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M Salim

Publications and source records attributed to M Salim.

At least 37 records · Page 2Linked to original sources

Expression of the human beta-amyloid protein of Alzheimer's disease specifically in the brains of transgenic mice.

The human beta-amyloid protein is deposited in senile plaques and in the cerebro-vasculature of people with Alzheimer's disease and Down's syndrome. The precise role of beta-amyloid in Alzheimer's disease pathology is presently unknown. To study the properties of beta-amyloid in vivo, we generated transgenic mice that harbor the gene for the carboxyl-terminal 100 amino acids of the human amyloid precursor protein, beginning with the beta-amyloid region, under control of the JC viral early region promoter. The mRNA is expressed exclusively in brain tissue. Further, we demonstrate increased levels of beta-amyloid immunoreactivity on fixed brain tissue. These animals will be useful as a model to study beta-amyloid deposition and its consequences.

Alzheimer Disease↗

The postmortem Alzheimer brain is a source of structurally and functionally intact astrocytic messenger RNA.

Although the precise role of astrocytes in the pathogenesis of Alzheimer's disease (AD) is currently undefined, studies carried out at the molecular level may lead to new insights into the functioning of this class of brain cells in dementia. In order to facilitate such investigations, methods are described that establish that structurally and functionally intact messenger RNA (mRNA) for an astrocytic marker, glial fibrillary acidic protein (GFAP), is present in the postmortem Alzheimer's disease brain after long postmortem intervals. Rapid preparative procedures were used to obtain poly(A)+ RNA from postmortem control and AD cortices. In vitro protein synthesis was carried out in a reticulocyte system. Relative to controls, AD mRNA synthesized a two-fold higher level of a 50,000 mol.wt. protein that was immunologically identified as GFAP. High levels of GFAP synthesis by purified mRNA from AD cortices was independent of age at death and postmortem interval up to 24 h. Northern blot hybridization using a cloned human GFAP riboprobe was used to evaluate postmortem GFAP mRNA stability. No appreciable degradation products of GFAP mRNA were observed on Northern blots for at least 10 h postmortem in poly(A)+ RNA extracted from the AD brain. The described methodology demonstrates that the postmortem AD brain is an excellent source of functionally and structurally intact astrocyte-specific mRNA.

Alzheimer Disease↗

Molecular cloning of amyloid cDNA derived from mRNA of the Alzheimer disease brain: coding and noncoding regions of the fetal precursor mRNA are expressed in the cortex.

To gain insight into factors associated with the excessive accumulation of beta-amyloid in the Alzheimer disease (AD) brain, the present studies were initiated to distinguish between a unique primary structure of the AD-specific amyloid precursor mRNA vis a vis other determinants that may affect amyloid levels. Previous molecular cloning experiments focused on amyloid derived from sources other than AD cases. In the present work, we cloned and characterized amyloid cDNA derived directly from AD brain mRNA. Poly(A)+ RNA from AD cortices was used for the preparation of lambda gt11 recombinant cDNA libraries. An insert of 1564 nucleotides was isolated that included the beta-amyloid domain and corresponded to 75% of the coding region and approximately equal to 70% of the 3'-noncoding region of the fetal precursor amyloid cDNA reported by others. On RNA blots, the AD amyloid mRNA consisted of a doublet of 3.2 and 3.4 kilobases. In control and AD cases, the amyloid mRNA levels were nonuniform and were independent of glial-specific mRNA levels. Based on the sequence analysis data, we conclude that a segment of the amyloid gene is expressed in the AD cortex as a high molecular weight precursor mRNA with major coding and 3'-noncoding regions that are identical to the fetal brain gene product.

Aged↗

Nucleotide sequence of an external transcribed spacer in Xenopus laevis rDNA: sequences flanking the 5' and 3' ends of 18S rRNA are non-complementary.

We have sequenced the external transcribed spacer (ETS) of a ribosomal transcription unit from Xenopus laevis, together with sections of the preceding non-transcribed spacer. Our analysis was carried out on the same cloned transcription unit as that from which the internal transcribed spacers (ITS) were previously sequenced. The ETS is approximately 712 nucleotides long and, like the ITS regions, is generally very rich in C plus G. Features of the sequence include an excess of oligo-C tracts over oligo-G tracts and a tract of 37 nucleotides consisting almost entirely of G and A residues. Parts of the sequence can give rise to stable internal secondary structures. However, in contrast to Escherichia coli, there is no potential for major base-pairing between the 18S flanking regions of the ETS and ITS. Further findings are that there are no initiation (ATG) codons in the ETS and that, as in other X.laevis rDNA cloned units, the sequence preceding the ETS is duplicated, with a few changes, in the "Bam island" sequence of the non-transcribed spacer.

Animals↗

Nucleotide sequence of Xenopus laevis 18S ribosomal RNA inferred from gene sequence.

18S ribosomal RNA in Xenopus laevis is 1,825 nucleotides long, as inferred from sequence analysis of an 18S gene. All the 40 rRNA methyl groups can be located in the sequence. Comparison with the yeast (Saccharomyces cerevisiae) 18S sequence reveals extensive regions of high homology interspersed with tracts having little or no homology. Regions of high homology contain almost all the RNa methyl groups. Major regions of low homology area considerably richer in C + G in Xenopus than in yeast.

Animals↗

Nucleotide sequence encoding the 5' end of Xenopus laevis 18S rRNA.

We have sequenced a region of cloned Xenopus laevis ribosomal DNA encompassing the last 24 nucleotides of the external transcribed spacer and the first 275 nucleotides of the 18S gene. The start of the 18S gene was identified by correlating the results obtained from RNA hybridization and fingerprinting with the DNA sequence. This 5' region of 18S rRNA contains five 2'-O-methyl groups and at least six pseudouridine residues. Several of these modified nucleotides are clustered into a relatively short region from nucleotides 99-124. Nucleotides 227-250 constitute a distinctive sequence of 24 consecutive G and C residues. Comparison with the first 160 nucleotides of a yeast 18S gene (25) reveals three blocks of high sequence homology separated by two short tracts where homology is low or absent. The external transcribed spacer sequences diverge widely from within a few nucleotides of the start of the 18S gene.

Animals↗

An improved vacuum collector for fungal spores.

An all-glass improved vaccum collector for fungal spores is described and its merits mentioned. The description of the required components is also given. This vacuum collector combines the merits of smaller dimension and greater efficiency by accommodating Conway Diffusion cells in the spore receiving vessel.

Methods↗

Extensive homologies between the methylated nucleotide sequences in several vertebrate ribosomal ribonucleic acids.

The methylated nucleotide sequences in the rRNA molecules of the following vertebrate cultured cells were compared: human (HeLa); hamster (BHK/C13); mouse (L); chick-embryo fibroblast; Xenopus laevis kidney. In each species the combined 18S, 28S and 5.8S molecules possess approx. 110-115 methyl groups, and the methylated oligonucleotides released after complete digestion of the rRNA by T1 ribonuclease encompass several hundred nucleotides. "Fingerprints" of the three mammalian methyl-labelled 18S rRNA species were qualitatively indistinguishable. "Fingerprints" of digests of 28S rRNA of hamster and mouse L-cells were extremely similar to those of HeLa cells, differing in one and three methylated oligonucleotides respectively. "Fingerprints" of methyl-labelled rRNA from chick and Xenopus strongly resembled those of mammals in most respects, but differed in several oligonucleotides in both 18S and 28S rRNA. At least some of the differences between "fingerprints" appear to be due to single base changes or to the presence or absence of methyl groups at particular points in the primary sequence. The findings strongly suggest that the methylated-nucleotide sequences are at least 95% homologous between the rRNA molecules of the two most distantly related vertebrates compared, man and Xenopus laevis.

Animals↗

Some aspects of psychiatric morbidity in the out-patient population of a general hospital.

A preliminary report on certain aspects of psychiatric morbidity in persons attending the medical out-patients department of the Institute of Post-graduate Medicine, Dacca, have been presented. Out of 652 cases who have been interviewed, 31% had purely psychogenic conditions, 45% were suffering from purely organic diseases and 14.8% complained of symptoms of both organic and psychogenic features. No apparent underlying aetiology have been detected in 8.6% of cases. Of the psychogenic group, neurotic disorders comprised the largest number in the sample; anxiety state and sexual neurosis in males were the commonest neurotic disorders. When the mixed groups are included, 44% of males and 49.8% of females had symptoms which were either purely psychogenic in nature or had conspicuous psychogenic component. Reason for such a high percentage of psychogenic component has been discussed. Most of the patients attending the out-patient department were within the age of 21 to 40 years. Attendance in the number of older age persons were less in the psychogenic group than with organic conditions. Further, in females a significant difference was observed between psychogenic and organic group patients above and below the age of 40 years. Patients younger than 40 years were more in purely psychogenic group compared to organic conditions. Most of the patients have been found to be married both in psychogenic and organic group. However, there was significant difference in attendance rate of single males in the psychogenic group were somewhat over-represented in the sample in comparison to purely organic group. There was no relation of marital states in cases of females.

Adult↗