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Biomedical subjects

K Patel

Publications and source records attributed to K Patel.

At least 163 records · Page 9Linked to original sources
PubMed1995

Interleukin-6 chaperones in blood.

There is increasing evidence that many, perhaps all, cytokines have a soluble form of their receptor in the systemic circulation at all times. There is also evidence that endogenous antibodies to some cytokines, including IL-6, are also found in blood. Initially these findings were evaluated in vitro, and associated with inhibiting the respective effects of those cytokines. However, it is now becoming clear that the in vivo effects are paradoxically the reverse of what is seen in vitro. As we have explained here for IL-6 it is evident that many or all of these molecules that bind and/or associate with IL-6 maintain this molecule in the systemic circulation and constitute a reservoir of masked, but potentially active IL-6. The mode of regulation of the biological activity of these IL-6-associated complexes remains unknown, but needs to be uncovered in order to pharmacologically exploit many of the potentially beneficial effects or to prevent any potential pathological effects.

Animals↗
PubMed1995

Cloning, sequencing, and expressional analysis of the chick homologue of follistatin.

Follistatin, a secreted glycoprotein, has been shown to act as a potent neural inducer during early amphibian development. The function of this protein during embryogenesis in higher vertebrates is unclear, and to further our understanding of its role we have cloned, sequenced, and performed an in-depth expressional analysis of the chick homologue of follistatin. In addition we also describe the expression pattern of activin beta A and activin beta B, proteins that have previously been shown to be able to interact with follistatin. In this study we show that the expression of follistatin and the activins do not always overlap. Follistatin was first detected in Hensen's node and subsequently in the region described by Spratt [1952] as the neuralising area. In older embryos it was also expressed in a highly dynamic manner in the hindbrain as well as in the somites. We also present evidence that follistatin may have a later role in the resegmentation of the somites. We were unable to detect the expression of activin beta A during early embryogenesis, whereas activin beta B was first expressed in the extending primitive streak and subsequently in the neural folds. The results from this study are consistent with a role for follistatin in neural induction but suggest it has additional functions unrelated to its inhibitory actions on activins.

Activins↗
PubMed1995

Fusion of the EWS gene to a DNA segment from 9q22-31 in a human myxoid chondrosarcoma.

Southern blot analyses revealed a rearrangement of the EWS gene in a skeletal human myxoid chondrosarcoma. Interphase fluorescence in situ hybridization (FISH) studies, using cosmid clones F7 and G9 that flank the EWS locus on 22q12, confirmed the presence of this EWS gene abnormality. Cloning the rearranged EWS DNA fragment and mapping by FISH demonstrated that the EWS gene is joined to DNA sequences localised in 9q22-31. These findings are consistent with previous cytogenetic reports of a recurrent t(9;22)(q22-31;q11-12) in the myxoid variant of chondrosarcoma and reveal involvement of the EWS gene in a fourth type of human sarcoma.

Adult↗
PubMed1995

Nuclear and cytoplasmic bcl-2 expression in endometrial hyperplasia and adenocarcinoma.

The bcl-2 proto-oncogene, which inhibits programmed cell death (apoptosis), has recently been found to be cyclically expressed in human endometrium. In order to investigate its role in endometrial hyperplasia and neoplasia, bcl-2 expression was studied in 25 cases of endometrial carcinoma and 20 cases of endometrial hyperplasia (eight simple, two complex, and ten atypical hyperplasias). Uniform intense cytoplasmic bcl-2 expression was found in all cases of non-atypical hyperplasia, and less strong positivity in eight out of ten cases of atypical hyperplasia. In well-differentiated carcinomas, nine out of ten showed weak to moderate bcl-2 expression, whereas six out of seven poorly differentiated carcinomas were bcl-2-negative. Moderately differentiated tumours were an intermediate group, with six out of eight being positive. Widespread localization of bcl-2 protein to the chromosomes of dividing cells was also demonstrated, regardless of cytoplasmic bcl-2 expression, with rare staining of interphase nuclei. Our findings suggest a role for bcl-2 in the natural history of endometrial neoplasia and studies are needed to determine its usefulness as a prognostic marker. The finding of bcl-2 localization to chromosomes has important implications for its mode and site of action.

Adenocarcinoma↗
PubMed1995

A mathematical model of flow through the terminal lymphatics.

Proper understanding of the mechanisms of fluid absorption and flow through the terminal lymphatics is essential for the control of several pathological conditions such as edema, bedsores and cancer. A mathematical model of the terminal lymphatics was developed using the principles of mechanics. Computer simulation results substantiate the hypothesis that fluid absorption and flow through the terminal lymphatics occur due to suction mechanisms of the adjacent contractile lymphatic segments and due to periodic fluctuations in the interstitial fluid pressure. In addition, the results suggested that increasing the length of a terminal lymphatic vessel beyond a certain limit does not cause further increase in fluid flow into the terminal lymphatic.

Biomedical Engineering↗
PubMed1995

Neutrophil elastase-alpha 1-antitrypsin in middle ear fluid in chronic otitis media with effusion.

Neutrophil elastase-alpha 1-antitrypsin was quantified in samples taken from middle ear effusions collected at operation from 17 children attending for elective myringotomy and grommet insertion. At the time of surgery the effusion was classified as serous or mucoid. Children with a recent history of infection or antimicrobial therapy were excluded. The quantification of immunoreactive neutrophil elastase was by means of enzyme-linked immunosorbant assay (ELISA). The mean value of neutrophil elastase-alpha 1-antitrypsin was 50.6 +/- 38.3 (SD) micrograms/ml in mucoid effusions, which was significantly higher (P < 0.05) than that in serous effusions (5.3 +/- 4.8 micrograms/ml). These results indicate that a mucoid effusion may reflect a more severe inflammatory response and that persistence of neutrophil activity in the middle ear mucosa may contribute to the persistence of at least one group of middle ear effusions.

Child↗
PubMed1995

Dopa responsive dystonia.

There may be insufficient awareness of dopa responsive dystonia (DRD), which has a characteristic diurnal variation of symptoms. Two children are reported in whom the diagnosis of DRD was missed. The first was thought to have hysteria and the second hereditary spastic paraparesis. A full history is vital for the diagnosis of this important treatable syndrome.

Child↗
PubMed1995

No-fault medical liability in Virginia and Florida. A preliminary evaluation.

State governments are experimenting with a variety of innovative approaches to the current tort system for medical malpractice liability. One such approach is to apply the concept of no-fault liability to medical practice. States such as Virginia and Florida have already adopted a limited version of such a concept. This article examines the problems of the current tort system, different types of no-fault medical insurance alternatives and their advantages, and the experiences of the states of Virginia and Florida with their limited no-fault malpractice insurance systems. The author concludes that the concept of no-fault compensation for medical malpractice is a promising remedy. However, it is a medicine that will require more testing before it can be pronounced a cure for the disease that plagues the current system.

Birth Injuries↗
PubMed1995

TGF alpha can act as a chemoattractant to perioptic mesenchymal cells in developing mouse eyes.

Growth factors are believed to play an important role in regulating cell fate and cell behavior during embryonic development. Transforming growth factor alpha (TGF alpha), a member of the epidermal growth factor (EGF) superfamily, is a small polypeptide growth factor. Upon binding to its receptor, the EGF receptor (EGFR), TGF alpha can exert diverse biological activities, such as induction of cell proliferation or differentiation. To explore the possibility that TGF alpha might regulate cell fate during murine eye development, we generated transgenic mice that express human TGF alpha in the lens under the control of the mouse alpha A-crystallin promoter. The transgenic mice displayed multiple eye defects, including corneal opacities, cataracts and microphthalmia. At early embryonic stages TGF alpha induced the perioptic mesenchymal cells to migrate abnormally into the eye and accumulate around the lens. In situ hybridization revealed that the EGFR mRNA is highly expressed in the perioptic mesenchyme, suggesting that the migratory response is mediated by receptor activation. In order to test this model, the TGF alpha transgenic mice were bred to EGFR mutant waved-2 (wa-2) mice. We found that the eye defects of the TGF alpha transgenic mice are significantly abated in the wa-2 homozygote background. Because the EGFR mutation in the wa-2 mice is located in the receptor kinase domain, this result indicates that the receptor tyrosine kinase activity is critical for signaling the migratory response. Taken together, our studies demonstrate that TGF alpha is capable of altering the migratory decisions and behavior of perioptic mesenchyme during eye development.

Animals↗
PubMed1995

Influence of inflammatory bowel disease on the distribution and concentration of pancreatic secretory trypsin inhibitor within the colon.

Gastrointestinal epithelia contain a powerful protease inhibitor called pancreatic secretory trypsin inhibitor (PSTI). Patients with inflammatory bowel disease have changes in mucus structure suggestive of increased proteolysis. We therefore examined the distribution and concentration of PSTI in the colon of normal subjects and patients with inflammatory bowel disease. In normal subjects (N = 12), mucosal levels of PSTI were approximately 200 ng/mg protein in all regions of the colon and was localized to goblet and endocrine cells. Mucosal PSTI levels in the (affected) left side of the colon of patients with active (N = 12) or quiescent (N = 10) ulcerative colitis were reduced (approximately 80% of control in descending colon, 55% of control in sigmoid colon, and 50% of control in rectum, all P < 0.01), whereas levels in the (unaffected) right side of the colon were normal. PSTI levels were also reduced to approximately 65% of control in colonic tissue affected by Crohn's disease (N = 6, P = 0.01) and immunostaining showed PSTI positivity within the ulcer-associated cell lineage. As the mucous layer is important in preserving mucosal integrity, our finding of prolonged reduction in mucosal PSTI levels after an episode of ulcerative colitis probably represents a long-term reduction in a mucosal defense mechanisms that could lead to increased susceptibility to episodes of inflammation.

Colitis, Ulcerative↗
PubMed1995

Essential thrombocythaemia followed by multiple myeloma in the same patient.

We describe a patient with essential thrombocythaemia who developed multiple myeloma 7 years after an initial diagnosis of essential thrombocythaemia. A 50-year-old white female presented in 1987 with a 2 year history of low backache, painful swollen ankles and burning feet. Her laboratory investigations suggested a diagnosis of essential thrombocythaemia. Initially she was treated with busulphan without much benefit for 6 months. Subsequently she was treated with hydroxyurea with significant relief of her symptoms and reduction in her platelet count. Seven years after her initial presentation she developed bone pains and anaemia with laboratory investigations confirming a diagnosis of multiple myeloma.

Female↗
PubMed1994

Sustained high levels of circulating chaperoned interleukin-6 after active specific cancer immunotherapy.

In a phase 1 study of recombinant interleukin-6 (rIL-6) in patients with advanced solid tumors (n = 15), we discovered that the endogenous IL-6 levels, in pretreatment plasma or serum samples, were distributed into two groups. One set of patients (designated "type 1"; n = 9) was characterized by low plasma IL-6 levels (48 to 1,700 pg/mL) as measured using enzyme-linked immunosorbent assays (ELISA) for IL-6. In the second set of patients (designated "type 2"; n = 6), IL-6 ELISAs showed high levels of plasma IL-6 (50 to 600 ng/mL). Neither group had detectable B9 hybridoma cell growth factor activity associated with the IL-6 in their pretreatment plasma or serum. Plasma C-reactive protein (CRP) levels were markedly elevated in type II patients suggesting that the circulating IL-6 was biologically active in vivo. In both groups of patients there was a small but significant increase in B9 activity in the plasma within three hours after rIL-6 administration (n = 5). Gel filtration profiles showed that circulating IL-6 in type 1 patients, 15 to 120 minutes after rIL-6 administration was of approximate mass 20 to 40 kD, whereas in type 2 patients, the IL-6 before and after exogenous rIL-6 administration was indistinguishable and was of an approximate mass of 200 kD. IL-6 immunoaffinity purification of the 200 kD complexes showed these to contain multiple isoforms of IL-6 (14 to 31 kD) and the soluble IL-6 receptor (sIL-6R; 50 to 55 kD). A distinguishing clinical history was that all of the type 2 patients had been actively immunized with an anti-idiotypic monoclonal antibody (MoAb) (MK2-23) 3 to 12 months before initiation of this study for advanced melanoma. An analysis of the plasma IL-6 content in other melanoma patients (n = 16) during antiidiotypic MoAb immunization indicated that marked (up to 600 ng/mL) and sustained (several months) elevations of circulating "chaperoned" IL-6 were induced by active immunization regimens.

Antibodies, Monoclonal↗
PubMed1994

Effect of Calphostin C (PKC inhibitor) on daunorubicin resistance in P388/ADR and HL60/AR cells: reversal of drug resistance possibly via P-glycoprotein.

Calphostin C is a potent and specific inhibitor of protein kinase C (PKC). In this investigation we examined the effect of Calphostin C (without prior exposure to light) on daunorubicin (DNR) accumulation and sensitivity to DNR in multidrug-resistant (MDR) murine leukemia P388/ADR and human myeloid leukemia HL60/AR cells. P388/ADR cells overexpress P-glycoprotein, whereas HL60/AR cells lack any expression of P-glycoprotein (both at mRNA and protein levels). Calphostin C, in a concentration-dependent manner, increased the accumulation of DNR in P388/ADR cells and partially reversed (threefold) the DNR resistance in P388/ADR cells but had no effect on either of the parameters in HL60/AR cells. Calphostin C-induced increased accumulation of DNR in P388/ADR cells was due to increased uptake and decreased efflux of DNR. Furthermore, Calphostin C increased the uptake and decreased the efflux of rhodamine 123 (a substrate for P-gp) in P388/ADR cells but had no such effect in P388 cells. In addition, Calphostin C without exposure to light did not inhibit PKC activity in any of the cell lines studied. Taken together, these data suggest that Calphostin C may reverse drug resistance via P-glycoprotein independently of its effect on PKC activity. Therefore, any data regarding the effect of Calphostin C on the reversal of MDR should be interpreted in the light of these findings.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Mapping of the human SAP1 (SRF accessory protein 1) gene and SAP2, a gene encoding a related protein, to chromosomal bands 1q32 and 12q23, respectively.

SAP1, SAP2, and ELK1 form a related subgroup of ETS-domain proteins that can form ternary complexes with the transcription factor SRF at the c-fos serum response element (SRE). SAP1 was identified by a genetic screen for proteins interacting with SRF expressed in yeast, and SAP2 by its homology with SAP1; ELK1 was previously identified by its homology to the ETS domain. cDNA probes were used to isolate cosmid and phage clones harboring genes encoding SAP1 and SAP2. These clones were subsequently used to map the genes to 1q32 and 12q23, respectively, by fluorescence in situ hybridization.

Chromosome Mapping↗
PubMed1994

Improved methodology for detecting bromodeoxyuridine in cultured cells and tissue sections by immunocytochemistry.

Detection of DNA synthesizing cells may often be achieved by immunocytochemical detection of bromodeoxyuridine (BrdU), which is rapid and appears to give similar results to those found using tritiated thymidine. However, the methodology for detection of BrdU involves a denaturation or digestion step to allow access of the antibody to BrdU incorporated into single- rather than double-stranded DNA. We wished to determine if microwave treatment could be used to enhance the detection of BrdU without the need for any other digestion/denaturation steps. An important consideration was to investigate whether such treatment produces a similar quantitative result, since BrdU detection is usually assessed on the basis of cell number rather than topographical distribution. We have found that microwave treatment can allow considerably lower antibody concentrations and eliminates the need for any other denaturation step. It also reduces the non-specific background staining found when using monoclonal antibodies on mouse tissue. We have performed cell counts and found that the number of BrdU positive cells remains constant for a range of different immunocytochemical parameters. We also report conditions where immunopositivity is adversely affected by changes in technique and describe the optimised conditions for obtaining reproducible results.

Animals↗
PubMed1994

Pneumatosis intestinalis in a child with AIDS and pseudomembranous colitis.

Pneumatosis intestinalis (PI) was first reported in three children and one adult with acquired immune deficiency syndrome (AIDS) in 1990. The microorganisms cultured from these patients included Cryptosporidium, rotavirus, cytomegalovirus, and Pseudomonas. We report the fourth child with AIDS and PI, and the first with PI to be associated with Clostridium difficile colitis.

AIDS-Related Opportunistic Infections↗
PubMed1994

Tissue-specific expression of neural cell adhesion molecule (NCAM) may allow differential diagnosis of neuroblastoma from embryonal rhabdomyosarcoma.

The MSD1 region of neural cell adhesion molecule (NCAM) was originally described as being spliced into the 120-kDa isoform of NCAM isolated from muscle. The 105 bp region is inserted between exons 12 and 13 and actually consists of three separate exons, MSD1a, MSD1b and MSD1c of 15, 48, 42 bp, respectively. In addition, a further exons consisting of a single triplet has been designated MSD1d, making the full insert size 108 bp. As the MSD1 region was originally described as being selectively expressed in muscle tissue, we have investigated whether it is also present on tumours of rhabdoid origins and whether its presence can be used as the diagnostic marker to distinguish other small round cell tumours of childhood, such as neuroblastoma. Using a variety of human tumour cell lines, we demonstrated the presence of the MSD1 region on all rhabdomyosarcomas investigated. However, neuroblastoma cell lines only expressed subcompartments of the MSD1 region. The MSD1c exon was not spliced into the NCAM molecules isolated from any of the neuroblastoma cell lines investigated. On the basis of this finding, it appears that neuroblastoma and rhabdomyosarcoma can be distinguished by the expression of MSD1c mini-exon. Further studies are underway to attempt to define a monoclonal antibody that recognises the region, using mice immunised with synthetic peptides, and to confirm the finding using fresh biopsy material.

Base Sequence↗