Novel band 3 variants (bands 3 Foggia, Napoli I and Napoli II) associated with hereditary spherocytosis and band 3 deficiency: status of the D38A polymorphism within the EPB3 locus

We report three novel variants of band 3 associated with hereditary spherocytosis: band 3 Foggia (311delC; ACCCAC → ACCAC), band 3 Napoli I (447insT; TCT → TTCT) and band 3 Napoli II (I783N; ATC → AAC). The first two mutations resulted in premature termination of translation, making one haploid set of band 3 mRNA unavailable. Since it affected a highly conserved position at the terminal end of transmembrane domain 11, the third mutation prevented one haploid set of band 3 from becoming incorporated or stabilized into the membrane. These three mutations resulted in a reduction of the band 3 level in the red cell membrane (by 20–25%) and were dominantly transmitted. The D38A substitution (GAC → GCC) is a low frequency change of band 3. In one compound heterozygote D38A/Napoli II, a markedly aggravated picture required early splenectomy. In contrast, the D38A change was not associated with deterioration in another compound heterozygote, carrying in trans , the previously recorded R760W mutation (CGG → TGG). In the aggravated case, SSCP analysis did not exhibit any additional change in the two EPB3 alleles. Nor did it show any alteration in the exons of the two ANK1 alleles, and the aggravating factor remained elusive. The D38A alteration should be regarded as an innocuous polymorphism.     

Systemic Active Suppression Is Not Necessary for Successful Allopregnancy

ABSTRACT: To investigate the role of systemic suppression during allopregnancy, CBA/J female mice were immunised against H-2^d prior to mating. Cytotoxic T lymphocyte (CTL) activity was tested at days 14–16 of pregnancy. A reduction of CTL activity was observed only in multiparous animals. Although a nonspecific suppression was detected in isopregnancy, suppression was more marked in allopregnancy. Conversely, the CTL activity observed in the spleen during the first pregnancy (iso or allo) was always significant in mice presensitized with 2 or 3 alloimmunizations prior to pregnancy. Such animals have in vivo effector cells, since allografts of Sarcoma Sal were rejected in secondary fashion in alloimmunized mice, while the fetus remained unharmed. These observations demonstrate that allospecific anti-MHC CTLs are specifically impaired in multiple allopregnancy, but also tend to rule out theories postulating that systemic suppression of CTL generation and function is required for successful allopregnancy.     

A study of allergens in celery with cross-sensitivity to mugwort and birch pollens

Sixty-one sera with positive RAST to mugwort pollen ( Artemisiae vulgaris ) were submitted to RASTs for birch pollen ( Betula verrucosa) and celery ( Apium graveolens ). In 36 cases RAST results were positive for celery. In addition, 23 sera presented specific IgE to birch pollen. The binding of specific IgE to individual allergens in celery, mugwort pollen and birch pollen was studied by the immunoblotting technique. This involved electrophoretic separation of allergenic extracts, electrotransfer of proteins onto nitrocellulose sheets and sensitive immunoenzymatic detection. Eighteen sera had specific IgE binding to two celery components of molecular weight around 15 kD. All these sera also detected a 15 kD allergen in mugwort and two allergens in birch of 14 kD and 16 kD molecular weight. The sera that did not detect the 15 kD bands in celery failed to react with both the 15 kD mugwort component and the 14 and 16 kD birch components. Specific cross-inhibitions of the detection of these allergens on immunoblots were obtained by pre-incubation of the sera with crude extract of the three species. These results strongly suggest that such allergens display some structural identity and that they could be at the origin of some cases of crossed hypersensitivity to celery, mugwort pollen and birch pollen.     

VERAPAMIL IN CARDIAC DYSRHYTHMIAS DURING ANAESTHESIA

The antidysrhythmic action of verapamil 20 mg was studied in383 patients lightly anaesthetized with halothane in oxygen.The drug effectively inhibited ventricular and supraventriculardysrhythmias and was without effect on sinus tachycardia ofadrenergic origins. Its possible modes of action have been discussed.It is suggested that it acts by preventing the function of calciumions, thereby causing a non-specific inhibition of the cardiacdysrhythmic reactions to sympathetic overactivity. It is concludedthat verapamil may be used safely for the control of supraventricularand ventricular dysrhythmias in lightly anaesthetized patients.Its use is contraindicated in patients with atrioventricularblock of any grade and in undigitalized patients with heartfailure.     

Quantifying Adaptation to Contact Lenses: Two Case Histories

ABSTRACT In the course of previous investigations, chloride concentration has been shown to be an eetive indicator of both hypotonic (reflex tear) and hypertonic (aberrant blink) tear shifts with contact lens presence. Described here are case histories which illustrate two diagnostic applications of this technique.     

Blocking of Protein Pancreatic Secretion by Maximal Secretion Infusion in the Dog

In conscious chronic gastric and pancreatic fistula dogs (Thomas cannula), secretin was perfused for three hours with a submaximal (GIH, 1.0 C.U./kg.) and a maximal dose (GIH, 8.0 C.U./kg.), according to the following schedule: 1. First hour submaximal stimulus; 2. second hour maximal stimulus; 3. third hour submaximal stimulus.
The alkaline and protein components of pancreatic secretion were analyzed in 20-minute sample collections throughout the three hours.
The same protocol was followed in anesthetized dogs subjected to a mid line laparotomy. A biopsy of the pancreatic gland was taken before (control) and at the end of each perfused dose. The secretion showed a significant increase of protein concentration and output when passing from the maximal to the last submaximal secretin perfusion dose. These findings correlate well with the piling up of zymogen and prozymogen granules in the apical zone of the acinar cells during maximal secretin perfusion, with their subsequent discharge into the acinar lumen upon abrupt reversal to the initial secretin submaximal dose.
The study confirms that secretin influences pancreatic protein secretion and indicates in addition, that pharmacologic doses of the hormone, have the capacity to block acinar cell zymogen granule release.     

Case Report: Secondary biliary cirrhosis possibly related to congenital hepatic fibrosis. Evidence for decreased number of portal branch veins and hypertrophic peribiliary vascular plexus

A 30-year-old man with presinusoidal portal hypertension was transplanted for cryptogenic cirrhosis. On the explanted liver, few intrahepatic stones, biliary cirrhosis, chronic cholangitis of the large bile ducts and a peculiar proliferation of small dilated bile ducts at the periphery of the portal tracts led to the diagnosis of secondary biliary cirrhosis and cholangitis, possibly linked to ductal plate malformation, including congenital hepatic fibrosis associated with a minor form of Caroli's disease. Ex vivo portogram and histology showed the paucity of portal vein branches and the hypertrophy of the peribiliary vascular plexus. This hypertrophy, which has been reported in livers with presinusoidal hypertension, is another indirect argument to suggest the diagnosis of congenital hepatic fibrosis.