Biomedical subjects

S N Jackson

Publications and source records attributed to S N Jackson.

8 recordsLinked to original sources

PubMed2004

MALDI matrices for biomolecular analysis based on functionalized carbon nanomaterials.

When used in small molar ratios of matrix to analyte, derivatized fullerenes and single wall nanotubes are shown to be efficient matrices for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The mixing of an acidic functionalized fullerene with a solution of bioanalyte, depositing a dried droplet, and irradiating with a pulsed nitrogen laser yields protonated or cationized molecular ions. Derivatized fullerenes could offer several advantages over conventional MALDI matrices: a high analyte ionization efficiency, a small molar ratios (less than 1) of matrix/analyte, and a broader optical absorption spectrum, which should obviate specific wavelength lasers for MALDI acquisitions. The major disadvantage to the use of fullerenes is the isobaric interference between matrix and analyte ions; however, it is overcome by using MALDI-ion mobility time-of-flight (IM-oTOF) mass spectrometry to preseparate carbon cluster ions from bioanalyte ions prior to TOF mass analysis. However, an alternative to the dried droplet preparation of fullerene MALDI samples is the aerosolization of matrix-analyte solutions (or slurries) followed by impacting the aerosol onto a stainless surface. We also demonstrate that the fullerene matrices can be used to acquire spectra from rat brain tissue.

Amino Acid Sequence↗

PubMed2001

Infrared matrix-assisted laser desorption/ionization of polycyclic aromatic hydrocarbons with a sulfolane matrix.

Infrared matrix-assisted laser desorption/ionization (IR-MALDI) of the polyaromatic hydrocarbons (PAHs) anthracene, benzo[a]pyrene, and dibenz[a,h]anthracene was performed using a 10.6-microm CO2 laser and a liquid matrix. Sulfolane (tetrahydrothiophene 1,1-dioxide) was found to be an effective matrix for PAH ionization: mass spectra obtained with a sulfolane matrix contain an intense molecular ion peak; interference from PAH fragment and matrix peaks is negligible in all cases. The main limitation of the sulfolane matrix is sample evaporation after 3 to 5 min in vacuum. This sample lifetime can be increased to between 15 and 30 min using a 2:1 (v/v) mixture of sulfolane and glycerol, but the resulting spectra have greater matrix interference and decreased shot-to-shot signal stability.

Anthracenes↗

PubMed2000

LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.

The lipodystrophies are a group of disorders characterized by the absence or reduction of subcutaneous adipose tissue. Partial lipodystrophy (PLD; MIM 151660) is an inherited condition in which a regional (trunk and limbs) loss of fat occurs during the peri-pubertal phase. Additionally, variable degrees of resistance to insulin action, together with a hyperlipidaemic state, may occur and simulate the metabolic features commonly associated with predisposition to atherosclerotic disease. The PLD locus has been mapped to chromosome 1q with no evidence of genetic heterogeneity. We, and others, have refined the location to a 5.3-cM interval between markers D1S305 and D1S1600 (refs 5, 6). Through a positional cloning approach we have identified five different missense mutations in LMNA among ten kindreds and three individuals with PLD. The protein product of LMNA is lamin A/C, which is a component of the nuclear envelope. Heterozygous mutations in LMNA have recently been identified in kindreds with the variant form of muscular dystrophy (MD) known as autosomal dominant Emery-Dreifuss MD (EDMD-AD; ref. 7) and dilated cardiomyopathy and conduction-system disease (CMD1A). As LMNA is ubiquitously expressed, the finding of site-specific amino acid substitutions in PLD, EDMD-AD and CMD1A reveals distinct functional domains of the lamin A/C protein required for the maintenance and integrity of different cell types.

Amino Acid Sequence↗

PubMed1998

A defect in the regional deposition of adipose tissue (partial lipodystrophy) is encoded by a gene at chromosome 1q.

Partial lipodystrophy (PLD), also known as "Dunnigan-Kobberling syndrome," is transmitted as a highly penetrant autosomal dominant disorder that is characterized by a dramatic absence of adipose tissue in the limbs and trunk, more evident in females than in males. In contrast, fat is retained on the face, in retro-orbital space, and at periserous sites. Associated metabolic abnormalities, including insulin resistance, hyperinsulinemia, and dyslipidemia, are referred to as "metabolic syndrome X" (Reaven 1988). Despite the intense interest in the genetic determinants underlying fat deposition, the genes involved in the lipodystrophic syndromes have not been identified. We ascertained two multigeneration families, with a combined total of 18 individuals with PLD, and performed a genomewide search. We obtained conclusive evidence for linkage of the PLD locus to microsatellite markers on chromosome 1q21 (D1S498, maximum LOD score 6.89 at recombination fraction .00), with no evidence of heterogeneity. Haplotype and multipoint analysis support the location of the PLD locus within a 21.2-cM chromosomal region that is flanked by the markers D1S2881 and D1S484. These data represent an important step in the effort to isolate and characterize the PLD gene. The identification of the gene will have important implications for the understanding of both developmental and metabolic aspects of the adipocyte and may prove useful as a single-gene model for the common metabolic disorder known as "syndrome X."

Adipose Tissue↗

PubMed1998

The diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel.

Hypertension is a common multifactorial disorder associated with considerable morbidity and mortality. The kidney plays a major role in the long term regulation of blood pressure. Liddle syndrome (pseudo-hyperaldosteronism) is one of a number of monogenic disorders of salt and water transport. In a kindred with at least four affected members suffering from Liddle syndrome, we confirmed by direct DNA sequencing the identity of a novel heterozygous mutation in h betaENaC, the gene encoding the beta subunit of the amiloride sensitive epithelial sodium channel which is expressed in the distal nephron. Single stranded conformational polymorphism analysis showed cosegregation of the mutant allele within the kindred with the Liddle phenotype. An insertion of an additional cytosine into a string of six located between codons 593 and 595 results in a sequence frameshift and is predicted to produce a protein truncated by 34 amino acids. The availability of a molecular diagnostic tool has implications for the management of hypertension and genetic counselling in families with Liddle syndrome.

Aldosterone↗

PubMed1997

Cabergoline treatment of acromegaly: a preliminary dose finding study.

OBJECTIVES: Studies of the dopamine agonist cabergoline in the treatment of hyperprolactinaemia have shown it to be a potent, long-acting and well-tolerated. The older dopamine agonist, bromocriptine, has traditionally had a place in the medical management of acromegaly, but poor patient tolerance of the high doses required, the need for multiple daily administration and incomplete biochemical responses have limited its role. We therefore sought to investigate the effect of cabergoline on growth hormone (GH) secretion in acromegaly and to define the most appropriate dose for suppression of GH DESIGN AND MEASUREMENTS: Patients with active acromegaly (defined as most recent random GH > 5 mU/l) were identified from the departmental clinical information system. After informed consent was obtained, basal GH levels were estimated during a 5 point day curve at least 2 months after withdrawal of any existing medical therapy for acromegaly. The cabergoline dose was escalated on a monthly basis for 4 months with a repeat 5 point GH day curve at the highest dose, and 0900 and 0930 GH estimations at the intermediate dose increment stages. Serum IGF-1 and prolactin were estimated on each occasion. Biochemical remission was defined as serum GH < 5 mU/l. PATIENTS: Eleven acromegalics were investigated. Previous treatment included surgery (7), radiotherapy (5) and bromocriptine (5). Three patients had not received any previous treatment. All had random GH persistently > 5 mU/l prior to the study. RESULTS: Ten patients completed the study. Of these, 7 showed a fall in the GH to < or = 33% and IGF-1 to < or = 67% of the basal value but only 2 achieved biochemical remission. All subjects showed maximum GH response at a dose of 0.5 mg daily of cabergoline. Four patients were unable to tolerate the maximum dose of 1 mg daily (nausea in one and nonspecific symptoms in three). The patient excluded from the analysis discontinued cabergoline and underwent surgery after 1 month because of worsening visual field defects. CONCLUSIONS: Cabergoline may be a useful adjunct to the currently available treatment for acromegaly, but rarely achieves the goal of mean GH < 5 mU/l. The maximum suppression of GH is achieved within the dose range 1 mg twice weekly to 0.5 mg daily.

Acromegaly↗

PubMed1997

Dunnigan-Kobberling syndrome: an autosomal dominant form of partial lipodystrophy.

Dunnigan-Kobberling syndrome is a form of partial lipodystrophy characterized by sparing of the face. Despite descriptions of six families since 1974, details of total body adipose tissue distribution and studies of carbohydrate and fat metabolism are lacking. The mode of inheritance also remains unclear, with most authors favouring an X-linked dominant transmission lethal in the hemizygous male. We examined 23 members of a family, of whom at least eight had partial lipodystrophy. Auxological evaluation and cross-sectional imaging showed absence of subcutaneous fat, presence of adipose tissue inside the body cavities, and skeletal muscle hypertrophy. Biochemical evaluation identified insulin resistance but revealed inadequate suppression of non-esterified fatty acids. In this family, male-to-male transmission supports an autosomal dominant mode of inheritance for Dunnigan-Kobberling syndrome.

Acanthosis Nigricans↗

PubMedDate not supplied

Matrix implanted laser desorption ionization (MILDI) combined with ion mobility-mass spectrometry for bio-surface analysis.

The implantation of low velocity massive gold cluster ions allows homogeneous incorporation of a metallic matrix into the near-surface region of rat brain tissues. Subsequent analysis by laser desorption ionization mass spectrometry yields spectra exhibiting molecular ion peaks in the mass range up to 35 kDa similar to those observed by matrix-assisted LDI. Matrix-implanted LDI when combined with ion-mobility preseparation promises to be a useful technique for molecular imaging of biotissues with a laser microprobe.

Animals↗