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PubMed1989

Activation and binding of opsonic fragments of C3 on encapsulated Cryptococcus neoformans by using an alternative complement pathway reconstituted from six isolated proteins.

Encapsulated Cryptococcus neoformans yeast cells are potent activators of the complement system. We examined the interaction of the yeast cells with an alternative complement pathway reconstituted from isolated factor D, factor B, factor H, factor I, C3, and properdin. Incubation of encapsulated cryptococci with the reconstituted pathway led to activation and binding of C3 fragments to the yeast cells that was quantitatively and qualitatively identical to that observed with normal human serum. Incubation with either normal serum or a mixture of isolated proteins led to binding of 4 x 10(7) to 5 x 10(7) C3 molecules to the yeast cells. The kinetics for activation and binding of C3 were identical, with maximum binding observed after a 20-min incubation. Immunoglobulin G was not needed for optimal activation kinetics. C3 fragments eluted from the yeast cells by treatment with hydroxylamine and subsequent analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated the presence primarily of iC3b on yeast cells incubated with either normal serum or the reconstituted pathway. Ultrastructural examination of the opsonized yeast cells showed that the cryptococcal capsule was the site for binding of C3 activated from normal serum or the reconstituted pathway, with a dense accumulation of C3 at the periphery of the capsule. Thus, incubation of encapsulated cryptococci in the reconstituted pathway led to deposition of opsonic complement fragments at a site that was appropriate for interaction with phagocyte receptors. Cryptococci opsonized with the reconstituted pathway showed a markedly enhanced interaction with cultured human monocytes compared with unopsonized yeast cells, indicating that the alternative pathway alone is opsonic for yeast cells. However, the results indicate that additional serum factors are needed for optimal opsonization of yeast cells because a 35% reduction in the number of cryptococci bound to macrophages was observed with cryptococci opsonized with the reconstituted pathway compared with that observed when yeast cells were opsonized with normal serum.

Complement Activation↗

PubMed2001

Role of the classical pathway of complement activation in experimentally induced polymicrobial peritonitis.

The complement system and the natural antibody repertoire provide a critical first-line defense against infection. The binding of natural antibodies to microbial surfaces opsonizes invading microorganisms and activates complement via the classical pathway. Both defense systems cooperate within the innate immune response. We studied the role of the complement system in the host defense against experimental polymicrobial peritonitis using mice lacking either C1q or factor B and C2. The C1q-deficient mice lacked the classical pathway of complement activation. The factor B- and C2-deficient mice were known to lack the classical and alternative pathways, and we demonstrate here that these mice also lacked the lectin pathway of complement activation. Using inoculum doses adjusted to cause 42% mortality in the wild-type strain, none of the mice deficient in the three activation routes of complement (factor B and C2 deficient) survived (mortality of 100%). Mortality in mice deficient only in the classical pathway of complement activation (C1q deficient) was 83%. Application of further dilutions of the polymicrobial inoculum showed a dose-dependent decrease of mortality in wild-type controls, whereas no changes in mortality were observed in the two gene-targeted strains. These results demonstrate that the classical activation pathway is required for an effective antimicrobial immune defense in polymicrobial peritonitis and that, in the infection model used, the remaining antibody-independent complement activation routes (alternative and lectin pathways) provide a supporting line of defense to gain residual protection in classical pathway deficiency.

Animals↗

PubMed1992

Physiological substrate for antidromic reciprocating tachycardia. Prerequisite characteristics of the accessory pathway and atrioventricular conduction system.

BACKGROUND: Although the anatomic "substrate" for the occurrence of antidromic reciprocating tachycardia (ART) has been previously examined, the underlying physiological substrate for this unusual arrhythmia in patients with the Wolff-Parkinson-White syndrome has not been thoroughly characterized. METHODS AND RESULTS: The electrophysiological properties of the accessory pathway and normal ventriculoatrial conduction system in 30 patients with ART and a single accessory pathway were compared with those observed in a control group of 36 patients without this arrhythmia to elucidate the critical physiological substrate essential for the development and maintenance of ART. Inducible ART had a mean cycle length of 286 +/- 31 msec. The average retrograde ventriculoatrial conduction system effective refractory period in ART patients was significantly less than that in the control group (244 +/- 32 versus 291 +/- 46 msec, p = 0.0002). All of the ART patients showed retrograde conduction over the normal conduction system at cycle lengths of less than or equal to 360 msec; 23 had 1:1 conduction to less than or equal to 300 msec, and 16 showed 1:1 propagation at cycle lengths of less than or equal to 260 msec. The shortest cycle length accompanied by 1:1 retrograde propagation over the normal conduction system in patients with ART was also significantly less than that observed in the control group (274 +/- 39 versus 347 +/- 73 msec, p less than 0.001). The accessory pathway anterograde ERP in ART patients with 1:1 retrograde conduction over the normal ventriculoatrial conduction system at cycle lengths of less than or equal to 360 was significantly less than that seen in comparable control patients (247 +/- 23 versus 284 +/- 56 msec, p = 0.001), and the accessory pathway location was significantly further from the atrioventricular node in 21 patients with ART undergoing surgery than that in 22 operated control patients (3.8 +/- 0.8 versus 2.9 +/- 0.8 mapping units, p = 0.0025) who also had retrograde ventriculoatrial conduction to cycle lengths of less than or equal to 360 msec. No significant differences in anterograde atrioventricular conduction system properties, retrograde accessory pathway refractoriness, or shortest ventricular pacing cycle lengths maintaining 1:1 conduction via the accessory pathway were observed between groups. CONCLUSIONS: This quantitative characterization of the properties of conduction and refractoriness of both the accessory pathway and ventriculoatrial conduction system and the relation between these characteristics and the accessory pathway location in ART patients provides additional insight into the prerequisites for the initiation and maintenance of this rhythm disturbance.

Adult↗

PubMed1992

Localization of the fast and slow pathways in atrioventricular nodal reentrant tachycardia by intraoperative ice mapping.

BACKGROUND: Atrioventricular (AV) nodal reentrant tachycardia is classically described as a reentrant rhythm entirely contained within the compact AV node. Although the concepts of longitudinal dissociation of two intranodal pathways and a distal common pathway are accepted, the proximal portion of the circuit remains undefined. Current reports suggest that the two pathways may be separable by atrial tissue and not contained entirely within the compact node. METHODS AND RESULTS: We used an ice mapping method to demonstrate the slow and fast pathways of the reentrant circuit and their relation to the atrial septum around the AV node. Six patients with the usual form (slow-fast) of AV nodal reentrant tachycardia were mapped during surgery. In most patients, antegrade slow pathway localization was posterior and inferior to the compact AV node along the tricuspid annulus; in two patients, it was superior along the tendon of Todaro. Retrograde fast pathway localization was anterior or superior to the compact AV node in all patients. In all patients, anatomic distinction was made between the two pathways and the compact node. CONCLUSIONS: We conclude that no upper common pathway exists within the compact AV node in the usual type of nodal reentrant tachycardia and that the perinodal atrial tissue is a requisite part of the tachycardia circuit.

Adolescent↗

PubMed1990

Identification of early developing axon projections from spinal interneurons in the chick embryo with a neuron specific beta-tubulin antibody: evidence for a new 'pioneer' pathway in the spinal cord.

The early development of interneurons in the chick embryo spinal cord was studied using a monoclonal antibody against a neuron-specific beta-tubulin isoform. Early developing interneurons were divided into two cell groups on the basis of their location and the pattern of growth of their axons. One group is composed of cells that establish a primitive longitudinal pathway (PL-cells), whereas the other group contains cells constituting a circumferential pathway (C-cells). The onset of axonal development in both cell groups occurs at stage (st.) 15 (embryonic day, (E), 2) in the branchial segments, which is prior to axonogenesis of motoneurons. PL-cells develop in the region between the floor plate and the motoneuron nucleus. Their axons are the first neuronal processes ('pioneer axons') to arrive in the ventrolateral marginal zone and they project both rostrally and caudally to establish a primitive longitudinal association pathway at the ventrolateral surface of the neural tube. This pathway is formed before axons of C-cells arrive in the ventrolateral region. The first C-cells are initially located in the most dorsal portion of the neural tube, whereas later appearing C-cells are also located in both intermediate and ventral regions of the neural tube. The axons of C-cells project ventrally, without fasciculating, along the lateral border of the neural tube. Some of their axons enter the ipsilateral ventrolateral longitudinal pathway at st. 17. We often observed apparent contacts and interactions between preexisting axons of PL-cells and newly arriving axons of C-cells. The axons of commissural C-cells first enter the floor plate at st. 17 and cross the midline at st. 18. Axons of C cells begin to join the contralateral ventrolateral longitudinal pathway at st. 18+ to st. 19. In the floor plate region, contacts between growth cones and axons were often observed. However, axons in the floor plate at these stages were not fasciculated. These observations establish the timing and pattern of growth of axons from two specific populations of early developing interneurons in the chick spinal cord. Additionally, we have identified an early and apparently previously undescribed 'pioneer' pathway that constitutes the first longitudinal pathway in the chick spinal cord.

Animals↗

PubMed1998

The role of clinical pathways in reducing the economic burden of stroke.

Clinical pathways are a potentially beneficial, but largely untested, management strategy for both improving healthcare efficiency and decreasing costs while also maintaining or improving quality of care. Although relatively few clinical pathways for stroke have been described in the medical literature and although the reported benefits have been mixed, more and more hospitals are adopting clinical pathways as a management strategy for patients with stroke. In published clinical pathways for acute stroke, the following benefits have been reported: (i) reduced use of expensive diagnostic studies; (ii) fewer complications (particularly the frequency of urinary tract infections and aspiration pneumonia); (iii) reduced duration of hospital stay; (iv) reduced patient charges; and (v) lower mortality. However, these reported benefits are not consistent across all studies and some outcomes are highly correlated. Despite potential benefits, many clinical pathway programmes fail because of inadequate planning and shortcomings of implementation. Effective implementation of clinical pathways requires strong administrative and medical staff leadership, active participation of all clinical disciplines involved in the care of patients on the pathway, provision of regular feedback to clinicians, sufficient resources, improved documentation, incorporation of the entire episode of care into the pathway, integration with ongoing quality and utilisation management programmes, and periodic evaluation and modification.

Cerebrovascular Disorders↗

PubMedDate not supplied

Occupational therapy benchmarks within orthopedic (hip) critical pathways.

OBJECTIVE: This study examined patient performance benchmarks for occupational therapy within orthopedic (hip) critical pathways. METHOD: Eight orthopedic (hip) critical pathways gathered from occupational therapy practitioners working in hospital and rehabilitation settings were examined to determine commonalities and differences of occupational therapy benchmarks, disciplines involved, and identified allowable variances. A comparison and contrast matrix was developed to provide a visual means of reviewing the data. RESULTS: Nursing, physical therapy, and occupational therapy were disciplines consistently involved in the pathways. Activities of daily living related to self-care were the most consistently used occupational therapy benchmark within the sample pathways, and functional transfers were the second most-used benchmark. The remaining occupational therapy benchmarks varied, and little commonality was found in their use. Frequency of use also varied among the eight pathways. Five of eight pathways specifically coded variances, with the remaining three providing space for explanation of the variance. CONCLUSION: Although these eight orthopedic (hip) critical pathways included occupational therapy benchmarks, further development and definition of the role of occupational therapy within subsequent orthopedic (hip) critical pathways is needed.

Benchmarking↗

PubMed1999

Effects of implementation of 18 clinical pathways on costs and quality of care among patients undergoing urological surgery.

PURPOSE: We evaluated the effects on the costs and quality of care of implementation of 18 clinical pathways for urological operations. MATERIALS AND METHODS: From April 1997 to March 1998 patients undergoing 1 of 18 urological operations were treated according to clinical pathways. The outcomes in terms of length of hospital stay and admission charges of these patients were compared with those of patients treated between April 1996 and March 1997 before clinical pathways were implemented. We also selected 7 clinically relevant quality indicators to assess the quality of care before and after clinical pathway implementation. RESULTS: Of the 1,784 patients undergoing urological surgery from April 1997 to March 1998, 1,382 (77.5%) were treated according to 1 of the 18 clinical pathways. Before implementation 1,279 of 1,615 patients (79.2%) underwent these procedures. The length of hospital stay decreased from 5.5 to 4.9 days (p < 0.01) and the average hospital admission charges decreased by 12.9% (p < 0.01) after implementation. Five of the quality indicators, including the rate of surgical complications, were significantly improved after pathway implementation. The hospitalization rate was not affected (1.3 before versus 0.8% after implementation, p = 0.18). Variations from the clinical pathways occurred in 543 cases (39.3%) and affected the length of hospital stay only (11.6%) or the admission charge only (12.9%) more often than both (7.8%, p < 0.01) or neither (7.0%, p < 0.01). The most common variances in these patients were patient related (30.8%). CONCLUSIONS: Implementation of multiple clinical pathways in a urology department can improve urological practice by decreasing the length of hospital stay, admission charges and rate of surgical complications, and by improving the quality of care.

Adolescent↗

PubMedDate not supplied

Judging the effectiveness of clinical pathways for pneumonia: the role of risk adjustment.

CONTEXT: Although observational studies suggest that clinical pathways may decrease costs and improve quality in hospitalized patients with community-acquired pneumonia, inferences from these studies are limited by potential selection bias and inadequate case-mix adjustment. OBJECTIVE: To compare the assessment of a clinical pathway for community-acquired pneumonia with and without adjusting for patient characteristics and disease severity. DESIGN: Retrospective cohort study. PATIENTS AND SETTING: Consecutive series of adult patients admitted with clinical diagnosis of community-acquired pneumonia, treated with either a clinical pathway (which included guidelines for antibiotics, tests, and ancillary care) or usual care. MAIN OUTCOME MEASURES: Total hospital charges, length of stay, clinical deterioration (requiring mechanical ventilation or intensive care unit transfer), and in-hospital mortality. We used multiple linear and logistic regression to adjust for patient case mix. RESULTS: Compared with patients receiving usual care (n = 275), patients in the pathway group (n = 97) were more likely to be treated by family physicians than specialists and had lower pneumonia severity scores. In the unadjusted analysis, total hospital charges were lower among pathway patients ($2456; 95% CI, $175 to $4737; P = 0.04); in the adjusted analysis, the difference in total charges was smaller (average reduction $1807; CI, $4164 lower to $549 higher; P = 0.13). In the unadjusted analysis, length of stay was lower among pathway patients (1.8 days lower; CI, 3.9 lower to 0.4 higher; P = 0.12); in the adjusted analysis, the difference in length of stay was smaller (0.9 days lower; CI, 3.2 lower to 1.3 higher; P = 0.4). Although unadjusted analysis showed significantly lower in-hospital mortality in pathway patients, this difference was not confirmed in the adjusted analysis. CONCLUSIONS: Clinical pathways may reduce costs and improve quality of care in community-acquired pneumonia. In nonrandomized studies, however, selection bias and case-mix differences may explain some of the apparent effectiveness.

Adult↗

PubMed2001

Stroke pathways.

Stroke pathways are task-orientated structured multidisciplinary care plans which detail essential steps and interventions during the period of care of a "typical" stroke patient. Pathway development and implementation are best achieved by an appointed champion leading a multidisciplinary team of health care workers and administrators, who will also be the end users of the pathway. Pathway development involves reviews of existing clinical practice guidelines and pathways, followed by documentation, interdigitation and prioritization of care requirements at different time points in the various spheres, taking into consideration local philosophies and practices. These spheres could include investigations, pharmacologic treatment, rehabilitative therapy, nursing measures, and patient education. This would result in evidence-based holistic quality care, wide support base, efficient service provision, reduced costs and length of stay, less practice variation, improved communication among disciplines, enhanced patient-staff relationship, ease of audit and research opportunities. Components of the pathway could include a patient summary sheet, multidisciplinary record of the various activities structured on a day-to-day basis, sign-off columns for staff responsible for performing those activity, variance sheet, and separate protocols for specific issues. Implementation requires training of users, pilot runs, feedback, regular revisions, monitoring of compliance, and analysis of variances. Widespread implementation of pathways may be hindered by lack of support, and concerns about increased time requirements and costs, stifling of innovation, restriction of application of clinical judgement, lack of applicability to all patients, misuse and legal issues. However, a well-designed pathway will ensure quality care in a cost-efficient manner, benefiting the patient, carer and the health care service.

Critical Pathways↗

PubMed2002

The mastectomy clinical pathway: what has it achieved?

INTRODUCTION: The mastectomy clinical pathway was developed to optimise the clinical care and cost management of breast cancer patients. The aim of this study was to prospectively assess the effect of the mastectomy pathway at the National University Hospital, Singapore over a 7-month period. MATERIALS AND METHODS: A prospective study was carried out on all breast cancer patients admitted for elective mastectomy between March and October 2001. As surrogates of optimised cost and care management, the length of stay and hospital costs, as well as the incidence of complications and unscheduled readmissions, were analysed. Non-pathway mastectomy patients treated from March to October 2000 were used as controls. A total of 83 patients who underwent mastectomy formed the pathway group, while 69 non-pathway patients acted as controls. RESULTS: Compared to controls, the mean length of hospital stay decreased significantly from 4.91 days to 4.10 days (P = 0.018) and the mean cost per case decreased significantly from $5,050 to $4,406 (P = 0.014) for those in the pathway group. There were no significant differences in the complications and unscheduled hospital readmission rates between the two groups (P > 0.05). CONCLUSION: The implementation of mastectomy clinical pathway has improved consistency in patient's treatment, the quality of patient outcome, and has reduced the costs of care and length of hospital stay. In addition, variance analysis of the mastectomy pathway has shown to be valuable for problem identification to improve patient care.

Adult↗

PubMed2003

A clinical pathway for laparoscopically assisted vaginal hysterectomy. Impact on costs and clinical outcome.

OBJECTIVE: To evaluate the cost of and clinical outcome of implementing a clinical pathway for laparoscopically assisted vaginal hysterectomy. STUDY DESIGN: A retrospective study of the case records of patients who underwent laparoscopically assisted vaginal hysterectomy before (May-December 1997) and after (January 1998-March 1999) implementation of a clinical pathway. Data regarding resource consumption and clinical outcome represented by 10 clinical indicators were collected. Student's t test and the chi 2 test were used, as appropriate. Statistical significance was set at P = .05. RESULTS: After implementation of the laparoscopically assisted vaginal hysterectomy clinical pathway, the average total fee decreased significantly, by 8.1% (P = .03), the average inpatient drug fee decreased by 50.6% (P < .01), and the laboratory fee dropped by 56.2% (P < .01). Furthermore, the length of hospital stay significantly decreased, from 6.90 to 4.08 days (P < .01); the average operation time decreased by 24.8% (P < .01); and the average anesthesia time decreased by 21.6% (P < .01). The pre-clinical pathway and post-clinical pathway complication rate did not differ statistically, but the rate of initiating intravenous antibiotic injections > 48 hours following surgery decreased by 76.2% in the clinical pathway group (P = .02). CONCLUSION: Implementation of a clinical pathway for laparoscopically assisted vaginal hysterectomy can improve health care outcomes by decreasing length of hospital stay and admission fees and by maintaining quality of care. The clinical pathway is a good policy for maintaining cost containment and high-quality patient care.

Adult↗

PubMedDate not supplied

Inpatient asthma clinical pathways for the pediatric patient: an integrative review of the literature.

BACKGROUND: Asthma is one of the most prevalent childhood chronic illnesses in the United States leading to nearly 190,000 pediatric hospitalizations yearly. In response to the increasing number of children with asthma being hospitalized, some institutions have developed and implemented clinical pathways and are now reporting their findings in the literature. The purpose of this paper was to conduct an integrative literature review of studies using an inpatient clinical pathway for the management of pediatric asthma. METHOD: Five research-based articles evaluating clinical pathways for the management of inpatient pediatric asthma were included in this review. The integrative review was conducted using the guidelines set forth by Ganong (1987). RESULTS: The results revealed that clinical pathways appear to be effective in reducing length of stay and hospital costs associated with inpatient pediatric asthma. The pathways were not as effective in reducing readmission rates or affecting clinical outcomes for patients such as increasing asthma education, the use of controller medications, spacers, and peak flow meters. PRACTICE IMPLICATIONS: Although the pathways are effective in reducing hospitalization costs associated with asthma, there was little reported improvement in clinical outcomes. Nurses should ensure that each pediatric asthma hospitalization provides an opportunity to promote education about asthma. This approach may lead to decreased asthma admissions and increased self and family management of pediatric asthma. Future research should focus on the clinical outcomes of patients using the inpatient pathways and also on the development of pathways to be used in outpatient settings that manage pediatric asthma.

Asthma↗

PubMed2005

[Usefulness of an all-in-one clinical pathway for transurethral resection of prostate].

We evaluated the usefulness of our original all-in-one clinical pathway for transurethral resection of the prostate (TUR-P) on 86 consecutive patients. There were 27 consecutive patients treated before introduction of the clinical pathway (group 1). Twenty-nine consecutive patients were treated just after the introduction of the clinical pathway (group 2) and 30 consecutive patients were treated one year after the introduction of the clinical pathway (group 3). Our pathway includes all items such as vital sign charts and events charts. Although the hospitalization ranged from 5 days to 12 days after introduction of the clinical pathway, the average length of hospital stay was shortened by 2.6 days in group 3. Although the duration of the postoperative indwelling urethral catheter ranged from 2 days to 7 days in the groups 2 and 3, the average duration was approximately 4 days in group 3. Postoperative complications did not differ among the three groups. The medical insurance claims decreased with the introduction of the clinical pathway. Our all-in-one clinical pathway is considered to be a good tool for not only reduction of health care costs but also giving higher quality and better service to patients.

Aged↗

PubMed2005

The use and modification of clinical pathways to achieve specific outcomes in bariatric surgery.

Clinical pathways are promoted for standardizing patient care and decreasing resource use without compromising outcome. Once established, we hypothesized that clinical pathways can then be used to modify patient care to achieve specific goals. Our aim was to evaluate a clinical pathway for the bariatric surgical patient that was initially designed to standardize care and later altered to modify the postoperative course. We retrospectively reviewed 150 consecutive patients undergoing open gastric bypass by a single surgeon. The first 50 patients were managed without a formal pathway, (group I). The next 50 were managed with a pathway that standardized care in order to reduce length of stay (LOS), (group II). For the final 50 patients, the pathway was modified to shorten nasogastric decompression time (group III). Patient information, blood loss (EBL), operative time, length of stay (LOS), nasogastric decompression, 30-day complication rates, and early readmissions were reviewed. The groups were similar with respect to gender, age, body mass index, American Society of Anesthesiologists (ASA) classification, and EBL. Operative time was significantly less in groups II and III compared to group I (82% and 68% vs. 38% <180 minutes, P < 0.05). LOS was shorter in groups II and III compared to group I (62% and 42% vs. 20% with a 4-day LOS, P < 0.05). Duration of nasogastric tube decompression was successfully decreased in group III when compared to groups I and II (76% vs. 14% and 6% 1 day or less, P < 0.05). Complication rates were significantly lower in group III as well (14% vs. 36% and 28%, P < 0.05). Standardizing patient care with a clinical pathway decreases LOS after bariatric surgery. An established clinical pathway can then be used to further modify patient care in order to achieve specific goals, such as shortened time of nasogastric decompression. This goal was accomplished without compromising patient outcome.

Adult↗

PubMed1992

Eosinophil granule cationic proteins regulate complement. I. Activity on the alternative pathway.

Eosinophil granules contain several cationic proteins that mediate tissue damage in allergic disease. The present study examined the capacity and mechanisms by which these cationic proteins regulate activity of the alternative pathway of C. Eosinophil peroxidase and eosinophil cationic protein inhibited formation of cell-bound alternative pathway C3 convertase, causing 50% inhibition of lysis at about 0.19 and 0.75 microgram/10(7) cellular intermediates, respectively. Major basic protein inhibited alternative pathway C3 activity by only 19% at 1.5 micrograms/10(7) cellular intermediates. Eosinophil-derived neurotoxin had no activity on the alternative pathway. The eosinophil granule proteins were examined for the mechanism by which they inhibited alternative pathway activity. Eosinophil peroxidase and major basic protein inhibited fluid phase factor B consumption in a reaction mixture that also contained factors D and C3b, eosinophil-derived neurotoxin had no activity on factor B consumption, and eosinophil cationic protein consumed factor B in the absence of C3b and factor D. Both eosinophil cationic protein and eosinophil peroxidase enhanced the decay of preformed alternative pathway convertase. Lysis of EAC4b,3b cellular intermediates formed to contain a low surface amount of C3b was more inhibited than was lysis of cells formed with a standard amount of C3b on the surface. This suggests that these eosinophil proteins acted predominantly on C3b to regulate alternative pathway activity. We also found that none of the eosinophil granule cationic proteins had any effect on later events after the formation of the C3 convertase. We conclude that although eosinophil-derived neurotoxin (isoelectric pH value (pI) = 8.9) does not regulate alternative pathway activity, the more highly charged eosinophil granule cationic proteins--major basic protein (pI = 10.9), eosinophil cationic protein (pI = 10.8), and eosinophil peroxidase (pI = 10.8)--do share the capacity to regulate C activity and may exert this activity in vivo.

Blood Proteins↗

PubMed1990

Pentose phosphate pathway in rat colonic epithelium.

The colonic cells of the large intestine are one of the most proliferative tissues of the animal body. The pentose pathway has an essential role in cell division and growth being the only pathway forming ribose 5-P necessary for all nucleotide and nucleic acid sunthesis. The pentose pathway may also provide reducing potential as NADPH for biosynthesis and C-3- C-8 glycolyl compounds. The maximum catalytic capacities of the reactions of the non-oxidative pentose pathway for the conversion of ribose 5-P to hexose and triose phosphates by the proximal and distal colon under feeding and starvation regimes are among the highest in the animal body. The qualitative presence of the oxidative pentose pathway was assessed by measurement of the C-1/C-6 ratio value of 1.67-1.82. Enzymes of the F-type and L-type pentose pathways are present in colonocytes and their maximum catalytic activities in colonocyte cytosol are reported. The contribution of the F-type pentose cycle to the total glucose metabolism of colonocytes, measured by the specific yield method, is negligibly low (approximately 1.5%). Colonic epithelial cells use glucose at a high rate (7.1 +/- 0.33 mumol min-1g-1 dry wt) and 79% of the glucose is converted to lactate. Arabinose 5-P has an intermediary role in the formation of keto pentose, sedoheptulose and hexose phosphates from ribose 5-P by colonocyte cytosol. The intermediary and reaction products of [1-13C] ribose 5-P dissimilation by colonocytes is investigated by 13C NMR spectroscopy. The 13C positional isotope distributions show labelling of C-1 and C-3 of hexose 6-phosphates consistent with either the theoretical predictions of the F-type pentose pathway or of the activities of exchange reactions catalysed by transketolase and/or transaldolase. Measurements of exchange reactions showed that the C-1/C-3 labelling of these compounds is mostly, if not wholly, attributable to exchange catalysis by these group transferring enzymes. The results suggest that the F-type PC has little role in the glucose metabolism of colonocytes and pentose phosphate formation may thus occur by a contribution (approx 20% of the total glucose metabolism) by the alternate L-type pathway.

Animals↗

PubMed1996

Visual motion-detection circuits in flies: parallel direction- and non-direction-sensitive pathways between the medulla and lobula plate.

The neural circuitry of motion processing in insects, as in primates, involves the segregation of different types of visual information into parallel retinotopic pathways that subsequently are reunited at higher levels. In insects, achromatic, motion-sensitive pathways to the lobula plate are separated from color-processing pathways to the lobula. Further parallel subdivisions of the retinotopic pathways to the lobula plate have been suggested from anatomical observations. Here, we provide direct physiological evidence that the two most prominent of these latter pathways are, indeed, functionally distinct: recordings from the retinotopic pathway defined by small-field bushy T-cells (T4) demonstrate only weak directional selectivity to motion, in striking contrast with previously demonstrated strong directional selectivity in the second, T5-cell, pathway. Additional intracellular recordings and anatomical descriptions have been obtained from other identified neurons that may be crucial in early motion detection and processing: a deep medulla amacrine cell that seems well suited to provide the lateral interactions among retinotopic elements required for motion detection; a unique class of Y-cells that provide small-field, directionally selective feedback from the lobula plate to the medulla; and a new heterolateral lobula plate tangential cell that collates directional, motion-sensitive inputs. These results add important new elements to the set of identified neurons that process motion information. The results suggest specific hypotheses regarding the neuronal substrates for motion-processing circuitry and corroborate behavioral studies in bees that predict distinct pathways for directional and nondirectional motion.

Animals↗