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Biomedical subjects

J G Hall

Publications and source records attributed to J G Hall.

At least 145 records · Page 8Linked to original sources

Speech rehabilitation in laryngectomees with tracheo-oesophageal fistulas and prostheses.

The Staffieri technique was used in 24 patients, but abandoned due to aspiration. The Blom-Singer or other prostheses were used in 40 cases, 50% achieved fluent speech, 15% spoke partially and 35% were not able to use the prostheses at all. Some complications are always met with in these cases: Dysphagia, leakage around the prostheses and difficulties with the function of the prostheses. The selection of suitable cases is important. Their cooperation and motivation must be ensured preoperatively, and in many cases like those living under poor social conditions or in older patients, this procedure should not be tried.

Humans↗

Studies on the adjuvant action of beryllium. IV. The preparation of beryllium containing macromolecules that induce immunoblast responses in vivo.

Solutions of BeSO4 were added to soluble macromolecules and the mixtures brought to neutrality. Under appropriate conditions much of the beryllium did not precipitate out as insoluble hydroxides but became attached to naturally occurring sulphated proteoglycans and polysaccharides (e.g. heparin, chondroitin sulphate, fucoidan, etc.) and to synthetic, sulphonated aromatic dyestuffs (e.g. trypan, Evans and Coomassie blues, Suramin, etc.). At physiological conditions of pH and ionic strength, these addition compounds were relatively stable and did not dissociate during dialysis. When such materials were injected s.c. into sheep (in doses containing about 50 micrograms Be), rapid lymphoproliferative responses took place in the regional nodes so that immunoblasts appeared in the efferent lymph in numbers that exceeded those provoked by powerful conventional antigenic stimuli. Significant amounts of the injected materials passed through the nodes and, in intact animals, became systematized. A method was devised for attaching beryllium to particulate carriers, such as lymphocytes or red cells that had been fixed with glutaraldehyde. The injection of suspensions of such materials also provoked vigorous immunoblastic responses, but the particulate materials did not pass beyond the regional node. In the doses usually used, none of these materials was grossly toxic and they may be suitable for consideration for development into a new type of immunostimulator cum adjuvant.

Adjuvants, Immunologic↗

Cis-trans isomerization of the proline residue in insulin studied by 13C NMR spectroscopy.

The natural abundance 13C NMR spectrum of bovine insulin contains two resonances at 49.6 and 48.9 ppm which have a 7:3 intensity ratio at 298 K. Use of the DEPT spectral editing technique shows them to be of CH2 multiplicity. On the basis of their chemical shifts, which are well-resolved from other peaks, they are assigned as the C delta carbon of proline in trans and cis forms respectively. Since insulin contains only a single proline residue, the site of the isomerization can be localized at the peptide bond linking Thr-27 and Pro-28. On heating, the two peaks broaden, coalesce at 308 K, and then sharpen to yield a single peak at higher temperatures. The barrier for this process was calculated to be 64 kJ mol-1 (at the coalesce temperature), which is at the lower end of the range observed for proline isomerization in small peptides. Computer-graphic studies based on the X-ray crystal structure of insulin were used to deduce the structural implications of the cis-trans isomerism in this globular protein.

Insulin↗

Clinical, genetic, and epidemiological factors in neural tube defects.

We examined clinical, genetic, and epidemiologic factors among 512 probands with nonsyndromal neural tube defects (NTDs). Data were analyzed after grouping the probands in four different ways with respect to pathological features and putative pathogenic mechanisms. Apparently unrelated congenital anomalies occurred more frequently among probands with craniorachischisis (62%), encephalocele (30%), or multiple NTDs (25%) than among probands with anencephaly (14.7%) or spina bifida (10.1%) (P much less than .0001). Unrelated congenital anomalies occurred less often among probands with low spina bifida (6.7%) than among probands with high spina bifida (19.5%). NTDs were seen in 7.8% of the siblings of probands with high spina bifida but in only 0.7% of the siblings of probands with low spina bifida, in 2.2% of the siblings of anencephalic probands, and in none of the siblings of probands with craniorachischisis, encephalocele, or multiple NTDS (P less than .001). In all 16 families in which two siblings had NTDs, both had either defects of the type associated with abnormal primary neurulation or defects of the type associated with abnormal canalization. High spina bifida and multiple NTDs were found more frequently than expected among the Sikh probands (P less than .02). The frequency of non-NTD congenital anomalies was higher among siblings of Sikh probands (8.8%) than among siblings of other probands (2.4%) (P less than .05). This excess was due to the occurrence of hydrocephalus without spina bifida in four of 68 siblings of Sikh probands.

Adult↗

Studies on the adjuvant action of beryllium. III. The activity in the plasma of lymph efferent from nodes stimulated with beryllium.

Efferent lymph from the popliteal or prefemoral lymph nodes was collected from unanaesthetized sheep before and after the injection of insoluble Be(OH)2 into the subcuticulum that was drained by the nodes. Sterile, cell-free plasma from lymph collected during the 48 hr after the injections, induced vigorous lympho-proliferative responses in naive lymph nodes after s.c. injection into autochthonous or allogeneic recipients. The same lymph had an adjuvant action when injected i.p. into both nude and euthymic rats. Many samples of such lymph were screened for biological activity in rats by noting the increase in the weight of the regional popliteal nodes that occurred after the test sample had been injected into the footpad. All the active samples were shown, by atomic absorbance spectroscopy, to contain beryllium, and we concluded that this metal, in the form of soluble Be-protein adducts, was probably the prime mover in all the observed responses.

Adjuvants, Immunologic↗

Lymphotoxic activity of methyl prednisolone in vitro--I. Comparative toxicity of methyl prednisolone in human cell lines of B and T origin.

The cytotoxic activity of methyl prednisolone was compared in EB-3(B), NALM-6(B), CCRF-CEM(T) and RPMI-8226 (plasma cell) cell lines derived from human lymphoid malignancies. Whereas EB-3 cells were steroid-sensitive, NALM-6 cells were partially sensitive and CCRF-CEM and RPMI-8226 were steroid resistant at concentrations of methyl prednisolone up to 10(-4) M. A high concentration of methyl prednisolone, 2.5 X 10(-3) M was toxic to all cell lines. Steroid-sensitivity did not correlate with the incorporation of [3H] dexamethasone and could not be mimicked by flurbiprofen, a non-steroidal anti-inflammatory agent. Both theophylline and di-butyryl cAMP were toxic towards NALM-6, EB-3 and CCRF-CEM cells; however, this toxicity was reversible and did not reflect the cells' sensitivities towards methyl prednisolone. Furthermore, elevated levels of cAMP in theophylline-treated cells, were not demonstrable in cells treated with methyl prednisolone at toxic or non-toxic concentrations of the steroid. Steroid-sensitive EB-3 cells exposed to 10(-5) M methyl prednisolone, produced a soluble factor which was toxic CCRF-CEM cells.

B-Lymphocytes↗

C-13 NMR spectral studies of the thyroid hormone transport protein, transthyretin and the pancreatic insulin storage moiety, the zinc-insulin hexamer.

The DEPT spectral editing technique was used to separate the CH, CH2 and CH3 resonances in the C-13 NMR spectra of transthyretin and the porcine zinc insulin hexamer. The advantages of this technique in terms of spectral simplification and sensitivity enhancement for 13C NMR of proteins is discussed. Spin-lattice relaxation time and nuclear Overhauser effect measurements of the backbone C-alpha and aliphatic sidechain carbons provided information about the dynamics of the proteins in solution and the relative mobility of some sidechain groups.

Animals↗

Use of genetic counselling services for neural tube defects.

Genetic counselling is recommended for parents of children with neural tube defects (NTDs) to inform them of the recurrence risks and the option of prenatal diagnosis. British Columbia provides an excellent site to examine the use by parents of genetic counselling services for NTDs. Genetic services for the entire province are centralized, and there is virtually complete ascertainment of all NTD births. The results from this study indicate that use of genetic counselling services is influenced by the type of NTD present and whether the index case was live or stillborn. Genetic counselling is most often sought after the birth of a liveborn infant with spina bifida.

Anencephaly↗

Dominantly inherited renal adysplasia.

We are reporting on 7 families with both unilateral and bilateral renal agenesis (or severe dysplasia). This condition, termed hereditary renal adysplasia (HRA) [Buchta et al, 1973], is an autosomal dominant trait with incomplete penetrance and variable expression. Review of the literature on familial renal agenesis suggests that HRA is more common than previously supposed and may account for most recurrences of bilateral renal agenesis (BRA), even when the parents are normal. There are no consistent phenotypic differences between sporadic and familial renal agenesis. Associated non-urogenital anomalies, although more frequent in sporadic cases, have been reported in HRA. Use of several approaches, including the Weinberg Proband Method, segregation analysis, and empiric risk estimation, leads to the conclusion that autosomal dominant inheritance is the most likely pattern of transmission for most cases of renal agenesis. Penetrance is between 50% and 90%. Ultrasound study of the kidneys of parents, sibs, and other relatives is recommended in all families in which there is an individual with unilateral or bilateral renal agenesis. The empiric risk for recurrence of BRA in sibs has been estimated at 3.5% [Carter, et al, 1979] but in the offspring of affected or obligate heterozygotes for HRA, the empiric risk of bilateral severe renal adysplasia is 15-20%.

Genes, Dominant↗

Lymphedema in Noonan syndrome: clues to pathogenesis and prenatal diagnosis and review of the literature.

The Noonan syndrome (NS) is a true multiple congenital anomalies (MCA) syndrome with numerous manifestations. An association with lymphedema has been noted, but its pathogenesis is not fully understood. Nine new cases and a review of the literature explore the role of lymphedema in NS, including its pathogenesis, presentations, and phenotypic effects. Consideration is given to developmental stage at time of onset, chronicity, resolution, and anatomic site. It appears likely that lymphedema is a much more frequent concomitant in NS than previously realized. The major source of lymphedema in NS appears to be a presently undefined dysplasia of lymphatic vessels of unknown cause. Further study of lymphedema may provide an understanding of its role in shaping the NS phenotype. Comparison with other MCA syndromes and animal models is made in this regard. Relevance to prenatal diagnosis and treatment is discussed.

Adult↗

Gonadal mosaicism in pseudoachondroplasia.

We report on a family in which a brother and sister have pseudoachondroplasia and normal parents. The brother married a normal woman, and they have 2 daughters; one of them has typical changes of pseudoachondroplasia, the other is normal. The most likely explanation in this family is gonadal (germinal cell) mosaicism in one of the grandparents. Other reports of possible autosomal recessive pseudoachondroplasia are reviewed. It is likely that gonadal mosaicism is responsible for a small percentage of cases with what appears to be a new mutation for pseudoachondroplasia.

Achondroplasia↗

Thanatophoric dysplasia and cloverleaf skull.

Nine infants with thanatophoric dysplasia (TD) and cloverleaf skull (CS) are reported. Twenty-two previously published CSTD cases are reviewed. These CSTD cases are compared to cases of TD without CS. It is concluded that there are two types of TD: type 1, with curved femora and very flat vertebral bodies; and type 2, with straight femora and taller vertebral bodies. Consistent but subtle histopathological characteristics differentiate the two types. Only a very few type 1 cases have CS, and the CS is mild. Almost all type 2 cases have severe CS.

Female↗

Morphine dependence in the rat: the appearance in the spinal cord of a dorsal root ganglion cell neurotrophic factor.

An increase in neurotrophic activity for the survival of dissociated sensory neurones has been found in the spinal cord of morphine dependent rats. This activity is not due to morphine itself and is not due to an increase in the nerve growth factor as antibodies to nerve growth factor fail to block the response. A new hypothesis is presented that some of the spinal effects of morphine dependence may be due to an increase in the level of neurotrophic factors as a response to an apparent denervation of the target cells in the spinal cord.

Animals↗

1-Methylisoguanosine: interaction with central adenosine receptors and lack of antagonism of its in vivo effects by a benzodiazepine antagonist.

1-Methylisoguanosine, a marine natural product analogue of adenosine, with moderate activity as a benzodiazepine receptor ligand, has previously been shown to have muscle-relaxant and hypothermic activity in mice in vivo. The present experiments showed that the benzodiazepine antagonist Ro15-1788 did not block the in vivo muscle-relaxant and hypothermic effects of 1-methylisoguanosine, suggesting that these particular actions are not due to interactions with benzodiazepine receptors. When applied by microiontophoresis near spontaneously-active neurones or neurones activated by ACh, DL-homocysteate or glutamate in the ventrobasal thalamus of anaesthetized rats, 1-methylisoguanosine had a depressant action; it was similar to adenosine in potency and in its ability to be antagonized by 8-(parasulphophenyl)theophylline. The depression was usually longer lasting than that caused by adenosine, consistent with previous neurochemical data showing it to be resistant to adenosine deaminase and a poor substrate for the uptake system for adenosine in the CNS. These results suggest that the major pharmacological/behavioural actions of 1-methylisoguanosine in vivo are more likely to be caused by an interaction with adenosine receptors, rather than with benzodiazepine sites.

Animals↗