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Biomedical subjects

J Hokanson

Publications and source records attributed to J Hokanson.

13 recordsLinked to original sources

Expression of the neutrophil chemokine KC in the colon of mice with enterocolitis and by intestinal epithelial cell lines: effects of flora and proinflammatory cytokines.

IL-10 plays an important role in preventing excessive inflammation to the normal flora in the intestinal lumen. The purpose of this study was to compare the effect of normal flora on inflammation in mice in which the IL-10 gene was disrupted. IL-10 knock-out mice housed in germfree conditions remained healthy while those housed in conventional conditions developed colitis after weaning, suggesting that IL-10 inhibits the adverse responses to luminal Ag. Crypt abscesses were present in virtually all of the diseased animals as evidenced by flattening of the epithelial cells and a large number of neutrophils in the lumen of the crypt. Since KC is a chemokine that is capable of recruiting neutrophils in mice, mRNA and protein for KC was measured. Increased levels of both KC mRNA and protein were detected in the colon of diseased mice. To determine whether the epithelial cells were capable of synthesizing KC and contributing to neutrophil accumulation in the crypts, a murine intestinal epithelial cell line (Mode-K) was shown to express mRNA and protein for KC. Two cytokines induced in association with colitis in these mice, TNF-alpha and IFN-gamma, increased the expression of KC mRNA and protein in murine epithelial cells. However, IL-10 was incapable of decreasing the induction of KC, even though the cells expressed the IL-10 receptor. These results suggest that the neutrophil chemokine KC is produced by gastrointestinal epithelial cells in response to inflammatory mediators that are expressed following exposure to normal flora in animals lacking IL-10.

Age Factors↗

Cold acclimation and endurance training in guinea pigs: changes in daily and maximal metabolism.

The physiological effects of training or cold acclimation on maximal oxygen uptake (VO2,max) and average daily metabolic rate (VO2,dav) of a small mammal, the guinea pig, are described. Young male guinea pigs were assigned to three experimental groups; control, endurance trained (70% VO2,max) or cold acclimated (5-7 degrees C) for six weeks. Measurements of VO2,max and VO2,dav were made before and after the treatments. VO2,max increased significantly in cold acclimated (+29%) and endurance trained (+23%) animals and was achieved at a higher maximal running speed compared to post-treatment controls. Maximal blood lactate concentration was significantly higher in cold acclimated compared to endurance trained animals. Endurance trained animals had a reduced VO2,dav compared to control animals, whereas cold acclimation raised VO2,dav in the cold as expected, but also at room temperature. All three groups showed a daily pattern in metabolic rate (night > day). In conclusion, both endurance training and cold acclimation lead to enhanced VO2,max and changes in resting oxygen consumption throughout the day.

Acclimatization↗

Cold acclimation and endurance training in guinea pigs: changes in lung, muscle and brown fat tissue.

The effects of an intermittent high intensity stimulus (running) or a chronic low intensity stimulus (cold acclimation) of oxidative metabolism on maximal oxygen uptake (VO2,max), lung O2 diffusing capacity (DLO2) and skeletal muscle as well as fat tissue mitochondrial content in growing guinea pigs are described. Young male guinea pigs were assigned to three experimental groups (n = 5): control (C), endurance trained (T; at 70% VO2max) or cold acclimated (CA; 5-7 degrees C) for six weeks. Animals were sacrificed at the end of the experimental period and tissue for morphometric analysis of the lung, muscle and interscapular fat was sampled. T and CA animals significantly increased weight specific VO2max by 23% and 29%, respectively. Despite a significant increase in absolute lung volume in T (+10%) and in weight specific lung volume in CA (+20%) neither absolute nor weight specific DLO2 was significantly affected by the experimental treatments. In trained animals the total volume of mitochondria remained unchanged in samples representative for the entire musculature but was significantly increased in M. vastus intermedius (+72%). Intramyocellular lipids increased significantly both in M. vastus intermedius (+244%) as well as in the whole body musculature (+164%). Cold acclimation increased the mitochondrial content of the interscapular fat pad by approximately 20-fold but had no effect on total mitochondrial volume in muscle. We conclude that the increase in oxygen demand resulting from exercise training or from cold acclimation could be accomodated by the existing lung diffusing capacity and did not induce a global change of oxidative capacity in skeletal muscle tissue in growing guinea pigs. Exercise training caused oxidative capacity to increase only in a locomotor muscle activated during running whereas cold acclimation greatly increased interscapular fat tissue oxidative capacity.

Acclimatization↗

Cytomegalovirus-enhanced induction of chromosome aberrations in human peripheral blood lymphocytes treated with potent genotoxic agents.

Human cytomegalovirus (HCMV) has been shown to increase the frequency of chromosome aberrations, primarily chromatid-type, in human peripheral blood lymphocytes (PBLs). Because HCMV persists in most humans, pathologically activates cells, and may perturb the cell cycle, we investigated the possibility that HCMV-infected cells have a modified sensitivity to chromosome damage induced by genotoxic chemicals. Uninfected PBLs exposed to bleomycin (3 to 100 micrograms/ml) demonstrated a linear increase in the frequency of chromosome aberrations. HCMV infection of PBLs at an intensity that did not cause detectable damage followed by exposure to the same concentrations of bleomycin resulted in a significant enhancement (p less than 0.01) in the frequency of chromosome aberrations relative to the effect of bleomycin alone. A more than additive enhancement of the frequency of chromosome aberrations was also noted in HCMV-infected PBLs exposed to 4-hydroxyaminoquinoline-1-oxide (4-HAQO; 0.1 to 0.3 micrograms/ml) relative to uninfected cells treated with 4-HAQO alone. No increase in the percentage of aberrant cells or the frequency of chromosome aberrations was observed in HCMV-infected cells treated with 4-nitroquinoline-1-oxide (4-NQO) relative to similarly treated uninfected PBLs. These results suggest that HCMV can potentiate the induction of chromosome aberrations in human PBLs caused by potent DNA damaging agents.

4-Hydroxyaminoquinoline-1-oxide↗

Fibroblast growth factor reserves the bacterial retardation of wound contraction.

Chronic granulating wounds were established in rats by excising burns inoculated with Escherichia coli. Recombinant human basic fibroblast growth factor was applied at dosages of 1, 10, and 100 micrograms/cm2 to the wounds of three groups of 20 animals on days 5, 9, 12, 15, and 18 after injury. The rate of wound closure was compared with that of similarly wounded animals treated with saline vehicle alone. High levels of bacteria caused significant retardation of wound contraction. The addition of basic fibroblast growth factor at the 100 micrograms/cm2 dosage level markedly improved the rate of wound closure whereas inert vehicles applied alone were ineffective. Since bacterial counts did not decrease in the basic fibroblast growth factor treated wounds, basic fibroblast growth factor was not inherently bactericidal. Histologic examination of the wounds treated with basic fibroblast growth factor showed increased cellularity with increased numbers of fibroblasts and round cells. These results suggest basic fibroblast growth factor can overcome the defect in healing created by bacterial infection, and this peptide may have efficacy in the management of the contaminated wound.

Animals↗

Use of red blood cells older than five days for neonatal transfusion.

Sick neonates often require periodic small volume transfusions (10 mL/kg) to replace blood drawn for laboratory monitoring during their hospital stay. We use red blood cells (RBCs), stored as CPDA-1 whole blood, up to their expiration date, and are unaware of any clinical problems with this practice. We proceeded to confirm our clinical impression by reviewing the hospital records of 22 transfused neonates who received a median of 2.5 RBC transfusions (range 1 to 11) with a volume of 16 mL (range 5 to 38) each, and total volume of 60 mL (range 16 to 152). The RBCs were stored a median of 7 days (range 2 to 27). Following transfusion, there was an increase (P less than .05) in hemoglobin (mean 2.8 +/- 1.6 gm/dL [SD]) and hematocrit (9.0% +/- 4.7%). The bilirubin also rose (0.6 +/- 1.5 mg/dL, P less than .05), but this was not considered clinically significant. No significant change occurred in pH or bicarbonate. Paradoxically, RBCs over 10 days of age resulted in a fall in potassium (-0.9 +/- 0.8 mEq/L, P less than .01), but not below 3.4 mEq/L. We could find no evidence by clinical observation or laboratory indexes that small volume transfusion of RBCs more than 5 days old was deleterious to the newborns studied. By using RBCs up to their expiration date, the number of donor exposures and the potential risk of transfusion-transmitted diseases can be decreased.

Blood Preservation↗

Treatment of diabetic foot infections: Wagner classification, therapy, and outcome.

A total of 850 cases of septic diabetic foot infections were reviewed in 355 patients. Age, sex, other chronic diseases, site, etiology, Wagner grade, treatment, and results were analyzed. One third of the patients were in their sixth decade of life. There were 180 women and 175 men. Chronic diseases included hypertension, congestive heart disease, and renal failure. Staphylococcus aureus was the most common bacteria. Treatment was considered to meet protocol standards if Wagner's algorithms and infectious disease principles were followed. Thirty-nine Wagner grade 0 infections were seen: only one was not treated appropriately. Eighty-eight percent treated per protocol healed and the one not treated appropriately failed. In grade 1, 79% of the 154 evaluable patients were treated appropriately with a 86% success rate versus a 53% success rate for those not treated per protocol. Of three quarters of the 64 patients with grade 2 infections treated according to protocol, 73% healed. One of those in grade 2 who was not treated according to protocol healed. In grade 3, 64% of the 251 patients were treated per protocol with a 79% success rate versus a 12% success rate for those who were not treated per protocol. Most of the 189 patients with grade 4 cases were treated according to protocol with 88% success; the 20 not treated per protocol had a 15% success rate. Thirty of the 32 grade 5 patients were treated per protocol and all but one healed. Protocol therapy had a statistically significant effect by chi 2 test in the treatment of all groups.

Adult↗

The natural history of lung cancer with pericardial metastases.

Sixty-five lung cancer patients with pericardial metastases were reviewed. The diagnosis was established antemortem in 30 patients. Median survival of the treated group for pericardial metastasis from the date of primary diagnosis of lung cancer was 22.5 weeks. Patients who did not receive treatment had a median survival of 1.75 weeks (P 0.01). Median survival, in the treated group, from the date of pericardial metastases was 21 weeks. Prolonged survival was seen in those who had involvement of pericardium only as the site of first metastases. Median survival of this group was 32.5 weeks as opposed to those who had pericardial as well as other metastases whose survival was 17.25 weeks (P 0.03). Radiation therapy appeared to be the best modality of treatment in this group of patients.

Adenocarcinoma↗

Bronchiolar wall changes in sudden infant death syndrome: morphometric study of a new observation.

Sudden infant death syndrome (SIDS) infants have significantly thicker and more cellular bronchiolar walls than control infants of similar age. A morphometric study of 25 SIDS and 18 control infants was undertaken to measure the bronchiolar wall thickness using a Cue-2 image analysis system. A mathematical formula (relative index) was used to compare the thickness of bronchioles of varying diameter. Data analysis using a nested design two-way analysis of variance and covariance of the measured bronchioles showed a significant difference between the SIDS and control infants with a P value less than .001. Manual counting of the cells in the bronchiolar walls and data analysis using an unpaired two-tailed t test showed that the SIDS infants had a significantly greater number of cells than control infants (P less than .01). Our preliminary results indicate that the cells in the bronchiolar wall are either peripheral nerve-derived (Schwann cells) or Langerhans cells. We postulate that these cells are increased in number in response to chronic hypoxia in SIDS infants.

Bronchi↗