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J M Graham

Publications and source records attributed to J M Graham.

At least 73 records · Page 4Linked to original sources
PubMed1997

A quick, easy and inexpensive method for the isolation of human peripheral blood monocytes.

A commercial monocyte isolation technique based on the OptiPrep density-gradient medium was up-scaled with respect to sample and reagent volumes. The results of 7 isolations are reported in which the average purity ranged from 87.9 to 96.4%. In all but the initial isolation, monocytes were defined as CD15+ dim CD4+ dim as assessed by flow cytometric analysis; in the first isolation, monocytes were defined by the traditional CD14+ CD4+ dim combination. The mean yield (the number of isolated monocytes relative to the number present in the buffy coat) of all isolations was 26.1%, with the individual yields ranging from 10.8 to 41.4%. The mean number of isolated monocytes per experiment was 3.6 x 10(6) monocytes for those isolations performed using 14 ml of buffy coat/OptiPrep mixture (n = 4). The isolated cells were viable (> 95%) and were not activated, according to HLA-DR expression. This technique is a convenient, tast (less than 2 h), relatively simple, and inexpensive alternative to traditional monocyte isolation techniques. The up-scaled version of this method also results in significantly higher numbers of monocytes per isolation than some traditional techniques. Furthermore, this is the first literature report of the use of the OptiPrep density-gradient medium for the isolation of monocytes.

CD4 Antigens↗
PubMed1997

Deletions of 20p12 in Alagille syndrome: frequency and molecular characterization.

Alagille syndrome is an autosomal dominant disorder comprising cholestasis (associated with intrahepatic bile duct paucity), characteristic facial appearance, and cardiac, ocular and skeletal defects. Multiple patients have been reported with deletions or translocation involving 20p11.23-p12, providing evidence for the localization of the disease gene to this region. Fifty-six Alagille syndrome patients have been studied by cytogenetic and/or molecular analysis to determine the frequency of detectable abnormalities of 20p12. Two of fifty-six patients studied by cytogenetic analysis had abnormalities: an interstitial deletion in one patient and a translocation in another. Of forty-five patients studied by molecular analysis, three were found to have deletions of 20p, including the two patients identified with cytogenetic abnormalities. Molecular and molecular cytogenetic (FISH) analysis of the translocation (46,XX,t(2;20)(q21.3p12)) demonstrated a deletion at the translocation breakpoint. The deletions identified in the three patients are overlapping, contributing to the delineation of an Alagille syndrome critical region within 20p12. This region lies between markers D20S41 and D20S162. The frequency of detectable cytogenetic abnormalities of 20p12 in this group of Alagille patients is 2/56 (3.6%), and the frequency of molecular deletions is 3/45 (6.7%). This is considerably lower than the frequency of deletions observed in contiguous gene deletion syndromes suggesting that Alagille syndrome may be caused by the alteration of a single gene.

Adolescent↗
PubMed1997

Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder.

We critique published incidences for fetal alcohol syndrome (FAS) and present new estimates of the incidence of FAS and the prevalence of alcohol-related neurodevelopmental disorder (ARND). We first review criteria necessary for valid estimation of FAS incidence. Estimates for three population-based studies that best meet these criteria are reported with adjustment for underascertainment of highly exposed cases. As a result, in 1975 in Seattle, the incidence of FAS can be estimated as at least 2.8/1000 live births, and for 1979-81 in Cleveland, approximately 4.6/1,000. In Roubaix, France (for data covering periods from 1977-1990), the rate is between 1.3 and 4.8/1,000, depending on the severity of effects used as diagnostic criteria. Utilizing the longitudinal neurobehavioral database of the Seattle study, we propose an operationalization of the Institute of Medicine's recent definition of ARND and estimate its prevalence in Seattle for the period 1975-1981. The combined rate of FAS and ARND is thus estimated to be at least 9.1/1,000. This conservative rate--nearly one in every 100 live births--confirms the perception of many health professionals that fetal alcohol exposure is a serious problem.

Female↗
PubMed1997

Surgical correction of incomplete cryptophthalmos in Fraser syndrome.

PURPOSE: To demonstrate favorable long-term visual outcome after ocular reconstruction in an infant with Fraser syndrome and with complete left cryptophthalmos. METHODS: Reconstruction of incomplete right cryptophthalmos in our patient was accomplished in a stepwise manner, beginning in the third week of life, by dissecting the eyelids from the cornea, reconstructing the conjunctival fornices with buccal mucosa, and repairing the upper lid coloboma in a flap reconstruction using the inferior eyelid margin. RESULTS: At age 3 years, the patient currently has good movement of the right eyelids when blinking, reasonable right tear function, and a visual acuity in the right eye between 20/200 and 20/360 on forced preferential looking. CONCLUSION: In selected cases of incomplete cryptophthalmos, oculoplastic and corneal surgery may result in useful vision and in good eyelid movement when blinking.

Abnormalities, Multiple↗
PubMed1997

GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS, M146510) was first described in 1980 in six newborns. It is a pleiotropic disorder of human development that comprises hypothalamic hamartoma, central polydactyly, and other malformations. This disorder is inherited as an autosomal dominant trait and has been mapped to 7p13 (S. Kang et al. Autosomal dominant Pallister-Hall syndrome maps to 7p13. Am. J. Hum. Genet. 59, A81 (1996)), co-localizing the PHS locus and the GLI3 zinc finger transcription factor gene. Large deletions or translocations resulting in haploinsufficiency of the GLI3 gene have been associated with Greig cephalopolysyndactyly syndrome (GCPS; M175700) although no mutations have been identified in GCPS patients with normal karyotypes. Both PHS and GCPS have polysyndactyly, abnormal craniofacial features and are inherited in an autosomal dominant pattern, but they are clinically distinct. The polydactyly of GCPS is commonly preaxial and that of PHS is typically central or postaxial. No reported cases of GCPS have hypothalamic hamartoma and PHS does not cause hypertelorism or broadening of the nasal root or forehead. The co-localization of the loci for PHS and GCPS led us to investigate GLI3 as a candidate gene for PHS. Herein we report two PHS families with frameshift mutations in GLI3 that are 3' of the zinc finger-encoding domains, including one family with a de novo mutation. These data implicate mutations in GLI3 as the cause of autosomal dominant PHS, and suggest that frameshift mutations of the GLI3 transcription factor gene can alter the development of multiple organ systems in vertebrates.

Abnormalities, Multiple↗
PubMed1997

Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome.

Pallister-Hall syndrome is a human developmental disorder that is inherited in an autosomal dominant pattern. The phenotypic features of the syndrome include hypothalamic hamartoma, polydactyly, imperforate anus, laryngeal clefting, and other anomalies. Here we describe the clinical characterisation of a family with 22 affected members and the genetic mapping of the corresponding locus. Clinical, radiographic, and endoscopic evaluations showed that this disorder is a fully penetrant trait with variable expressivity and low morbidity. By analysing 60 subjects in two families using anonymous STRP markers, we have established linkage to 7p13 by two point analysis with D7S691 resulting in a lod score of 7.0 at theta = 0, near the GLI3 locus. Deletions and translocations in GLI3 are associated with the Greig cephalopolysyndactyly syndrome. Although Greig cephalopolysyndactyly syndrome has some phenotypic overlap with Pallister-Hall syndrome, these two disorders are clinically distinct. The colocalisation of loci for these distinct phenotypes led us to analyse GLI3 for mutations in patients with Pallister-Hall syndrome. We have previously shown GLI3 mutations in two other small, moderately affected families with Pallister-Hall syndrome. The linkage data reported here suggest that these larger, mildly affected families may also have mutations in GLI3.

Abnormalities, Multiple↗
PubMed1997

Hallucinosis in idiopathic Parkinson's disease.

BACKGROUND: Hallucinosis is a complication of the treatment of idiopathic Parkinson's disease commonly thought to afflict older, chronically medicated, cognitively impaired patients. However, patients with idiopathic Parkinson's disease of short duration experiencing hallucinosis on relatively low doses of dopaminergic medication have been found. The aim, therefore, was to investigate the homogeneity of a population of patients with idiopathic Parkinson's disease and hallucinosis. METHODS: The clinical, demographic, and cognitive correlates of hallucinosis were investigated in a sample of 129 patients with idiopathic Parkinson's disease. RESULTS: There were two subgroups of patients with idiopathic Parkinson's disease experiencing hallucinosis. In patients with a disease duration of five years or less, hallucinosis was associated with rapid progression of the motor component of the disease but not cognitive impairment. In patients with idiopathic Parkinson's disease of longer than five years duration, hallucinosis was associated with postural instability, global cognitive impairment, and lack of depressive affect. In all patients with idiopathic Parkinson's disease, hallucinosis was more prevalent when they were treated with a direct acting dopamine receptor agonist. Hallucinosis was not associated with age at onset of idiopathic Parkinson's disease or dosage of dopaminergic medication. CONCLUSION: Hallucinosis in idiopathic Parkinson's disease is heterogeneous, falling into two groups. The difference in the pathophysiological basis of hallucinosis in these two groups of patients is discussed.

Aged↗
PubMed1997

Chromosomes 22q11 deletion syndrome: an update and review for the primary pediatrician.

Chromosome 22q11 deletion syndrome is a relatively newly described syndrome that encompasses the majority of patients previously felt to have velo-cardio-facial syndrome, DiGeorge syndrome, and conotruncal anomaly face syndrome. The disorder is characterized by a deletion of band 11 on the long arm of chromosome 22 most often recognized by fluorescent in situ hybridization (FISH) techniques. Extensive laboratory investigations are currently ongoing to uncover the specific genes involved and their functions. Phenotypically, individuals present with congenital heart disease, palatal abnormalities, facial dysmorphism, and developmental delay, as well as variable degrees of immunodeficiency, hypocalcemia, and endocrine abnormalities. The primary care physician has an important role in caring for these patients and their families. We review the current state of knowledge regarding chromosome 22q11 deletion syndrome, with an emphasis on the clinical presentation and on prevention and treatment of the known complications associated with this multisystem disorder. Chromosome 22q11 deletion syndrome can be inherited in an autosomal dominant fashion or result from a de novo deletion or translocation. Hence, this syndrome may have significant reproductive risks to affected individuals and families.

Abnormalities, Multiple↗
PubMed1997

Investigation of the role of lipids in the assembly of very low density lipoproteins in rabbit hepatocytes.

Our aims were i) to determine which lipids colocalize with newly synthesized apolipoprotein (apo) B in the lumen of the rough endoplasmic reticulum (RER), and thus may play a role in the stabilization and/or translocation of this protein; and ii) to determine the intracellular sites of assembly of lipids into very low density lipoprotein (VLDL). In order to do this, we have developed a new method for the separation of ER-derived microsomes on self-generated gradients of iodixanol. Rabbit liver microsomes were resolved into two broad peaks, the lighter peak contained smooth vesicles and the heavier peak contained rough vesicles. Each peak was collected in a number of subfractions. A single gradient thus separates the initial events in the secretion process (RER fractions), from later events (smooth endoplasmic reticulum (SER) fractions). The microsomal fractions were separated into membranes and lumenal contents, and the mass of apoB and VLDL lipids determined by ELISA or high performance thin-layer chromatography, respectively. The biosynthetic relationships of apoB and lipids were investigated, in timed or chase experiments, by incubation of isolated rabbit hepatocytes with radiolabeled precursors of apoB or lipids, followed by isolation and analysis of the microsomal fractions. The results indicate that very small amounts of triacylglycerol, cholesterol, and cholesteryl ester co-localize with apoB into the lumen of the RER. The bulk of the VLDL lipids were in the lumen of the SER. However, some newly synthesized triacyl-glycerol, phospholipid, cholesterol, and cholesteryl ester were also transferred to the lumen of the RER and were chased into the SER lumen. Double-labeling experiments showed that cholesteryl ester produced from newly synthesized cholesterol (labeled with [3H]mevalonate and [14C]oleate) was almost exclusively present in the RER, while cholesteryl ester in the SER was labeled only with [14C]oleate. Thus, distinct intracellular lipid-pools may be involved at different stages in the assembly of VLDL.

Acyltransferases↗
PubMed1996

Immunodeficiency as a component of recognizable syndromes.

Immunodeficiency occurs in numerous genetic syndromes. While it is the dominant manifestation in primary immunodeficiencies, immune deficits may also be seen in a variety of other recognizable syndromes. Immunodeficiency has been reported in 64 such conditions, adding to the 45 recognized primary immunodeficiencies. These uncommon syndromes with immune defects can present with: (a) growth deficiency (11 syndromes with disproportionate or proportionate short stature), (b) specific organ system dysfunction (18 with gastrointestinal, dermatologic, or neurologic abnormalities), (c) inborn errors of metabolism (13), (d) miscellaneous anomalies (10), or (e) chromosome anomalies (12). In most of the disorders, only some of the affected patients have immune defects. However, in 27 syndromes, immunodeficiency is a constant finding. We briefly review the clinical manifestations of each syndrome and delineate the specific associated immune defects. In most syndromes, the connection between the immune and other defects is unknown. Recognition of these conditions involving both the immune and other organ systems may facilitate accurate diagnosis and management as well as yield information regarding genes critical for the development of the involved systems.

Chromosome Aberrations↗
PubMed1996

A novel method for the rapid separation of plasma lipoproteins using self-generating gradients of iodixanol.

We describe a new method for the rapid fractionation of plasma lipoproteins, which makes use of a new non-ionic, iodinated, density gradient medium, iodixanol, commercially available as Optiprep(TM). The method is simple: plasma or serum is mixed with iodixanol followed by centrifugation in a vertical or near vertical rotor. Separation of VLDL, LDL and HDL can be achieved in 3 h and the lipoprotein fractions are comparable in density and composition with those prepared using conventional salt based gradients. Each class of lipoprotein can be removed in a single fraction, or a profile of lipoprotein distribution can be obtained using a gradient fractionator. Because the medium is inert, fractions from the gradient can be analysed by agarose gel electrophoresis or assayed for lipid content or apolipoprotein composition by SDS-PAGE without removing the iodixanol. Small differences in electrophoretic mobility of HDL and LDL across several gradient fractions suggest that subfractionation of these classes may occur. The new method is simple, rapid and versatile with potential application for preparation of lipoproteins and for analysis of lipoprotein profiles in the research or clinical laboratory.

Apolipoproteins↗
PubMed1996

Posterior rhinoscopy revisited.

Posterior rhinoscopy remains a valuable yet often difficult examination by conventional means. Fibreoptics, although providing an excellent alternative, may not always be available. We have combined a St. Clair Thomson's mirror with a Lack's metallic tongue depressor for ease of examination and patient cooperation. It is possible to examine the nasopharynx with 6 mm, 8 mm, 10 mm and 12 mm mirrors. The instrument may be boiled, is sturdy, economical and extremely useful in paediatric practice.

Endoscopes↗
PubMed1996

Cochlear implantation in superficial siderosis.

Superficial siderosis is a rare central nervous system disorder characterized by deafness, ataxia, and pyramidal signs. The hearing loss is believed to be predominantly neural and is usually progressive and bilateral. Careful assessment is therefore necessary to determine the best approach to hearing rehabilitation. A case is presented of superficial siderosis in a young woman who has benefitted significantly from cochlear implantation using the Nucleus device.

Adult↗
PubMed1996

Exclusion of candidate loci and cholesterol biosynthetic abnormalities in familial Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) was originally described in 1980 in six sporadic cases of children with structural anomalies including hypothalamic hamartoma, polydactyly, imperforate anus, and renal and pulmonary anomalies. In 1993, the first familial cases were reported, including affected sibs and vertical transmission. Three of these families are sufficiently large to allow initial evaluation by linkage studies to candidate genes or loci. We have evaluated candidate loci for PHS based on three clinical observations. The first is a patient with PHS-like malformations, including a hypothalamic hamartoma, and an unbalanced translocation involving 7q and 3p. The second is a family with familial PHS where the founder's father had an autosomal dominant hand malformation previously mapped to 17q. The third is the phenotypic overlap of PHS and Smith-Lemli-Opitz syndrome. In this report, we exclude these loci as candidates for linkage to the PHS phenotype on the basis of lod scores of less than-2.0. We conclude that hypothalamic hamartoma is not specific to PHS and that the dominant hand malformation in one of the families was a coincidence. To evaluate the relationship of PHS to Smith-Lemli-Opitz syndrome, we analysed levels of cholesterol and intermediate metabolites of the later stages of cholesterol biosynthesis. There is no evidence of a generalised disorder of cholesterol biosynthesis in patients with familial PHS. On genetic and biochemical grounds, we conclude that PHS and Smith-Lemli-Opitz syndrome are not allelic variants of a single locus.

Cholesterol↗