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Biomedical subjects

P Patel

Publications and source records attributed to P Patel.

At least 181 records · Page 10Linked to original sources
PubMed1992

Multipoint linkage analysis of the short arm of chromosome 11 in non-insulin dependent diabetes including maturity onset diabetes of youth.

Members of three families with maturity onset diabetes of youth (MODY) and seven with "common" type 2 diabetes were typed for six DNA markers (H-RAS, INS, HBBC, PTH, CALC1, CAT) on the short arm of chromosome 11. Using conventional pairwise linkage analysis, close linkage in the MODY families was excluded for all six markers. By multipoint analysis and a genetic map of the short arm of chromosome 11, MODY was excluded from a region of at least 35 and up to 60 centiMorgans (cM) on the short arm of chromosome 11. Multipoint analysis in the type 2 families also excludes linkage to the INS, H-RAS region of at least 3 and up to 30 cM. This study using multipoint linkage analysis in non-insulin dependent diabetes provides strong evidence against a role for mutations in or around the insulin gene in the causation of MODY or type 2 diabetes in the families studied.

Chromosomes, Human, Pair 11↗
PubMed1992

Immunotoxic potential of antiviral drugs: effects of ganciclovir and (S)-1-(3-hydroxy-2-phosphonylmethoxy propyl) cytosine on lymphocyte transformation and delayed-type hypersensitivity responses.

In the present studies, we examined the in vitro and in vivo effects of ganciclovir (DHPG) and a relatively new nucleoside analogue, (S)-1-(3-hydroxy-2-phosphonylmethoxy propyl) cytosine (HPMPC), on lymphocyte responses to T cell mitogens and delayed-type hypersensitivity (DTH) responses to dinitrofluorobenzene (DNFB). Initially, responses of mouse splenic mononuclear cells and human peripheral blood mononuclear cells to PHA and con A were evaluated in vitro in the presence of each drug. Both drugs inhibited the responses to each mitogens; however, DHPG had a greater inhibitory effect on con A responses of human and mouse lymphocytes than did HPMPC. Also, spleen cells from mice treated for 7 days with DHPG responded less well to PHA stimulation than cells from untreated or HPMPC-treated mice. No effect of either drug was observed on con A responses. Treatment of mice with either drug decreased the development of DTH responses, with HPMPC having a greater inhibitory effect than DHPG. The results from the present studies suggest that both DHPG and HPMPC may have inhibitory effects on the development of certain immune functions at high dosages, but at drug concentrations that were therapeutic in animal model studies, little inhibitory effects were observed.

Animals↗
PubMed1992

Squamous cell carcinoma of the nasal vestibule.

We reviewed 30 patients with squamous cell carcinoma of the nasal vestibule to present our experience of their management and to evaluate the prognostic factors that may influence their outcome. For T1 lesions radiotherapy remains the treatment of choice, because of the superior cosmetic result. Fifteen (68 per cent) out of 22 patients with T2 lesions were treated with primary radiotherapy. Surgery however, was eventually required in 16 (72 per cent) out of 22 patients, either as a primary treatment (seven patients) or as salvage surgery (nine patients). For the larger T3 lesions the treatment of choice is surgery followed by post-operative radiotherapy where appropriate. Regional nodal metastases at the time of presentation were a significant indicator of local and regional recurrence and of prognosis. The cause specific five-year survival for patients with an uninvolved neck (22 patients) was 100 per cent compared with 38 per cent for patients with nodal metastases at presentation (eight patients). Elective treatment for uninvolved regional nodes is not considered necessary.

Adult↗
PubMed1992

Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes.

We describe a codon 299 mutation in the glucokinase gene in a British pedigree with maturity-onset diabetes of the young (MODY) resulting in a substitution of glycine to arginine. One out of fifty patients diagnosed with classical late-onset type 2 diabetes mellitus was also found to have this mutation. All nine relatives of this patient who have inherited the mutation have type 2 diabetes, although six others without the mutation are also present with diabetes. The discovery that glucokinase mutations can cause MODY and was also found in ten affected members of a pedigree with type 2 diabetes in which MODY had not previously been considered indicates that diagnosis based on molecular pathology will be helpful in understanding the aetiology of type 2 diabetes.

Adolescent↗
PubMed1992

Measuring visual neglect in acute stroke and predicting its recovery: the visual neglect recovery index.

An overall measure of the recovery of visual neglect in patients with an acute stroke is described: The "Visual Neglect Recovery Inde" (VNRI) expresses the amount of visual neglect on a battery of visual neglect tests as a percentage of complete recovery from the maximal visual neglect measurable. The principles underlying the development of the index are similar to those involved in the development of the Motricity Index for hemiplegia. A population of 68 survivors of stroke who presented with visual neglect at two to three days were followed for up to six months. The VNRI showed that neglect was greater in those with right hemisphere stroke than in those with left hemisphere stroke and that recovery was most rapid over the first 10 days and reached a plateau at three months. Most patients, including many with severe initial visual neglect, showed little visual neglect at three months. Stepwise regression analysis showed that the severity of visual neglect at three months and at six months post-stroke could be predicted by the severity of visual neglect and the presence of anosognosia at two to three days. A regression equation was produced which may enable clinicians to select patients for intensive treatment of visual neglect.

Acute Disease↗
PubMed1992

Linkage analysis of glucokinase gene with NIDDM in Caucasian pedigrees.

NIDDM has a strong genetic component, as evidenced by the high level of concordance between identical twins. The nature of the genetic predisposition has remained largely unknown. Recently, the glucokinase gene locus on chromosome 7p has been shown to be linked to a subtype of NIDDM known as MODY in French and British pedigrees, and glucokinase mutations have been identified. To study the relationship between the glucokinase gene and NIDDM, we performed a linkage analysis in 12 Caucasian pedigrees ascertained through a proband with classical NIDDM. The LINKAGE program was used under four models, including autosomal dominant and recessive, with individuals with glucose intolerance counted as either affected or of unknown status. Linkage was significantly rejected with the dominant models (LOD scores -4.65, -4.25), and was unlikely with the recessive model when glucose intolerance was considered as affected (LOD score -1.38). These findings suggest that mutations in or near the glucokinase gene are unlikely to be the major cause of the inherited predisposition to NIDDM in Caucasian pedigrees, but do not exclude a role for this locus with a polygenic model, or a major role in some pedigrees.

Adult↗
PubMed1992

Linkage analysis of maturity-onset diabetes of the young with microsatellite polymorphisms. No linkage to ADA or GLUT2 genes in two families.

MODY is a form of NIDDM inherited as an autosomal dominant condition. We studied the linkage of MODY to two loci: ADA and GLUT2 in two large pedigrees with nonradioactive microsatellite polymorphic systems. A positive linkage of ADA to MODY was recently demonstrated in the large RW pedigree. Formal linkage analysis excluded a tight linkage between ADA and MODY with a LOD score of -5.82 and -2.24 at a recombination fraction of 0.01 in the two families. This result suggests genetic heterogeneity in the molecular basis of MODY. GLUT2 is a candidate gene that is expressed in the liver and beta-cells of pancreatic islets. In the two families studied, the disease did not cosegregate with GLUT2 alleles. The LOD scores for GLUT2 were -7.79 and -1.9 at a recombination fraction of 0.001 in the two families, thus providing evidence against the involvement of GLUT2 in MODY.

Adenosine Deaminase↗
PubMed1992

Metastases of carcinoma of the larynx.

The status of the cervical lymph nodes is the single most important prognostic factor in head and neck cancer, and the management of metastatic disease plays an important role in the treatment of carcinoma of the larynx. Clinical assessment of the neck is not very accurate, and the role of newer imaging techniques such as CT, MRI and Ultrasound guided Fine Needle Aspiration Cytology is being assessed, in order to improve upon the results of clinical palpation alone. The site of the primary tumour within the larynx is an important factor in affecting the frequency and the pattern of lymph node metastases to the neck. Indications for the use of surgery and radiotherapy for the elective and therapeutic management of lymph node metastases of carcinoma of the larynx are discussed with reference to the various sites of the primary tumour.

Diagnostic Imaging↗
PubMed1991

Direct haplotype determination by double ARMS: specificity, sensitivity and genetic applications.

We have developed a novel double Amplification Refractory Mutation System (double ARMS) using a highly polymorphic region 5' to the human delta-globin gene as a model system. The double ARMS approach involves using two allele-specific ARMS primers simultaneously during DNA amplification by the polymerase chain reaction (PCR). The resulting system is highly sensitive and more specific than single ARMS. In addition, this approach enables the elucidation of the relationship of polymorphic sites on the same chromosome and thus allows the direct determination of haplotypes. We have also demonstrated that this system can be used in conjunction with inverse PCR, the resulting double ARMS inverse PCR (DARMSI-PCR) may allow haplotype determination on polymorphic sites which are separated further apart than the length limit imposed by PCR. The double ARMS approach has numerous other applications in molecular biology including HLA typing, virology, forensic pathology and the investigation of the phenomenon of chimerism following bone marrow transplantation.

Alleles↗
PubMed1991

Response of Müller cells to growth factors alters with time in culture.

We have developed an explant culture technique, using the retinae of newborn guinea pigs, that reliably yields cultures of Müller cells showing uniform morphology and phenotype. Since the guinea pig retina is avascular and lacks astrocytes, Müller cells are the only glial cell-type and the only vimentin-positive population present. Virtually all passaged cells (greater than 98%) contain vimentin-positive intermediate filaments and no glial fibrillary acidic protein (GFAP) has been detected using a range of GFAP antibodies known to label astrocytes in the guinea pig optic nerve. Most vimentin-positive cells were also labeled with an antibody to carbonic anhydrase II, an enzyme which in the retina is specific for Müller cells. Proliferating Müller cells were identified within the inner nuclear layer of retinal fragments as early as 2 days in culture using bromodeoxyuridine (BrdU) and vimentin double labeling. Cultured Müller cells change their growth characteristics with successive passaging. The length of the cell cycle increases from 25.4 h for cells at first passage, to 66.7 h for cells at fourth passage. Altered responses to mitogens were also observed with passaging. First-passage cultures responded to basic fibroblast growth factor (bFGF) but not to several other factors tested including interleukin-2 (IL-2). In contrast, older cultures were highly responsive to IL-2 but showed a minimal response to bFGF. The altered responsiveness to mitogens observed in vitro may be relevant to changes in growth control of Müller cells in the developing and mature retina. The guinea pig retina provides an ideal mammalian tissue for generating Müller cell cultures that are free of astrocytes, endothelial cells, and pericytes, the most frequent contaminants of retinal glial cultures. The monolayers obtained show a high degree of homogeneity and are well suited for studies of Müller cell function.

Animals↗
PubMed1991

Multiple restriction fragment length polymorphisms at the GLUT2 locus: GLUT2 haplotypes for genetic analysis of type 2 (non-insulin-dependent) diabetes mellitus.

The liver/islet glucose transporter (GLUT2) is expressed in the liver and in the Beta cells of pancreatic islets and is a candidate gene for the inherited defect in Type 2 (non-insulin-dependent) diabetes mellitus. A series of restriction fragment length polymorphisms have been identified using a GLUT2 cDNA probe with five restriction enzymes in a British white Caucasian population. Five independent restriction fragment length polymorphisms detected by restriction enzymes EcoRI (two restriction fragment length polymorphisms termed EcoRI-1, EcoRI-2), TaqI (two restriction fragment length polymorphisms termed TaqI-1, TaqI-2), and BclI (BclI-2) were used to construct GLUT2 haplotypes. Significant linkage disequilibrium was observed between four polymorphic sites EcoRI-2, TaqI-1, TaqI-2 and BclI-2 but linkage disequilibrium was not observed with EcoRI-1 polymorphic site and the other four sites. The frequencies of GLUT2 restriction fragment length polymorphisms and haplotypes in 50 Type 2 diabetic subjects and 50 non-diabetic control subjects show no significant differences suggesting that it is unlikely that there is a single major defect of this gene contributing to the inherited susceptibility to Type 2 diabetes in a Caucasian population.

Alleles↗
PubMed1991

Coinjection strategy for visual identification of transgenic mice.

Transgenic mice were generated by coinjection of a dominant marker gene that induces fur and eye pigmentation (a tyrosinase minigene) plus an unrelated DNA construction that has a gamma-glutamyl transferase (gamma GT) promoter linked to a ras oncogene. Mice transgenic for gamma GT-ras could be identified in the first and all subsequent generations by simple visual inspection for pigmentation. Furthermore, the gamma-glutamyl transferase promoter was active in kidney but not skin of the transgenic mice, indicating that the cointegrated DNA was active and independently expressed. These results confirm that the tyrosinase minigene can be used for coinjections to allow rapid visual identification of transgenic mice.

Animals↗
PubMed1991

On using the linear-quadratic model in daily clinical practice.

To facilitate its use in the clinic, Barendsen's formulation of the Linear-Quadratic (LQ) model is modified by expressing isoeffect doses in terms of the "Standard Effective Dose," Ds, the isoeffective dose for the "standard" fractionation schedule of 2 Gy fractions given once per day, 5 days per week. For any arbitrary fractionation schedule, where total dose D is given in N fractions of size d in a total time T, the corresponding "Standard Effective Dose," Ds, will be proportional to the total dose D and the proportionality constant will be called the "Standard Relative Effectiveness," SRE, to distinguish it from Barendsen's "Relative Effectiveness," RE. Thus, Ds = SRE.D. The constant SRE depends on the parameters of the fractionation schedule, and on the tumor or normal tissue being irradiated. For the "simple" LQ model with no time dependence, which is applicable to late reacting tissue, SRE = [(d + delta)/(2 + delta)], where d is the fraction size and delta = alpha/beta is the alpha/beta ratio for the tissue of interest, with both d and delta expressed in units of Gy. Application of this method to the Linear Quadratic model with a time dependence, the "LQ + time" model, and to low dose rate brachytherapy will be discussed. To clarify the method of calculation, and to demonstrate its simplicity, examples from the clinical literature will be used.

Brachytherapy↗