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Biomedical subjects

M Zubair

Publications and source records attributed to M Zubair.

17 recordsLinked to original sources

Lactational performance of Quackenbush Swiss line 5 mice.

We evaluated 2 strains of mice for their utility in the investigation of nutritional and molecular regulatory mechanisms of lactation. The lactational performance and milk composition were characterized for an inbred mouse strain, inbred Quackenbush Swiss line 5 (QSi5) selected persistently for fecundity, and a nonselected strain, CBA. The milk yield assessed by changes in BW in response to suckling of sustainable litter sizes for each strain was 3-fold greater (P < 0.001) in QSi5 mice than the CBA strain. The QSi5 mice also produced milk more efficiently (P < 0.001) than CBA mice, despite having the same quantity of mammary tissue per unit of BW. Milk composition did not vary between strains or by stage of lactation, with the exception of lactose concentration, which was greater (P = 0.003) in QSi5 mice. Expression of epsilon-casein was > or = 10-fold greater, and alpha(S1)-casein was > or = 3-fold greater, during mid and late lactation compared with early lactation in both strains, whereas kappa-casein underwent an apparent alteration in posttranslational modifications in both strains from early to mid lactation. Changes in casein composition coincided with an increased susceptibility to proteolytic degradation; hence milk from early lactation may be more readily degraded to facilitate digestion in the neonate. The greater milk synthetic capacity of QSi5 mice over the lactation cycle provides a useful model for studies of nutritional and molecular regulation of lactation.

Animals↗

The paternal methylation imprint of the mouse H19 locus is acquired in the gonocyte stage during foetal testis development.

BACKGROUND: Germline-specific differential DNA methylation that persists through fertilization and embryonic development is thought to be the 'imprint' distinguishing the parental alleles of imprinted genes. If such methylation is to work as the imprinting mechanism, however, it has to be reprogrammed following each passage through the germline. Previous studies on maternally methylated genes have shown that their methylation imprints are first erased in primordial germ cells (PGCs) and then re-established during oocyte growth. RESULTS: We have examined the timing of the reprogramming of the paternal methylation imprint of the mouse H19 gene during germ cell development. In both male and female PGCs, the paternal allele is partially methylated whereas the maternal allele is unmethylated. This partial methylation is completely erased in the female germline by entry into meiosis, establishing the oocyte methylation pattern. In the male germline, both alleles become methylated, mainly during the gonocyte stage, establishing the sperm methylation pattern. CONCLUSION: The paternal methylation imprint of H19 is established in the male germline and erased in the female germline at specific developmental stages. The identification of the timings of the methylation and demethylation should help to identify and characterize the biochemical basis of the reprogramming of imprinting.

Animals↗

Multiple imprinted sense and antisense transcripts, differential methylation and tandem repeats in a putative imprinting control region upstream of mouse Igf2.

The mouse insulin-like growth factor 2 (Igf2) locus is a complex genomic region that produces multiple transcripts from alternative promoters. Expression at this locus is regulated by parental imprinting. However, despite the existence of putative imprinting control elements in the Igf2 upstream region, imprinted transcriptional repression is abolished by null mutations at the linked H19 locus. To clarify the extent to which the Igf2 upstream region contains autonomous imprinting control elements we have performed functional and comparative analyses of the region in the mouse and human. Here we report the existence of multiple, overlapping imprinted (maternally repressed) sense and antisense transcripts that are associated with a tandem repeat in the mouse Igf2 upstream region. Regions flanking the repeat exhibit tissue-specific parental allelic methylation patterns, suggesting the existence of tissue-specific control elements in the upstream region. Studies in H19 null mice indicate that both parental allelic methylation and monoallelic expression of the upstream transcripts depends on an intact H19 gene acting in cis. The homologous region in human IGF2 is structurally conserved, with the significant exception that it does not contain a tandem repeat. Our results support the proposal that tandem repeats act to target methylation to imprinted genetic loci.

Alleles↗

Structure and expression of the mouse L23mrp gene downstream of the imprinted H19 gene: biallelic expression and lack of interaction with the H19 enhancers.

The human L23 (mitochondrial)-related protein gene, located 40 kb downstream of the imprinted H19 gene, is biallelically expressed. We have cloned and characterized its mouse homolog, L23mrp, which maps to the conserved syntenic region on mouse chromosome 7. The promoter of L23mrp is a CpG island that is transcribed ubiquitously, but at different levels, in different fetal tissues. Allele-specific expression analysis revealed that both parental alleles are equally active. Since the enhancers located between H19 and L23mrp had been shown to be involved in the imprinted expression of Ins-2, Igf-2, and H19, we asked whether they also influence L23mrp. Analysis of mice with a targeted deletion of the enhancers demonstrated that they were not disrupted in the expression of L23mrp. These findings indicate that L23mrp is functionally insulated from the Ins-2/Igf-2/H19 domain in terms of both imprinting and enhancer action.

Alleles↗

Pediatric electrical burns: management strategies.

The purpose of the present study was to analyse the course of patients hospitalised with electrical burn wounds in the past 25 years at a major children's hospital in the United States in order to devise safe and cost effective management strategies for these patients. The study was a retrospective chart review of patients with electrical injuries admitted to the hospital between 1971 and 1995. We identified 127 children who were included in the study. Injuries resulted from biting an electrical cord (oral injury) (n = 48), placing an object into an electrical socket (outlet injury) (n = 33), contacting a low voltage wire or appliance indoors (low voltage household injury) (n = 25), contacting a high voltage wire outdoors (high voltage wire injury) (n = 18), or being struck by lightning (n = 3). A retrospective review revealed that the great majority of patients with low voltage electrical injuries did not need admission to the hospital and could have been cared for on an outpatient basis. Almost every patient with high voltage injury had a justified admission due to the severity of the injury. On the basis of these results we conclude that we can safely reduce the number of admissions to the hospital for children with low voltage minor electrical injuries.

Adolescent↗

Nucleotide sequence of a 28-kb mouse genomic region comprising the imprinted Igf2 gene.

The mouse insulin-like growth factor II gene (Igf2) is physically linked to the insulin II gene (Ins2) and both are subject to tissue-specific genomic imprinting. The paternal-specific expression of Igf2 has been associated with hypermethylation of some CpG sites in the 5' flanking region and in the body of the gene. As a first step in analyzing the structural features of this imprinted locus, we here report the complete nucleotide sequence of Igf2, including all introns and the intergenic region adjacent to Ins2. This 28-kb segment of mouse chromosome 7 exhibits 80% overall identity with the corresponding rat sequence and has a high GC content of 52%. In addition to the known CpG island within the second Igf2 promoter, another island was identified approximately 2 kb 5' to the first exon. Other features of this locus include a 35-fold tandem repeat of an 11-bp sequence that overlaps Igf2 pseudo-exon 2, and a B2 repeat element in the intergenic region between Ins2 and Igf2. The GC-richness and the presence of CpG islands associated with tandem repeats are common features of imprinted genes and thus may play a role in the imprinting mechanism.

Animals↗

Cardiopulmonary resuscitation in intensive care unit and non-intensive care unit patients. Immediate and long-term survival.

OBJECTIVE: To determine the effect of location within the hospital and preexisting electrocardiographic rhythm on the outcome of cardiopulmonary resuscitation, the cardiopulmonary resuscitation records for a 3-year period, including 668 hospitalized patients, were retrospectively reviewed. RESULTS: Resuscitation was successful in only 12 patients in the intensive care unit (3.3%) and 43 patients not in the intensive care unit (14.0%), 20 of whom were on a telemetry unit. Patients who survived to discharge had similar 1-year survival rates regardless of initial hospital location, although intensive care unit patients had the best 3-year survival rate, and there were no survivors at 3-years in the group that received cardiopulmonary resuscitation in the nonmonitored hospital bed. Survival was best with an initial cardiac rhythm of ventricular tachycardia or fibrillation, but all non-ventricular tachyarrhythmias were associated with survival. Age was not an apparent factor, while survival to hospital discharge favored whites over blacks. CONCLUSIONS: Futile resuscitative efforts are routinely performed in part because physicians and patients are unaware of outcome results and factors that influence survival. A wider recognition of the limitations of cardiopulmonary resuscitation should lead to advanced directives that reflect this awareness, with substantially more patients choosing not to have cardiopulmonary resuscitation.

Advance Directives↗

Streptomyces ATP nucleotide 3'-pyrophosphokinase and its gene.

Streptomyces ATP nucleotide 3'-pyrophosphokinase is an extracellular, ribosome-independent, and stringent factor-mimic ppGpp synthetase with an unusually broad acceptor spectrum. The gene-containing DNA fragments cloned from chromosomal DNA of a producer S. morookaensis into pIJ699 and pUC plasmids were found to express the active enzyme in the transformed S. lividans TK24 and enteric E. coli JM109 and nitrogen-fixing Klebsiella pneumoniae M5a1 and 5022, respectively. Base sequence of the structural gene and the deduced amino acid sequence exhibited little homology to those of E. coli stringent factor and related proteins. Growth retardation was seen in some transformants.

Base Sequence↗

Isradipine in Asian patients with hypertension.

Isradipine, a new calcium antagonist, was administered to 51 Pakistani patients with hypertension (36 women, 15 men; mean age 47 years) over an 8-week period. Mean sitting systolic, and sitting and standing diastolic blood pressure was significantly reduced, and mean standing systolic blood pressure tended to decrease. Laboratory values, and both sitting and standing heart rates were not significantly affected by isradipine treatment. At the end of 8 weeks, 41.2% of patients were receiving isradipine 1.25mg twice daily, and 58.8% were receiving 2.5mg twice daily. Isradipine was found to be effective and well tolerated in Pakistani patients with mild to moderate hypertension.

Adult↗

Prevalence of coronary heart disease in Pakistani patients suffering from maturity onset diabetes mellitus.

In a group of 500 ambulant Pakistani patients suffering from diabetes mellitus, electrocardiographic evidence of coronary heart disease was present in 45 (9%). The frequency was higher in the males (12.1%) as compared to females (7.2%). The male diabetics with coronary heart disease had significantly high mean serum cholesterol values as compared to those without it. A positive family history of ischaemic heart disease, and the presence of small vessel disease as well as hypertension were more frequently associated with coronary heart disease. The overall frequency of hypertension was 21.2 per cent in this group of diabetics.

Adult↗

Diagnostic evaluation of hypertension: pilot study in a hypertension clinic.

Two hundred and eighty-two (282) patients suffering from hypertension were evaluated for the detection of secondary forms of hypertension. Apart from clinical and routine laboratroy investigation in each, straight film of abdomen, intravenous pyelography (IVP), isotope renography and aortography were done in 174, 51, 109 and 2 cases respectively. Evidences of secondary hypertension was present in 22(7.8%) of which renal aetiology was probable in all but 4. Of the 10 patients with a primary kidney condition, possible renal aetiology was unsuspected in only one patient with unilateral renal hypoplasia. In 8 patients with renal involvement due to systemic disease, or in 4 with non-renal causes, the aetiological diagnosis was suggested by the clinical situation. In view of low yield of curable hypertension and high cost, IVP and renography should only be employed selectively and not as routine investigations.

Adult↗