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Biomedical subjects

P Russell

Publications and source records attributed to P Russell.

At least 181 records · Page 10Linked to original sources
PubMed1995

A comparison of Plague vaccine, USP and EV76 vaccine induced protection against Yersinia pestis in a murine model.

The median lethal dose (MLD) of a pathogenic strain of Yersinia pestis was established by three routes of administration in three strains of mouse. There was no significant difference between the MLDs in the different strains of mouse. The MLD by the subcutaneous route in Balb/C and an outbred line was approximately 1 c.f.u.; the MLD following intraperitoneal administration was tenfold higher. There were significant differences in the mean times to death after administration of the challenge by different routes. The relative efficacy of a live attenuated vaccine strain of Y. pestis (EV76) was compared with that of the formaldehyde-killed vaccine (Plague vaccine, USP). EV76 protected against high challenge doses (up to 5.75 x 10(6) MLD), though immunized animals showed side effects of varying severity. The killed vaccine was less effective in terms of dose-protection (deaths occurred after challenge with 4000 MLD) and several of the vaccinated animals suffered sub-lethal, plague-related sequelae to the challenge.

Animals↗
PubMed1995

Bacillus Calmette-Guerin (BCG) enhances monocyte- and lymphocyte-mediated bladder tumour cell killing.

A cytotoxicity assay was used to study the action of bacillus Calmette-Guerin (BCG) and cytokines on four human bladder cancer cell lines. Monocytes and lymphocytes from peripheral blood were incubated with or without BCG or cytokines for 24 h, after which [3H]thymidine-labelled target cells were added and the 72 h percentage specific release determined. BCG had a direct cytotoxic effect against tumour cells and significantly enhanced monocyte/macrophage and enhanced lymphocyte cytotoxicity against one cell line (UCRU-BL-17). Supernatants (SNs) from BCG-activated monocytes/macrophages and lymphocytes increased the percentage specific release of [3H]thymidine from UCRU-BL-17 cells. Interferon alpha (IFN-alpha) and interleukin 2 (IL-2) were cytotoxic towards UCRU-BL-17. No synergy occurred between BCG and cytokines at the concentrations tested. The results suggest that BCG is superior to IFN-alpha, interferon gamma (IFN-gamma) and IL-2 in enhancing cell-mediated cytotoxicity.

Carcinoma, Transitional Cell↗
PubMed1995

The effect of high-dose medium- and long- term progestogen exposure on endometrial vessels.

A total of 19 paraffin-embedded endometrial tissue blocks were obtained from high-dose progestogen-exposed patients. A labelled streptavidin-biotin-alkaline phosphatase method was used with antibodies against von Willebrand factor (vWF) and CD34. The density of CD34 and vWF positive (CD34+ and vWF+) vessels in progestogen-exposed endometria (103 +/- 9.6/mm2 and 106 +/- 8.7/mm2) was significantly lower than in endometria from women with normal cycles (169 +/- 9.3/mm2 and 136 +/- 8.0/mm2) (P < 0.05). In women with normal menstrual cycles the concentration of CD34+ vessels was significantly higher than the number of vWF+ vessels (P = 0.0001). By comparison, the concentration of CD34+ vessels was similar to the concentration of vWF+ vessels in progestogen-exposed endometria. The ratios of vascular density as determined by vWF+ and CD34+ staining the control and progestogen groups were 0.81 and 1.05 respectively (P = 0.0001). Dilated venules were seen in the progestogen group. This study has demonstrated firstly that CD34 antibody detected the endothelial cells in a higher proportion of small endometrial vessels than vWF, and secondly that high-dose progestogen exposure significantly decreased the density of microvessels and increased the number of dilated venules in endometrium.

Antigens, CD↗
PubMed1995

A new improved sub-unit vaccine for plague: the basis of protection.

In this study, we have determined the limit of protection achievable by immunisation with sub-units of Yersinia pestis against the development of plague in an experimental animal model. Co-immunisation with the purified culture-derived F1 and the recombinant V sub-units afforded a greater level of protection than with either sub-unit alone. The protection given by the combined sub-units was several orders of magnitude greater than that afforded by the whole cell killed (Cutter USP) vaccine and was equivalent to that achieved by vaccination with EV76, the live attenuated Y. pestis vaccine strain. However, the combined sub-unit vaccine has clear advantages over the live vaccine in terms of safety of use and absence of side-effects.

Animals↗
PubMed1995

Active immunization with recombinant V antigen from Yersinia pestis protects mice against plague.

The gene encoding V antigen from Yersinia pestis was cloned into the plasmid expression vector pGEX-5X-2. When electroporated into Escherichia coli JM109, the recombinant expressed V antigen as a stable fusion protein with glutathione S-transferase. The glutathione S-transferase-V fusion protein was isolated from recombinant E. coli and cleaved with factor Xa to yield purified V antigen as a stable product. Recombinant V antigen was inoculated intraperitoneally into mice and shown to induce a protective immune response against a subcutaneous challenge with 3.74 x 10(6) CFU of virulent Y. pestis. Protection correlated with the induction of a high titer of serum antibodies and a T-cell response specific for recombinant V antigen. These results indicate that V antigen should be a major component of an improved vaccine for plague.

Animals↗
PubMed1995

Diagnosis of follicular thyroid lesions by proton magnetic resonance on fine needle biopsy.

Most thyroidectomies are currently performed for diagnostic purposes. It has been established that proton magnetic resonance spectroscopy (MRS) on excised thyroid tissue can distinguish normal thyroid from invasive carcinomas (P < 0.0001). The purpose of this study was to assess whether the same discrimination could be obtained preoperatively from fine needle biopsy (FNB). This has clinical importance because cytological examination of fine needle aspirates cannot distinguish between benign and malignant follicular thyroid lesions. Here we demonstrate a sensitivity of 95% for proton MRS to correctly identify clinically or histologically proven carcinoma. MRS measurements were made on FNB specimens (containing as few as 10(6) cells) from solitary thyroid nodules. MR assessment of FNB was inconsistent with that of the corresponding tissue in only 6.5% of cases. The discrimination between cancer and normal tissue was based on altered cellular chemistry measured as a one-dimensional spectral ratio of resonances from the amino acid lysine and lipid. Benign follicular lesions were separated into two groups: 67% with a spectral ratio similar to malignant thyroid tumors, and 33% with a spectral ratio comparable to that in normal thyroid tissue. Thus, in contrast with histopathology, MRS offers a method for assessment of FNB of follicular lesions with the potential to identify a biologically benign group, which could avoid thyroid surgery for purely diagnostic purposes.

Adenocarcinoma, Follicular↗
PubMed1994

A role for Hsp90 in cell cycle control: Wee1 tyrosine kinase activity requires interaction with Hsp90.

Wee1 protein kinase regulates the length of G2 phase by carrying out the inhibitory tyrosyl phosphorylation of Cdc2-cyclin B kinase. Mutations were isolated that suppressed the G2 cell cycle arrest caused by overproduction of Wee1. One class of swo (suppressor of wee1 overproduction) mutation, exemplified by swo1-26, also caused a temperature sensitive lethal phenotype in a wee1+ background. The swo1+ gene encodes a member of the Hsp90 family of stress proteins. Swo1 is essential for viability at all temperatures. Swo1 coimmunoprecipitates with Wee1, showing that the two proteins interact. The swo1-26 mutant undergoes premature mitosis when grown at a semi-permissive temperature. These data strongly indicate that formation of active Wee1 tyrosine kinase requires interaction with Swo1, perhaps in a manner analogous to the previously demonstrated interaction between Hsp90 and v-src tyrosine kinase. These observations demonstrate a unexpected role for Hsp90 in cell cycle control.

Amino Acid Sequence↗
PubMed1994

Low molecular weight protein-tyrosine phosphatases are highly conserved between fission yeast and man.

Cdc25 protein phosphatase dephosphorylates tyrosine 15 of Cdc2, thereby activating Cdc2/cyclin B kinase, which then brings about mitosis. A fission yeast (Schizosaccharomyces pombe) cDNA expression library was screened for clones that rescue cdc25-22. In addition to the cdc25+ and pyp3+ protein-tyrosine phosphatase genes, a third gene was discovered. This gene, named stp1+ (small tyrosine phosphatase), encodes a approximately 17.5-kDa protein that is approximately 42% identical to members of an unusual class of small (approximately 18 kDa) cytosolic phosphatases previously known to exist only in mammalian species. The biological functions of these proteins are unknown, but they have vigorous protein-tyrosine phosphatase activity in vitro and have a sequence motif, Cys-X5-Arg, that is present at the active sites of all known types of protein-tyrosine phosphatases. Sequence homology between S. pombe Stp1 and its mammalian homologs is particularly high in the active site region of the proteins. Rescue of cdc25-22 by overproduction of Stp1 protein is probably due to an ability of Stp1 to dephosphorylate tyrosine 15 of Cdc2. Disruption of stp1+ causes no obvious phenotype. The fact that Stp1 homologs are highly conserved between yeast and man suggests that they have important functions.

Amino Acid Sequence↗
PubMed1994

ntf1+ encodes a 6-cysteine zinc finger-containing transcription factor that regulates the nmt1 promoter in fission yeast.

The nmt1+ gene of the fission yeast Schizosaccharomyces pombe is subject to transcriptional repression mediated by thiamine. The promoter of nmt1+ has been used to construct a series of vectors that are now commonly used for the regulated expression of genes in S. pombe. In this report, we described ntf1+, a gene involved in regulating nmt1+ expression. The ntf1+ gene was cloned in a high copy suppressor screen that utilized a construct, nmt1:wee1+, in which expression of the mitotic inhibitor Wee1 tyrosine kinase was placed under the control of the nmt1 promoter. ntf1+ encodes a 706-amino acid protein that shares substantial homology with a family of Cys6 zinc finger-containing transcription factors typified by GAL4 from Saccharomyces cerevisiae. Increased gene dosage of ntf1+ greatly increases both the repressed and derepressed activity of the nmt1 promoter. Cells having a disrupted version of ntf1+ are viable thiamine prototrophs, but basal expression from the nmt1 promoter is greatly reduced. These data demonstrate that Ntf1 plays an important role in regulating nmt1 expression.

Amino Acid Sequence↗
PubMed1994

The integrity of mammalian lenses in organ culture.

A method to quantitate protein leakage was developed to assess the integrity of mammalian lenses in organ culture. Protein leakage into the culture medium was found to be a strong indicator of lens integrity. Rat lens incubation medium that contained more than 14 micrograms protein per lens after 1 hr was indicative of lens damage. Damaged lenses almost always exhibited lens opacities within 24 hr. However, on occasion, a lens predicted by this method to be damaged would maintain clarity at the 24 hr timepoint. In these instances, damage was confirmed by the inability of the lens to accumulate [3H]choline and 86RbCl from the medium at levels equivalent to undamaged lenses. When the protein concentration of the incubation medium was greater than 14 micrograms per lens, there was a concomitant impairment of lens transport function. This indicates that quantitation of protein leakage is a better predictive measure of lens viability than is lens clarity. Rat lenses were oxidatively stressed by exposure to a bolus of hydrogen peroxide (final concentration, 1 mM). Within 24 hr, the lenses exhibited cortical opacities and the protein concentration of the medium was significantly increased over the controls. Western and slot blot analyses of the media revealed the presence of lens crystallins. beta B2-crystallin was the major component leaking from damaged lenses. The incubation media from control lenses exhibited no protein leakage. Comparative studies with Rhesus monkey lenses yielded similar data.

Animals↗
PubMed1994

Proton magnetic resonance and human cervical neoplasia. II. Ex vivo chemical-shift microimaging.

Proton chemical-shift imaging at 8.5 T has been used to detect malignant foci in small (6 mm3) biopsies from the human uterine cervix. Images based on the lipid resonances of frankly malignant cells discriminate between tumor tissue and host stroma and distinguish invasive from preinvasive cervical cancer (n = 7). With this method, foci of malignant cells were revealed in 500 micron slices with an in-plane resolution of 40 by 160 microns. The MR intensity maps reflected the local distribution of malignant cells as assessed by histopathology. The lower signal-to-noise ratio inherent for these non-water-based images was improved by applying postacquisitional matched Gaussian window functions, thus effecting a substantial increase in contrast with minimal loss in spatial resolution.

Adenocarcinoma↗
PubMed1994

Proton magnetic resonance and human thyroid neoplasia. I: Discrimination between benign and malignant neoplasms.

PURPOSE: Thyroid nodules are very common, yet the vast majority are biologically benign. The extreme difficulty facing the clinician selecting potentially malignant thyroid nodules for surgery was the subject of a recent editorial by Ernest L. Mazzaferri in the American Journal of Medicine (93:359-362, 1992). Here we evaluate the potential of proton magnetic resonance spectroscopy (1H MRS) to provide a solution to this problem. PATIENTS: Thyroid tissue from fifty-three patients undergoing partial or total thyroidectomy for solitary thyroid nodules were assessed by 1H MRS. RESULTS: When compared with the histologic diagnosis, 1H MRS distinguished normal thyroid tissue (n = 8) from invasive papillary (n = 9), anaplastic (n = 1), and medullary (n = 1) carcinomas with P values of < 0.0001, based on altered cellular chemistry. The same magnetic resonance (MR) criteria categorized pathologically proven follicular carcinoma (n = 8) (established as such by the presence of capsular or vascular invasion at the periphery of the tumor, or by the presence of metastases in the patient) with the other thyroid cancers (P < 0.0001). All other "benign" follicular neoplasms (n = 34), including five atypical follicular adenomas, were assessed by the same 1H MRS criteria and found to fit into one of the two above categories, viz. analogous to benign or malignant thyroid tissue. CONCLUSIONS: Proton MRS has the potential to separate out a group of truly benign follicular neoplasms from follicular tumors (both follicular adenomas and follicular carcinomas) that have an atypical follicular pattern on cytologic examination. This is the first report of an objective diagnostic procedure that has the potential to obviate surgical excision in a significant number of patients with benign follicular adenomas, independent of exhaustive histopathologic assessment.

Adenoma↗
PubMed1994

Differentiation and angiogenic growth factor message in two mammalian lens epithelial cell lines.

Lens epithelial cells in culture can sometimes be induced to form spheroid aggregates termed lentoid bodies, composed of cells exhibiting various characteristics of the more highly differentiated lens fiber cells. However, lentoid bodies are often slow to form, and the ability to produce them declines with serial subculture. It was therefore of interest to establish and/or characterize lens epithelial cell lines capable of forming lentoid bodies. The differentiation state was assessed in lentoid bodies formed by each of two lens epithelial cell lines, the transformed alpha TN4 cell line from mouse and the nontransformed N/N1135A cell line from rabbit. Lentoid and monolayer cultures of each cell line were examined for transcripts of the lens-specific alpha A-crystallin ("alpha A"), gamma D-crystallin ("gamma D"; formerly gamma 1-crystallin) and MP26 genes. alpha TN4 lentoid bodies contained 2.5 times the alpha A RNA found in monolayer cells, but lacked detectable gamma D and MP26 RNA. None of the three markers were detected in either lentoid or monolayer N/N1135A cultures grown under the conditions described. Lentoid body formation alone, therefore, does not indicate the extent of differentiation occurring. At least some of the changes in cell adhesion occurring during lentoid body formation involve laminin-like and fibronectin-like interactions, and are reminiscent of those observed during embryonic lens formation. Finally, vascular endothelial growth factor mRNA was absent from the lens but present in alpha TN4 cells, suggesting a mechanism whereby the lens tumors of the founder mouse became vascularized.

Amino Acid Sequence↗
PubMed1994

Alpha B-crystallin accumulation in human astroglioma cell line U373MG is stress-dependent and phosphorylation-independent.

alpha B-crystallin, a major lens protein, is present in non-lenticular tissues. Although alpha B-crystallin possesses chaperone-like activity, its physiological significance outside the lens is unclear. Recent studies suggest that stress-induced mechanisms of alpha B-crystallin accumulation are dependent upon the type of insult. To further investigate this possibility, the response of alpha B-crystallin to different stress conditions was examined in the human astroglioma U373MG cell line which constitutively expresses alpha B-crystallin. Exposure of this cell line to 25 microM cobalt chloride and heat stress resulted in increased accumulation of alpha B-crystallin. Exposure to cobalt chloride resulted in a 6-fold (water-soluble) and 5-fold (water-insoluble) increase in alpha B-crystallin, 4 h after the initial exposure to cobalt. The water-soluble fraction of U373 cells subjected to heat shock at 42 degrees C for 30 min and harvested after 1 h exhibited a 4.5-fold increase in the level of alpha B-crystallin over the control levels. Approximately 2 h after the removal of the cells from the heat stress, the level of alpha B-crystallin in the urea-soluble fraction increased 3-fold. Although alpha B-crystallin accumulation initially increased in response to both the cobalt and heat shock challenges, analysis of the pattern of protein accumulation indicates that there are differences in the mechanism of alpha B-crystallin induction which are dependent on the type of stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Astrocytoma↗