Effects of a metalloproteinase that truncates P-selectin glycoprotein ligand on neutrophil-induced cardiac dysfunction in ischemia/reperfusion

This study was designed to test the effects of polymorphonuclear leukocytes (PMNs) in the presence and absence of a P-selectin blocker, mocarhagin, in provoking cardiac dysfunction in isolated perfused rat hearts following ischemia and reperfusion. Control rat hearts not subjected to ischemia were perfused without blood cells for 80 min. Additional control rat hearts were perfused with 100 x 10(6) PMNs in the presence and absence of 0.2 microgram/ml mocarhagin over a 5-min perfusion followed by a 45-min observation period. No significant reduction in coronary flow (CF), left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dt max) was observed at the end of the observation period in any non-ischemic group. Similarly, global ischemia (I) for 20 min followed by 45 min of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of PMNs. I/R hearts perfused with PMNs exhibited decreases of 50-60% in all measurements of cardiac function (P < 0.001). These PMN perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity indicating a significant PMN infiltration, and enhanced P-selection expression on the coronary microvascular endothelium. All cardiodynamic effects as well as MPO accumulation and PMN infiltration were attenuated markedly by the metalloproteinase, mocarhagin, which inhibits P-selectin-mediated cell adhesion by cleaving its high-affinity receptor, PSGL-1, present on neutrophils. These results provide evidence that neutrophils provoke post-reperfusion cardiac dysfunction, and that this may be largely due to P-selectin-induced adherence of neutrophils to the endothelium.     

Opsin localization and rhodopsin photochemistry in a transgenic mouse model of retinitis pigmentosa

In budding yeast, a protein kinase called Gin4 is specifically activated during mitosis and functions in a pathway initiated by the Clb2 cyclin to control bud growth. We have used genetics and biochemistry to identify additional proteins that function with Gin4 in this pathway, and both of these approaches have identified members of the septin family. Loss of septin function produces a phenotype that is very similar to the phenotype caused by loss of Gin4 function, and the septins are required early in mitosis to activate Gin4 kinase activity. Furthermore, septin mutants display a prolonged mitotic delay at the short spindle stage, consistent with a role for the septins in the control of mitotic events. Members of the septin family bind directly to Gin4, demonstrating that the functions of Gin4 and the septins must be closely linked within the cell. These results demonstrate that the septins in budding yeast play an integral role in the mitosis-specific regulation of the Gin4 kinase and that they carry out functions early in mitosis.     

Cloning and characterization of cDNA for human adenylate kinase 2A

Considerable genomic microdiversity has been reported previously among Helicobacter pylori isolates. We have constructed genome maps of four unrelated H. pylori strains (NCTC11637, NCTC11639, UA802 and UA861) using pulsed-field gel electrophoresis (PFGE) with NotI and NruI, hybridization with extracted PFGE DNA fragments and probing with 17 gene probes. These strains of H. pylori were compared with a fifth unrelated H. pylori strain NCTC11638 mapped previously. Considerable diversity in gene arrangement was evident among the five H. pylori maps, and no consistent gene clustering was found. The association of only four genes, katA (catalase gene), vacA (vacuolating cytotoxin gene), hpaA (a putative adhesin gene), and pfr (bacterial ferritin gene) were generally conserved within approximately the same 25% of the genome; however, the order of these genes also varied. Our study demonstrates that macrodiversity, i.e. variability in gene order, in addition to microdiversity, is a characteristic of the H. pylori genome.     

Closed management and percutaneous fixation of unstable proximal humerus fractures

BACKGROUND: In dealing with displaced proximal humerus fractures, there is still much controversy in treatment modalities. The latest investigations emphasize the concept of minimal exposure and rigid fixation. METHODS: The technique of closed reduction and percutaneous fixation with cannulated screws and k-pins was performed on 19 patients with two- and three-part proximal humerus fractures. The outcomes were evaluated with a mean follow-up of 21 months. RESULTS: All except one case had a solid union of the fracture. Sixteen of 19 patients (84%) acquired good or excellent results according to Neer's classification. No further collapse or avascular necrosis was found. CONCLUSION: The method of closed reduction and percutaneous fixation, although technically demanding, yields satisfactory results in displaced proximal humerus fracture. Cannulated screws provided rigid fixation that was the underlying tenet for early functional retrieval.     

Short duration of neutralizing antibody titers after pre-exposure rabies vaccination with suckling mouse brain vaccine

OBJECTIVE: To determine whether a Pasteurella haemolytica A1 mutant that is unable to produce membrane lipoproteins has reduced susceptibility to complement-mediated killing, and to characterize the mutant strain. SAMPLE POPULATION: 12 sera from cattle resistant to P haemolytica challenge exposure after vaccination with P haemolytica or its antigens, or after natural exposure. PROCEDURES: Complement-mediated killing assays were performed, using wild-type and mutant strains and, as antibody source, various immune sera from cattle that were resistant to P haemolytica challenge exposure. Antibody response to whole-cell antigens produced by mutant and wild-type strains, production of outer membrane proteins and iron-regulated outer membrane proteins by the 2 strains, and growth of the 2 strains in various media were analyzed. RESULTS: Compared with wild-type P haemolytica, the lipoprotein mutant strain had increased susceptibility to bovine complement-mediated killing. Aside from the lipoproteins that are not produced by the mutant, immunoblot analysis did not reveal differences between immunoreactive antigens that are produced by the 2 strains. Some iron-regulated, outer membrane proteins, which usually are only produced by P haemolytica under iron-deficient conditions, were produced constitutively by the mutant. The mutant grew to a lower final cell density and at a lower rate under conditions likely to reflect those encountered in vivo. CONCLUSIONS: Lack of 3 membrane lipoproteins resulted in enhanced susceptibility to bovine complement-mediated killing. Site-specific mutagenesis of genes encoding P haemolytica membrane lipoproteins alters production of iron-regulated outer membrane proteins by P haemolytica. Growth characteristics of the mutant suggested that it may have reduced capacity for survival in vivo.     

A Chinese cultural perspective of nursing care behaviours in an acute setting

This study carried out in Hong Kong, identified 29 Chinese patients' perceptions of the importance of nursing care behaviours in an acute setting using a Chinese language translated version of the CARE-Q instrument. Patients ranked items concerned with 'giving the patients' treatments and medication on time' as the most important and 'sits down with the patient' as the least important. Comparisons are made with the results from other cultures and specific Chinese cultural interpretations are drawn to provide direction for nursing care of Chinese patients in Hong Kong and worldwide.     

Assessment of myocardial viability by dobutamine echocardiography, positron emission tomography and thallium-201 SPECT: correlation with histopathology in explanted hearts

OBJECTIVES: We examined the relationship among viability assessment by dobutamine echocardiography (DE), positron emission tomography (PET) and thallium-201 single-photon emission computed tomography (TI-SPECT) to the degree of fibrosis. BACKGROUND: DE, PET and TI-SPECT have been shown to be sensitive in identifying viability of asynergic myocardium. However, PET and TI-SPECT indicated viability in a significant percentage of segments without dobutamine response or functional improvement after revascularization. METHODS: Twelve patients with coronary artery disease and severely reduced left ventricular function (EF 14.5+/-5.2%) were studied with DE prior to cardiac transplantation: 5 had additional PET and 7 had TI-SPECT studies. Results of the three techniques were compared to histologic findings of the explanted hearts. RESULTS: Segments with >75% viable myocytes by histology were determined to be viable in 78%, 89% and 87% by DE, PET and TI-SPECT; those with 50-75% viable myocytes in 71%, 50% and 87%, respectively. Segments with 25-50% viable myocytes showed response to dobutamine in only 15%, but were viable in 60% by PET and 82% by TI-SPECT. Segments with <25% viable myocytes responded to dobutamine in 19%; however, PET and TI-SPECT demonstrated viability in 33% and 38%, respectively. Discrepant segments without dobutamine response but viability by PET and SPECT had significantly more viable myocytes by pathology than did those classified in agreement to be nonviable but had significantly less viable myocytes than those classified in agreement to be viable (p < .001). CONCLUSIONS: These findings suggest that contractile reserve as evidenced by a positive dobutamine response requires at least 50% viable myocytes in a given segment whereas scintigraphic methods also identify segments with less viable myocytes. Thus, the methods may provide complementary information: Nuclear techniques appear to be highly sensitive for the detection of myocardial viability, and negative tests make it highly unlikely that a significant number of viable myocytes are present in a given segment. Conversely, dobutamine echo may be particularly useful for predicting recovery of systolic function after revascularization.     

Short-term effects of nicotine on bone and calciotropic hormones in adult female rats

Quantitative measurement of sound-induced discomfort and pain thresholds showed that migraineurs (n = 65) were significantly more sensitive than headache-free controls (n = 80), both during and outside attack (p < 0.0001). Patients tested with head pain had lower thresholds than those tested without pain (p < 0.01). Migraine with and without aura did not differ as to sound sensitivity. There were no significant differences in thresholds between the symptomatic and nonsymptomatic sides (p > or = 0.78). Patients with unilateral headache or pain of pulsating character were more sensitive than those with bilateral headache or pressing pain (p < 0.05). Phonophobia did not correlate significantly with duration, frequency, or severity of attacks. The main results were in accordance with a questionnaire study concerning subjective evaluation of sound sensitivity. Similarities between phonophobia and photophobia in migraine provide evidence that both phenomena share a common pathophysiological mechanism in this condition.     

Immunization with synthetic peptide segments of a sperm protein impair fertility in rats

The nucleotide sequence of the cDNA encoding a sperm protein (rSMP-B) was determined in a previous study. Two peptide segments corresponding to the extracellular domain of the deduced sperm polypeptide were synthesized as multiple antigen peptide (MAP) and designated as rSMP-229 and rSMP-230. Polyclonal antibodies were raised against the two MAPs. Sera obtained from rabbits immunized with rSMP-230 interacted with human and rabbit sperm membrane proteins with estimated molecular sizes of 72 and 20.1 kD, respectively. Adult female and male rats were immunized with the MAPs and their fertilities determined. Immunization of female rats with rSMP-229 and rSMP-230 induced infertility in 25% and 83% of the treated animals, respectively. All male rats immunized with rSMP-229 remained fertile; whereas animals immunized with rSMP-230 did not mate with normal cycling female rats. Three impotent male rats were found to regain their mating potency 45 days after the last booster injection. These findings demonstrated that immunization with rSMP-230 induced a reversible impotency in male rats. Serum testosterone and LH levels were reduced in rSMP-230-immunized male rats and were elevated in rSMP-229-immunized animals. Histopathological examination of sections of testes from male rats immunized with rSMP-230 showed impairment of spermatogenesis and sloughing of germ cells into the lumen of the seminiferous tubules. The testes of male rats immunized with rSMP-229 showed normal morphology and active spermatogenesis with scattered foci of nodular hyperplasia of Leydig cells in the interstitial areas. In conclusion, immunization with synthetic peptide segments corresponding to different domains of a deduced sperm protein induced infertility in a significant number of female rats and transient impotency in male rats.