC responses consistent with the suppression of naturally occurring suppressor cells with a resulting pure helper effect. Irradiated T-cell-depleted suspensions failed to produce this effect as did heat killed T cells, whereas mitomycin C treated T cells gave effects similar to irradiated T cells. These findings are consistent with a lack of requirement of cell division for a T-cell helper effect and a requirement of mitosis or another irradiation sensitive, mitomycin C sensitive process for a T-suppressor cell effect. These studies have potential relevance in the evaluation of subpopulations of human lymphoid cells involved in antibody production in normal individuals and in disease states.

B-Lymphocytes↗
PubMed1977

Focal nodular hyperplasia of the liver associated with high-dosage estrogens.

A patient developed benign nodular hyperplasia of the liver after long-term, high-dose estrogen therapy. A 10.5-cm benign liver nodule appeared after three years of high-dose estrogen therapy and was resected. Fourteen months later, while still receiving estrogen, a 4.5-cm nodule and multiple small nodules were seen on angiography. Four months after estrogen was discontinued, the larger liver nodule disappeared and the smaller ones decreased.

Adult↗
PubMed1977

Activation of human B lymphocytes. IV. Regulatory effects of corticosteroids on the triggering signal in the plaque-forming cell response of human peripheral blood B lymphocytes to polyclonal activation.

In vitro hydrocortisone in physiologic and pharmacologically attainable concentrations caused a marked enhancement of the PWM-induced PFC response of normal human peripheral blood B lymphocytes. This effect was seen only when hydrocortisone was added within the first 24 hr of culture and only when hydrocortisone and PWM were present together in cultures. Only suprapharmacologic concentrations of hydrocortisone (10(-3) M) were capable of suppressing early B cell activation. Late stages of antibody production and secretion were resistant to suppression by even these extraordinarily high concentrations. Hydrocortisone did not replace the T cell requirement of PWM-induced PFC responses. A single dose of in vivo hydrocortisone (400 mg) to normal adult volunteers did not produce this enhancing effect when PFC responses were measured in vitro in the absence of hydrocortisone. The data strongly suggest that the enhancing effect of hydrocortisone was due not to elimination of naturally occurring suppressor cells, but to a modulation of the triggering signal either directly on the B cell itself or via the balance of positive and negative T cell regulation of B cell activation.

Adult↗
PubMed1976

Activation of human B lymphocytes. II. Cellular interactions in the PFC response of human tonsillar and peripheral blood B lymphocytes to polyclonal activation by pokeweed mitogen.

A recently described system for the induction and assay of plaque-forming cells (PFC) following polyclonal stimulation of human B lymphocytes was employed to delineate the cellular requirements for pokeweed mitogen (PWM)-induced activation of human tonsillar and peripheral blood B lymphocytes. It was found that the process was not dependent on the presence of monocytes, but was dependent on the presence of T cells. T cell depleted suspensions of tonsillar as well as peripheral blood lymphocytes had markedly diminished if not absent PFC responses following PWM stimulation. The PFC responses of T cell depleted cultures of tonsil and blood could be reconstituted by adding back T cells. T cell supernatants could also reconstitute the PFC response of T cell depleted tonsillar lymphocytes but not of T cell depleted blood lymphocytes, thus suggesting a more stringent T cell requirement of the PWM-induced PFC response of blood lymphocytes. Enrichment for T cells on the other hand enhanced PFC responses in both organs, particularly in those cultures which had low responses in unfractionated suspensions demonstrating the requirement of optimal T cell help for maximal PFC responses. This study demonstrates the feasibility and effectiveness of this PFC system in elucidating some of the complex regulatory processes associated with the activation of human B lymphocytes.

B-Lymphocytes↗