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We examined the role of C activation in ischemia reperfusion injury by inhibiting C activation in a rat model of mesenteric arterial occlusion. In anesthetized rats, 60 min of mesenteric arterial occlusion was followed by 3 h of reperfusion. PBS alone or containing soluble C receptor 1 (3 or 6 mg) was administered i.v. Controls underwent laparotomy without ischemia. Relative serum C activities were assessed by hemolytic assay, neutrophil (polymorphonuclear leukocyte) sequestration by tissue content of myeloperoxidase (MPO) activity, intestinal mucosal injury by histologic grading, lung vascular permeability by the ratio of bronchoalveolar lavage to blood concentration of radiolabeled BSA, and endothelial cell injury was quantified by measurement of plasma factor VIII-related Ag. After reperfusion, PBS-treated animals had increased intestinal MPO (0.048 +/- 0.007 U/g) compared to sham (0.022 +/- 0.005 U/g (p less than 0.05)) and intestinal mucosal injury score (2.490 +/- 0.221) compared to sham (0.331 +/- 0.045 (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion reduced intestinal MPO (0.017 +/- 0.003 U/g (p less than 0.05)) and mucosal injury (1.733 +/- 0.168 (p less than 0.05)) compared to PBS control. PBS-treated animals also demonstrated increased lung MPO (0.314 +/- 0.025 U/g vs 0.085 +/- 0.018 in sham (p less than 0.05)) and increased lung permeability (bronchoalveolar lavage/blood cpm 11.32 +/- 1.35 x 10(-3) vs sham 2.22 +/- 0.19 x 10(-3) (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion or at reperfusion reduced the lung permeability (bronchoalveolar lavage/blood cpm 3.90 +/- 0.79 x 10(-3) and 5.08 +/- 0.75, respectively (both p less than 0.05)) compared to PBS control, but did not reduce lung MPO (0.342 +/- 0.031 U/g and 0.246 +/- 0.025), respectively. Treatment with sCR1 also reduced the release of factor VIII-related Ag, 5-day mortality, and C hemolytic activity. In this model, C is a major mediator of intestinal injury and extraintestinal injury.

Chronically neutropenic patients from a phase I/II protocol were studied for neutrophil (PMN) abnormalities related to therapeutic use of granulocyte-macrophage colony-stimulating factor (GM-CSF). We analyzed phenotype by flow cytometry to measure indirect immunofluorescent staining and activation of transcription by in situ hybridization. PMN count increased in seven of 17 patients. For the group, PMN expression of complement receptors, CR1 and CR3, increased after GM-CSF administration (P less than .005), while expression of class 1 and FcR III was stable. PMN from both of the patients studied by in situ hybridization demonstrated increased expression of CR1 transcript, which in one case coincided in time and intensity with the course of increased CR1 expression, while in the second case the presence of CR1 mRNA increased but lagged behind the increased CR1 protein expression. Thus, PMN activation was observed after GM-CSF infusion, as indicated by increased complement receptor expression. This effect was due both to translocation of receptors from a preformed intracellular pool to the cell surface, and to transcriptional regulation leading to increased receptor synthesis.

cDNA from the C4b-binding site of the human C3b/C4b receptor (CR1) was used to find homologous sequences in the guinea pig. This cDNA identified an 18S mRNA species in guinea pig spleen, but not liver. Probing of a guinea pig spleen cDNA library identified clones with identical 1.5-kb inserts, which also hybridized to mRNA in spleen, but not liver. Sequence analysis of the insert revealed a single long open-reading frame coding for a 20,000 Mr protein consisting of two short consensus repeat motifs homologous to human CR1, and unique sequence at the amino- and carboxy-terminals of the short consensus repeats. This sequence did not encode peptides with features of transmembrane domains or signal peptides. Antibody to this complement receptor-related protein-beta galactosidase fusion protein recognized a 20,000 Mr protein in SDS lysates of guinea pig spleen, lymph node, lymphocytes, neutrophils, and peritoneal macrophages. Immunoprecipitation of human serum by this antibody revealed an 180,000 Mr protein reacting both with the anti-guinea pig protein antibody and with anti-human CR1 antibody. Immunoprecipitation of guinea pig serum revealed no protein reacting with the anti-guinea pig protein antibody. Tissue staining of cultured peritoneal macrophages with this antibody showed intracellular staining, as opposed to membrane staining obtained with anti-guinea pig Ig antibody. The lack of membrane expression was confirmed by surface protein radiolabeling experiments and by fluorescent staining of surface proteins. Thus, we have identified a guinea pig protein with homology to human CR1, which may have an unusual property for this class of proteins in that it appears to be intracellular.

Direct release of CO 2 gas to achieve a cost-effective method of atmospheric CO 2 enrichment has not been proven feasible under field conditions. We hypothesized that greater efficiency of application would occur by applying CO 2 via carbonated water and that application would also result in beneficial modifications of the soil environment. Our objectives were to evaluate crop, soil, and atmospheric CO 2 responses to application of carbonated water under pressure through a drip irrigation system (...)

The dependence of intestinal ischemia-reperfusion injury on the classical complement pathway has been shown with the complement antagonist (sCR1) and complement-specific knockout mice. Using C5 deficient mice, we show that the membrane attack complex mediates local injury.Mice underwent intestinal ischemia-reperfusion. Albumin leak and histologic evidence were compared in wildtype mice, wildtypes treated with sCR1, neutrophil-depleted wildtypes, C5-deficient mice, and C5-deficient mice reconstituted with wildtype serum. Neutrophil tissue levels in injured C5-deficient and wildtype intestines were compared.C5-deficient mice had a reduction in injury similar to mice treated with sCR1. Injury was restored by reconstitution with wildtype serum. Wildtype injury was unaffected by neutrophil depletion. Injured intestines of C5-deficient and wildtype mice had similar neutrophil levels. Immunohistochemistry of wildtype and reconstituted C5-deficient mice demonstrated injured intestinal epithelium although C5-deficient mice and sCr1-treated mice were similar to sham mice.C5-deficient animals are protected from local injury. Injury is unaffected by neutrophil depletion, and the presence of neutrophils in injured tissue is independent of C5. Local injury is C5 dependent, but the action of C5a on granulocytes is not required. Therefore the membrane attack complex mediates local injury.

Endotoxin shock is a life-threatening syndrome associated with a Gram-negative infection and mediated by a systemic inflammatory response. As a major effector of inflammation, the complement system has been implicated in both the pathogenesis and the protection from endotoxin shock. To clarify the role of complement in endotoxin shock, we have used mice totally deficient in either complement component C3 or C4. We found that both the C3- and C4-deficient mice were significantly more sensitive to endotoxin than wild-type controls. The endotoxin-challenged complement-deficient mice failed to clear endotoxin efficiently from the circulation and this led to excess consumption of C1 inhibitor protein (C1 INH), a major regulator of both complement and the contact system of blood coagulation. Replacement of C1 INH rescued the endotoxin-challenged complement-deficient mice from shock and death. These findings suggest a novel therapy for treatment of endotoxemia with C1 INH protein.

The current trend toward the invasion of commerce into medical care, an arena formerly under the exclusive purview of physicians, is seen by the authors as an epic clash of cultures between commercial and professional traditions in the United States. Both have contributed to US society for centuries; both have much to offer in strengthening medical care and reducing costs. At the same time, this invasion by commercialism of an arena formerly governed by professionalism poses severe hazards to the care of the sick and the welfare of communities: the health of the public and the public health. Some of these hazards are briefly listed and reviewed, together with a brief outline of standards that might be established nationally to abate these hazards. A national agency in the private sector is proposed, the National Council on Medical Care, to set standards and provide an approval mechanism that would then be the basis for state enforcement through licensing. Two models for such an initiative are outlined, one based on the National Academy of Sciences as the initiating force, and the other on an initiative provided by a consortium of national charitable foundations interested in health policy. In both cases, wide support from the national foundations would be essential. In the case of the academy model, some government funds might also be available without loss of the freedom of a private-sector initiative. Some operational options for such a national council, its membership, and the conduct of its affairs are briefly outlined as a basis for further discussion.

Torsion of an intraabdominal testicular tumor is a rare event. We report a new case and review the literature.A review of the literature was carried out in order to identify reported cases of an intraabdominal testicular tumor undergoing torsion of its vascular pedicle. Data on histologic type, common presenting signs and symptoms, radiographic studies, and adjuvant therapy were tabulated.There are 36 reports of an intraabdominal testicular tumor presenting with torsion. The most common histologic types, in descending order, were seminoma, sarcoma, teratoma, embryonal carcinoma, and choriocarcinoma. Common presenting signs and symptoms included pain and/or tenderness, fever, nausea and/or vomiting, and a palpable mass. Most seminoma patients received adjuvant radiation therapy whereas one patient with choriocarcinoma received adjuvant chemotherapy.Although a rare event, the diagnosis of torsion of an intraabdominal testicular tumor should be considered in any patient presenting with an acute abdomen and a history of cryptorchidism. The presence of a mass may raise the index of suspicion. Preoperative investigation with computed tomography scanning may aid surgical planning.

The study of the intrinsic regulation of complement has uncovered a broad array of proteins with differing specificities and physicochemical properties. This will allow application of these proteins, native or modified, to the problem of controlling inflammation. The availability of sCR1, as the first such agent, has permitted further definition of those adverse clinical situations which are complement-dependent. The use of sCR1 as a drug might be anticipated in situations of thermal injury, ARDS, septic shock, and ischemia/reperfusion injury, such as myocardial infarction after thrombolytic therapy. sCR1 may also serve as the tool with which to unravel and possibly treat xenograft rejection. It can be anticipated that other such specific inhibitors will become available.

One hundred and twelve bilateral thyroidectomies for solitary thyroid nodules with suspected malignancy were performed. The incidence of malignancy in the 112 primary nodules was 42%. Twenty-nine of the 112 contralateral lobes (26%) contained malignancy, which was unsuspected in 80%. Of these 29, 20 were foci of papillary canceror = 5 mm and 9 were larger papillary tumors or follicular carcinoma. We analyzed these 112 patients to determine whether there was a simple method to identify those patients at risk for contralateral, unsuspected malignancy. With use of the AMES clinical staging retrospectively, 70 of the 112 patients were classified as having low-stage disease. Fifty percent (35) had cancers on the primary side and 27% (19) on the contralateral side. Of these 19 contralateral cancers, 14 were papillary cancersor = 5 mm, 4 were papillary cancer5 mm and one was a 1.5 cm follicular carcinoma, a similar distribution as in the whole group of 112. When the AMES analysis then excluded those thought to be at risk for multicentricity or papillary carcinoma and examined female patients only with nonpapillary frozen sections, nonpapillary aspiration cytological results, and no history of radiation exposure, no further reduction in the proportion of contralateral cancers (7 of 26, 27%) was found. Fifty-five of the 112 patients underwent preoperative ultrasound scans. In those cases in whom the contralateral lobe had no intraoperative palpable or preoperative sonographic mass, 5 of 20 still had contralateral cancers, but all were papillaryor = 5 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

We examined the role of C activation in ischemia reperfusion injury by inhibiting C activation in a rat model of mesenteric arterial occlusion. In anesthetized rats, 60 min of mesenteric arterial occlusion was followed by 3 h of reperfusion. PBS alone or containing soluble C receptor 1 (3 or 6 mg) was administered i.v. Controls underwent laparotomy without ischemia. Relative serum C activities were assessed by hemolytic assay, neutrophil (polymorphonuclear leukocyte) sequestration by tissue content of myeloperoxidase (MPO) activity, intestinal mucosal injury by histologic grading, lung vascular permeability by the ratio of bronchoalveolar lavage to blood concentration of radiolabeled BSA, and endothelial cell injury was quantified by measurement of plasma factor VIII-related Ag. After reperfusion, PBS-treated animals had increased intestinal MPO (0.048 +/- 0.007 U/g) compared to sham (0.022 +/- 0.005 U/g (p less than 0.05)) and intestinal mucosal injury score (2.490 +/- 0.221) compared to sham (0.331 +/- 0.045 (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion reduced intestinal MPO (0.017 +/- 0.003 U/g (p less than 0.05)) and mucosal injury (1.733 +/- 0.168 (p less than 0.05)) compared to PBS control. PBS-treated animals also demonstrated increased lung MPO (0.314 +/- 0.025 U/g vs 0.085 +/- 0.018 in sham (p less than 0.05)) and increased lung permeability (bronchoalveolar lavage/blood cpm 11.32 +/- 1.35 x 10(-3) vs sham 2.22 +/- 0.19 x 10(-3) (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion or at reperfusion reduced the lung permeability (bronchoalveolar lavage/blood cpm 3.90 +/- 0.79 x 10(-3) and 5.08 +/- 0.75, respectively (both p less than 0.05)) compared to PBS control, but did not reduce lung MPO (0.342 +/- 0.031 U/g and 0.246 +/- 0.025), respectively. Treatment with sCR1 also reduced the release of factor VIII-related Ag, 5-day mortality, and C hemolytic activity. In this model, C is a major mediator of intestinal injury and extraintestinal injury.

The Richards function serves as a tool for growth (W) analysis by means of absolute growth rate (AGR), i.e. dW/dt, and relative growth rate (RGR), i.e. d(loge W)/dt. More information may be gained using the second derivative d2W/dt2, and the third derivative d3W/dt3 of the Richards function to determine the times when the second derivative time curve achieves a maximum, minimum, and zero. The latter separates growth acceleration and retardation. Exponential growth occurs as long as (RGR)2 is less than the relative acceleration rate added to a tolerance value. This period of growth does not extend to the point of maximum acceleration of the growth curve. The points of maximum and minimum acceleration are at equal time distances from the point of inflection. A straight line phase of growth is approximated between the times when d2W/dt2 is maximum and minimum. Thus, a mathematical model for the analysis of aging changes is presented. Methodology described here should be applicable to any biological system or subsystem. As an application, derivatives of the Richards function are used to provide information on potato (Solanum tuberosum L.) tuber kinetics.

cDNA from the C4b-binding site of the human C3b/C4b receptor (CR1) was used to find homologous sequences in the guinea pig. This cDNA identified an 18S mRNA species in guinea pig spleen, but not liver. Probing of a guinea pig spleen cDNA library identified clones with identical 1.5-kb inserts, which also hybridized to mRNA in spleen, but not liver. Sequence analysis of the insert revealed a single long open-reading frame coding for a 20,000 Mr protein consisting of two short consensus repeat motifs homologous to human CR1, and unique sequence at the amino- and carboxy-terminals of the short consensus repeats. This sequence did not encode peptides with features of transmembrane domains or signal peptides. Antibody to this complement receptor-related protein-beta galactosidase fusion protein recognized a 20,000 Mr protein in SDS lysates of guinea pig spleen, lymph node, lymphocytes, neutrophils, and peritoneal macrophages. Immunoprecipitation of human serum by this antibody revealed an 180,000 Mr protein reacting both with the anti-guinea pig protein antibody and with anti-human CR1 antibody. Immunoprecipitation of guinea pig serum revealed no protein reacting with the anti-guinea pig protein antibody. Tissue staining of cultured peritoneal macrophages with this antibody showed intracellular staining, as opposed to membrane staining obtained with anti-guinea pig Ig antibody. The lack of membrane expression was confirmed by surface protein radiolabeling experiments and by fluorescent staining of surface proteins. Thus, we have identified a guinea pig protein with homology to human CR1, which may have an unusual property for this class of proteins in that it appears to be intracellular.

To glimpse what lies beyond our horizon, it is wise to examine the terrain from whence we come. Since World War II, surgical research has functioned in four modes.

Carbon dioxide concentrations measured within and above a strawberry plant (Fragaria × ananassa) canopy were significantly higher during enrichment with carbonated water or 900 kg CO2 ha-1 hr-1 applied as gas. Both sources were applied to the base of the plants through drip irrigation tubing under a black polyethylene mulch (0.025 mm) covering or over bare unmulched soil. Mulch affected the concentrations at the top of the strawberry canopy differently for the two sources of CO2 enrichment. Carbonated water was found to reduce the pH of the calcareous soil at the research site (pH 8.2) during and between irrigations. The greatest single pH reduction was 2.6 pH units during irrigation measured in mulched soil; significant soil pH reductions were detected as long as 28 days after irrigation underneath the mulch. Soil pH “duration” below pH 7.4 was 70% greater considering mulch and carbonated water vs. no mulch and carbonated water irrigation.

An index “internal slope” derived from the cumulative frequency distribution of individual seed leachate conductivities is related to seed quality; the larger the index value the less variation among individual seeds in a sample (100 seeds) and the higher the seed quality. We have recently developed data acquisition/instrurment control/data smoothing/data analysis software which accesses frequency and cumulative frequency distributions of individual seed conductivities and the derived index on an almost continuous basis from the start of the first soaking.At present, lack of convergence with regard to curve fitting may occur necessitating multiple sampling times. A “window in time” approach is described whereby index estimates during a two-hour interval within the index stability phase are averaged. Evidence of the method's ability to assess seed vigor will be presented.

Activation of the human alternative pathway of complement (C) by surfaces requires the initial deposition of C3b by fluid-phase C3 convertase and sustained C3 cleavage by C3 convertases fixed to the surface. Nonactivating particles have previously been characterized by an inability to sustain the function of C3 convertases on their surfaces because these sites were susceptible to the regulatory action of the control proteins. Pronase converts the mouse erythrocyte (E) from an activator to a nonactivator by markedly decreasing the ability of the cell to affix C3b generated by a fluid-phase C3 convertase; this conversion is unrelated to the action of the control proteins on bound C3b. The capacity of antibody and its F(ab')2 or Fab' fragments to restore the alternative pathway-activating function of pronase-treated mouse E indicates that the contribution of antibody is mediated by its combining site without a requirement for bridging or for the Fc portion. The fab'-dependent activation of the alternative pathway of C relates to the deposition of C3b on the particle surface, which is a first and continuing step in alternative pathway activation. The antibody effect is not directed to the action of the regulatory proteins. Thus, particle-dependent activation of the alternative C pathway has been shown for the first time to be abolished and restored by cell surface-directed mechanisms that function independently of the regulatory proteins.

An experimental design developed usingAcetabularia permits a novel approach to studies of cytoplasmic genetic functions. The site of the genes for the enzymes of the plastid pigment pathways were examined by 1. determining pigment content per cell and per chloroplast in intact cells and during long periods of enucleate cell growth, 2. comparing pigment synthetic activities of plastids isolated from intact and enucleate cells at various times postenucleation and 3. comparing the ability of intact and enucleate cells to modulate pigment content in response to various light regimens.

A linear polynomial model is presented $$Y = \beta _0 + \beta _1 X_1 + \beta _2 X_2 + \beta _3 X_3 + \xi $$ where Y = plant yield of tubers > 1 cm diameter, X1 = revised growing degree days $$\begin{gathered} RGDD = \frac{{max temp \left( { \leqslant 30^ \circ C} \right) + \min temp \left( { \geqslant 4.4^ \circ C} \right)}}{2} - 4.4^ \circ C \hfill \\ - \frac{{min temp \left( { > 4.4^ \circ C} \right) - 4.4^ \circ C}}{2} \hfill \\ \end{gathered} $$ X2 = total insolation in cal cm-2 at 350 to 1150 nm and X3 = mean daily air temperature range in °C. The β0 and ξ, (Y intercept and error term) and β1, β2 and β3 coefficients are derived from fitting the experimental data. The model was developed by growing ‘Kennebec’ in large containers at sites ranging from 1533 m to 3198 m elevation under shaded (48% insolation reduction) and unshaded conditions at 39° to 41° N latitude. Mean maximum and minimum temperatures and insolation ranged from 29°C to 19°C, 14°C to 6°C, and 200 cal cm−2 day−1 to 530 cal cm2 day−1 respectively. Soil matric potential and soil fertility were not included as variables in the model since they were physically controlled. The model does not include the period from planting to emergence since environment was not permitted to vary differentially. A highly significant multiple linear model with a coefficient of determination of 0.93 was obtained. It is suggested that including the revision $$ - \frac{{min temp \left( { > 4.4^ \circ C} \right) - 4.4^ \circ C}}{2}$$ in the heat input estimation (GDD) as well as air temperature range, emphasizes the influence of respiration on productivity. The model should be tested further and adapted as a practical method for predicting potato yield under “grower” conditions.

Performance of raw seeds of 2 lettuce, Lactuca sativa L., cultivars was compared with that of seeds from the same lots that had received 7 different seed coatings. Total emergence and coefficient of variability Of plant weights at 20 days were equal for coated and raw seeds in most instances. Coated seeds emerged 1 to 2 days later than raw seed and resulted in lower seedling weights. Seed coatings make possible precision planting of lettuce with apparently no sacrifice in overall performance.

Potato tubers of Solanum tuberosum cv. Kennebec, produced at elevations from 1533 to 3198 m at 2 levels of insolation per site were grown in a greenhouse at 1533 m to determine the effect of the parental clone's environment on the performance of the succeeding generation. Rate of emergence, early vegetative growth, and tuber growth increased with increasing elevation of the parental clone but there was no significant difference in vegetative growth or tuber yield at vine senescence. The environment of the parental clone had no direct influence on the photosynthetic activity of the clonal progeny, but an inverse relationship between bulking efficiency and altitude of seed tuber production was evident. Shading of the parental clone at each elevation had little influence on the succeeding generation.

Water and nitrogen loss from field soil cropped to head lettuce with furrow irrigation was measured during three seasons in a semi-arid region. Water applications were reduced during the latter ⅓ of the growth period in an attempt to conserve N and water in the root zone. Approximately 5 acre feet of water was applied to grow the crop. One-fifth of the applied water drained off and one-half percolated below the root zone. Eighty-nine lb./acre of NO3-N was leached. Two-thirds of the water and three-fourths of the N (soil and applied) which were lost below the root zone were lost during germination. Reducing the total volume of water applied by 1½ acre feet did not reduce water or N loss appreciably and had a deleterious effect on the crop. Very little N was lost as a result of runoff, but much was moved to the bed tops after the first irrigation. Implications of these findings are discussed.

Activation of the human alternative pathway of complement (C) by surfaces requires the initial deposition of C3b by fluid-phase C3 convertase and sustained C3 cleavage by C3 convertases fixed to the surface. Nonactivating particles have previously been characterized by an inability to sustain the function of C3 convertases on their surfaces because these sites were susceptible to the regulatory action of the control proteins. Pronase converts the mouse erythrocyte (E) from an activator to a nonactivator by markedly decreasing the ability of the cell to affix C3b generated by a fluid-phase C3 convertase; this conversion is unrelated to the action of the control proteins on bound C3b. The capacity of antibody and its F(ab')2 or Fab' fragments to restore the alternative pathway-activating function of pronase-treated mouse E indicates that the contribution of antibody is mediated by its combining site without a requirement for bridging or for the Fc portion. The fab'-dependent activation of the alternative pathway of C relates to the deposition of C3b on the particle surface, which is a first and continuing step in alternative pathway activation. The antibody effect is not directed to the action of the regulatory proteins. Thus, particle-dependent activation of the alternative C pathway has been shown for the first time to be abolished and restored by cell surface-directed mechanisms that function independently of the regulatory proteins.

In five typical hospitals, and a specialized treatment center, more than half of all patients--and 60 percent of all costs--were attributable to repeated admissions for the same disease. The fiscal and clinical nature of repeated hospitalization suggests changes for national health policy. These will require more sensitive identification of patients "at risk" of recidivism, and insurance mechanisms that relate more rationally and equitably to long-term needs.