Search PubMed⌕ Search

Biomedical subjects

R Kay

Publications and source records attributed to R Kay.

At least 109 records · Page 6Linked to original sources
PubMed1995

Expression cloning of oncogenes by retroviral transfer of cDNA libraries.

a cDNA library transfer system based on retroviral vectors has been developed for expression cloning in mammalian cells. The use of retroviral vectors results in stable cDNA transfer efficiencies which are at least 100-fold higher than those achieved by transfection and therefore enables the transfer and functional screening of very large libraries. In our initial application of retroviral transfer of cDNA libraries, we have selected for cDNAs which induce oncogenic transformation of NIH 3T3 fibroblasts, as measured by loss of contact inhibition of proliferation. Nineteen different transforming cDNAs were isolated from a total of 300,000 transferred cDNA clones. Three of these cDNAs were derived from known oncogenes (raf-1, lck, and ect2), while nine others were derived from genes which had been cloned previously but were not known to have the ability to transform fibroblasts (beta-catenin, thrombin receptor, phospholipase C-gamma 2 and Spi-2 protease inhibitor genes). The Spi-2 cDNA was expressed in antisense orientation and therefore is likely to act as an inhibitor of an endogenous transformation suppressor. Seven novel cDNAs with transforming activities, including those for three new members of the CDC24 family of guanine nucleotide exchange factors, were also cloned from the retroviral cDNA libraries. Retroviral transfer of libraries should be generally useful for cloning cDNAs which confer selectable phenotypes on many different types of mammalian cells.

3T3 Cells↗
PubMed1995

Spiral computed tomography angiography in the assessment of middle cerebral artery occlusive disease.

There has been no report on the use of spiral computed tomography angiography (CTA) in the investigation of intracranial cerebral artery stenosis. A prospective pilot study was conducted to investigate the feasibility of CTA in the diagnosis of intracranial occlusive disease and its correlation with transcranial Doppler. With transcranial Doppler, 10 patients with acute ischaemic stroke with middle cerebral artery stenosis or occlusion were identified. There were seven middle cerebral artery stenoses and five middle cerebral artery occlusions. The CTA confirmed all diagnoses by transcranial Doppler except in one patient with middle cerebral artery occlusion in whom the embolus had probably propagated. The results showed that CTA is feasible and potentially useful in the diagnosis of middle cerebral artery occlusive disease. Further studies are required to assess its validity, sensitivity, and specificity in the diagnosis of middle cerebral artery occlusive disease.

Arterial Occlusive Diseases↗
PubMed1995

Prevalence of migraine and other headaches in Hong Kong.

From July 1992 to March 1993, we conducted a community-based prevalence survey of migraine and other types of recurrent headache by a telephone interview of 2,240 households with 7,356 persons aged 15 and above. 311 patients with recurrent headache were successfully interviewed. Of these, 101 were clinically validated. The overall prevalence rates were 1% for migraine, 2% for tension-type headache and 1% for unclassified headache. Adjusted for misclassification and non-response, the estimated prevalence rates for the three categories were 1.5, 3 and 0.4%, respectively. Agreement between clinical method and questionnaire interview was good for migraine, fair for tension-type headache and poor for unclassified headache. For all three types of recurrent headache, there was a female preponderance with a peak in the 25-44 age group. The prevalence of migraine was much lower than in Western communities but higher than that found in mainland China [1-8]. Common predisposing and aggravating factors for all three types of headaches as reported by the patients were mental stress, physical exertion and menstruation among females. Despite the low prevalence, the overall socioeconomic impact to a populous community is considerable.

Adolescent↗
PubMed1995

Contralateral reflux after unilateral ureteral reimplantation in patients with a history of resolved contralateral reflux.

PURPOSE: We determined the risk of contralateral reflux after unilateral ureteral reimplantation in patients with a history of resolved contralateral reflux. MATERIALS AND METHODS: We reviewed our experience with 53 children who underwent unilateral ureteral reimplantation for primary vesicoureteral reflux. RESULTS: Postoperative contralateral reflux occurred in 5 of 11 children (45%) with a history of bilateral reflux that had resolved preoperatively on the contralateral side and 4 of 42 (10%) with no history of contralateral reflux. CONCLUSIONS: Strong consideration should be given to performing bilateral ureteral reimplantation in children with unilateral reflux and a history of resolved contralateral reflux.

Child, Preschool↗
PubMed1995

Technical considerations in the repair of cloacal vaginal deformities.

Various techniques of vaginal repair used in the reconstruction of cloacal deformities are discussed. In 4 years we performed primary reconstruction of cloacal anomalies in 4 children, 3 of whom had hydrocolpos and 1 vaginal agenesis. Vaginal reconstruction was done using a variety of techniques tailored to the primary anomaly. Distal vaginal occlusion related to ischemia occurred in 2 patients and in both the vagina was successfully reconstructed at a second stage procedure. Overall cosmetic and functional results were good. All patients are dry but require clean intermittent catheterization and 3 currently require a bowel regimen at followup of 18 months to 4 years.

Cloaca↗
PubMed1995

Patterns of metastatic spread in prepubertal yolk sac tumor of the testis.

Of the 212 patients with yolk sac tumors of the testis registered in the prepubertal testis tumor registry of the American Academy of Pediatrics, Section on Urology, we report on 33 who presented with metastatic disease. Metastases occurred to the retroperitoneum alone in 9 cases, sites consistent with hematogenous spread of disease alone in 13, sites consistent with lymphatic and hematogenous spread in 6, and sites not clearly documented in the registry in 5. These findings, which show a hematogenous predilection in the spread of metastases, suggest that retroperitoneal lymph node dissection has no routine role in the treatment of the child who presents with yolk sac tumor of the testis.

Child↗
PubMed1995

Streptococcus suis infection in Hong Kong.

Twenty-five patients were admitted to two hospitals in Hong Kong for Streptococcus suis infection between 1984 and 1993. Among them, 15 (60%) had an occupational exposure to pigs or pork, and four had a clear history of skin injury up to 16 days before admission. Examination of the cerebrospinal fluid of 21 patients confirmed the presence of meningitis in every case; the remaining four patients who did not have lumbar punctures had each presented with arthritis, bronchopneumonia, endocarditis and pyrexia without neck stiffness. The only fatality was a patient admitted in septicaemic shock with evidence of meningitis and disseminated intravascular coagulation. Of the 24 survivors, 16 (67%) acquired varying degrees of hearing loss as a result of meningitic involvement. All the isolates of S. suis were sensitive to penicillin or ampicillin, which was used alone or in combination with other antibiotics for every patient. Two patients had a relapse of symptoms when penicillin was stopped, but were successfully treated after the antibiotic was resumed for a total of 6 weeks. Over 100 cases of S. suis infection have been described previously, with a geographic distribution heavily biased towards Northern Europe and Southeast Asia. Lack of awareness of this unique zoonosis may be a reason why it is not diagnosed more readily elsewhere.

Adult↗
PubMed1995

Evenoming by Bungarus multicinctus (many-banded krait) in Hong Kong.

We describe the clinical course of two cases of envenoming by the many-banded krait (Bungarus multicinctus). A man developed generalized paralysis and respiratory failure with transient hypertension. Nerve conduction studies revealed normal motor and sensory conduction velocities with reduced motor unit action potential amplitudes consistent with neuromuscular blockade. He showed a slight transient response to the banded krait (B. fasciatus) antivenom but required ventilatory support for 8 days. After the fourth day, there was some response to treatment with anticholinesterase. Another man developed diplopia, dysphagia and leg weakness but recovered spontaneously after 48 hours.

Adult↗
PubMed1994

Selection of retrovirally transduced hematopoietic cells using CD24 as a marker of gene transfer.

We have investigated the use of a cell surface antigen as a dominant selectable marker to facilitate the detection and selection of retrovirally infected target cells. The small coding region of the human cell surface antigen CD24 (approximately 240 bp) was introduced into a myeloproliferative sarcoma virus (MPSV)-based retroviral vector, which was then used to infect day 4 5-fluorouracil (5-FU)-treated murine bone marrow cells. Within 48 hours of termination of the infection procedure CD24-expressing cells were selected by fluorescent-activated cell sorting (FACS) with an antibody directed against the CD24 antigen. Functional analysis of these cells showed that they included not only in vitro clonogenic progenitors and day 12 colony-forming unit-spleen but also cells capable of competitive long-term hematopoietic repopulation. Double-antibody labeling studies performed on recipients of retrovirally transduced marrow cells showed that some granulocytes, macrophages, erythrocytes, and, to a lesser extent, B and T lymphocytes still expressed the transduced CD24 gene at high levels 4 months later. No gross abnormalities in hematopoiesis were detected in mice repopulated with CD24-expressing cells. Our results show that the use of the CD24 cell surface antigen as a retrovirally encoded marker enables the rapid, efficient, and nontoxic selection in vitro of infected primary cells, facilitates tracking and phenotyping of their progeny, and should provide a unique tool to identify elements that regulate the expression of transduced genes in the most primitive hematopoietic cells.

Animals↗
PubMed1994

Mapping of CD24 and homologous sequences to multiple chromosomal loci.

The human cell surface antigen, CD24, is a glycosyl phosphatidylinositol (GPI)-linked glycoprotein that has been implicated in the differentiation and activation of granulocytes and B lymphocytes. Changes in expression of the antigen occur at critical times during B lineage development. CD24 was cloned by its homology to mouse heat-stable antigen. Southern blot analysis suggested the presence of multiple CD24 related sequences in the human genome. We have now mapped CD24 homologous sequences to chromosomes 6q21, 15q21-q22, and Yq11 by screening a panel of somatic cell hybrid DNAs and by in situ hybridization. At least two additional homologues, one located on chromosome 1 at band p36 and one tentatively mapped to chromosome 20, that are distantly related to CD24 were identified. Southern analysis of male and female DNA samples confirmed the presence of CD24 homologous sequences on the human Y chromosome. Sequencing of DNA fragments amplified from monochromosomal somatic cell hybrids showed that the CD24 cDNA was derived from a transcript originating from a gene on chromosome 6. The CD24 gene on the Y chromosome had many base changes compared to the cDNA but had retained an open reading frame, leaving open the question of whether this gene is functional. Both ATGs in the translation initiation region of CD24 homologous sequences on chromosome 15 were converted to GTGs, making it unlikely that this gene, if functional, encodes a protein similar to CD24. CD24, therefore, is a member of a multigene family, but it remains to be determined whether any of the related genes are functional.

Antigens, CD↗
PubMed1994

Defective development of thymocytes overexpressing the costimulatory molecule, heat-stable antigen.

Heat-stable antigen (HSA) is a small, glycosyl phosphatidylinositol-anchored protein that can act as a costimulatory molecule for antigen-dependent activation of helper T cells. In addition to being expressed on antigen-presenting B cells, HSA is also expressed during the initial stages of T cell development in the thymus. HSA levels are very high on immature CD4-, CD8- double negative thymocytes, but are reduced on CD4+, CD8+ double positive cells undergoing selection in the thymus, and are entirely eliminated when these cells differentiate into immunologically competent CD4+ or CD8+ single positive T cells. To examine the potential roles of this molecule in T cell development and selection, we generated transgenic mice in which HSA was highly expressed on all classes of thymocytes. The consequence of deregulated HSA expression was a pronounced reduction in the numbers of double positive and single positive thymocytes, whereas the numbers of their double negative precursors were largely unaffected. These results demonstrate that downregulation of HSA expression at the double positive stage is a critical event in thymocyte development. The depletion of thymocytes resulting from HSA overexpression begins at the same time as the onset of negative selection, suggesting that HSA may provide signals that contribute to determining the efficiency of this process.

Animals↗
PubMed1994

Primary testicular and paratesticular tumors of childhood.

Testicular and paratesticular neoplasms are uncommon tumors of childhood. Consequently, the experience gained with regard to their optimal management is limited in any given children's cancer centre. Here we review the classification, diagnosis, and staging of testicular and paratesticular neoplasms and subsequently discuss the more frequently occurring ones: germ cell tumors, gonadal stromal tumors, gonadoblastoma, tumors of the supporting tissue, lymphomas and leukemias, tumor-like lesions, secondary tumors, and tumors of the adnexa.

Adolescent↗
PubMed1994

Cloacal anomalies: role of vesicostomy.

The purpose of this report is to discuss the use of vesicostomy in the treatment of cloacal anomalies. In 4 years, the authors have performed primary reconstruction in four children who had cloacal anomalies. Three children had hydrocolpos, which in two cases failed to decompress with tube vaginostomy or clean intermittent catheterization. In both cases, cutaneous vesicostomy effectively prevented urinary sepsis, which allowed the children to thrive before definitive reconstruction was performed. Vesicostomy is technically simple to perform and is easily reversed without loss of bladder volume. Further, it lends itself well to definitive reconstruction of cloacal anomalies.

Cloaca↗
PubMed1994

Response to thymectomy in Chinese patients with myasthenia gravis.

Myasthenia gravis was diagnosed in 48 patients between 1985 and 1991 in this Chinese community. Thymectomy was performed on 36 patients and the mean postoperative follow-up period was 49 months. Significant improvement was seen in 72% of the thymectomised patients, with 33% achieving complete remission. Patients with mild generalised myasthenia at presentation or those found to have thymic hyperplasia had the best prognosis. Patients with more severe symptoms or those with an underlying thymoma also responded favourably. Only patients with ocular myasthenia or those with a normal or atrophic thymus gland had no more than an even chance of gaining significant improvement. Although previous reports suggested a high prevalence of ocular myasthenia and of thymoma among Chinese myasthenic patients, the present study has found no evidence that they respond differently to thymectomy than their Western counterparts.

Adolescent↗
PubMed1994

Relation of neurohumoral activation to clinical variables and degree of ventricular dysfunction: a report from the Registry of Studies of Left Ventricular Dysfunction. SOLVD Investigators.

OBJECTIVES: This study examined the relation between neurohumoral activation and severity of left ventricular dysfunction and congestive heart failure in a broad group of patients with depressed left ventricular function who were not recruited on the basis of eligibility for a therapeutic trial. BACKGROUND: Previous studies have established the presence of neurohumoral activation in patients with severe congestive heart failure. It is not known whether the activation of these neurohumoral mechanisms is related to an impairment in left ventricular function. METHODS: From the 6,273 patients recruited into the Studies of Left Ventricular Dysfunction Registry (SOLVD), a subgroup of 859 patients were randomly selected, and their plasma norepinephrine, plasma renin activity, arginine vasopressin and atrial natriuretic peptide levels were correlated with clinical findings, New York Heart Association functional class, left ventricular ejection fraction and drug use. RESULTS: There was a weak but significant correlation between ejection fraction and an increase in plasma norepinephrine (rho = -0.18, p < 0.0001), plasma renin activity (rho = -0.24, p < 0.0001) and arginine vasopressin (rho = -0.12, p < 0.003). The only exception was atrial natriuretic peptide, which showed the best correlation to ejection fraction (rho = -0.37, p < 0.0001). Deterioration in functional class was associated more with increases in atrial natriuretic peptide (p = 0.0003) and plasma renin activity (p = 0.0003) and less with an increase in plasma norepinephrine. Of the clinical variables, elevated jugular venous pressure and third heart sound (S3) gallop were significantly associated with increased levels of plasma norepinephrine, plasma renin activity and atrial natriuretic peptide. We then compared the relation of neurohormones with clinical signs, functional status, ejection fraction and drug therapy and controlled for mutual interactive effects. After adjustment, a decrease in ejection fraction was still significantly related to an increase in plasma norepinephrine, plasma renin activity and atrial natriuretic peptide. In contrast, only a difference between functional classes I and III/IV was associated with an increase in plasma renin activity and atrial natriuretic peptide levels. CONCLUSIONS: Neurohumoral activation in patients with heart failure is related to severity of left ventricular functional depression, and this relation is independent of functional class or concomitant drug therapy.

Aged↗
PubMed1994

Renal cell carcinoma arising in a regressed multicystic dysplastic kidney.

Controversy surrounds the management of multicystic dysplastic kidney. Recent advances in radiological imaging have resulted in a higher incidence of its detection, and they provide an accurate noninvasive means of diagnosis and followup. Consequently, the need for surgical removal of these lesions is being reevaluated. We report a case of renal cell carcinoma arising from solid renal dysplasia associated with a regressed multicystic dysplastic kidney. We emphasize the potential risk of nonoperative management of these lesions and further define the spectrum of malignant degeneration associated with renal dysplasia.

Adolescent↗
PubMed1994

Magnetic resonance imaging of pelvic tumors in children.

Pelvic tumors in children may be large, complex and of unknown origin. Preoperative radiological information regarding tumor localization and extent becomes essential in these cases for proper staging and surgical planning. Magnetic resonance imaging (MRI) offers the ability to enhance the surgical preparation of children who present with a pelvic mass. Advantages of MRI over computerized tomography include improved soft tissue characterization, signal enhancement of neuroendocrine tumors and multiplanar imaging. These features better define the origin, size and extent of tumors. In addition, no ionizing radiation is required. Several examples of pelvic tumors are presented. The new anatomical information provided by MRI altered surgical planning previously based on computerized tomography findings alone.

Adolescent↗