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Biomedical subjects

A H Clark

Publications and source records attributed to A H Clark.

At least 19 recordsLinked to original sources

Interfacial tension in phase-separated gelatin/dextran aqueous mixtures.

The effect of solute concentrations on interfacial tension was investigated in phase-separated mixtures of dextran and gelatin over a range of concentrations that covered different tie-lines and different positions on one tie-line. The investigations were carried out using equilibrated gelatin-rich and dextran-rich phases in a computer-controlled Couette device at 40 degrees C (above the gelation point of gelatin) and interfacial tensions were measured using the retracting drop method. The results show that the interfacial tension can be related to the length of the tie-line or to the difference in the concentration of dextran (or gelatin) in the separated phases. Interfacial tension increases as either of these parameters increases. For concentrations lying on any single tie-line, the interfacial tension is constant and independent of the concentration of biopolymers. Also, the addition of small amounts of low molecular weight dextran to a dextran-rich phase does not significantly affect the interfacial tension between the gelatine-rich and dextran-rich phases. Experimental results were also compared with theoretical predictions of the interfacial tension using a Flory-Huggins based analysis of the measured tie-line data. Reasonable agreement was found between predicted and measured values, indicating that this approach captures the basic physics of the system.

Dextrans↗

Influence of thermal history on the structural and mechanical properties of agarose gels.

Using a multitechnique approach, two temperature domains have been identified in agarose gelation. Below 35 degrees C, fast gelation results in strong, homogeneous and weakly turbid networks. The correlation length, evaluated from the wavelength dependence of the turbidity, is close to values of pore size reported in the literature. Above 35 degrees C, gelation is much slower and is associated with the formation of large-scale heterogeneities that can be monitored by a marked change in the wavelength dependence of turbidity and visualised by transmission electron microscopy. Curing agarose gels at temperatures above 35 degrees C, and then cooling them to 20 degrees C, produces much weaker gels than those formed directly at 20 degrees C. Dramatic reductions in the elastic modulus and failure strain and stress are found in this case as a result of demixing during cure. An interpretation, based on the kinetic competition between osmotic forces (in favor of phase separation) and elastic forces (that prevent it) is proposed.

Elasticity↗

Heat-induced gelation of globular proteins: part 3. Molecular studies on low pH beta-lactoglobulin gels.

Heat-set gels and aggregates from beta-lactoglobulin (beta-Lg), one of the major globular proteins from milk, have been studied on a molecular distance scale using negative-staining transmission electron microscopy (TEM), wide-angle X-ray diffraction (WAXD), and Fourier transform infrared spectroscopy (FTIR). The microscopy showed long linear aggregates forming in solutions at pH 2 (and sometimes 2.5) after prolonged heating. While there appeared to be no differences in aggregates formed under these conditions in H(2)O as compared with D(2)O, at all other pH and pD values, and in the presence of added salt, much shorter linear aggregates were formed. These became slightly more extended the further the pH was removed from pI. Wide-angle X-ray diffraction (WAXD) showed a diffuse beta-sheet halo at 2θ=19 degrees in patterns for both dried native and aggregated protein (irrespective of pH) with only a small change (sharpening) of this feature on heat treatment. Solution FTIR spectra, measured at pD=2, 2.5, 3, and 7, during heating, indicated shoulder development at 1612 cm(-1) in the carbonyl-stretching Amide I region diagnostic of a modest increase in intermolecular beta-sheet. In terms of the shoulder size, no distinctions could be made between acid and neutral aggregate structures. At all pHs, beta-lactoglobulin showed only limited secondary and tertiary structural changes in aggregation, in contrast to previous studies of insulin aggregation, where highly ordered crystalline fibrils were indicated. The current work has implications both in structural studies of food biopolymers and in ongoing studies of pathological protein self-assembly in disease states, such as spongiform encephalopathies.

Animals↗

Interpenetrating network formation in gellan--agarose gel composites.

Thermal, mechanical, turbidity, and microscope evidence is provided which strongly suggests molecular interpenetrating network (IPN) formation by mixtures of the bacterial and seaweed polysaccharides gellan and agarose. There is no evidence for synergistic coupling of the networks, and simple phase separation (demixing) can definitely be ruled out. Some changes in the gellan gelling behavior are suggested, however, by the increased gellan effective concentrations implicit in cure curve data. The dependence of this effect on the agarose nominal concentration seems consistent with a previous model that focused on gelling parameters, and changes in these rather than real concentration effects. In large deformation mechanical tests, the influence of agarose added to gellan is to re-enforce the network (higher compression and shear moduli, higher stresses-to-break) without significantly changing the strain to break, or the gellan brittle failure mechanism.

Algorithms↗

Comparison of different scoring systems for immunohistochemical staining.

AIM: To carry out an objective assessment of two systems of scoring immunohistochemical staining, evaluating interobserver and intraobserver error. METHODS: 92 cervical tumours underwent immunohistochemical staining for p53 and epidermal growth factor receptor. Staining was assessed using two methods: a standard 4 point scale and a descriptive method, performed by three observers. Interobserver and intraobserver error were assessed for both scoring methods. RESULTS: In terms of interobserver error between three observers, no difference was found between a simple 4 point scale method of evaluation and the use of a highly circumscribed method. In all evaluations, interobserver error was scored as moderate (kappa w 0.48-0.49). However, evaluation of immunohistochemical staining by a panel of observers led to a marked improvement in the interobserver error scores (kappa w 0.63). CONCLUSIONS: There should be standardisation of immunohistochemical staining and scoring methods. More attention should be paid to measurement of interobserver and intraobserver error in studies. Use of a panel of tissue control slides and consensus scoring by several observers can lead to improvement in reproducibility.

ErbB Receptors↗

Localized amyloidosis of the parotid gland: a case report and review of the localized amyloidosis of the head and neck.

BACKGROUND: Localized amyloidosis in the head and neck is a rare and benign process. METHODS: We present the first case report in the literature of localized amyloidosis of the parotid glands and also comprehensively review the literature regarding localized amyloidosis of the head and neck. RESULTS: Amyloidosis affecting the head and neck region is uncommon and is mostly in the form of localized amyloidosis. Larynx is the commonest site of involvement and accounts for 0.2% to 0.5% of benign laryngeal tumors. Laryngeal involvement could be either diffuse subepithelial deposition or discrete tumor nodules. Although localized amyloidosis occurs much more frequently in the oral cavity and pharynx, only seven cases of nasopharyngeal amyloidosis and eight cases of nasal septum amyloidosis have been reported. There is no documentation to suggest that localized amyloidosis can progress to systemic amyloidosis. Local surgical excision is the treatment of choice for laryngeal amyloidosis and laser excision is probably the best. CONCLUSION: While localized amyloidosis of the head and neck region is rare, it should be recognized, understood, evaluated, and properly treated.

Aged↗

Papillary endothelial hyperplasia (Masson's tumour) of the maxillary sinus.

In 1923, Masson described a neoplastic process consisting of papillary hyperplasia of the endothelial cells, with a consequent obliteration of the vascular lumen, followed later by degenerative changes. Masson coined the term vegetant intravascular haemangioendothelioma, however, these days it is more commonly known as papillary endothelial hyperplasia (PEH), or by the pseudonym, Masson's tumour. Although relatively rare, there are numerous accounts of PEH in the literature, describing its predilection for the head and neck region. Our case report describes the finding of a PEH within the paranasal sinuses, a site not previously mentioned even in the largest of series found on literature search. We will then discuss the relevant histological features of the lesion, and its natural history.

Aged↗

Shear modulus-temperature meltdown profiles of gelatin and pectin gels. A cascade theory description.

In this paper, a cascade theory approach to biopolymer gelation is developed to describe variation of the shear modulus with temperature for thermoreversible gels. The broadness of this 'melting transition' is seen to depend crucially on the enthalpy of cross-linking, while the critical gel melting temperature is determined by additional factors such as the entropy of cross-linking, the polymer concentration, the molecular weight, and the number of cross-linking sites. On using the model to fit experimental data for specific gelatin and pectin systems, it was found that the behaviour of gelatin (sharp melting transition and low melting temperature) is a consequence of the large negative enthalpy and entropy of cross-linking, while, in contrast, the broad melting transition and high melting point of the pectin system are consistent with much smaller negative values for these parameters.

Animals↗

Ca2+ channel antagonists and inhibition of protein kinase C each block contraction but not depolarization to 5-hydroxytryptamine in the rabbit basilar artery.

The Ca2+ channel antagonists nifedipine and verapamil each significantly inhibited (50-100%) the smooth muscle contraction induced in response to either 5-hydroxytryptamine (1 microM, 5-HT) or 20 mM K+ (K(+)-physiological salt solution) in the basilar artery. Simultaneous measurements of smooth muscle membrane potential showed that changes in potential were not modified at this time. A similar inhibitory action against the smooth muscle contraction but not the depolarization to 5-HT was obtained with the putative protein kinase C and phospholipase C inhibitors, 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (10 microM, H7) and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (70 microM, NCDC). These data indicate that 5-HT-induced Ca2+ influx through voltage sensitive channels is important for smooth muscle contraction but not depolarization in the rabbit basilar artery.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Glutathione S-transferase expression in benign and malignant ovarian tumours.

Glutathione S-transferase sub-types alpha, mu and pi were assessed by immunocytochemistry in 109 biopsies of ovarian tissue, comprising malignant epithelial tissue in 86 cases and tissue of ovarian origin considered to be normal in 23. Glutathione S-transferase pi was the most prevalent, being present in all except one malignant epithelium studied and 83% of non-malignant tissue. There were no significant differences in the overall distribution of positive staining for alpha, mu and pi in the malignant and non-malignant biopsies, although the intensity of staining was greater in the malignant epithelium. Stromal staining was in general more pronounced in the malignant biopsies, and this was particularly prominent in the case of the alpha sub-type. Positive staining was seen more frequently in the less well-differentiated tumours, and a diffuse cytoplasmic pattern was the most common observation in tumours of moderate and poor differentiation. There was no significant association between survival and the presence or absence of sub-type staining of alpha and mu sub-type. For the sub-type pi, patient survival was found to correlate with the intensity of staining (on a 0-(+++) scale). Those patients showing resistance to cytotoxic chemotherapy were found to have a higher intensity of staining for GST pi than responding patients.

Antineoplastic Combined Chemotherapy Protocols↗

Endothelium-dependent contractile responses to 5-hydroxytryptamine in the rabbit basilar artery.

1 5-Hydroxytryptamine (5-HT) and 5-carboxamidotryptamine (5-CT) stimulated additional, endothelium-dependent contractions in rabbit isolated basilar arteries which had been submaximally contracted with either histamine or potassium chloride. 2 The additional contractions to 5-HT were not altered by the 5-HT2 antagonist, ketanserin (1 microM), but were abolished in the presence of the cyclo-oxygenase inhibitor indomethacin (3 microM). 3 The additional smooth muscle contraction stimulated by 5-HT was increased in the presence of the competitive substrate inhibitor for nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). 4 Neither of the selective 5-HT agonists, 8-hydroxy-dipropylaminotetralin (8-OH DPAT) or alpha-methyl 5-HT stimulated endothelium-dependent contraction, but these agonists did reduce the rate at which histamine-induced tension spontaneously declined. This effect represented a direct action on the smooth muscle cells, as it was independent of the presence of endothelial cells. 5 Smooth muscle relaxation was not obtained in response to 5-HT, whether or not indomethacin was present to block endothelium-dependent contraction. None of the other selective 5-HT agonists, 5-CT, 8-OH DPAT or alpha-methyl 5-HT produced endothelium-dependent smooth muscle relaxation, when applied against a background of contraction. 6 These data show that endothelium-dependent smooth muscle contraction can be produced by stimulating 5-HT receptors in the partially contracted rabbit basilar artery. Similar contraction to 5-CT indicates an involvement by 5-HT1 receptors. The susceptibility of the contractions to indomethacin suggest they are mediated by a metabolite of arachidonic acid.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Reoperative thyroid surgery.

BACKGROUND: Patients with thyroid cancer are sometimes denied repeat thyroid operations for fear of an increased risk of complications. METHODS: We therefore reviewed our experience in 114 patients with benign or malignant thyroid tumors who underwent 116 thyroid reoperations with or without other procedures. All patients had undergone at least one prior thyroid operation and 16 patients had undergone from two to four thyroid operations before referral. The initial histologic diagnosis before reoperation was thyroid carcinoma in 79 patients, papillary carcinoma in 47 patients, follicular carcinoma in 17 patients, medullary carcinoma in 9 patients, and Hürthle cell carcinoma in 6 patients. Benign disease was present in 35 patients. In 62 patients with cancer, reoperations were performed because of suspected persistent or recurrent disease; one of these patients underwent two reoperations by us. In 17 patients reoperation was to complete total thyroidectomy, primarily so that radioactive iodine could be used to scan for and treat metastatic disease. RESULTS: Among the 116 reoperations, 102 were completion total thyroidectomy, 8 were near-total or subtotal thyroidectomy, and 6 were completion lobectomy. Histologic examination at reoperation revealed thyroid carcinoma in 51 cases (64%) among the 79 patients who had undergone 80 operations for previous thyroid cancer. Recurrent or persistent cancer was present in 49 of 63 (78%) reoperations for patients with papillary, medullary, and Hürthle cell cancer but in only 2 of 17 (12%) patients with follicular cancer. Cancer also occurred in 8 cases (22%) of the 36 reoperations in 35 patients who initially had benign lesions. Complications included one permanent and one transient palsy of the recurrent laryngeal nerve; both occurred on the side of a previous partial or subtotal lobectomy. Other complications included temporary hypoparathyroidism in four patients, seromas in two patients, and a keloid in one patient. CONCLUSIONS: This study documents that reoperations can be performed with minimal morbidity. Thus patients should not be denied the chance to undergo removal of a persistent tumor or the remnant normal thyroid tissue because of the fear of complications.

Adolescent↗

5-hydroxytryptamine-stimulated accumulation of 1,2-diacylglycerol in the rabbit basilar artery: a role for protein kinase C in smooth muscle contraction.

1. 5-Hydroxytryptamine (5-HT) produced a concentration-dependent increase in the membrane concentration of 1,2-diacylglycerol (DG) in the rabbit isolated basilar artery, but did not stimulate the hydrolysis of membrane phosphoinositide. 2. The 5-HT-induced accumulation of DG could be blocked with the putative phospholipase C inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC; 70 microM), but not with the protein kinase C inhibitor, 1-(5-isoquinolinesulphonyl)-2-methyl piperazine (H7; 50 microM). 3. Direct stimulation of protein kinase C with phorbol 12,13-dibutyrate (PDBu) produced sustained smooth muscle contraction which was fairly rapid in onset and could be reversed by H7 but not by NCDC. The inactive phorbol, 4 alpha phorbol 12,13-dideceonate, did not produce contraction in the basilar artery. 4. 5-HT-induced contractions (1 nM-100 microM) were blocked or greatly reduced in the presence of the protein kinase inhibitor H7 or polymyxin B, and with the phospholipase C inhibitor, NCDC. The concentrations of these inhibitors which abolished contraction to 5-HT, did not alter smooth muscle contraction produced in response to 30 mM K(+)-physiological salt solution (PSS). 5. These data suggest that DG production and the subsequent activation of PKC forms an important component of the cerebrovascular contractile response to 5-HT. As the DG does not appear to arise from membrane phosphatidylinositol, it appears that 5-HT can stimulate the production of this second messenger in cerebral arteries by a mechanism which is different from peripheral arteries.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Calcium-induced gelation of low methoxy pectin solutions--thermodynamic and rheological considerations.

Rheological changes occurring during the gelation of low methoxy pectins in the presence of calcium ions were investigated. The onset of gelation was found to correspond to the same macroscopic rheology (i.e. value of G') whatever the gelling conditions. Sol-gel diagrams for calcium pectin systems were mapped out in terms of calcium level, temperature and pectin concentration. The thermodynamic parameters for the cross-linking process were derived.

Calcium↗

Florid granulomatous reaction in a seminoma.

A case of seminoma of the testis complicated by an extensive granulomatous reaction is reported. This reaction was so florid that a benign condition was initially considered until further material for histology was examined and the correct diagnosis made.

Adult↗

Concentration dependence of the order-disorder transition of carrageenans. Further confirmatory evidence for the double helix in solution.

The temperature-induced changes in optical rotation which are associated with the order-disorder transition of carrageenans have been analysed to investigate the concentration dependence and hence to attempt to derive the number of polysaccharide chains involved in the ordered species at equilibrium. The consequences of the known polydispersity have been analysed by computer-modelling and it is shown that this need not cause misleading results. For iota-carrageenan segments of 0.1 M NaCl and 0.1 M KCl solution the results point to a two-chain state and therefore support the proposed double helix model. For chi-carrageenan segments the apparent average number of molecules involved in the ordered state at equilibrium is 3.7, suggesting that if double helices form here they aggregate further. The method of investigation may be generally applicable to measuring the number of chains which associate in ordered states in aqueous solutions of polysaccharides.

Carrageenan↗