Enhanced association of plasminogen/plasmin with lesional epidermis of bullous pemphigoid

The distribution of plasminogen/plasmin, the central proteolytic component of the plasminogen activator/plasmin system was analysed in lesional skin of bullous pemphigoid by using monoclonal antibodies (MAbs) specific for distinct epitopes of the plasminogen/plasmin molecule. Four groups of MAbs were used: (i) MAbs HD-PG 1 and HD-PG 2, specific for epitopes associated with the lysine-binding sites I (kringle domain 1 + 2 + 3) and II (kringle domain 4) of plasminogen/plasmin, (ii) MAbs HD-PG 6 and HD-PG 7, specific for the lysine binding site I only, (iii) MAbs HD-PG 12 (formerly designated P 2) and HD-PG 18, specific for non-kringle domains of glu- and lys-plasminogen, and (iv) MAb HD-PG 13 which recognizes glu-plasminogen, only. The basal cell layers of normal skin consistently reacted with MAb HD-PG 12, whereas only faint staining was seen with the other MAbs in the same biopsies. In contrast, all anti-plasminogen/plasmin MAbs strongly stained lower and intermediate epidermal cell layers of fully developed bullous pemphigoid lesions.     

Alanine scan and N-methyl amide derivatives of Ac-bombesin[7-14]. Development of a proposed binding conformation at the neuromedin B (NMB) and gastrin releasing peptide (GRP) receptors

Alanine and N-methylation scans together with molecular modelling were implemented in order to propose a binding conformation of the minimum active fragment of bombesin (BB), Ac-BB[7-14], to the gastrin releasing peptide (GRP) and neuromedin B (NMB) receptors. These data are also used to critically evaluate the previously proposed binding conformations such as x-helix and antiparallel β-sheets. This shows that the previously reported conformations do not satisfy the experimental data. A new binding conformation of Ac-BB[7-14] is proposed consisting of three consecutive y-turns followed by a bend and finishing with two y-turns. This low energy conformation (analogous to a fragment of thymidylate synthase, 2TSC) of bombesin stabilized by five internal hydrogen bonds, and with the side chains of residues Trp⁸ and Leu¹³ held on the same side of the peptide, is in agreement with the experimentally observed data. This and the results of molecular modelling may aid in the synthesis of conformationally restricted high affinity bombesin analogues and/or high affinity template-based GRP or NMB receptor agonists and antagonists.     

Erythrocyte uroporphyrinogen decarboxylase activity in 80 unrelated patients with porphyria cutanea tarda

To estimate the prevalence of the subgroups of porphyria cutanea tarda (PCT), erythrocyte uroporphyrinogen decarboxylase (UD) activity was measured in 80 unrelated patients with PCT, and in 45 of their relatives by using pentacarboxyl-porphyrinogen III as substrate. The subgroups were differentiated by analysis of the urinary porphyrins of the patients and 119 of their relatives. Of the patients, 77.5% were found to be suffering from the sporadic form of PCT (type I PCT), and 22.5% from the familial form (type II PCT). Every patient with PCT had previously been affected by alcohol, oestrogen or some other liver-damaging factor. The relative frequency of familial PCT was higher in females (nine of 15) than in males (nine of 65), which suggests that inheritance of the gene for type II PCT may predispose to oestrogen-precipitated PCT. The onset of type II PCT occurred at a lower age than that of type I (42.6 vs. 47.0 years). The findings suggest an increased risk of precipitating factors in carriers of an inherited UD deficiency.     

The treatment of normospermic infertility by gamete intrafallopian transfer (GIFT)

Summary. Gamete intrafallopian transfer (GIFT) was applied in 207 treatment cycles in 73 couples. The pregnancy rate in cycles with only one (2/21, 9·5%) or two (2/29, 6·9%) oocytes transferred was significantly less than that in which four oocytes (36/116, 31·0%) were replaced. The collection of more than four oocytes did not influence the pregnancy rate in that treatment cycle. The overall pregnancy rate was 24·2% (50 of 207) and was similar in the four infertility groups studied (non-occlusive tubal disorders, endometriosis, cervical factor and unexplained infertility) with 28 (56%) of the pregnancies delivered at 20 weeks. The pregnancy wastage included 4 (8%) ectopic pregnancies and 3 (6%) late pregnancy losses. The 12 multiple pregnancies occurred following the transfer of three and four oocytes.     

Uroporphyrinogen decarboxylase deficiency in hepatoerythropoietic porphyria: further evidence for genetic heterogeneity

Catalytic and immunoreactive erythrocyte uroporphyrinogen decarboxylase was measured in a woman with hepatoerythropoietic porphyria (HEP). The uroporphyrinogen decarboxylase activity was 24% of the mean value for normal controls and the concentration of the immunoreactive enzyme (106 ng/mgHb), measured with the rocket immunoelectrophoresis technique, did not differ from that of healthy controls. Consequently, catalytically inactive, cross-reactive immunological material (CRIM) was present, and the patient was CRIM-positive. This enzyme activity and immunoreactive enzyme concentration differs from those for previously known HEP patients, and represents a new mutation, evidence for heterogeneity in inherited uroporphyrinogen decarboxylase deficiency.     

The mechanism of blood pressure variability: Study in patients with fixed ventricular pacemaker rhythm

Background: Several studies have shown that heart rate variabilityplays an anti-oscillatory role in the regulation of blood pressurevariability in humans. We tested whether systolic blood pressurevariability in patients with a fixed ventricular pacemaker rhythmdiffers from that in patients with sinus rhythm. Methods and Results: In 18 patients with a fixed ventricularpacemaker rhythm and in ten age-matched patients with sinusrhythm the systolic blood pressure oscillation and the low andhigh-frequency spectral components of systolic blood pressurewere studied in the resting supine position during spontaneousbreathing and during forced deep ventilation of 6 cycles. min^–1.Patients with a pacemaker had a higher amplitude of systolicblood pressure oscillation than control subjects during spontaneousbreathing (13.5 ± 2.0 mmHg vs 6.4 ± 1.6 mmHg,P=0.035), and a slight but not significant difference also persistedduring forced deep ventilation (19.0 ± 2.3 mmHg vs 15.0± 2.3 mmHg, P=0.18). The increment in systolic bloodpressure fluctuation from spontaneous breathing to forced deepventilation was less marked in the pacemaker group than in thecontrol subjects (40% vs 130%, P=0.43). Although all the systolicblood pressure spectral components of the pacemaker patientswere higher during both spontaneous breathing and forced deepventilation, the differences between the two groups did notreach statistical significance. Conclusions: Our observations in patients with a fixed ventricularpacemaker rhythm suggest that the mechanical effects on theintrathoracic vessels and the consecutive stroke volume changesare responsible for respiration-related systolic blood pressureoscillation and reflex systolic blood pressure changes.