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Biomedical subjects

M M Ziegler

Publications and source records attributed to M M Ziegler.

At least 19 recordsLinked to original sources
PubMed1992

Impairment of macrophage activation and granuloma formation by protein deprivation in mice.

Protein-calorie malnutrition predisposes to infection by intracellular pathogens, but the basis for this predisposition is unclear. We studied the effect of protein deprivation on mouse peritoneal macrophage function and on granuloma formation during infection by bacille Calmette-Gueŕin (BCG). Injection of lipopolysaccharide (LPS) to induce inflammation elicited fewer peritoneal cells from mice fed a 2.5% protein diet than from mice fed an isocaloric chow in which protein calories constituted 24% of the total. LPS-elicited macrophages from protein-deprived mice demonstrated a reduction in spreading, total cell protein, cell lactate dehydrogenase, and release of superoxide anion (O2-) in response to stimulation. Priming in vitro by interferon (IFN)-gamma for enhanced release of O2- was also significantly impaired in protein-deprived mice. This defect was reversible by repletion with 24% protein diet for 10 days. Impairment of macrophage function in protein-deprived mice was further evidenced by an impaired capacity to express Ia antigen in response to IFN-gamma and by reduced production of IL-1 activity in response to LPS. Infection by BCG in protein-deprived mice was characterized by impaired granuloma development in liver, lungs, and spleen. Thus, in this model, protein deprivation significantly impaired macrophage activation, as assessed by morphologic, metabolic, and functional criteria. This impairment might compromise immune effector mechanisms dependent on macrophage activation, including rejection of intracellular pathogens.

Animals↗
PubMed1992

Establishment of animal liver metastatic model for C-1300 murine neuroblastoma and immunotherapy for it using OK-432, streptococcus preparation.

Intrasplenic administration of 1 x 10(6) C-1300 murine neuroblastoma cells induced spleen tumor in 78.6% of mice and liver metastasis in 64.3%. When mice were pretreated with carrageenan, an antimacrophage agent, the incidence of spleen and liver tumors in this system was lower, possibly due to the rebound increase in macrophage activity following the disappearance of the carrageenan effect. Continuous daily intraabdominal injection of 1 KE of OK-432 streptococcus preparation markedly reduced the appearance of liver metastasis (P less than 0.01), whereas the spleen mass was not reduced to such an extent. However, the survival rate of the OK-432-treated group did not differ greatly from that of the nontreated group. These results demonstrate the usefulness of the model of liver metastasis induced by intrasplenic administration of tumor cells and the effectiveness of OK-432 against liver metastasis formation.

Animals↗
PubMed1992

Management and survival of meconium ileus. A 30-year review.

Cystic fibrosis patients born with meconium ileus (MI) have had an improved outcome over the last three decades. The authors reviewed the impact of surgical management and long-term nutritional care on the survival of patients with MI. Of the 59 cases of MI seen from 1959 to 1989, 48 cases were managed operatively using either the Bishop-Koop ileostomy (BK), the Mikulicz ileostomy, primary resection and anastomosis (RA), or ileostomy. Six-month survival of MI has improved from 37% to 100%. Nonoperative cases (n = 11) had 100% long-term survival. The RA survivors required less late operative intervention (20%) as compared with other surgical patients (81%). A comparison of serial growth percentiles of CF patients with MI with those of their non-MI CF peers showed similar long-term decreases. These data confirm: (1) There is an improved survival for MI independent of the surgical procedure; (2) The BK ileostomy is an effective and time-tested MI treatment; (3) Primary resection and anastomosis in selected cases may have a lower surgical morbidity rate; and (4) Meconium ileus does not adversely affect the long-term nutritional outcome of CF patients.

Chi-Square Distribution↗
PubMed1991

Low-dose interferon gamma renders neuroblastoma more susceptible to interleukin-2 immunotherapy.

Neuroblastoma remains a common and deadly childhood tumor, resistant to both surgical and chemo/radiotherapeutic intervention in its advanced stages. The role of immunotherapy in such cancers has yet to be defined. In previous work, we found that the addition of interferon gamma (IFN-gamma) to 3-day in vitro tissue cultures of the murine neuroblastoma C1300, led not only to the tumor's increased cell surface expression of the immunologically important major histocompatibility complex (MHC) class I antigen, but also to an increased susceptibility of such modified tumor to subsequent lymphokine activated killer (LAK) cell lysis. In this study, we sought to determine the in vivo applicability of these findings. Initial dose-response studies helped define a regimen of rIFN-gamma's administration that upregulated MHC class I without activating host natural killer (NK) activity. A/J mice bearing 7-day-old subcutaneous C1300 were randomized to receive daily morning injections of either 0, 25,000, 50,000, or 100,000 U of rIFN-gamma intraperitoneally for 6 days. Animals were killed at days 3, 6, and 9 after initiation of rIFN-gamma therapy, and tumors were excised, digested, and stained for both MHC class I and II expression. At the time of sacrifice, splenocytes from each animal were tested for NK cytotoxicity toward YAC (an NK-sensitive lymphoma) and C1300. These studies defined 3 days of therapy with 25,000 U as a "priming" dose that increased expression of class I with minimal impact on NK activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

The role of reperfusion injury in occlusive intestinal ischemia of the neonate: malonaldehyde-derived fluorescent products and correlation of histology.

Oxygen free radical reperfusion products may play a critical role in neonatal occlusive intestinal ischemia. We report a comparative analysis of light microscopy- and malonaldehyde (MDA)-derived fluorescent products as a measure of lipid peroxidation in occlusive intestinal ischemia in the rat. Weanling rats (n = 25) underwent cross clamping of the common mesenteric artery followed by various intervals of reperfusion; blood was sampled from the common mesenteric vein and the ileum was simultaneously biopsied. Blind-light microscopic scoring of the ischemic intestine was used. Fluorescent products were extracted using a chloroform/methanol/acidic water solvent extraction and measured with a spectrophotofluorometer using excitation/emission wavelengths of 360 and 430 nm, respectively. A trend was observed with prolonged reperfusion. Accumulation of fluorescent products correlated directly with the interval of reperfusion. Graded intervals of vascular occlusion produced progressive intestinal injury, but light microscopic analysis was not a sensitive index to distinguish the influence of graded reperfusion intervals. These data confirm a role for both ischemia and reperfusion in occlusive intestinal injury in the neonate and suggest that MDA accumulation may be a sensitive index of the reperfusion component of such injury.

Animals↗
PubMed1991

Influence of nutrition on anti-tumor activity.

Nutritionally supporting the malnourished tumor bearing host may not benefit the disease outcome, but, rather, may preferentially "feed the cancer". We hypothesized that repletion is beneficial only when it augments an anti-tumor immune response. To support this hypothesis, 240 A/J mice were assigned to isocaloric dietary groups (24%, 5%, or 2.5% protein). On day 14 the mice received either immunogenic C1300- neuroblastoma (NB) or non-immunizing TBJ-NB. On day 21 half of the restricted animals were repleted with 24% protein chow. At day 35, chromium-release cell-mediated cytotoxicity was measured. In the group of mice that received 2.5% protein chow, nutritional repletion specifically augmented anti-tumor activity for C1300-NB which elicits a host immune response (33.78 L.U. (repleted) vs 3.47 L.U. (depleted) p less than 0.01), in contrast, nutritional repletion was detrimental for non-immunizing TBJ-NB, where further depression of cytotoxicity was seen (1.37 L.U. (repleted) vs 2.06 L.U. (depleted) 0 less than 0.01). This suggests that the influence of nutritional repletion in tumor nearing animals is dependent on the integrity of host's anti-tumor immunity.

Animals↗
PubMed1990

Tumor immunization. Improved results after vaccine modified with recombinant interferon gamma.

The purpose of this study was to determine if a 3-day in vitro culture of the murine neuroblastoma C1300 with 500 U/mL of recombinant interferon gamma resulted in a protective crossreactivity to parent C1300. Twenty A/J mice received either a vaccine of 1 x 10(6) irradiated C1300 tumor cells intradermally or an equivalent inoculum of C1300 that had been incubated in recombinant interferon gamma (C1300*). One week later, all animals were rechallenged with 1 x 10(6) viable C1300. Animals immunized with C1300* had a significantly delayed early tumor incidence that translated into a survival advantage for the group. At the time of tumor rechallenge, a significantly increased level of nonspecific systemic immunity was conferred by the C1300* immunization. Thus, modification of tumor with recombinant interferon gamma before introduction as a vaccine may improve that vaccine's protective capability.

Animals↗
PubMed1990

Nutrition and cancer in children.

The information generated to date regarding the nutritional status of children with cancer indicates that malnutrition is seen in patients in the later stages of their malignant disease or is iatrogenic because of their intensive therapy. Malnourished children suffer from inadequate growth, including the potential of delayed cerebral development, and they are more susceptible to infection. Nutritional therapy has been shown to reverse the malnutrition independent of the cancer treatment. In doing so, the nutritional support aids in the delivery of and tolerance to the antitumor therapy. What is not possible, however, is making ineffective or marginally effective anticancer therapies effective by nutritional support. Therapy that is ineffective, such as chemotherapy for Stage III or IV neuroblastoma in children, cannot be altered by nutritional support. However, a patient's nutritional state may affect the disease outcome in that complication rates are much higher in malnourished patients. In such children with PCM, nutritional support may make delivery of therapy possible, but it will not affect the ultimate disease outcome unless the anticancer therapy is inherently successful. A well-nourished child is easier to treat and is physiologically more stable. Such children, therefore, have an improved prognosis and lower morbidity and mortality, provided effective therapy is available for the cancer.

Cachexia↗
PubMed1979

Sequelae of prolonged ventilatory support for pediatric surgical patients.

The evolution of intensive prolonged respiratory support has been a major development in improving survival in the critically-ill child. That intensive respiratory support can be maintained for prolonged periods of time even in the home with survival of good babies is the subject of this report. In a 3-yr period, 2112 surgical patients were admitted to intensive care facilities with an over-all survival of 95%. Ventilatory support was required in 368 (17.4%) of these children, and survival in this group was 75.3%. Prolonged mechanical ventilation was necessary in 13 of the 368 children (3.5%) for a mean support time of 359 days (range 101 to 1095). Of these 13 children, 4 died while hospitalized (30.8%), and 3 died subsequently after being discharged (23.1%) for a total mortality of 53.8%. However, 6 children (46.2%) survive, 3 free of ventilatory support and 3 being weaned from their machine at home. The greatest cost in this expensive program was delivered to the survivors and psycho-social and developmental data confirm that these children are good babies with favorable long-term prognoses.

Child↗
PubMed1979

Covalent structure of subunits of bacterial luciferase: NH2-terminal sequence demonstrates subunit homology.

The heterodimeric subunit structure of bacterial luciferase was demonstrated more than 10 years ago. The enzymes from both Beneckea harveyi and Photobacterium fischeri have since been studied in detail; they each consist of two nonidentical subunits, designated alpha and beta. Both are required for bioluminescence activity, with the active center apparently confined to the alpha subunit. Amino acid sequence analysis of the NH2 termini of the alpha and beta subunits of the B. harveyi and P. fischeri luciferases not only confirms the earlier observation that the alpha subunits are homologous but also demonstrates that the NH2-terminal sequences of the beta subunits of the luciferases from the two genera are homologous. Furthermore, within each luciferase, the NH2-terminal sequences of the alpha and beta subunits are similar, suggesting the possibility that the genes coding, for alpha and beta may have arisen by gene duplication, presumably prior to divergence of the lines leading to present-day luminous bacteria.

Amino Acid Sequence↗
PubMed1978

Mesenchymal hamartoma of the liver in infants.

Mesenchymal hamartoma of the liver is a rare benign tumor of childhood which has been confused with various other benign liver lesions, particularly vascular hamartomas which are mesodermal but not mesenchymal. The mass, frequently cystic, is characterized by an admixture of epithelial structures in a loose connective tissue stroma with fluid accumulation suggestive of lymphangiomatous channels. Four patients are presented and reviewed with 25 previously reported cases. The patients, usually asymptomatic, present during the first two years of life with progressive abdominal distention, which may be rapid because of increasing fluid content in the connective tissue stroma and cysts. Exploration and biopsy may be necessary before definitive excision. The present cases include a newborn, the youngest known, and a case in which radiation resulted in hyalinization of the mesenchyme, decrease in fluid content, and easlier resection. Respiratory distress and signs of vena caval obstruction due to intra-abdominal pressure were noted. Prognosis after extirpation is very good.

Diagnosis, Differential↗
PubMed1977

Surgical manifestations of eosinophilic gastroenteritis in the pediatric patient.

Eosinophilic gastroenteritis, an inflammatory bowel disease of unknown etiology, occurs in one of 10,000 admissions to this Children's Hospital. We had added 4 cases to the 11 retrieved from a literature review. The inflammation is characterized by mature eosinophils predominating a transmural process which may produce pain, obstruction, perforation, bleeding, or fistulae. All levels of the gastrointestinal tract are involved, but stomach (25.9%) and small bowel (66.7%) lesions are most common. Eosinophilia occurs in 61% of children and allergy in 13%. X-rays may demonstrate a diffuse or localized process. Operative intervention may be necessary to exclude tumors or regional enteritis, and at times to extirpate complications of local disease, but conservative therapy is the treatment of choice for this exacerbating-remitting disease.

Adolescent↗