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Biomedical subjects

K M Young

Publications and source records attributed to K M Young.

At least 37 records · Page 2Linked to original sources
PubMed1993

Isolation of feline eosinophils via peritoneal lavage.

Fourteen cats were inoculated orally with 1 of 2 infective doses of Toxocara canis to induce eosinophilia. Cats were subsequently challenge exposed twice via intraperitoneal injection with 1 of 2 T canis antigen preparations. Peritoneal lavage was performed 2 days after antigenic challenge exposure, and eosinophils in the peritoneal lavage fluid were quantified. None of the cats developed clinical signs of disease after infection. All cats developed peripheral eosinophilia after infection. Significant (P < 0.05) difference in mean eosinophil count from the lavage fluid was observed between lavage 1 (prechallenge exposure) and lavages 2 and 3 (postchallenge exposure) in both groups of cats. Significant difference in eosinophil count was not found between cats given different doses of eggs. After initial challenge exposure, significantly (P < 0.05) more eosinophils were obtained from cats given antigen preparation 2 (prep-2) than from those given antigen prep-1. This difference was no longer observed after the second challenge exposure with higher doses of either antigen prep-1 or prep-2. In cats given antigen prep-2, significant difference was not found between lavages 2 and 3. However, in cats given antigen prep-1, eosinophil count was significantly (P = 0.005) greater in fluid obtained from lavage 3, compared with eosinophil count from lavage 2. Mean +/- SEM percentage of eosinophils in the fluid from lavage 3 in all cats was 70.8 +/- 2.2%. Other cell types included macrophages, neutrophils, lymphocytes, and mast cells. Gross postmortem findings were mild. One- to 3-mm nodular white foci of inflammation were observed on the serosal surfaces of the liver, spleen, kidneys, and omentum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Acetic, lactic and citric acids and pH inhibition of Listeria monocytogenes Scott A and the effect on intracellular pH.

The effects of acetic, lactic and citric acids and pH on the growth and intracellular pH (pHin) of Listeria monocytogenes Scott A were documented and compared for total acid concentrations ranging from 50 mmol ml-1 to 250 mmol ml-1 for acetic and lactic acids and from 25 mmol ml-1 to 100 mmol ml-1 for citric acid. Initial pH values ranged from 4.7 to 6.0. Although the growth rate of L. monocytogenes Scott A was slower when incubated at 25 degrees C than at 37 degrees C, the relative acid and pH inhibition was identical at both temperatures. As the initial pH values decreased and/or the total acid concentrations increased, the growth rates of L. monocytogenes Scott A decreased. Compared at equal initial pH values and on an equimolar total acid basis, the relative inhibition effect was generally acetic > lactic > citric. When based on initial undissociated acid concentrations, the inhibition effect was citric > lactic > acetic. The effect of differing acid and pH environments on pHin was determined. At equimolar total acid concentrations, the pHin of the cell was changed the least by citric acid and the most by acetic acid. Growth rates were influenced by the pHin and the acid used to adjust the system.

Acetates↗
PubMed1990

Human rTNF alpha augments anti-bacterial resistance in mice: potentiation of its effects by recombinant human rIL-1 alpha.

Treatment with human recombinant tumour necrosis factor-alpha (rTNF alpha) significantly enhanced resistance to Listeria monocytogenes infection in mice. The level of protection (which was dose-dependent and maximal at approximately 1.0 microgram per mouse) was similar to that previously reported for the monokine rIL-1 alpha, although somewhat greater amounts of rTNF alpha than rIL-1 alpha were required. Combined administration of suboptimal concentrations of rTNF alpha and rIL-1 alpha resulted in significant enhancement of resistance beyond that obtained with either monokine alone, whereas further increases in anti-listeria resistance were not observed at doses of rTNF alpha or IL-1 alpha that were themselves capable of inducing substantial protection. Combined administration of rTNF alpha and rIL-1 alpha was associated with a delay in onset and lessening in severity of the lymphopenia that accompanied L. monocytogenes infection. The reduced bacterial burden in the spleens and livers of mice treated with rTNF alpha and rIL-1 alpha was associated with a more rapid decline in serum colony-stimulating activity. Peritoneal macrophages from rTNF alpha- and rIL-1 alpha-treated listeria-infected mice did not demonstrate enhanced anti-listeria activity in vitro. These results provide further evidence for the potential benefits of rTNF alpha and other cytokines in promoting anti-bacterial resistance. They further suggest that use of combinations of cytokines is a strategy worthy of further consideration.

Animals↗
PubMed1989

Administration of purified anti-L3T4 monoclonal antibody impairs the resistance of mice to Listeria monocytogenes infection.

Anti-L3T4 monoclonal antibody (GK1.5) treatment significantly impaired the antilisteria resistance of mice as manifested by increased recovery of listeriae from the spleens and livers of anti-L3T4-treated mice and by greater severity of damage to the liver and other organs. Anti-L3T4-treated mice demonstrated a profound decrease in their T cell-mediated responses to Listeria monocytogenes and its products; they failed to develop delayed type hypersensitivity to soluble listeria antigens in vivo, and their spleen cells proliferated poorly in response to stimulation by either mitogens or listeria antigens in vitro. Spleen cells from control listeria-infected mice produced significant amounts of gamma interferon when stimulated with listeria antigens in vitro, whereas under the same conditions spleen cells from anti-L3T4-treated listeria-infected mice failed to produce detectable gamma interferon. Anti-L3T4 treatment resulted in a slight increase in serum colony-stimulating activity as compared with control listeria-infected mice, probably as a result of the increased bacterial burden in these animals. Despite the dramatic decrease in T-cell activities, anti-L3T4-treated mice succeeded in clearing L. monocytogenes from the spleen and liver in a manner that was only slightly delayed as compared with control listeria-infected mice. In addition, anti-L3T4-treated listeria-immunized mice exhibited a moderate degree of enhanced resistance to rechallenge with L. monocytogenes, and their spleen cells were able to transfer a limited degree of antilisteria resistance to naive recipient mice. Both of these responses, however, were diminished as compared with those of control listeria-immunized mice in the same experiments. Although these observations establish a critical role for L3T4+ cells in the development of maximal resistance to listeriosis, they also suggest that compensatory mechanisms may allow mice to develop considerable antilisteria resistance even when L3T4+ cell activities are substantially reduced.

Animals↗
PubMed1989

Treatment of mice with human recombinant interleukin-2 augments resistance to the facultative intracellular pathogen Listeria monocytogenes.

The effects of exogenously administered human recombinant IL-2 (hrIL-2) on resistance to Listeria monocytogenes infection were examined. Intravenous injection of hrIL-2 significantly enhanced antibacterial resistance in both BDF1 and C3H/HeJ mice. The beneficial effect of hrIL-2 was observed with as little as 0.6 micrograms per mouse, whereas optimum protection occurred at 6 micrograms per mouse, hrIL-2 was equally protective when administered concomitant with the listeriae or up to 24 h prior to infection; it had little effect if given after the bacterial challenge. Kinetic experiments indicated that both the peak bacterial burden and the time lag before L. monocytogenes began to be cleared from the spleen and liver were reduced in hrIL-2-treated mice as compared with control mice. Histopathological examination of spleens and livers confirmed that hrIL-2-treated Listeria-infected mice experienced considerably less damage to these organs than did control mice. Spleen cells from Listeria-infected mice exhibited depressed levels of mitogen-induced proliferation coincident with the peak bacterial burden in the spleen and liver and during the subsequent recovery from the infection. Administration of hrIL-2 to uninfected mice had no effect on spleen cell proliferation in response to mitogens in vitro, nor did hrIL-2 treatment restore normal levels of splenocyte proliferative responses to Listeria-infected mice. In addition, hrIL-2 treatment resulted in attenuated levels of serum colony-stimulating activity in infected mice as compared with control infected mice. Coadministration of both hrIL-2 and human recombinant interleukin-1 alpha at various dose and time combinations had no detectable additive or synergistic effect. Although these data do not suggest an obvious mechanism of action, they clearly demonstrate that hrIL-2 can augment host defense against the facultative intracellular pathogen L. monocytogenes.

Adjuvants, Immunologic↗
PubMed1989

Separate and combined effects of recombinant interleukin-1 alpha and gamma interferon on antibacterial resistance.

Our laboratory has previously reported that administration of murine recombinant interleukin 1 alpha (rIL-1 alpha) substantially enhanced the resistance of mice to Listeria monocytogenes infection. Other investigators have reported that gamma interferon (IFN-gamma) plays a pivotal role in antilisteria resistance. In the present study, we have defined doses of human rIL-1 alpha that enhanced the antilisteria resistance of mice. We then addressed the possibility that combined immunotherapy with rIL-1 alpha and recombinant IFN-gamma (rIFN-gamma) might result in an additive or synergistic enhancement of antibacterial resistance. Simultaneous administration of rIL-1 alpha and rIFN-gamma enhanced antilisteria resistance (at 3 days after infection) to a greater extent than did either cytokine alone, although the results did not imply a synergistic action between the two cytokines. Experiments which examined the effects of the timing of cytokine administration indicated that maximal protection was observed when rIL-1 alpha and rIFN-gamma were administered together concomitantly with the L. monocytogenes challenge. When we compared the separate and combined protective effects of rIL-1 alpha and rIFN-gamma throughout the course of a primary L. monocytogenes infection, we observed an additive effect of the two cytokines only at 3 days after challenge, the time at which the peak bacterial burden occurs in the spleens and livers of infected mice. Histopathological comparisons of livers and spleens from cytokine-treated and control listeria-infected mice verified that cytokine treatment reduced the severity of tissue damage in cytokine-treated listeria-infected mice. In an attempt to provide a potential mechanism for the protective effects of rIL-1 alpha and rIFN-gamma administration, we compared levels of colony-stimulating activity in sera from cytokine-treated and control listeria-infected mice. The highest levels of colony-stimulating activity were detected in sera from control listeria-infected mice; somewhat lower levels were found in sera from listeria-infected mice that received rIL-1 alpha and rIFN-gamma either alone or in combination.

Animals↗
PubMed1989

In vitro immune monitoring of antibody response in dogs given chemoimmunotherapy for lymphoma.

Clinical remission in 30 dogs with lymphoma was induced with a combination of vincristine, L-asparaginase, cyclophosphamide, and doxorubicin HCl, administered sequentially, and then an autochthonous tumor cell vaccine, given intralymphatically, as maintenance therapy. Humoral antibody amounts were monitored in 11 dogs, using a solid-phase bead-type radioimmunoassay. The median survival of the 30 dogs was 13 months from the start of chemotherapy (range, 7 to 25 months; mean, 13.8). The median remission duration was 16 weeks (range, 9 to 98 weeks; mean, 26.8). Correlation between increase in amount of humoral antibody was significant (P = 0.0001 to 0.012), before and after chemoimmunotherapy, in dogs responding to therapy, compared with that in dogs not responding to therapy.

Animals↗
PubMed1988

Chemotherapy versus chemotherapy with intralymphatic tumor cell vaccine in canine lymphoma.

Fifty-eight dogs with lymphoma were treated with combination chemotherapy (vincristine, cyclophosphamide, L-asparaginase, and doxorubicin HCl [VCAA]) followed by intralymphatic autochthonous tumor cell vaccine (CI). Thirty dogs received chemotherapy alone (VCAA). There was no overall significant difference in survival times between the two groups, although there was a trend toward prolonged survival in the CI group. Asymptomatic dogs (Stage A) and dogs less than 7 years of age with Stage A disease treated with CI had significantly longer survival. Dogs treated with CI had a significantly longer first remission. Regardless of treatment group, male dogs had significantly longer remission times compared with female dogs.

Age Factors↗
PubMed1988

Effects of murine recombinant interleukin 1 alpha on the host response to bacterial infection.

The effects of exogenously administered rIL-1 alpha on elimination of viable listeriae from the liver and spleen during the course of a primary Listeria monocytogenes infection was studied. Similar numbers of L. monocytogenes were recovered from rIL-1 alpha-treated and control mice at up to 24 h after infection; however, by 48 h after infection more than 1 log10 fewer viable L. monocytogenes were recovered from the spleens of rIL-1 alpha-treated mice than from Listeria-infected controls. The difference in bacterial burden between IL-1 alpha-treated and control mice increased with time; by 7 days after infection viable L. monocytogenes had been eliminated from most rIL-1 alpha-treated mice, whereas control mice still harbored 10(4) to 10(5) L. monocytogenes per spleen and liver. Histopathologic examination confirmed that rIL-1 alpha-treated mice suffered considerably less damage to the spleen, liver, lung, and brain than did control mice. To determine whether rIL-1 alpha-mediated protection indirectly by augmenting the release of other cytokines, we determined serum levels of colony-stimulating activity and IFN activity in rIL-1 alpha-treated and control Listeria-infected mice. Treatment with rIL-alpha elicited an early burst of serum colony-stimulating activity as compared with sera from Listeria-infected control mice. These data suggest that exogenous administration of rIL-1 initiates release of colony-stimulating activity, and perhaps other cytokines, that accelerate the protective response of the infected host. Prophylactic augmentation of antimicrobial resistance by administration of rIL-1 alpha may be worthy of further evaluation.

Animals↗
PubMed1987

Megakaryocytopoiesis: incorporation of tritiated thymidine by small acetylcholinesterase-positive cells in murine bone marrow during antibody-induced thrombocytopenia.

The ability of small acetylcholinesterase-positive (SACHE) cells to incorporate tritiated thymidine (3H-TdR) was studied in the bone marrow of mice made acutely thrombocytopenic by injection of guinea pig antimouse platelet serum (APS) and in control mice injected with normal guinea pig serum (NS). 3H-TdR was administered in vivo, and bone marrow was collected at various time points thereafter. The initial labeling index (LI) for both groups was about 30%. After four hours, the LI increased and reached peak values at 48 hours, but was lower in thrombocytopenic animals. The lower peak LI in APS-treated animals may be the result of both a faster rate of influx of unlabeled cells into the acetylcholinesterase (AChE) positive cell compartment and efflux of more heavily labeled, and probably polyploid, SACHE cells into the compartment of recognizable megakaryocytes. In both groups the increasing LI occurred concomitantly with a decreasing mean grain count. This may indicate cellular division by some fraction of SACHE cells. Heterogeneity in nuclear morphology was also demonstrated, and the frequency of individual morphologies was altered in APS-treated animals. In addition, cells that incorporated 3H-TdR were larger than those that did not. This group of small cells appears to represent a pivotal point in megakaryocytopoiesis in which the switch from mitosis to endomitosis is occurring.

Acetylcholinesterase↗
PubMed1986

Intralymphatic autochthonous tumor cell vaccine in canine lymphoma.

Canine lymphoma is analogous to non-Hodgkin's lymphoma and is responsive to similar cytotoxic agents. The purpose of this study was to investigate a tumor cell vaccine delivered via peripheral lymphatics as maintenance therapy after induction of remission with chemotherapy. Thirty dogs with histologically confirmed lymphoma were treated with chemoimmunotherapy, and were induced into remission with combination chemotherapy, followed by intralymphatic (IL) autochthonous tumor cell vaccines as maintenance therapy. All dogs received two cycles of chemotherapy and at least three vaccine infusions. The median survival was 13 months with 11/30 (36%) still alive at 1-3 years follow-up. The median remission duration was 16 weeks while on IL vaccines alone. The survival time and remission duration is longer than previously reported in canine lymphoma.

Animals↗
PubMed1985

Chemotherapy of advanced mammary adenocarcinoma in 14 cats.

Fourteen cats with advanced mammary adenocarcinoma were treated with doxorubicin HCl and cyclophosphamide. All cats had inoperable or recurrent disease, and 9 cats had metastasis to the thorax. Eleven of the cats were available for long-term evaluation; 3 had complete response to chemotherapy, with survival times of 180, 283, and 344 days; 2 had partial response, with survival times of 45 and 149 days; 2 had stabilization of disease, with survival times of 170 and 182 days; and 4 had no response, with survival times of 4, 47, 67, and 106 days.

Adenocarcinoma↗
PubMed1985

Myeloproliferative disorders.

Myeloproliferative disorders are uncommon in the dog and may be classified as chronic or acute. Excessive proliferation of mature cells leads to an overproduction of terminally differentiated blood cells (chronic MPD). Inability of cells to mature results in the accumulation of poorly differentiated blast cells in the peripheral blood and bone marrow (acute MPD). Because the lesion appears to be at the level of the hematopoietic stem cell, all cell lines in the bone marrow may be affected. Diagnosis depends upon the accurate identification of neoplastic cells and the absence of other diseases associated with bone marrow hyperplasia. The prognosis for chronic MPD is guarded, whereas for acute MPD it is grave. Accurate identification of these disorders in animals is important. Investigation and greater understanding of the pathophysiologic mechanisms may lead to more lasting therapeutic successes in the future.

Animals↗
PubMed1980

DNA sequence analysis of prm-mutations of coliphage lambda.

Nucleotide sequence changes associated with mutation of the prm promoter of bacteriophage lambda have been determined. Prm-mutations have been assigned to two classes. Class I mutations appear to affect the interaction of RNA polymerase with prm; six class I mutations affect four sites, located 14, 33, 38, and 39 bp preceding the prm transcription startpoint. Class II mutations appear to owe their Prm-phenotype to a change in OR, which could prevent activation of prm by repressor. All three class II mutations are in OR 1.

Bacteriophage lambda↗
PubMed1980

Medicare episodes of illnesses: a study of hospital, skilled nursing facility, and home health agency care.

This paper analyzes charges incurred under the Medicare program for inpatient hospital, skilled nursing facility (SNF), and home health agency (HHA) care for 1976. This research was made possible through the construction of a new data set which links a beneficiary's use of these three services. Summary highlights reveal that an overwhelming majority of the 7.5 million Medicare episodes of illness do not involve post-hospital SNF or HHA care. Those episodes of illness that use only hospital care are substantially (53%) cheaper than all other episodes. A large percentage of these charge differences reflect the greater number of hospital days of care associated with post-hospital care services. However, an analysis of the beneficiaries' demographic characteristics suggests that persons who use post-hospital care generally differ from those who receive only hospital care. We found that persons who use post-hospital SNF or HHA, or both types of care are likely to be female, to have cancer, diabetes, fractured bones or a central nervous or vascular system disease, and to be older than persons who do not use these types of care. The data also show that a beneficiary's area of residence greatly influences the amount and types of care received. Persons who reside in the New England, Middle Atlantic and Pacific Divisions are more likely to receive post-hospital care services than person who live elsewhere in the United States. These persons also incur among the highest per capita institutional charges in the United States. Part of this variation in institutional charges per capita is explained by the high input price index found in these areas, and in some cases by the high quantity of services index.

Age Factors↗
PubMed1975

Hepatic metabolism of genetically diabetic (db/db) mice. I. Carbohydrate metabolism.

Hepatic carbohydrate metabolism in genetically diabetic mice (db/db) and their normal littermates has been studied. In db/db mice, body water was below normal and declined with age. The liver of db/db mice was abnormally large in relation to the metabolic mass of the body at all ages studied. In db/db mice, hepatic glycogenolysis, glycogen synthesis, glycogen synthetase, and phosphorylase were markedly increased. Gluconeogenesis from alanine or lactate in perfused livers of db/db mice was greater than normal per 100 g body water. Activities of fructose-1, 6-biophosphatase, glucose-6-phosphatase, glucokinase + hexokinase, and pyruvate kinase were elevated in livers of db/db mice. Diabetic mouse livers perfused with lactate showed a markedly reduced concentration of P-enolpyruvate and clear "forward crossover" between fructose-1, 6-P2 and fructose-6-P. In vivo glucose clearance, measured with [3-3H]glucose, in db/db mice was 170% that of normal mice. Data presented indicate that in livers of db/db mice: 1) glucose production is elevated prior to hyperglycemia, 2) glycogen turns over more rapidly, and 3) glycolytic and gluconeogenic enzymes are elevated paradoxically. These abnormalities are discussed from the viewpoint of their etiology.

Animals↗