Monoclonal antibodies to human platelet glycoprotein IIb beta that initiate distinct platelet responses

Hybridomas secreting monoclonal antibodies (MoAbs) to human platelet membrane glycoprotein IIb (GPIIb) were prepared by fusing cells of a mouse myeloma line to spleen cells from a BALB/c mouse immunized with purified GPIIb. Six of the hybridomas secreted MoAbs that recognized epitopes on the 23,000-dalton, disulfide-linked subunit of GPIIb, GPIIb beta. All six of these MoAbs agglutinated platelets in the absence of calcium. The agglutination titers of three of the MoAbs, however, were enhanced between 2 and 6 log2 dilutions when titrated in the presence of mmol/L of calcium. The enhancement in titer was the result of MoAb- induced platelet activation followed by platelet aggregation, a reaction that could also be initiated by the monovalent Fab fragments prepared from one of the MoAbs. The MoAbs did not significantly agglutinate platelets from patients with Glanzmann's thrombasthenia, confirming biochemical evidence that there is a paucity of GPIIb beta in the membranes of these cells. Our results show that MoAbs to epitopes on GPIIb beta initiate distinct platelet responses; therefore, they should be useful for studying the ways in which regions of surface glycoproteins are involved in platelet-platelet interactions. In addition, these reagents may prove of value in diagnosing and typing patients with Glanzmann's thrombasthenia.     

Minactivin expression in human monocyte and macrophage populations

Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or "tissue"-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone.     

p53基因cDNA突变及其蛋白高表达与大肠癌预后关系

１００份大肠癌组织，用ＲＴ－ＰＣＲ－ＳＳＣＰ检测Ｐ５３基因ＣＤＮＡ突变；ＰＡｂ１８０１单抗免疫组化检测Ｐ５３基因蛋白搞表达并对大肠癌术对后病人作５年生存随访，比较上述２结果与大肠癌预后的关系，１００例大肠癌中，ＲＴ－ＰＣＲ－ＳＳＣＰ显示５１例大肠癌Ｐ５３基因ＣＤＮＡ突变，ＰＡｂ１８０１阳性率６２％，Ｐ５３基因ＣＤＮＡ突变和Ｐ５３基因蛋白高表达与Ｄｕｋｅｓ分期无关，Ｐ５３基因ＣＤＮＡ突变与Ｐ５３基因     

Ultrastrukturelle Veränderungen am Nierenparenchym durch ESWL unter Acetylsalicylsäure (ASS)

BACKGROUND: The risk of hemorrhagic complications after extracorporeal shock-wave lithotripsy (ESWL) increases in patients with aspirin intake, but the hematoma-inducing mechanism has not been understood completely at the ultrastructural level. METHODS: The effect off shock-waves on the kidneys of male Wistar-rats (n=24) was investigated in an experimental setting using a special ESWL device. Ultrastructural examination was performed by light-, transmission electron- and scanning electron microscopy. RESULTS: Shock-wave induced tissue damage appeared in all kidneys independently of aspirin intake. Endothelial detachment, lethal cell injury, gaps and mechanical disruption of the glomerular basement membrane were regularly found. After 1 week, repair processes were completed with evidence of permanent fibrosis in some cases. CONCLUSIONS: ESWL can induce modest as well as fatal damage to renal tissue cells. Therefore, after an ESWL-induced hematoma a second ESWL should not be performed within 1 week of the first treatment.     

Changes in fatigability of the striated anal canal after childbirth

Aim Anal manometry is an established assessment tool for patients with faecal incontinence. Fatigue rate index (FRI) has been shown to discriminate between symptomatic patients and controls. The aim of this study was to compare manometry and fatigability of the anal canal in nulliparous women before and after childbirth. Method An air‐filled manometry device was used to record maximum resting and squeeze pressures, fatigue rate (recorded over 20 s) and FRI. Recordings were made before and after vaginal delivery. Results Nineteen women were studied. Resting anal canal pressure was not significantly different before and after delivery (57.1 ± 13.6 vs 51.1 ± 11.9 cmH₂O, P = 0.1). Squeeze pressure was significantly lower postpartum (106.5 ± 43.6 vs 75.5 ± 45.6 cmH₂O, P < 0.001). Fatigue rate was significantly reduced postpartum (?129.5 ± 74.7 vs?76.1 ± 54.8 cmH₂O/min, P = 0.001), but FRI was not significantly altered (1.23 ± 1.49 vs 1.41 ± 1.27 min, P = 0.09). Conclusion Maximal squeeze pressure and fatigue rate of the anal canal are significantly reduced after childbirth. Resting anal canal pressure and FRI are not significantly different.     

Transient bacteraemia: a possible cause of sudden life threatening events

The concept proposed is that transient bacteraemia occurring in otherwise healthy individuals can cause acute life threatening events due to bacterial toxaemia even though the bacteraemia is rapidly cleared (<20 min). This is most likely to occur in infancy at around two to three months of age when anti-toxin IgG reaches its nadir. Sudden unexpected death in infancy, acute life threatening events, haemorrhagic shock and encephalopathy, and the triad of retinal haemorrhage, encephalopathy and bilateral thin film subdural haematomata are conditions which could be caused by this mechanism. Investigations need to be directed to measuring bacterial toxins in blood, CSF and urine; anti-toxin IgG in blood; and bacterial specific nucleic acid sequences in blood, CSF and urine using polymerase chain reaction in order to confirm recent bacteraemia. Furthermore the upper respiratory tract bacterial flora should be mapped in cases and appropriately matched live healthy community controls. Sudden onset, profound life threatening physiological dysfunction occurring in later life could also be caused by a similar mechanism and should be investigated in a similar way; candidate conditions include epilepsy, migraine, stroke and cardiac arrhythmias.