Search PubMed⌕ Search

Biomedical subjects

H Jones

Publications and source records attributed to H Jones.

At least 127 records · Page 7Linked to original sources

Inhibitory effect of the TRFK-5 anti-IL-5 antibody in a guinea pig model of asthma.

To investigate the role of IL-5 in airway hyperreactivity and pulmonary eosinophilia, we used a model of allergic asthma in guinea pigs and a neutralizing monoclonal antibody (TRFK-5) directed against murine IL-5. Sensitized guinea pigs were challenged with 1% ovalbumin (OVA) aerosol and assessed for airway eosinophilia (by bronchoalveolar lavage [BAL] and histologic evaluation of airway tissue) and bronchoconstrictor responsiveness to substance P (SP) (as RL100 and Cdyn40) 24 h later. OVA challenge of sensitized animals caused a significant increase in airway responsiveness to SP, with a 4.9-fold decrease in RL100 and a 4.7-fold decrease in Cdyn40. Accompanying this increased sensitivity to SP was a 9-fold increase in eosinophils recovered in BAL and a 4- to 5-fold increase in eosinophils in intrapulmonary bronchial tissue. Intraperitoneal treatment with 10 mg/kg of the IL-5 antibody 2 h before OVA challenge blocked BAL and lung tissue increases in eosinophils but had no effect on the development of airway sensitivity to SP. In contrast, similar treatment with 30 mg/kg of this antibody blocked OVA-induced increased sensitivity to SP as well as BAL and lung tissue eosinophilia. These data suggest a critical and possibly independent role for IL-5 in allergic airway hyperresponsiveness and the accumulation of eosinophils within the lung of the guinea pig.

Animals↗

Relationship between immunohistochemically detectable p53 protein and prognostic factors in head and neck tumors.

This study examined the relationship between immunohistochemically detectable p53 protein and prognostic factors in squamous cell carcinoma of the head and neck (SCCHN). Twenty-seven tumor specimens were evaluated utilizing a panel of three monoclonal antibodies (MAbs) directed against different epitopes of the p53 protein (PAb 421, PAb 1801, and PAb 240). The overall incidence of p53 protein detection with a panel of MAbs was 78%, which was significantly higher than with any one of the tested antibodies. Comparison of the tumors that were negative for p53 with tumors that stained positive with one or multiple antibodies, however, revealed no statistically significant differences with respect to the stage of disease, metastatic node involvement, size of the primary tumor, or degree of tumor differentiation. The results of our study suggest that levels of p53 protein, although commonly immunohistochemically detected in head and neck tumors, do not correlate with known prognostic factors for SCCHN.

Adult↗

Renal hypoplasia and postnatally acquired cortical loss in children with vesicoureteral reflux.

We reviewed histologically 86 nephrectomy specimens from patients with vesicoureteral reflux (with or without ureterovesical obstruction) to investigate the relationship between coexisting hypoplasia and postnatally acquired cortical damage. Hypoplasia was assessed independently of the acquired cortical loss using medullary ray glomerular counting. Severe hypoplasia (glomerular number < 25% of normal) was detected in 47 of 86 patients. These patients underwent nephrectomy at a significantly younger age than those with minimal or no hypoplasia (P < 0.01). There was no significant relationship between the severity of hypoplasia and the presence or absence of obstruction. Severe acquired cortical loss was found in 68 of 86 patients. There was no significant association between the severity of cortical loss and the presence or absence of obstruction, age at nephrectomy or degree of coexisting hypoplasia. The findings suggest a strong association of hypoplasia and vesicoureteral reflux. Therefore, early postnatal presentation with minimal renal function need not necessarily reflect a failure of management but rather a pre-existing limitation of renal capacity. Furthermore, in a significant proportion of fetuses with ultrasonographic evidence of urinary tract abnormality, renal pathology may be present prior to the time at which in utero surgical intervention may be considered.

Adolescent↗

Meningococcal disease in Wales: clinical features, outcome and public health management.

In Wales, in 1988, 119 patients with meningococcal disease were identified, so giving a crude annual incidence of 4.2 patients per 100,000 population. The combined classical clinical features of fever, vomiting, neck stiffness, headache and purpuric rash were identified in only 9% of patients. Fever and vomiting were the commonest symptoms, both being present in 60% of patients. A rash was noted in 77% of patients but neck stiffness in only 39%. Rash was more common in children, headache and photophobia in adults. A total of 13 patients died, the fatality rare increasing with age from 3% in infants to 20% in older teenagers and adults. Only 15% of 75 patients admitted to hospital by general practitioners were known to have received intravenous or intramuscular penicillin before admission as recommended by the Chief Medical Officers of the Health Departments in the U.K. Only 24% of patients received rifampicin to clear nasopharyngeal carriage before or at discharge from hospital. Altogether, 375 household contacts of patients were identified. At least 84% of them received chemoprophylaxis.

Acute Disease↗

Metastatic prostatic carcinoma presenting as left-sided cervical lymphadenopathy: a series of 11 cases.

Eleven cases of metastatic prostatic carcinoma in cervical lymph nodes as a primary presenting sign were identified in a survey of 250 cervical lymph node biopsies from men. The diagnosis was clinically unsuspected in all cases. All occurred on the left side of the neck. These 11 cases represented 11% of all metastatic carcinomas in the neck and 20% of those with left-sided involvement. The diagnosis was readily confirmed by immunostaining for prostate specific antigen and prostate specific acid phosphatase. Six patients are alive and well at an average of 25.8 months and five others survived for an average of 34.4 months, the combined survival being 29.7 months. This contrasts with the dismal fate of patients with metastatic adenocarcinoma from other sites who all died at an average of 2 months from diagnosis. Prostatic carcinoma should always be considered in the differential diagnosis of metastatic carcinoma in cervical lymph nodes in elderly men, as appropriate treatment results in worthwhile prolongation of life.

Adenocarcinoma↗

Immunoreactivity of alpha smooth muscle actin in salivary gland tumours: a comparison with S100 protein.

Antibodies against alpha smooth muscle actin (ASMA) and S100 protein were applied to paraffin wax embedded sections from 40 salivary gland tumours and seven normal salivary glands. The results indicate that ASMA is useful in the diagnosis of epithelial-myoepithelial carcinoma, but is otherwise only of limited use in diagnostic practice. An unexpected finding was the failure of ASMA to react with myoepitheliomas.

Actins↗

Apolipoprotein gene expression in analbuminemic rats and in rats with Heymann nephritis.

The nephrotic syndrome results from altered glomerular permselectivity, causing urinary protein loss, reduced albumin concentration, oncotic pressure (pi), and hyperlipidemia. Hepatic lipid and apolipoprotein synthesis increases and lipoprotein catabolism decreases. Decreased lipoprotein catabolism follows the onset of proteinuria but is not associated with hereditary analbuminemia [Nagase analbuminemic rat (NAR)] if proteinuria is absent. We measured plasma apolipoproteins (apo) AI, B, and E levels, their mRNA concentrations in liver, and the transcription rate of each mRNA in rats with Heymann nephritis (HN) or NAR to determine which alterations occurred in NAR alone without proteinuria. Plasma apo AI, B, and E were increased in both HN and NAR. Cholesterol and apo AI were inversely proportional to pi and independent of urinary protein loss or the presence of albumin in plasma. In contrast, triglycerides (TGs) were significantly greater in HN and were increased out of proportion to apo B. The concentration of apo AI mRNA increased in liver of both HN and NAR as did apo AI transcription. Apo E mRNA increased in neither HN nor NAR, whereas apo B mRNA increased only in HN. Transcription of neither apo B nor E increased. Plasma apo AI levels are likely to be regulated transcriptionally at the level of protein synthesis, whereas plasma apo B and E levels are regulated either posttranscriptionally, at the level of protein catabolism, or at both sites. Lipoproteins rich in TG and poor in apo B appear after the development of proteinuria but not as a consequence of analbuminemia alone. The accumulation of TG-rich apo B containing lipoproteins in rats with HN may result from impaired lipolysis occurring as a consequence of proteinuria.

Animals↗

Arginine augments neither albuminuria nor albumin synthesis caused by high-protein diets in nephrosis.

Dietary protein independently modulates albuminuria (U(Alb)V) and albumin synthesis (AlbSyn) in nephrotic rats. While some amino acids are without effect on renal hemodynamics, arginine (Arg) augments renal blood flow and glomerular filtration rate, increases AlbSyn in tissue culture and isolated perfused livers, and could be one specific amino acid causing both decreased glomerular permselectivity and increased AlbSyn. Nephrotic rats were fed 10% casein (LP); 30% casein (HP); 30% casein with the inhibitor of nitric oxide (NO) synthesis N omega-nitro-L-arginine methyl ester (HP + L-NAME); 10% casein supplemented with Arg and amino acids that are Arg precursors of or are derived from Arg (proline, glutamate, and aspartate) in an amount in the increment between 10 and 30% casein (ArgAA); ArgAA supplemented with NH4 acetate to provide a diet isonitrogenous to 30% casein (ArgAA + NH4); or 10% casein plus an incomplete mixture of amino acids (Inc) containing the increment in histidine, phenylalanine, tryptophan, tyrosine, lysine, glycine, alanine, serine, threonine, cysteine, and methionine provided when the diet was changed from 10 to 30% casein. U(Alb)V increased significantly in HP and by a significantly greater amount in HP + L-NAME, but did not change in LP, ArgAA, or ArgAA + NH4. U(Alb)V tended to increase in Inc, was significantly greater than in LP or in ArgAA + NH4, but less than in HP. AlbSyn ([3H]phenylalanine incorporation) was no different in Inc than in HP, and was significantly greater than in either ArgAA + NH4 or LP. Increased AlbSyn results from increased ingestion of one or more of amino acids in Inc, but not from Arg or its precursors or products or from total dietary nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

Interleukin-5 modulates eosinophil accumulation in allergic guinea pig lung.

Based on its involvement in eosinophil biology, interleukin 5 (IL-5) may play a role in the pulmonary eosinophilia associated with allergic reactions. We have examined that hypothesis using a neutralizing antibody to IL-5 in ovalbumin-sensitized guinea pigs challenged with aerosolized antigen. The extent of eosinophilia has been quantitated in bronchoalveolar lavage (BAL) and by histologic evaluation of lung tissue sections. Acute intraperitoneal administration of a rat IgG, monoclonal antibody to murine IL-5 derived from TRFK-5 cells prevented lung and BAL eosinophilia in a dose-dependent fashion at and above 10 micrograms per guinea pig. Treatment with either an experimentally irrelevant, isotype-matched antibody from GL113 cells or with heat-denatured IL-5 antibody was without effect. These studies demonstrate the importance of IL-5 to pulmonary eosinophilia in challenged, allergic guinea pigs.

Animals↗

A biomechanical study of two methods of internal fixation of unstable fractures of the femoral neck. A preliminary study.

A model of an unstable femoral neck fracture was used in this study to compare the axial and torsional displacement obtained when the neck was fixed by a compression hip screw (CHS) and side plate, or three Knowles pins. Six paired, embalmed femora were mounted on a special, custom-made jig that grasped the femoral head and shaft securely. A standardized osteotomy was made with an oscillating saw, bisecting the distance between the lower cartilaginous portion of the femoral head and the intertrochanteric line. A 5-mm thick slice of bone was excised from the posteromedial quadrant of the distal fragment. The right or left femur in each pair was then randomly assigned to internal fixation with either three Knowles pins or a keyed CHS plus a 130 degrees four-hole side plate. After potting of the specimens and application of rosette strain gauges, axial displacements were measured during the application of in-plane and out-of-plane compressive loads. The resistance to torsion was also determined. There were no statistical differences between the two devices for compressive or torsional loading using this model.

Biomechanical Phenomena↗

Spindle-cell glioblastoma or gliosarcoma?

'Gliosarcomas' have long been considered to be mixed gliomas and sarcomas. The present study failed to define criteria which clearly delineate 'gliosarcomas' from glioblastoma multiforme and suggests that 'gliosarcomas' should be considered as spindle cell glioblastomas. A total of six cases originally diagnosed as 'gliosarcomas' were compared with four cases of glioblastoma multiforme. No clinical or prognostic features were defined which would clearly separate 'gliosarcomas' from glioblastoma multiforme. Macroscopically, biopsies from 'gliosarcomas' ranged from firm, apparently well-circumscribed tumours to poorly circumscribed lesions with a soft consistency resembling glioblastoma multiforme. Histology revealed a continuous spectrum in which 'gliosarcomas' with large reticulin-rich areas of spindle cells merged with typical glioblastomas containing only small islands of spindle cells and reticulin staining. Immunocytochemistry for glial fibrillary acidic protein (GFAP); S100 protein and alpha-smooth muscle actin (ASMA) showed that the majority of cells in reticulin-poor areas of 'gliosarcoma' and glioblastomas expressed S100 protein and GFAP; many expressed ASMA and some expressed both GFAP and ASMA. Spindle cells in reticulin-rich areas of 'gliosarcomas' and glioblastomas most frequently expressed ASMA but many cells also expressed S100 protein and GFAP; some cells expressed both GFAP and ASMA. The results of this study and a review of the literature suggests that there is a clinical, radiological and pathological continuum with glioblastoma and 'gliosarcoma' at different ends of the spectrum. It is suggested, therefore, that most, if not all, 'gliosarcomas' be redesignated as spindle cell glioblastomas and not be considered as a mixture of glioma and sarcoma.

Actins↗

Branched-chain amino acids augment neither albuminuria nor albumin synthesis in nephrotic rats.

Both albuminuria (UalbV) and albumin synthesis (AlbSyn) are modulated by dietary protein in nephrotic rats, but the agent(s) linking diet to altered UalbV and AlbSyn is unknown. Others have reported that branched-chain amino acids (BCAA) cause neither increased renal blood flow nor glomerular filtration rate (GFR) normally induced by dietary protein nor increased blood glucagon thought to be necessary for protein-mediated effects on renal hemodynamics. The effect of BCAA on UalbV is unknown. Because BCAA increase AlbSyn in tissue culture and after a fast, it is possible that feeding BCAA may increase AlbSyn but not UalbV in nephrosis. Nephrotic rats were fed either 8.5% casein (LP); 21% casein (NP); 8.5% casein supplemented with valine, leucine, and isoleucine to the total amount provided by a 21% casein diet (2.37%) (LBC); or 8.5% casein plus 12.5% BCAA providing a diet isonitrogenous to 21% casein (HBC). UalbV and AlbSyn were significantly greater in NP compared with LP, LBC, or HBC and were the same in the latter three groups. Glucagon was infused into nephrotic rats fed 8.5% casein either subcutaneously or intraperitoneally in quantities sufficient to increase plasma levels to over 10 times control but had no effect on UalbV. The ability of dietary protein to increase AlbSyn or UalbV is not a result of total alpha-amino nitrogen intake but is a result of the specific amino acid composition of the diet and must result entirely from the effect of one or more non-BCAA. Increased blood glucagon alone has no effect on UalbV.

Albuminuria↗

Alpha-smooth muscle actin as a marker for soft tissue tumours: a comparison with desmin.

The immunoreactivity of a range of vascular and non-vascular smooth muscle tumours, rhabdomyosarcomas, and non-myoid lesions has been examined with the use of a monoclonal antibody to smooth muscle-specific actin and the muscle intermediate filament, desmin. In all cases of smooth muscle-derived tumours, the alpha-actin antibody yielded superior results. Staining of the myofibroblasts of fibromatoses was also seen. In contrast to desmin, immunoreactivity was not exhibited by rhabdomyosarcomas. We propose that this monoclonal antibody to alpha-smooth muscle actin is a useful addition to the panel of reagents used for the characterization of soft tissue proliferations and tumours. The technical aspects of the application of this monoclonal antibody to immunohistochemistry are discussed.

Actins↗