Isolation and mapping of a polymorphic DNA sequence pYNM17 on chromosome 9q (D9S6).
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Biomedical subjects
Publications and source records attributed to C Martin.
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Crayfish muscle fibres were voltage-clamped at E = -80 mV membrane potential and superfused for about 10 min with Li+ saline (Na+ replaced by Li+) which contained picrotoxin to block inhibitory post-synaptic currents. Addition of veratridine (100 mumol/l) caused intense fluctuations in the voltage clamp current within 20-60 s due to vigorous asynchronous quantal release of excitatory transmitter from the nerve terminals distributed over the muscle fibre surface. Most likely, this quantal release resulted from loading the nerve terminals with Li+ via voltage-gated Na+ channels activated by veratridine. However, in the presence of Li+ quantal release was only transient; the quantal release rate, ñ, attained a maximum of congruent to 10,000 quanta/s and then declined exponentially with tau congruent to 10 to 20 s. Removal of Li+ and reapplication of normal Na+ increased ñ a second time. The amount of quanta released in the presence of Na+ was about an order of magnitude larger than that released previously in the presence of Li+. In preparations pretreated with Li+ superfusate for t greater than 45 min no marked quantal release could be elicited by veratridine. The experiments suggest an inhibitory effect of intraterminal Li+ on the quantal release process.
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Grafts of the anterior limb bud introduced at embryonic day 4 between histoincompatible chick embryos were subject to chronic, mild rejection beginning from several weeks to several months after birth. In contrast, quail wing buds similarly grafted into chickens started to be rejected at the first or second week after birth and finally autoamputated. Embryonic thymus epithelium from donor quail (before it had been colonized by hemopoietic cells) was grafted into chicks. A chimeric thymic epithelial stroma was generated in which the lymphocytes of the chick acquired the capacity to recognize the grafted limb as self either permanently or for a protracted period of time. In such thymic chimeras the grafted wings were not rejected.
We report the Raman spectra of reduced and oxidized nicotinamide adenine dinucleotide (NADH and NAD+, respectively) and adenosine 5'-diphosphate ribose (ADPR) when bound to the coenzyme site of liver alcohol dehydrogenase (LADH). The bound NADH spectrum is calculated by taking the classical Raman difference spectrum of the binary complex, LADH/NADH, with that of LADH. We have investigated how the bound NADH spectrum is affected when the ternary complexes with inhibitors are formed with dimethyl sulfoxide (Me2SO) or isobutyramide (IBA), i.e., LADH/NADH/Me2SO or LADH/NADH/IBA. Similarly, the difference spectra of LADH/NAD+/pyrazole or LADH/ADPR with LADH are calculated. The magnitude of these difference spectra is on the order of a few percent of the protein Raman spectrum. We report and discuss the experimental configuration and control procedures we use in reliably calculating such small difference signals. These sensitive difference techniques could be applied to a large number of problems where the classical Raman spectrum of a "small" molecule, like adenine, bound to the active site of a protein is of interest. The spectrum of bound ADPR allows an assignment of the bands of the bound NADH and NAD+ spectra to normal coordinates located primarily on either the nicotinamide or the adenine moiety. By comparing the spectra of the bound coenzymes with model compound data and through the use of deuterated compounds, we confirm and characterize how the adenine moiety is involved in coenzyme binding and discuss the validity of the suggestion that the adenine ring is protonated upon binding. The nicotinamide moiety of NADH shows significant molecular changes upon binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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Two methods to bursectomize chick embryos before hemopoietic cell seeding of the bursa of Fabricius were compared in this work: section of the tail region at E3 including the presumptive bursal territory, and selective removal of the bursa at E5. Hatching ability is better with the former method, but survival rate and effectiveness of bursectomy are favored with the second, novel technique. Moreover, selective removal of the bursa at E5 can be followed by in situ engraftment of a quail bursa and construction of quail-chick bursal chimeras. The immune response of bursaless birds and bursal chimeras has been studied. Total absence of the bursa does not prevent a few B cells from differentiating and nonspecific Ig (IgM and/or IgG) from being secreted. As reported previously, bursaless birds, however, are unable to mount an immune response by producing specific antibodies. This immune function is restored by the graft of a quail bursa. The microenvironment of the bursa, although heterospecific, allows the expansion of the B cell population and generates the repertoire of the B cell antigen receptors. This process takes place during late embryonic and early postnatal life because the grafted quail bursal stroma is subjected to immune rejection from 2 to 3 wk after birth in all chimeras, which are, however, perfectly immunocompetent.
Nerve terminals on the superficial abdominal extensor muscle and the claw opener muscle of small crayfish were loaded with sodium by bath application of 100 mumol/l veratridine in superfusates where normal Ca2+ was removed (low-Ca2+ superfusate). In both preparations this caused an increase in spontaneous quantal release of excitatory and inhibitory transmitter which was evaluated by means of the noise analysis technique. About 2.5 min after application of veratridine, when spontaneous quantal release had largely ceased, the normal Ca2+ concentration was reestablished. This increased transiently the quantal release rate a second time. However, release activated by Ca2+ application was much more vigorous at the superficial abdominal extensor muscle than at the claw opener. At the superficial abdominal extensor muscle on average about 8% of the total number of quanta could be released in low Ca2+ and 92% in normal Ca2+ superfusate, while at the claw opener 75% of the quanta were released in low Ca2+ and 25% in normal Ca2+ superfusate. The experiments suggest that intraterminal sodium has a differential effect in the terminals of the two preparations. Possibly, the intraterminal source from which Na+ may liberate Ca2+ is more restricted in the superficial abdominal extensor muscle than in the opener muscle of the claw.
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A large collection of good genetic markers is needed to map the genes that cause human genetic diseases. Although nearly 400 polymorphic DNA markers for human chromosomes have been described, the majority have only two alleles and are thus uninformative for analysis of genetic linkage in many families. A few known marker systems, however, detect loci that respond to restriction enzyme cleavage by producing a fragment that can have many different lengths. This polymorphism is due to variation in the number of tandem repeats of a short DNA sequence. Because most individuals will be heterozygous at such loci, these markers will provide linkage information in almost all families. Ten oligomeric sequences derived from the tandem repeat regions of the myoglobin gene, the zeta-globin pseudogene, the insulin gene, and the X-gene region of hepatitis B virus, were used to develop a series of single-copy probes. These probes revealed new, highly polymorphic genetic loci whose allele sizes reflected variation in the number of tandem repeats.
Increasing numbers of patients with the acquired immunodeficiency syndrome (AIDS) are being reported. In the US literature the eye complications have been well documented but because so few cases of AIDS have been reported in South Africa, the retinal complications are largely unknown to those treating these patients. The retinal complications are due to cytomegalovirus (CMV) retinitis. The patient described here developed the typical signs in both eyes. It is essential to examine the fundi of AIDS patients regularly. The presence of cotton-wool spots always precedes CMV retinitis, which leads to blindness; it is also of prognostic significance since all reported patients with CMV retinitis have died.
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In has been suggested that monitoring of blood levels of serum proteins could be of value in order to assess the prognosis of trauma patients. A study was set up to assess the value of albuminaemia, prealbuminaemia, transferrin and ceruleoplasmin levels in intensive care unit patients admitted after multiple trauma including head injury. This study involved 43 patients (31 men and 12 women), with a mean age of 26 years (range: 15 and 71 years). Two patients had extradural haematoma. The other patients had brain contusion associated with extradural haematoma (5 cases), subdural haematoma (1 case) and open brain wound (1 case). All these patients were sedated with penthiobarbital, paralysed with pancuronium bromide and mechanically ventilated. Serum protein levels were measured on the first and eighth days of the stay in the intensive care unit. In these patients that survived, there was a significant decrease in albuminaemia and transferrin levels, no change in prealbuminaemia and a significant increase in ceruleoplasmin levels. Ten patients died during the study. They presented a greater decrease in albuminaemia and prealbuminaemia as compared with the survivors. There was no difference in the evolution of ceruleoplasmin and transferrin levels between the two groups. Thus, whilst the difference between survivors and non-survivors was significant for the group, for the individual patient the difference was too small to be of any prognostic value.
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An immunohistochemical and ultrastructural study of 14 cases of persistent and generalized lymphadenopathy (PGL), acquired immune deficiency syndrome (AIDS) related, revealed florid follicular hyperplasia, follicular dendritic cell (FDC) lysis, lymphoid follicle invaginations, increased presence of T8 cells in germinal center, immature sinus histiocytosis (monocytoid B-cells), and inversion of T4/T8 ratio in the paracortical area. Electron microscopic examination showed viral particles of morphologic characteristics consistent with human immunodeficiency virus (HIV) virions attached to the processes of FDC in three of the nine cases studied. Lesions of the germinal center dendritic cell network are the cardinal feature of PGL. This finding lends support to the idea of a viral aggression directed against FDC as the cause of disregulation of the B-cells.
The effects of suxamethonium, and of vecuronium given after three subparalyzing (priming) doses, on the time of onset of neuromuscular blockade and on the resultant intubating conditions were compared. This study involved five groups of 10 patients (ASA class I or II) who were premedicated with flunitrazepam 0.015 mg kg-1 i.m. Anaesthesia was induced with thiopentone 6 mg kg-1 and fentanyl 0.003 mg kg-1. In groups 2, 3 and 4 the patients were given a priming dose of vecuronium 0.01, 0.015 and 0.02 mg kg-1, respectively. Three minutes later the intubating dose of vecuronium was given: 0.1 mg kg-1 (group 1), 0.09 mg kg-1 (group 2), 0.085 mg kg-1 (group 3), 0.08 mg kg-1 (group 4). When the electromyographic response was 95% of control, the trachea was intubated. In groups 2, 3 and 4, the onset time was significantly decreased compared with group 1. Increasing the priming dose from 0.01 mg kg-1 did not offer any advantage. The duration of blockade (time from the intubating dose to 15% recovery) was not significantly increased with any priming dose. In group 5, the trachea was intubated after suxamethonium 1.5 mg kg-1. Mean onset time, which was significantly shorter than in the other groups, was half that of the groups that received a priming dose. Intubation conditions were better in group 5 than in the other groups (P less than 0.01).
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