Search PubMed⌕ Search

Biomedical subjects

R A Martin

Publications and source records attributed to R A Martin.

At least 73 records · Page 4Linked to original sources
PubMed1991

Effects of CI-949, a novel antiallergy compound, on host resistance in mice.

The effect of CI-949, a novel inhibitor of allergic mediator release, on immune function was assessed with holistic mouse models of immunocompetence. Resistance to the bacterial pathogens Listeria monocytogenes and Streptococcus pneumoniae and the B16F10 melanoma cell line was used to evaluate the potential of CI-949 to affect immune function. CI-949 treatment of female B6C3F1 mice increased pulmonary tumor burden at 100 mg/kg/day in the B16F10 melanoma model, with a no effect level of at least 50 mg/kg/day. A correlation was seen between decreased clearance of the B16F10 cells and increased tumor burden. However, CI-949 produced this effect only at the maximum tolerated dose. No effect of the drug was seen in the S. pneumoniae model. Host resistance to L. monocytogenes was increased after CI-949 administration, with the no adverse effect level in this model being at least equivalent to the top dose of 100 mg/kg/day. Therefore, the immune system does not appear to be adversely affected or to be a specific target for CI-949 even at an overtly toxic dose.

Animals↗
PubMed1991

Cytokine production and lymphocyte transformation during stress.

The production of interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN gamma) and blast transformation in peripheral blood mononuclear cells were assessed in medical students writing an academic examination. Blood samples were obtained on three occasions: (1) 1 month prior to the examination during a period of relatively low academic demand; (2) immediately after the examination; and (3) 10 days later. Results indicated that immune responses were significantly different immediately after the examination compared with the baseline and postexam measures. Lymphocyte responsiveness to both concanavalin A and pokeweed mitogen was decreased, as was the production of IFN gamma, supporting earlier reports of immunosuppression after relatively commonplace stressors. In contrast to predictions, IL-1 beta production was significantly elevated after the examination. Cortisol levels were also measured, but did not change across the three sample points. Our finding of an increase in IL-1 beta production suggests that stress may have different effects on different cell populations by enhancing the responses of monocytes and depressing those of lymphocytes.

Adult↗
PubMed1991

Degradation of growth hormone releasing factor analogs in neutral aqueous solution is related to deamidation of asparagine residues. Replacement of asparagine residues by serine stabilizes.

The incubation of a solution of the human growth hormone releasing factor analog, [Leu27] hGRF(1-32)NH2 at pH 7.4 and 37 degrees, resulted in extensive degradation of the sample. The major degradation products were identified as the peptides [beta-Asp8, Leu27] hGRF(1-32)NH2 and [alpha-Asp8, Leu27] hGRF(1-32)NH2, produced by deamidation of the Asn8 residue. When tested as growth hormone (GH) secretagogues in cultured bovine anterior pituitary cells, [beta-Asp8, Leu27] hGRF(1-32)NH2 was estimated to be 400-500 times less potent than the parent Asn8 peptide, while [alpha-Asp8, Leu27] hGRF(1-32)NH2 was calculated to be 25 times less potent than the parent Asn8 peptide. Three additional analogs of [Leu27] hGRF(1-32)NH2 containing either Ser or Asn at positions 8 and 28 were prepared and evaluated for their GH releasing activity and stability in aqueous phosphate buffer (pH 7.4, 37 degrees). Based on disappearance kinetics, [Leu27] hGRF(1-32)NH2 had a half-life of 202 h while the other analogs had the following half-lives: [Leu27, Asn28] hGRF(1-32)NH2 (150 h); [Ser8, Leu27, Asn28] hGRF(1-32)NH2 (746 h); and [Ser8, Leu27] hGRF(1-32)NH2 (1550 h). After 14 days, incubated samples of the Asn8 analogs lost GH releasing potency, while the Ser8 analogs retained full potency. The potential for loss of biological activity brought about by deamidation of other engineered peptides and proteins should be considered in their design.

Amides↗
PubMed1991

Species differences in response to photohemolytic agents.

Species differences in red blood cell susceptibility to the photohemolytic agents chlorpromazine, menadione and tetracycline were examined in mouse, rat, dog, and human blood. Menadione and tetracycline (25 microM) hemolyzed mouse but not dog, rat, or human red blood cells (RBC) when irradiated with UV light but not in the dark. Chlorpromazine (25 microM) produced a photohemolytic response in all four species with mouse and rat RBC lysing fastest followed by human then dog cells. Investigations into the nature of these species differences suggested that the size of mouse RBC may contribute to its high sensitivity to photohemolytic agents. An investigation of the effect of UV light on key antioxidant enzymes revealed species differences in enzyme inactivation. These data suggest that mouse RBC may be particularly vulnerable to phototoxic agents, especially those compounds which produce active oxygen species and, therefore, may prove more useful than human RBC as a model for predicting phototoxic potential of some chemical entities.

Animals↗
PubMed1991

Cleft palate repair.

Cleft palates are congenital or acquired and effect the primary palate (lip) or the secondary (hard and soft) palate. Surgical repair of congenital cleft palate is indicated at an early age. Preservation of maximal tissue and tissue blood supply and a tension-free closure of the defect are requisite for successful repair. Multiple surgical procedures are often performed prior to resolution of this problem. Aspiration pneumonia is often present concurrently and should be treated with appropriate antibiotic therapy.

Anesthesia, Inhalation↗
PubMed1991

Effect of left hepatic vein ligation on hepatic circulation, function, and microanatomy in dogs.

Eighteen healthy dogs were allotted to 3 groups (n = 6 dogs each). All dogs were evaluated at the beginning of the study by complete physical examination; total and differential WBC counts; serum biochemical analysis (alanine transaminase and alkaline phosphatase activities and bilirubin and albumin concentrations); sulfobromophthalein excretion, ammonia tolerance, and glucagon response testing; portal and intraparenchymal pressure determinations; operative mesenteric portography; and histologic assessment of hepatic biopsy specimens. The left hepatic vein was ligated completely in dogs of groups 1 and 2. Group-3 (control) dogs had a ligature placed loosely around the left hepatic vein. Dogs of groups 1 and 3 were reevaluated 24 hours after surgery by use of the aforementioned hematologic and biochemical tests. Group-1 dogs were reevaluated by use of portal and intraparenchymal pressure determinations, jejunal vein portography, and complete necropsy at 48 hours after surgery. At 4 weeks after surgery, dogs of groups 2 and 3 were reevaluated by use of all aforementioned tests. Results indicated transient hepatic congestion, which resolved by the fourth postoperative week. Longstanding effect on hepatic structure, circulation, or function was not found. We concluded that left hepatic vein ligation in clinically normal dogs does not cause severe or permanent liver damage.

Alanine Transaminase↗
PubMed1990

Interleukin 6 is essential for antibody secretion by human in vivo antigen-induced lymphoblastoid B cells.

In vivo immunization of normal subjects with a variety of antigens generates circulating lymphoblastoid (LB) B cells, which in vitro spontaneously secrete significant levels of specific antibody. Since activation and initial differentiation of these cells occurs in vivo, they provide a useful model for the study of the later stages of B cell maturation. In the present study, we investigated the requirement of interleukin 6 (IL-6) for the "spontaneous" in vitro production of IgG-Tet by LB B cells. Addition of IL-6 to cultures of LB B cells in medium supplemented with 10% fetal calf serum failed to increase the levels of IgG-Tet produced in vitro. However, addition of anti-IL-6 antibodies decreased IgG-Tet production as much as 70%, and this inhibition could be reversed by the addition of IL-6. LB B cells cultured in serum-free medium in order to restrict endogenous IL-6 production secreted only low levels of antibody, unless exogenous IL-6 was added. Addition of 2.5 units/ml of IL-6 to serum-free cultures induced an increase in IgG-Tet secretion nearly comparable to that seen in cultures supplied with serum. The magnitude of the increase in IgG-Tet secretion in response to exogenous IL-6 was inversely related to the number of cells in culture, which was due in part to increased endogenous IL-6 production in cultures with higher cell concentrations. Experiments including hydroxyurea in serum-free cultures indicated that IL-6-dependent enhancement of LB B cells' IgG-Tet secretion was not primarily mediated by cell growth. These observations suggest that in vivo generated LB B cells are not totally committed to antibody secretion, and that IL-6 is essential for in vivo antigen-induced LB B cells to reach the antibody-secreting stage.

Antibodies↗
PubMed1990

Vertebral lymphosarcoma in a cat.

Lymphosarcoma of the cauda equina in a domestic shorthair cat invaded the body of L7 and cranial portion of the sacrum. Clinical signs consisted of acute ambulatory paraparesis, tail paralysis, and dyschezia. Radiographically, there was evidence of bone lysis. Surgical exploration yielded a diagnosis, but did not induce improvement in the cat, which was subsequently euthanatized. Neurologic signs were similar to those associated with sacral nerve root avulsion injuries in cats.

Animals↗
PubMed1990

Rotational strength of double-pinning techniques in repair of transverse fractures in femurs of dogs.

Transverse midshaft fractures of femurs from freshly euthanatized dogs were stabilized by means of 6 methods: (1) 3.5-mm bone plate and screws, (2) single intramedullary pin, (3) double intramedullary pins retrograded proximally and driven distally to the level of the femoral trochlea, (4) double intramedullary pins retrograded distally and driven proximally into the trochanteric region, (5) double intramedullary pinning in Rush pin fashion, and (6) multiple intramedullary pinning that filled the medullary cavity at the fracture site. All bones were subjected to torsional stress. The measured strain was converted to forces of torque and correlated with bone diameter to normalize the data. The forces of torque from each fixation technique were compared with each other and with the mean torque force necessary to fracture intact femurs. Torsional shear applied to plated femurs resulted in failure at a mean level of 33.8% of the calculated theoretic moment. Torsional forces were concentrated at one end of the plate and catastrophically failed at that point, whereas the fracture site remained rigidly fixed. There was no significant difference in the initial moment of torsional failure between the single intramedullary pin technique (0.05 Nm) and the double-pinning techniques (0.03 to 0.04 Nm). The multiple-pinning technique was 1.8 to 3 times as effective in resisting rotational forces, compared with the other pinning techniques, but not significantly so.

Animals↗
PubMed1990

Identification of lipoprotein lipase immunoreactive protein in pre- and postheparin plasma from normal subjects and patients with type I hyperlipoproteinemia.

Postheparin plasma is a convenient source for the measurement of lipoprotein lipase (LPL) in humans. Previous studies have focused on the measurement of LPL catalytic activity, and have been unable to conveniently measure the LPL protein or identify possibly different plasma forms of the enzyme. Pre- and postheparin plasma was treated with a highly specific antibody raised against bovine milk LPL and the immunoprecipitate was analyzed by Western blotting. In normal subjects there were several species of LPL in plasma. A 56 kD protein increased after heparin injection, and likely represented active LPL. The anti-LPL antibody reacted specifically with this 56 kD protein, and also reacted specifically with proteins at 52 kD, 69 kD, as well as a 20 kD breakdown product. In addition, using peptide mapping, the 56 kD protein was structurally similar to the 52 and 69 kD LPL proteins. The antibodies were affinity purified, biotinylated, and used to quantitate LPL immunoreactive mass using an enzyme-linked immunosorbent assay (ELISA). LPL immunoreactive mass was present in all subjects in preheparin plasma. In postheparin plasma, five patients with type I hyperlipoproteinemia displayed decreased LPL immunoreactive mass when compared to normal subjects, although there was a wide range of specific activity of the small amount of enzyme present. When the LPL from the plasma of the patients was immunoprecipitated and Western blotted, there was considerable heterogeneity in the appearance of the LPL forms, and an overall decrease in LPL protein. Thus, several different immunoreactive LPL proteins were present in pre- and postheparin plasma. In preheparin plasma, as well as in patients with type I hyperlipoproteinemia, there was decreased immunoreactive LPL protein, and the LPL protein that was present was of low specific activity.

Heparin↗
PubMed1989

Malignant clear cell hidradenoma of the lip.

An interesting variety of cutaneous tumors of the head and neck, tumors of the eccrine differentiation, are seldom recognized. The most recent reports of these tumors appear in the dermatologic literature, probably due to the majority of them being located in the trunk and the extremities. Malignant varieties of these tumors do exist and must be treated as aggressively as more common tumors of the head and neck region. Tumors with eccrine differentiation are among a large variety of cutaneous tumors that present in the head and neck. These tumors are far less common than basal cell and squamous cell carcinomas of the head and neck. Malignant clear cell hidradenomas, a variant of the more common benign clear cell hidradenoma, is one such type of tumor of the eccrine differentiation. This is a rare tumor seldom reported in sites of the head and neck. A case of a 47-year-old white male with such a tumor of the lower half of his lip is presented. This report is particularly concerned with the histopathology of the tumor, its unique etiology, and the applicability of the lip switch flap (Stein-Abbe-Estlander) in the reconstruction of the surgical defect following total tumor excision.

Adenoma, Sweat Gland↗
PubMed1989

AIDS with disseminated histoplasmosis.

This report is a description of two Ohio cases of acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis, with discussion of diagnosis and treatment of this combination. The patient in case 1 developed disseminated histoplasmosis as the first significant symptomatic medical condition of his life. The patient in case 2 presented with severe pharyngitis, but without signs or symptoms specific to the lungs. Amphotericin B alone does not eradicate histoplasmosis in an AIDS patient. The best therapy at present is a full course of amphotericin B followed by a lifetime regimen of ketoconazole to prevent relapse. Family physicians in the District of Columbia, Texas, Maryland, Louisiana, Missouri, Illinois, Arizona, and Puerto Rico should be particularly vigilant in looking for the combination of these two diseases.

Acquired Immunodeficiency Syndrome↗