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Biomedical subjects

D Nam

Publications and source records attributed to D Nam.

12 recordsLinked to original sources

Observations on haemoglobin types in three breeds of Omani goats.

Haemoglobin (Hb) types were studied in three breeds of Omani goats, Batinah (n = 22), Jebel Akhdar (n = 27) and Dhofari (n = 85). Type A was the only adult Hb observed in adult Batinah and Jebel Akhdar goats. In contrast, only 34% of the Dhofari goats were homozygous for Hb A, while 66% were heterozygous for Hb A and Hb B. Dhofari goats with type AB could further be differentiated into those with approximately 67% type A and 33% type B and those with approximately 33% type A and 67% type B. None of the goats was homozygous for type B. Seventeen kids observed from birth exhibited different levels of fetal Hb, dependent upon whether they developed the adult phenotype AA or AB. Kids that became homozygous for type A were born with approximately 90% Hb F and 10% Hb A. In contrast, goats that developed the heterozygous AB phenotype were born with only 30-60% Hb F, the remaining Hb being types A and B. These findings are not in accordance with previous reports that kids are born without any adult Hb. Hb F was no longer detectable in any of the three breeds of goats at 49 days of age. There was no evidence of Hb C, the pre-adult form of Hb.

Aging↗

Role of corticosterone in ethyl carbamate-induced immunosuppression in female BALB/c mice.

We have recently demonstrated that the antibody response to the T-cell-dependent antigen, sheep red blood cells (SRBCs), was suppressed by ethyl carbamate in female BALB/c mice. At the same doses, ethyl carbamate decreased in the numbers of splenic macrophages, B cells, total T cells, CD4(+) T cells and CD8(+) T cells. In addition, the serum level of corticosterone was increased dose-dependently. To investigate the possible role of corticosterone in ethyl carbamate-induced immunosuppression, the antibody response to SRBCs and the subpopulation changes of splenocytes and thymocytes were determined in naive, sham-operated and adrenalectomized (ADX) female BALB/c mice. When the mice were treated intraperitoneally with 400 mg/kg ethyl carbamate, the antibody response was significantly suppressed by ethyl carbamate in naive and sham-operated mice in accompanying the decrease in spleen and thymus weights and/or the increase in the level of serum corticosterone. Meanwhile, the antibody response was not suppressed by ethyl carbamate in the ADX mice. The splenic numbers of total cells, macrophages, B and T cells, and CD4(+) cells were decreased by ethyl carbamate in naive and sham-operated mice. Meanwhile, each cell number was comparable with control in the ADX mice. The flow cytometric analyses on thymocytes did not show obvious differences as seen in the spleen. Finally, when the ADX mice were treated intraperitoneally with 25 mg/kg corticosterone, the antibody response was significantly suppressed. Taken together, our present results suggested that corticosterone might be, at least partially, responsible for ethyl carbamate-induced immunosuppression in female BALB/c mice.

Adrenalectomy↗

New dopamine receptor, D2(Longer), with unique TG splice site, in human brain.

Brain dopamine receptor agonists alleviate the signs of Parkinson's disease, while dopamine receptor antagonists alleviate hallucinations and delusions in psychosis. The dopamine type 2 receptor (or D2) is blocked by antipsychotic drugs, including even the "atypical" drugs such as clozapine or remoxipride, in direct relation to their clinical potencies. Compared to the long form of the D2 receptor (D2(Long)), the short form (D2(Short)) may be three times more sensitive to benzamide antipsychotic drugs. Hence, it is essential to identify additional variants of dopamine receptors for which more selective antipsychotic drugs can be found. Although no family linkage has been found between the D2 receptor and schizophrenia, there can be brain region abnormalities in the RNA transcript expression of dopamine receptors. Therefore, in order to identify variant dopamine D2 receptors, we searched for mutations in the RNA transcripts for the dopamine D2 receptor in the striatum of post-mortem brains from individuals who died with psychosis, including schizophrenia. A new splice variant of the D2 receptor, D2(Longer), with a unique TG splice site, was found in one control brain and in two psychotic brains.

Adult↗

Long-term effects of nitrous oxide anaesthesia on laboratory and clinical parameters in elderly Omani patients: a randomized double-blind study.

AIMS: This study examined the long-term effects of nitrous oxide anaesthesia on serum levels of cobalamin and folate, red cell folate levels and haematological parameters, and neurological status in elderly Omani patients. METHODS: Sixty-nine consecutive patients undergoing ophthalmic surgery were randomly and double-blind assigned to nitrous oxide or propofol anaesthesia. They met the following entry criteria: age 55 years or above, no major organ failure, no clinical signs or symptoms of cobalamin or folate deficiency, mean cell volume (MCV) </= 96 fl, haematocrit (Hct) higher than 0.3 and no cobalamin and/or folate substitution therapy during the preceding months. Serum levels of cobalamin and folate, red cell folate levels, and haematological parameters were measured prior to anaesthesia and 3-5 weeks later. At that time, the patients also underwent thorough neurological examination. RESULTS: Data of 51 patients were complete and considered for analysis. In both nitrous oxide and propofol group, the range of exposure time was comparable (+/-1 h). In the nitrous oxide group, a slight but significant decrease in haemoglobin, Hct, and red blood cell count (RBC) (P < 0.001) was observed, whereas there was a mild increase in mean cell haemoglobin (MCH) and mean cell volume (P < 0.05). In addition, there was a significant decrease in serum folate levels (P < 0.05). Hct and RBC decreased slightly in the propofol group (P < 0. 05), whereas there was a small increase in MCH. There was no difference between the two anaesthetics with regard to serum cobalamin and red cell folate levels, but there was a significant decrease in serum folate levels in the nitrous oxide group compared to those in the propofol group. Three patients with pre-existing low red cell folate levels, who were randomized to nitrous oxide anaesthesia, developed clinical symptoms of folate deficiency. CONCLUSION: This study showed that short-term (40-80 min) nitrous oxide anaesthesia did not affect cobalamin levels but reduced serum folate levels in this elderly population. Although this reduction was clinically irrelevant, some patients with pre-existing asymptomatic folate deficiency developed nitrous oxide-induced folate deficiency.

Aged↗

A human serotonin-7 receptor pseudogene.

Although the serotonin-7 receptor was cloned several years ago, its localization in brain tissues remains confusing because of the existence of a related expressed pseudogene, the sequence of which has not hitherto been reported. During the course of searching for related receptor genes, we also searched for this pseudogene to determine its sequence. Human genomic DNA was screened for dopamine and serotonin receptor-like genes, using the polymerase chain reaction method and degenerate oligonucleotide primers based on the similar sequences in the transmembrane-6 and -7 regions of the serotonin-5A, the serotonin-7, and the dopamine D2, D3 and D4 receptors. This resulted in one of the clones having a 115 bp fragment, of which 89% of the bases were identical to the transmembrane-6 and -7 regions of the serotonin-7 receptor sequence. The fragment was radiolabelled and used to screen a human fetal brain cDNA library. A novel cDNA clone of 1326 bp was isolated. Based on the nucleotide sequence, 88% of the bases in this sequence of the pseudogene are identical to the human serotonin-7 receptor coding sequence. However, compared to the serotonin-7 receptor DNA sequence, the pseudogene sequence has nucleotide deletions and insertions, resulting in frame-shifts and stop codons. It was concluded that this sequence represented a pseudogene related to the serotonin-7 receptor gene.

Amino Acid Sequence↗

The human serotonin-7 receptor pseudogene: variation and chromosome location.

We report a variation of the pseudogene for the serotonin-7 receptor in human DNA. Human genomic DNA was amplified, using the polymerase chain reaction method and degenerate oligonucleotide primers for serotonin receptor-like genes. A novel gene DNA sequence of 1325 bp was found. Based on nucleotides, this gene is 88% identical to the serotonin-7 receptor coding sequence. Compared with the previously known serotonin-7 receptor pseudogene, this pseudogene has 1 nucleotide deletion and 4 nucleotide mutations. The gene is located on human chromosome 12 at 12p12.3-p13.2.

Chromosomes↗

A polymorphic dinucleotide repeat in the human dopamine D5 receptor gene promoter.

Previously, we have reported the cloning and characterization of the 5'-flanking region of the human dopamine D5 receptor encoding gene (D5) and that the major transactivation domain was 119-182 bp upstream of the transcriptional start site [Beischlag, T.V. et al., Biochemistry, 34 (1995) 5960-5970]. Within this region existed a small dinucleotide repeat termed (TC)13. In this report, we describe the screening of genomic DNAs from 18 unrelated individuals by single-strand conformation polymorphism (SSCP) analysis. SSCP analysis revealed the existence of two additional alleles, termed (TC)12 and (TC)14. Neither form significantly altered D5 promoter-mediated luciferase activity when compared to that of the wild-type control, suggesting that small differences in the number of dinucleotide repeats are not likely of any functional consequence for D5 transactivation.

Base Sequence↗

Dopamine and serotonin receptors: amino acid sequences, and clinical role in neuroleptic parkinsonism.

This review summarizes the amino acid sequences of the human dopamine and serotonin receptors and their human variants. The review also examines the receptor basis of the atypical antipsychotic drugs that elicit less parkinsonism than the typical antipsychotics. Because the dissociation constant of a drug varies with the radioligand, the dissociation constants of many neuroleptics are here summarized for the dopamine D2-, D4- and serotonin S2A-receptors using different radioligands. Radioligands of low solubility in the membrane (having low tissue/buffer partition) result in lower values for the neuroleptic dissociation constants, compared to radioligands of high membrane solubility. Such studies yield the intrinsic K value for a neuroleptic in the absence of a competing ligand. Clozapine, for example, has an intrinsic K value of 1.6 nM at the D4-receptor, in agreement with the value of 1.6 nM when directly measured with [3H]clozapine at D4. However, because clozapine competes with endogenous dopamine, the in vivo clozapine concentration to occupy 75% of the dopamine D4-receptors is derived to be approximately 13 nM. This agrees with the value of 12 to 20 nM in the plasma water (or spinal fluid) observed in treated patients. Moreover, in L-DOPA psychosis (in Parkinson's disease), the clozapine concentration for 75% blockade of D4 is predicted to be approximately 3 nM. This agrees with the value of approximately 1.2 nM observed by Meltzer et al. in plasma water (Neuropsychopharmacology, 12, 39-45 (1995)). This analysis supports the concept and practical value of the intrinsic K values. Some atypical neuroleptics (remoxipride, clozapine, perlapine, seroquel and melperone) have high intrinsic K values (ranging from 30 to 88 nM) at the D2-receptor, making them displaceable by high levels of endogenous dopamine in the caudate/putamen. In contrast, however, typical neuroleptics (i.e., those that typically cause parkinsonism) have intrinsic K values of 0.3 to 6 nM, making them less displaceable by endogenous dopamine. A relationship exists between the neuroleptic doses for rat catalepsy and the D2/D4 ratio of the intrinsic K values. Thus, the atypical neuroleptics appear to fall into two groups, those that bind loosely to D2 and those that are selective at D4.

Amino Acid Sequence↗

Frequency and clinical significance of erythrocyte genetic abnormalities in Omanis.

The frequencies of four malaria associated erythrocyte genetic abnormalities have been established in 1000 Omani subjects. They are: homozygous alpha+ thalassaemia (-alpha/-alpha) 0.45; high Hb A2 beta thalassaemia trait 0.015; sickle trait (Hb A/S) 0.061; and glucose 6 phosphate dehydrogenase deficiency (Gd-): males 0.27, females 0.11. From our data the alpha+ (-alpha/) thal gene (confirmed by Southern blotting) is pandemic in this population. Moreover, in spite of the very high frequency of Gd-, oxidative haemolytic syndromes are very uncommon. Also preliminary data indicate that among the Omani population with sickle cell disease, homozygosity of the alpha+ gene markedly modifies the clinical picture.

Adolescent↗

Estimation of fibrinogen-fibrin related antigen by continuous flow analysis.

A precise method for the determination of fibrinogen-fibrin related antigen (FR antigen) in an automated tanned red cell haemagglutination inhibition system is described. In a continuous flow system aliquots of serum are mixed with a dilution of rabbit anti-human fibrinogen serum. The FR antigen neutralizes the anti-fibrinogen serum and on addition of tanned human red cells sensitized with human fibrinogen, the cells agglutinate according to the remaining anti-fibrinogen activity. The agglutinates are removed and the remaining free cells are haemolysed with saponin and the colour measured at 550 nm. The density of the colour formed is in proportion to the amount of FR antigen present. The range in 102 normal males was 4.8 plus or minus 2.4 mug/ml. A significant increase in the levels of FR antigen throughout pregnancy was found, the highest levels being in the latter half of the third trimester. The levels of FR antigen in 31 normal urines was 0.46 plus or minus 0.44 mug/ml.

Adult↗