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Biomedical subjects

D A Clark

Publications and source records attributed to D A Clark.

At least 325 records · Page 18Linked to original sources

Strain-dependence and cellular aspects of the acceleration of age-dependent shift in class-specific helper and suppressor activity in the thymus of MRL/Mp mice by the LPR gene.

Previous studies of the immunoregulatory activity of thymocytes from SJL/J mice have shown loss of suppressor activity for the antibody response by 24 weeks of age with appearance of helper activity. At the same time, suppressor cells developed which inhibit the generation of cytotoxic T lymphocytes (CTL). We now show a similar pattern of helper and suppressor activity in MRL/Mp mice. Presence of the lpr/lpr genotype significantly accelerated the onset of these changes in thymocyte activity. A similar pattern of thymocyte activity was not detected in C57B1/6 mice. In aged MRL-lpr mice, evidence of increased suppressor cell activity for the CTL response could be demonstrated in spleen, and the suppressor was sensitive to treatment with anti-thy 1.2 + complement. The magnitude of the deficiency in the CTL response in MRL-lpr mice was greater than could be accounted for by suppressor cell activity alone. Measurement of the frequency of CTL precursors (CTLP), the yield of CTL per CTLP, and the ability to produce and to respond to interleukin 2 (IL-2) indicated that a drop in CTLP frequency, subnormal generation of IL-2, and probably an intrinsic defect in the responsiveness of MRL-lpr CTLP to IL-2 was contributing to the defective CTL response. We were not able to link suppressor T cells with reduced responsiveness to IL-2. Ageing involves different patterns of change in immunoregulatory T-cell subsets in different strains of mice, depending on their genetic constitution. The general implications of this conclusion for prediction of immune dysfunction with age in genetically distinct members of an outbred population are discussed.

Aging↗

Preliminary characterization of two types of suppressor cells in the human uterus.

Survival of the mammalian fetus in an immunologically hostile host has been shown to be determined by the properties of the tissue at the maternal-fetal interface. Suppressor cells have been found in the decidua in both murine and human systems. This study was carried out to further characterize these cells and to determine whether they were present in abnormal early pregnancies and in the endometrium at the time of implantation. Suppressor cells appear in the endometrium after ovulation, and their activity is present in the decidua of successful pregnancies but is absent in missed abortions. Two types of cells have been identified. An early phase large cell appears to be hormone dependent, and later phase small cell appears to be trophoblast dependent. This would suggest that suppressor cells may play a role in protecting the fetal allograft, from the time of implantation, against maternal immunity, thereby allowing a pregnancy to succeed.

Abortion, Missed↗

Continuous gastric pH measurement in young and older healthy preterm infants receiving formula and clear liquid feedings.

Gastric pH was recorded with an intragastric pH electrode for 12 h in two groups of healthy, preterm infants with similar birth weights (range 1.4 to 2.0 kg). Group I infants (n = 13) were less than 7 days old and Group II infants (n = 10) were 7-15 days old. Infants were fed three formula feedings and one clear liquid feeding during the study. In Group I, mean gastric pH measured at 15-min intervals was above 4.0 for 3 h after either feeding. In Group II mean gastric pH was lower particularly after clear liquid feedings, where it remained below pH 4.0 for the entire 3-h postprandial period. The percent of monitored time at gastric pH less than 4.0 was low in Group I--15.2 +/- 4.2% and 20.6 +/- 6.4% after formula and clear liquid, respectively. The percent time was greater in Group II--42.7 +/- 8.0% and 61.9 +/- 7.3% after formula and clear liquid, respectively. In the younger preterm infant, gastric pH does not appear sufficiently low to support peptic activity.

Age Factors↗

An investigation of two self-report measures of obsessional phenomena in obsessive-compulsive adolescents: research note.

A number of studies have recently demonstrated the clinical utility of objective self-report inventories in the assessment of obsessive-compulsive disorders in adults. To date, the usefulness of these instruments has not been demonstrated with obsessive-compulsive adolescents. In the present study the Leyton Obsessional Inventory and the Maudsley Obsessional-Compulsive Inventory were administered to 11 obsessive-compulsive adolescents and a group of 10 anxious non-obsessional patients. The obsessional adolescents scored significantly higher than the controls on the Maudsley total score and checking factors alone. Possible explanations of the results are discussed.

Adolescent↗

Obsessive-compulsive adolescents and their parents: a psychometric study.

The present study examined obsessive personality traits and achievement expectations of parents with an obsessive-compulsive adolescent. The Leyton Obsessional Inventory (LOI) and rating scales of occupational and educational aspirations and expectations were administered to both parents and the adolescent of 12 families with an obsessional adolescent and 10 families having an anxious, nonobsessional son or daughter. The parents' LOI scores were similar in the two groups, though higher than normal adults on the trait and resistance scales. The obsessional adolescents perceived their parents to hold significantly higher career demands for them than the anxious adolescents.

Achievement↗

Selective localization of a bone marrow cell subpopulation at the implantation site in murine decidua.

Recent studies of the surface markers on cells in murine decidua have suggested that a proportion of the cells originate from the bone marrow. To examine directly the migration of bone marrow cells to decidua, we labeled whole bone marrow with TRITC and counted the number of cells appearing in decidua following adoptive transfer to virgin or allopregnant C3H mice. Labeled cells were readily identified in decidua by 3 hours after injection, and fewer cells were seen in the lining of the virgin uterus compared to allopregnant recipients. The presence of labeled cells could not be explained by blood contamination. The TRITC-labeled cells were found preferentially at the implantation sites, and while labeled bone marrow cells could be found in spleen as well as in decidua, adoptively transferred TRITC-labeled spleen cells localized preferentially in spleen and lymph nodes draining the uterus rather than in decidua. Velocity sedimentation analysis showed that the labeled bone marrow cells lodging in decidua were small lymphocytic cells (S = 2.5-4 mm/hr) and appeared to derive preferentially from small-sized bone marrow cells (S less than 4.3 mm/hr). These observations indicate that a subpopulation of bone marrow cells selectively homes to the implantation site in decidua during successful allopregnancy. The possible significance of this observation is discussed.

Animals↗

Necrotizing enterocolitis: intraluminal biochemistry in human neonates and a rabbit model.

The intestinal contents of 17 neonates with necrotizing enterocolitis were analyzed for pH, carbohydrate, protein, and bacteria. The intraluminal pH was less than 5.0 (16/17). Sufficient carbohydrate and bacteria capable of fermenting the carbohydrate to organic acids were found. The intraluminal protein content was greater than 5 g/dl. The variables of acid and protein were then examined in a rabbit intestinal loop model. The hemorrhagic response in individual loops was measured using Cr51 tagged red blood cells such that the microliters of blood per centimeter intestine could be determined. Loops with organic acid and protein had significantly (p less than 0.01) more intramural blood than control loops. Organic acid (possibly generated by bacterial mixed acid fermentation of carbohydrate) in the presence of protein promotes intramural hemorrhage similar to that seen in neonates with necrotizing enterocolitis.

Animals↗

Bupivacaine alters red blood cell properties: a possible explanation for neonatal jaundice associated with maternal anesthesia.

Cord blood was incubated with lidocaine, mepivacaine, bupivacaine, or buffer and red blood cell filterability was determined. Only bupivacaine at either 1 or 2 micrograms/ml prolonged filterability by an average of 58 to 65% over red cells treated with buffer alone. Tritiated bupivacaine was bound to a greater extent to red cell ghosts from cord blood (24.6 +/- 5.8%) than to adult red cell ghosts (14.6 +/- 2.6%). Finally, we determined red cell survival in 13-day-old rats injected with bupivacaine or buffer. At 2 h after injection, buffer-treated animals had a red cell survival of 96.9 +/- 3.3%, whereas 2-h survival was reduced to 82.6 +/- 8.7% for the animals injected with bupivacaine. Our results suggest that the neonatal jaundice associated with maternal anesthesia, especially bupivacaine, may be related to the observations that these agents cross the placenta, bind to the red cell membrane and reduce its filterability, resulting in shortened red cell survival.

Adult↗

Effects of alterations in the immunocompetent status of Mus musculus females on the survival of transferred Mus caroli embryos.

The role of the immune system in promoting the midterm death of Mus caroli embryos transferred to the Mus musculus uterus was studied in vivo by transferring M. caroli blastocysts to recipients with altered immune status. Transfers of embryos to chimaeric mothers (Mus musculus in equilibrium Mus caroli), which were expected to be tolerant of species antigens, resulted in survival of M. musculus embryos but death of M. caroli embryos. The preferential survival of M. musculus embryos was explained by showing that M. musculus embryos can survive in the M. caroli uterus. Transfers to T cell-deficient mice of genotype nu/nu and to NK cell-deficient mice of genotype bg/bg as well as treatment of normal transfer recipients with Cyclosporin A or anti-Ia antiserum failed to prolong survival. However, immunization of recipients with M. caroli lymphocytes promoted more rapid and uniform failure of the interspecies pregnancy. Cytotoxic cells were detected in the resorbing embryos on Day 10.5 in immune pregnancies and on Day 12.5 in non-immune pregnancies and these cells were promiscuous in their pattern of lysis, showing equal reactivity against M. caroli, transfer recipient and 3rd party target cells. These experiments show that failure of M. caroli embryos in the M. musculus uterus is complex, but probably does not involve responses by classical cytotoxic T lymphocyte or natural killer cell pathways. Participation of the immune system in the resorption process, however, is confirmed and is associated with generation of promiscuous cytolytic cells.

Animals↗

Active suppression of host-vs-graft reaction in pregnant mice. VI. Soluble suppressor activity obtained from decidua of allopregnant mice blocks the response to IL 2.

The mammalian fetus expresses a variety of antigens against which the maternal immune system can react and which in an allogeneic mating bears paternal transplantation antigens. Although these antigens may be expressed on the fetal trophoblast cells that contact maternal uterine decidua, the "fetal allograft" is not usually rejected. Previous studies have demonstrated the presence of nonspecific non-thymus-derived suppressor cells in the lymph nodes draining the uterus and in decidua of laboratory mice undergoing first allogeneic pregnancy. These suppressor cells appeared to be small lymphocyte cells that inhibit the generation of cytotoxic T lymphocytes (CTL) in vitro and in vivo and elaborate a nonspecific non-MHC-restricted soluble suppressor activity when cultured for 48 hours at 37 degrees C in vitro. We now report that soluble suppressor activity obtained from the decidua (DS) of allopregnant C3H/HeJ mice inhibits both the primary and secondary (memory) CTL response in vitro but does not inhibit lysis of target cells by preformed CTL. DS did not suppress the proliferation of YAC lymphoma cells, P-815 cells, or a C3H placental trophoblastoma line. Suppressor activity was obtained from anti-thy-1.2 + complement-resistant cells in the decidua, could also be obtained from the decidua of allopregnant CD1 nu/nu mice, and was associated with a single peak of activity of approximately 100,000 daltons on Sephacryl 200 chromatography. Suppression could not be overcome by adding either crude or HPLC-purified IL 2 to the mixed lymphocyte cultures in vitro, and both crude and column-purified suppressor factor inhibited the IL 2-dependent proliferation of H-Y cells (a cloned T cell line with NK activity). Furthermore, DS inhibited the IL 2-dependent generation of cytotoxic effector cells in vitro in the absence of allogeneic stimulator cells. Thus, a soluble suppressor factor obtained from non-T cells present in the decidua of successfully allopregnant mice could block the response to IL 2 and inhibit the generation of both specific and nonspecific cytotoxic effector cells. The significance of this inhibition with respect to survival of the "fetal allograft" is discussed.

Animals↗

Quantitation of human megakaryocyte progenitors (CFU-M) in plasma clot culture by an indirect immunoperoxidase method.

We have developed an indirect immunoperoxidase method to detect human megakaryocytic colonies in plasma clot culture. A monoclonal antibody directed against platelet glycoprotein IIb/IIIa complex is incubated with plasma clots fixed to gelatin-coated slides with methanol. This antibody is subsequently linked to horseradish peroxidase by means of an avidin-biotin sandwich technique. Megakaryocytic colonies are identified by precipitation of benzidine by the horseradish peroxidase. This method detects growth of megakaryocytic colonies in culture, which is dependent on factors present in leukocyte-conditioned medium and is linear with respect to the concentration of human light-density nonadherent bone marrow cells plated at a concentration of 1.5-7 X 10(5) cells/ml. This method is simple to apply, uses objective criteria for recognition of megakaryocytes, and leaves cultures mounted and stained for permanent record.

Adult↗

Glottic carcinoma. The roles of surgery and irradiation.

The treatment of 336 patients with squamous cell carcinoma of the glottic larynx seen at the University of Virginia Medical Center from 1960 through 1977 was reviewed. Two hundred eighty-five patients form the basis of this report. Patients were grouped by stage and by other prognostic factors. Five-year actuarial survival, recurrences, salvage therapy, complications, second primaries, and incidence in patients younger than 45-years-old were examined. The actuarial 5-year survivals are Stage I, 96%; Stage II, 88%; Stage III, 65%; and Stage IV, 57%. Early glottic carcinoma responded equally well to radiation therapy or surgery, and mortality from intercurrent disease was more common than death from glottic carcinoma. Anterior commissure involvement was not found to significantly decrease prognosis in Stage I disease. Within Stage II, patients with impaired true cord mobility had a significantly decreased survival, 71%, versus 93% for Stage II carcinoma with mobile cords. Surgery was superior to irradiation when cord mobility was impaired or fixed. Surgical salvage was successful in 70% of cases when the cords were originally mobile but 11% when cord motion had been impaired or fixed. Patients younger than age 45 years presented with more advanced disease, but by stage, treatment response did not differ from the remaining older group. Based on this review and from data reported in the literature, the authors recommend curative radiation therapy in patients with glottic carcinoma where the vocal cords are fully mobile. When cord mobility is impaired or fixed, the inclusion of surgery in the initial management results increased survival over irradiation alone. Recognizing that glottic carcinoma is often part of a multisystem disease, individualization of treatment is especially important in these advanced tumors.

Actuarial Analysis↗

Weight gain: a response to transfusion in selected preterm infants.

A group of low-birth-weight infants with daily weight gains that were below the expected mean for postnatal age were examined to determine the effects of RBC transfusion on their weight gain. The mean hemoglobin concentration (+/- SD) in 13 infants (birth weight less than 1,500 g) prior to transfusion was 8.5 +/- 1.6 g/dL and 11.4 +/- 2.1 g/dL after transfusion. When a comparison was made between the daily weight gain for the week prior to transfusion with the week following transfusion, the mean daily weight gain (+/- SD) increased from 20.8 +/- 4.6 g to 28.0 +/- 6.3 g. Among the six infants with pretransfusion hemogloblin concentrations of less than 7.5 g/dL, the increase in daily weight gain was greatest (a rise from 22.6 +/- 4.0 g to 34.1 +/- 4.9 g). Improvements in weight gain were associated with a decrease in metabolic rates as determined by declines in oxygen consumption.

Age Factors↗