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Biomedical subjects

G Kenneth Haines

Publications and source records attributed to G Kenneth Haines.

31 records · Page 2Linked to original sources
PubMed2003

The H+/K+-ATPase (proton) pump is expressed in human laryngeal submucosal glands.

OBJECTIVES/HYPOTHESIS: Diagnosis and treatment of gastroesophageal and laryngopharyngeal reflux disease has significantly increased over recent years. The larynx is highly sensitive to the effects of LPRD and is similarly responsive to proton pump inhibitor pharmacotherapy. The hypothesis of the study was that proton pump activity exists in the human larynx and plays a functional role in normal and/or pathological laryngeal tissue. STUDY DESIGN: Pathological investigation. METHODS: Two fresh human cadaveric larynges (one male and one female larynx) were obtained as part of an exempt protocol from the Human Subjects Committee and were formalin fixed and paraffin embedded. Banked human stomach tissue was also obtained for use as comparative positive and negative control specimens. Sections were immunostained with monoclonal antibodies reactive with both alpha and beta subunits of the H+/K+-ATPase (proton) pump. Specimens were reviewed for staining pattern and intensity. RESULTS: Stomach parietal cells (known to produce gastric acid) exhibited strongly positive staining for both the alpha and beta subunits of the proton pump. There was no staining in stomach cells that were not morphologically consistent with the parietal cell. In the human larynx there were strong focal and identical staining patterns in the serous cells and ducts of the minor seromucinous glands by both alpha and beta monoclonals to the proton pump. There was variable staining in the laryngeal epithelium that was thought to be consistent with artifact staining resulting from tissue processing. CONCLUSION: The H+/K+-ATPase (proton) pump is present in serous cells and ducts of submucosal glands in the human larynx. Proton pump inhibitor pharmacotherapy may have a site of action in seromucinous glands of the human larynx, with possible relevance for patients treated for chronic laryngitis with or without laryngopharyngeal reflux disease.

Adenosine Triphosphatases↗
PubMed2003

Identification of thyroid hormone receptors in the human larynx.

PURPOSE: Thyroid hormone is essential for normal development, growth, and function of the majority of tissues. Among the many clinical signs associated with hypothyroidism, alterations in the voice may occur even in cases of mild thyroid failure, suggesting that the larynx is a target tissue for thyroid hormone. The objective of our study is to further understand the effects of thyroid hormone on the larynx by first identifying the presence and locations of its receptors. METHODS: Two human cadaveric larynges (one male and one female) were harvested, formalin-fixed, and paraffin-embedded. Sections were immunostained with antibodies reactive with the two identified thyroid hormone receptors, TR-alpha and TR-beta. The slides were examined under light microscopy. RESULTS: Both male and female specimens revealed consistent patterns of staining for thyroid hormone receptors. The staining pattern for TR-alpha included the fibrous connective tissue of the lamina propria, the cartilage, and the glandular elements. The staining pattern for TR-beta included the fibrous connective tissue of the lamina propria only. No receptors were identified in the respiratory mucosa or muscle. CONCLUSIONS: Thyroid hormone receptors are present in both the male and the female human larynx. These findings imply a role for thyroid hormone within the human larynx, through both TR-alpha and TR-beta.

Cartilage↗
PubMed2003

Renal cell carcinoma, chromophobe type, with collecting duct carcinoma and sarcomatoid components.

We report a case of a 72-year-old man with a chromophobe renal cell carcinoma that had both sarcomatoid and collecting duct carcinoma components. The 7-cm tumor occupied the entire lower pole of the kidney and infiltrated the renal parenchyma and the pelvic-calyceal system. Histologically, it had an area of classic chromophobe renal cell carcinoma that merged into a sarcomatoid component. Closely intermixed with the sarcomatoid component was a collecting duct carcinoma component characterized by highly pleomorphic, epithelioid cells arranged in cords, nests, and tubulomicrocystic structures. The cords, nests, and tubules were associated with a florid desmoplastic stromal response and numerous inflammatory cells. In addition, dysplastic changes were noted in adjacent nonneoplastic collecting duct epithelium. Immunohistochemical studies confirmed the presence of 3 distinct components in this patient's tumor. To the best of our knowledge, this is the first reported case of a chromophobe renal cell carcinoma with sarcomatoid and collecting duct carcinoma components.

Aged↗
PubMed2002

Sensitization of IFN-gamma Jak-STAT signaling during macrophage activation.

A general paradigm in signal transduction is ligand-induced feedback inhibition and the desensitization of signaling. We found that subthreshold concentrations of interferon-gamma (IFN-gamma), which did not activate macrophages, increased their sensitivity to subsequent IFN-gamma stimulation; this resulted in increased signal transducer and activator of transcription 1 (STAT1) activation and increased IFN-gamma#150;dependent gene activation. Sensitization of IFN-gamma signaling was mediated by the induction of STAT1 expression by low doses of IFN-gamma that did not effectively induce feedback inhibition. IFN-gamma signaling was sensitized in vivo after IFN-gamma injection, and STAT1 expression was increased after injection of lipopolysaccharide and in rheumatoid arthritis synovial cells. These results identify a mechanism that sensitizes macrophages to low concentrations of IFN-gamma and regulates IFN-gamma responses in acute and chronic inflammation.

Animals↗
PubMed2002

The contribution of accessory toxins of Vibrio cholerae O1 El Tor to the proinflammatory response in a murine pulmonary cholera model.

The contribution of accessory toxins to the acute inflammatory response to Vibrio cholerae was assessed in a murine pulmonary model. Intranasal administration of an El Tor O1 V. cholerae strain deleted of cholera toxin genes (ctxAB) caused diffuse pneumonia characterized by infiltration of PMNs, tissue damage, and hemorrhage. By contrast, the ctxAB mutant with an additional deletion in the actin-cross-linking repeats-in-toxin (RTX) toxin gene (rtxA) caused a less severe pathology and decreased serum levels of proinflammatory molecules interleukin (IL)-6 and murine macrophage inflammatory protein (MIP)-2. These data suggest that the RTX toxin contributes to the severity of acute inflammatory responses. Deletions within the genes for either hemagglutinin/protease (hapA) or hemolysin (hlyA) did not significantly affect virulence in this model. Compound deletion of ctxAB, hlyA, hapA, and rtxA created strain KFV101, which colonized the lung but induced pulmonary disease with limited inflammation and significantly reduced serum titers of IL-6 and MIP-2. 100% of mice inoculated with KFV101 survive, compared with 20% of mice inoculated with the ctxAB mutant. Thus, the reduced virulence of KFV101 makes it a prototype for multi-toxin deleted vaccine strains that could be used for protection against V. cholerae without the adverse effects of the accessory cholera toxins.

Animals↗
PubMed2002

Interleukin-13 gene therapy reduces inflammation, vascularization, and bony destruction in rat adjuvant-induced arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial pannus formation, leukocyte infiltration, and angiogenesis. Adenoviral production of interleukin-13 (IL-13) reduces levels of proinflammatory mediators in an explant model of RA synovial tissue in vitro. To assess this approach in an animal model of arthritis, we compared intra-articular injections of an adenovirus producing rat IL-13 (AxCArIL-13), a control virus, and rat ankles receiving phosphate-buffered saline (PBS) in rat adjuvant-induced arthritis (AIA). We demonstrate that IL-13 levels are normally low in ankles throughout the course of rat AIA. We show that administration of AxCArIL-13 before arthritis onset significantly reduces ankle circumference, paw volume, bony destruction, the number of polymorphonuclear cells (PMNs), the quantity of blood vessels, and levels of monocyte chemoattractant protein (MCP)-1 in ankles. When administered as a treatment to inflamed ankles, AxCArIL-13 decreases articular index scores, paw volumes, bony destruction, vascularization, tumor necrosis factor-alpha (TNF-alpha) levels, and the quantity of monocytes, lymphocytes, and PMNs. Thus, increasing IL-13 levels significantly ameliorates the course of rat AIA, suggesting that similar strategies for the treatment of human RA are worthy of further study.

Adenoviridae↗
PubMed2002

Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue.

Angiopoietins (Ang) are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis. We have compared the distribution of the receptor tyrosine kinase (Tie) and the Ang ligands in synovial tissues from normal subjects and those with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemical analysis was used to determine the expression of Ang-1, Ang-2, Tie1 and Tie2 in synovial tissue of normal subjects and those with RA and OA. Ang-1, Ang-2, Tie1 and Tie2 mRNA and protein expression were quantified in synovial tissues and RA synovial tissue fibroblasts with real-time reverse transcription polymerase chain reaction and western blot analysis. In RA, Ang-1 positive immunostaining on lining cells, macrophages and endothelial cells was significantly higher than in OA and normal synovial tissue. The expression pattern of Ang-2 in synovial tissue was similar in RA and OA, whereas the Ang-2 expression was low in normal tissue. Synovial tissue from subjects with RA and OA showed a significant upregulation of Tie1 on lining cells, macrophages and endothelial cells compared to that from normal subjects. Tie2 was significantly upregulated in the RA and OA synovial tissue lining cells, macrophages and smooth muscle cells compared to normal synovial tissue. Generally Ang-1, Ang-2, Tie1 and Tie2 mRNA levels were higher in RA synovial tissue compared to normal and OA synovial tissues, and RA synovial tissue fibroblasts. Western blot analysis also demonstrated greater Tie1 and Tie2 protein expression in RA and OA synovial tissue compared to RA synovial tissue fibroblasts. In conclusion, the dominance of Ang-1 mRNA and protein expression over Ang-2 is in agreement with an active neovascularization in RA synovial tissue.

Angiopoietin-1↗
PubMed2002

Expression of glutathione s-transferase pi in benign mucosa, Barrett's metaplasia, and adenocarcinoma of the esophagus.

BACKGROUND: Glutathione s-transferase pi (GSTpi) is an enzyme that provides cellular protection against redox-mediated damage by free radicals, which have been implicated in carcinogenesis. METHODS: Forty-three consecutive specimens from 19 patients were reviewed to identify samples of squamous mucosa, Barrett's metaplasia, adenocarcinoma, and peritumoral inflammation. Serial sections were stained with an anti-GSTpi polyclonal antibody, and GSTpi expression was quantified for each histologic group. RESULTS: GSTpi expression was diminished in peritumoral mononuclear inflammatory cells (p <.001) compared with squamous epithelium, Barrett's metaplasia, or adenocarcinoma. Barrett's metaplasia exhibited decreased GSTpi expression compared with squamous mucosa (p =.045). GSTpi expression by >50% of adenocarcinoma cells was associated with an increased risk (2.25x) of disease at last follow-up. CONCLUSIONS: GSTpi is prominently expressed in esophageal squamous mucosa and adenocarcinoma. Mononuclear cells may be susceptible to oxidative damage secondary to weak GSTpi production. GSTpi may protect the tumor cells themselves from the cytotoxic effects of free radicals. The biochemical role of GSTpi expression in malignant transformation deserves further investigation.

Adenocarcinoma↗
PubMed2002

Bilateral vocal process papillomas: report of a case.

We describe a case of bilateral vocal process lesions in a 65-year-old man. His history was strongly suggestive of vocal process granulomas: previous gastroesophageal reflux, intubation, smoking, and oral squamous cell carcinoma. Medical management with a proton-pump inhibitor, reflux precautions, voice therapy, and adequate hydration yielded no results. Subsequent surgical intervention revealed that he had squamous papillomas. We also provide a brief review of vocal process granulomas and squamous papillomas.

Aged↗
PubMed2000

Temporal expression of inflammatory cytokines and chemokines in rat adjuvant-induced arthritis.

OBJECTIVE: To examine cytokine and chemokine production during the evolution of rat adjuvant-induced arthritis (AIA), a model of rheumatoid arthritis. METHODS: Clinical and laboratory assessment of the course of AIA was performed over a 47-day period. Levels of the cytokines tumor necrosis factor a (TNFalpha), interleukin-1beta (IL-1beta), and IL-6, as well as levels of the chemokines macrophage inflammatory protein 1alpha (MIP-1alpha) and JE, the murine homolog of monocyte chemoattractant protein 1, were determined by enzyme-linked immunosorbent assay in the sera and joints of AIA and control rats. Synovia from AIA rats were (immuno)histochemically analyzed. Results of cytokine and chemokine measurements were correlated with clinical and laboratory markers of inflammation and histology. RESULTS: Early (before day 14 post adjuvant injection) and later phases of AIA could be distinguished. Cytokine and chemokine production was increased in AIA versus control rats. The production of TNFalpha, IL-1beta, MIP-1alpha, and, as determined earlier, epithelial neutrophil-activating peptide 78-like protein was abundant prior to and during the course of AIA, while that of IL-6 and JE was elevated in the late phase of AIA. Cytokine and chemokine levels were correlated with the clinical symptoms of arthritis and blood neutrophil counts. Joint levels of IL-1beta showed correlation with synovial lining proliferation and neutrophil ingress into AIA synovium. CONCLUSION: Cytokines and chemokines are involved in the clinical, laboratory, and histologic changes underlying AIA. The production of these mediators may be temporally and spatially regulated. These findings may be important for the optimal timing of cytokine and chemokine targeting.

Animals↗
PubMedDate not supplied

Nitric oxide and apoptosis during human head and neck squamous cell carcinoma development.

PURPOSE: Apoptosis index (AI), Bcl-2, and Bax have shown prognostic significance in head and neck squamous cell carcinoma (HNSCCa). Other areas of research have implicated nitric oxide (NO) or its various intermediate species in both proapoptotic and antiapoptotic processes. We have previously shown that NO-generating enzymes are significantly increased during the stepwise progression to HNSCCa. The aim of this study was to explore the interrelationship of NO and a known consequence of NO-related oxidative stress, apoptosis, during this step-wise process. MATERIALS AND METHODS: Formalin fixed-paraffin embedded tissue samples of 10 normal oral mucosa, 15 reactive/dysplastic lesions, and 17 HNSCCa lesions studied previously were subjected to the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP labeling (TUNEL) assay as well as immunohistochemical staining against Bcl-2, Bax, and p53. Patient charts were reviewed and clinical data were compared. The study pathologist (G.K.H) reviewed these slides blinded to patient identifiers or clinical data. The number of immunopositive cell nuclei or staining intensity was graded, noting the pattern of immunostaining. These staining characteristics were compared with the results of immunostaining previously obtained for endothelial constitutive NO synthase (ecNOS) and nitrotyrosine. RESULTS: Compared with normal oral mucosa, the AI, Bcl-2, Bax, Bcl-2/Bax intensity and frequency ratios, and mutant p53 intensity significantly changed in reactive/dysplastic and HNSCCa lesions (P <.001 for all). Correlations between the staining characteristics of the antigens studied are presented. Furthermore, perilesional inflammatory cells showed staining in the TUNEL assay. CONCLUSIONS: In a set of tissue samples previously well characterized, these new findings implicate a link between NO and the induction of apoptotic cell death in HNSCCa development.

Antibodies, Monoclonal↗
PubMedDate not supplied

Long-term effects of FloSeal packing after endoscopic sinus surgery.

BACKGROUND: A previous study by our group showed increased adhesions and granulation tissue in ethmoid cavities packed with FloSeal (FS) compared with those packed with thrombin-soaked gelatin foam after endoscopic sinus surgery (ESS). That study included 20 patients whose cavities were graded 6-8 weeks postoperatively. The goal of this study was to report long-term follow-up on this cohort. METHODS: At least 1 year follow-up was available in 18/20 patients. The number of office procedures required to lyse adhesions during the follow-up period was tabulated also. Pathology was available from one patient who underwent lysis of adhesions on an FS side. The histopathological findings are presented. RESULTS: The mean follow-up period was 21.4 (+/- 2.3) months, and none of the 18 patients required revision ESS during this interval. The overall incidence of adhesions (p = 0.013) and the number requiring lysis of adhesions (p = 0.046) were both greater in the FS group. During the interval between previous study evaluation (6-8 weeks postop) and last follow-up, five FS sides required a total of seven procedures to lyse adhesions. Silent adhesions were observed in an additional five FS sides. Although asymptomatic adhesions were observed in two thrombin-soaked gelatin sides at last examination, none underwent lysis. Biopsy of an adhesion from a patient packed with FS 25 months earlier revealed incorporated foreign material. CONCLUSION: FS appears to be associated with scar tissue formation and may be incorporated into recovering mucosa. Use of FS may increase the degree of postoperative care required after ESS.

Cohort Studies↗