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Biomedical subjects

K Hussain

Publications and source records attributed to K Hussain.

At least 37 records · Page 2Linked to original sources
PubMed2001

p57(KIP2) expression in normal islet cells and in hyperinsulinism of infancy.

Most cases of hyperinsulinism of infancy (HI) are caused by mutations in either the sulfonylurea receptor-1 (SUR1) or the inward rectifying K(+) channel Kir6.2, two subunits of the beta-cell ATP-sensitive K(+) channel (K(ATP) channel). Histologically, HI can be divided into two major subtypes. The diffuse form is recessively inherited and involves all beta-cells within the pancreas. Focal HI consists of adenomatous hyperplasia within a limited region of the pancreas, and it is caused by somatic loss of heterozygosity (LOH), including maternal Ch11p15-ter in a beta-cell precursor carrying a germ-line mutation in the paternal allele of SUR1 or Kir6.2. Several imprinted genes are located within this chromosomal region, some of which, including p57(KIP2) and IGF-II, have been associated with the regulation of cell proliferation. Using double immunostaining, we examined p57(KIP2) expression in different islet cell types, in control pancreases from different developmental stages (n = 15), and in pancreases from patients with both diffuse (n = 4) and focal HI (n = 9). Using immunofluorescence and computerized image analysis, we quantified IGF-II expression in beta-cells from patients with focal HI (n = 8). Within the pancreas, p57(KIP2) was specifically localized to the endocrine portion. beta-Cells demonstrated the highest frequency of expression (34.9 +/- 2.7%) compared with approximately 1-3% in other cell types. The fraction of beta-cells expressing p57(KIP2) did not vary significantly during development. beta-Cells within the focal lesions did not express p57(KIP2), whereas IGF-II staining inside focal lesions was mildly increased compared with unaffected surrounding tissue. In conclusion, we demonstrate that p57(KIP2) is expressed and is paternally imprinted in human pancreatic beta-cells. Loss of expression in focal HI is caused by LOH and is associated with increased proliferation and increased IGF-II expression. Manipulation of p57(KIP2) expression in beta-cells may provide a mechanism by which proliferation can be modulated, and thus this gene is a potential therapeutic target for reversing the beta-cell failure observed in diabetes.

Cell Nucleus↗
PubMed2000

Prolonged ambulatory colonic manometric studies using endoclips.

BACKGROUND: It is difficult to study human colonic motility under physiologic conditions. An important limitation associated with prolonged colonic recording is the failure of the sensors to resist normal expulsive forces. METHOD: In this article we describe a method of endoscopically positioning a manometric catheter by using clips in conjunction with a solid-state catheter. With the use of a rotatable clip-fixing device loaded on to a colonoscope, the manometric catheter was clipped to the colonic mucosa. RESULTS: Recordings for up to 120 hours were obtained from 6 subjects without apparent migration of the catheter assembly. No complications were noted, the catheter does not interfere with defecation, and defecation does not result in its expulsion. CONCLUSION: The current technique will allow reliable ambulatory measurements over prolonged periods of time in relatively comfortable and unrestrained subjects. This technique should increase our understanding of normal and abnormal colonic motility.

Colon↗
PubMed2000

The inaccuracy of venous and capillary blood glucose measurement using reagent strips in the newborn period and the effect of haematocrit.

The purpose of this study was to compare the accuracy of capillary and venous reagent strip tests (RST) against a reference plasma glucose method, and to assess the impact of haematocrit. One hundred and eighty infants admitted to the Neonatal Unit had blood glucose measured by reagent strip tests using capillary and venous blood samples. Venous plasma glucose was assayed by the Hexokinase method. Each infant had a venous haematocrit performed in the Neonatal Unit. Comparable inaccuracies were noted with both capillary and venous reagent strip tests at all levels. The mean difference between capillary RST and plasma glucose was 0.058 mmol/l (S.D. 1.39). The corresponding mean venous RST plasma glucose difference was 0.138 mmol/l (S.D. 0.96). The two means were statistically different from each other (P = 0.024), but this difference disappeared if the comparison was made only in babies with a PCV of 35-55%. At higher haematocrits (PCV >55%, N= 96) the mean difference between venous RST and plasma glucose was significantly more than the mean difference between capillary RST and plasma glucose (0.018 versus 0.295. P = 0.002). Hence the higher the haematocrit the more inaccurate the venous RST. This study confirms the limited value of reagent strip tests in the assessment of blood glucose in the neonatal period. It suggests that venous RST may be more inaccurate in comparison to capillary and that high haematocrits have a greater effect on venous RST than capillary RST.

Blood Chemical Analysis↗
PubMed2000

A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.

Usher syndrome type 1 describes the association of profound, congenital sensorineural deafness, vestibular hypofunction and childhood onset retinitis pigmentosa. It is an autosomal recessive condition and is subdivided on the basis of linkage analysis into types 1A through 1E. Usher type 1C maps to the region containing the genes ABCC8 and KCNJ11 (encoding components of ATP-sensitive K + (KATP) channels), which may be mutated in patients with hyperinsulinism. We identified three individuals from two consanguineous families with severe hyperinsulinism, profound congenital sensorineural deafness, enteropathy and renal tubular dysfunction. The molecular basis of the disorder is a homozygous 122-kb deletion of 11p14-15, which includes part of ABCC8 and overlaps with the locus for Usher syndrome type 1C and DFNB18. The centromeric boundary of this deletion includes part of a gene shown to be mutated in families with type 1C Usher syndrome, and is hence assigned the name USH1C. The pattern of expression of the USH1C protein is consistent with the clinical features exhibited by individuals with the contiguous gene deletion and with isolated Usher type 1C.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Short limbed skeletal dysplasia associated with combined immunodeficiency and congenital subglottic stenosis: a new constellation of features.

A newborn male is described with an association of short limbed dwarfism with hip dislocation, combined immunodeficiency characterized by absent B cells and CD4 lymphopaenia and congenital subglottic stenosis. This constellation of abnormalities is distinct from other described skeletal dysplasias associated with immunodeficiency such as ADA deficiency and cartilage hair hypoplasia.

CD4 Lymphocyte Count↗
PubMed2000

Practical management of hyperinsulinism in infancy.

Hyperinsulinism in infancy is one of the most difficult problems to manage in contemporary paediatric endocrinology. Although the diagnosis can usually be achieved without difficulty, it presents the paediatrician with formidable day to day management problems. Despite recent advances in understanding the pathophysiology of hyperinsulinism, the neurological outcome remains poor, and there is often a choice of unsatisfactory treatments, with life long sequelae for the child and his or her family. This paper presents a state of the art overview on management derived from a consensus workshop held by the European network for research into hyperinsulinism (ENRHI). The consensus is presented as an educational aid for paediatricians and children's nurses. It offers a practical guide to management based on the most up to date knowledge. It presents a proposed management cascade and focuses on the clinical recognition of the disease, the immediate steps that should be taken to stabilise the infant during diagnostic investigations, and the principles of definitive treatment.

Genetic Therapy↗
PubMed2000

Management of hyperinsulinism in infancy and childhood.

Hyperinsulinism (HI) in infancy presents a formidable challenge for the paediatrician as it is one of the most difficult problems to manage in contemporary paediatric endocrinology. Although there have been major advances in understanding the condition over the last five years, the neurological outcome remains poor choice, and the choice of treatments continue to be unsatisfactory. This review article updates the management of HI derived from a Consensus Workshop held by the European Network for Research into Hyperinsulinism (ENRHI) in 1999.

Blood Glucose↗
PubMed1999

Free split and segmental latissimus dorsi muscle transfer in one stage for facial reanimation.

The authors report the experience in facial reanimation using free innervated split and segmental latissimus dorsi muscle flap one-stage transfer in 86 patients with longstanding facial palsy. The segmental latissimus dorsi was taken from the distal part of the muscle so that the muscle flap had an ultra-long neurovascular pedicle of 13 to 17.5 cm in length. The muscle flap was made thinner by splitting the segmental muscle. The split segmental muscle flap was transferred to the paralyzed side of the face with its ultra-long neurovascular pedicle passing through a tunnel in the upper lip to the normal side of the face. The neurovascular pedicle of the muscle flap was anastomosed with the facial nerve, artery, and veins, respectively, on the normal side of the face. The operation was designed without the cross-facial nerve graft stage. From 1986 to October of 1997, 86 patients with long-standing facial paralysis were treated in our department. The duration of facial palsy in this series ranged from 1.5 to 51 years. A satisfactory result was obtained in 80 cases, evaluated at 8 months to 2 years postoperatively. The expression movement of the soft tissues of the face can be seen not only over transferred muscle but also on the paralyzed muscle covered by the splitting muscle flap. It is supposed that this is the result of muscle-muscle neurolization. Study of 66 specimens of latissimus dorsi muscle in the cadavers is discussed.

Adolescent↗
PubMed1998

Identification of a Theileria annulata antigen expressed in multiple stages of the parasite life cycle.

In order to identify sporozoite surface molecules which may be involved in invasion and could act as potential vaccine candidates, a number of Mabs were raised in mice against T. annulata sporozoites. These were assayed for their ability to block sporozoite invasion of bovine peripheral blood mononuclear (PBM) cells in vitro. One of these, Mab 4B11, was found to neutralize sporozoite invasion to a high degree and to recognize a group of sporozoite antigens on Western blots. A T. annulata lambdagt11 genomic expression library was screened with Mab 4B11 and a positive clone containing a 900-bp insert (KP8) analysed further. Data from Southern and Northern blotting indicated that the gene containing the KP8 sequence, termed sporozoite and macroschizont gene 2 (spm2), was expressed both in T. annulata sporozoites and in later parasite life-cycle stages, macroschizont-infected leucocytes and piroplasms. The KP8 sequence was expressed in E. coli as a fusion protein with glutathione-S-transferase (GST) using the vector pGEX1lambdaT. Bovine antiserum raised against GST-KP8 recognised a single high molecular weight molecule on Western blots corresponding to one of the antigens recognised by Mab 4B11, expressed in sporozoites, macroschizont-infected leucocytes, and piroplasms. While our evidence suggests that the spm2 molecule alone is not responsible for sporozoite neutralization, it is a multistage antigen likely to function both in T. annulata sporozoites and in subsequent parasite life-cycle stages.

Amino Acid Sequence↗
PubMed1997

A prospective study of PET-FDG imaging for the assessment of head and neck squamous cell carcinoma.

The main aim of the study was to evaluate the use of positron emission tomography using fluoro-deoxyglucose (PET-FDG) imaging for the detection of squamous cell carcinoma of the head and neck. Fifty-four consecutive patients with malignancies involving the head and neck were studied prospectively. Thirty-one patients presented with primary disease and 23 were suspected of recurrent or residual disease. All patients underwent full clinical staging, PET-FDG scans and anatomical imaging, 37 underwent computed tomography (CT), 13 magnetic resonance (MR) and four had both CT and MR. Clinical assessment, CT/MR, PET-FDG and histological examination were all evaluated independently of each other. All 31 primary head and neck malignant tumours were detected by PET-FDG. Based on 16 patients who underwent neck dissections, the sensitivity and specificity of PET-FDG for detecting nodal disease was 67% and 100% respectively, compared with clinical assessment of 58% and 75% and CT/MR of 67% and 25%. In all 12 patients, PET-FDG correctly identified the presence of absence or recurrent or residual disease. PET-FDG staged 13 post-treatment necks with an accuracy of 100% as compared to CT/MR which was accurate in 7 of 13 and clinical assessment which was accurate in eight. Three sites of abnormal tracer uptake unrelated to malignancy were recorded as incidental findings (mandibular osteomyelitis, 1: post glossectomy site, 2). PET-FDG was more accurate than CT/MR for identifying primary and recurrent tumours as well as metastatic lesions in the neck. If these diagnostic properties of PET-FDG are confirmed in further prospective studies, it could prove a valuable adjunct for the management of head and neck cancer.

Aged↗
PubMed1997

Role of fine needle aspiration cytology in the management of the discrete parotid lump.

A review of fine needle aspiration cytology (FNAC) indicates that the technique can distinguish benign from malignant parotid, disease in 93% of patients evaluated. However, a surgery of 34 head and neck oncologists revealed that making this distinction when an apparently benign parotid lump was being investigated did not normally alter the surgical management for in the presence of low-grade cancer survival is not improved with radical surgery. As FNAC does not alter treatment of a discrete parotid lump, no consensus is currently possible regarding its most appropriate use. Perhaps its value is as a screening procedure and to provide a little more information when advising the patient.

Biopsy, Needle↗
PubMed1996

Conservation of neutralizing determinants between the sporozoite surface antigens of Theileria annulata and Theileria parva.

The sporozoite surface antigens SPAG-1 of Theileria annulata and p67 of Theileria parva are postulated to contain determinants necessary for host cell invasion and/or recognition and are both being considered as candidates for inclusion in subunit vaccines. Preliminary data suggest that these are related molecules. In this paper we describe the investigation of the relationship between these sporozoite antigens further by analysis of the immunological cross-reactivity using Mabs and sera raised against each antigen. The cross-reactions were examined by carrying out Western blots, IFA tests, and in vitro sporozoite neutralization assays. In addition, sequence comparison data which clearly establish that these surface antigens are encoded by related genes are presented. The regions of SPAG-1 identified as containing cross-reactive epitopes recognized by p67 antiserum correlated to regions of high predicted homology between p67 and SPAG-1, which are located at their respective N- and C-termini. Furthermore, p67 and SPAG-1 were found to contain cross-reactive determinants responsible for neutralization of sporozoite infectivity in vitro, and at least some of these were located in the C-termini of both molecules. The relevance of these findings to the possible roles for these molecules in host cell invasion is discussed.

Amino Acid Sequence↗
PubMed1996

Validation and clinical application of computer-combined computed tomography and positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose head and neck images.

BACKGROUND: Positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (PET-FDG) improves the detection of head and neck squamous cell cancer (HNSCC), but lacks anatomical detail. The accuracy of registered computed tomography/magnetic resonance (CT/MR) and PET-FDG in delineation of HNSCC at the primary site and its clinical application was investigated. METHOD: Preoperatively 30 patients were staged clinically and each had either CT (23), MR (5), or both CT and MR (2) scans, as well as CT/MR-PET-FDG registration. Tumor margins or infiltration of specific anatomical landmarks on the different scans were compared and judged against histology. RESULTS: For primary tumors CT-PET-FDG (97%) and MR-PET-FDG (100%) delineated the tumor more accurately than CT (69%) or MR (40%) alone. Similarly, CT-PET-FDG (98%) and MR-PET-FDG (100%) were better than CT (70%) and MR alone (80%) in identifying tumor invasion of specific anatomical structures. Management was altered in 7 of 30 patients. The registered images were particularly useful in delineating tumor extension in the infratemporal fossa, maxilla and mandible, and identifying recurrences obscured by scar tissue. CONCLUSIONS: It is possible to accurately register CT, MR, and PET-FDG data sets in the head and neck. The initial results show that registered CT/ MR-PET-FDG images provide additional clinically relevant information over that obtained from clinical evaluation or conventional CT/MR imaging.

Carcinoma, Squamous Cell↗